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1) Dean T. Jamison, Joel G. Breman, Anthony R. Measham, George Alleyne, Mariam Claeson,
David B. Evans, Prabhat Jha, Anne Mills, and Philip Musgrove, eds. 2006. Disease Control
Priorities in Developing Countries, 2nd ed. New York: Oxford University Press.

2) Alan D. Lopez, Colin D. Mathers, Majid Ezzati, Dean T. Jamison, and Christopher J. L.
Murray, eds. 2006. Global Burden of Disease and Risk Factors. New York: Oxford University

1   Diabetes: The Pandemic and Potential Solutions ............................................................................................................                       1
    Disease Control Priorities in Developing Countries
    K. M. Venkat Narayan, Ping Zhang, Alka M. Kanaya, Desmond E. Williams, Michael M. Engelgau, Giuseppina Imperatore, and Ambady
2   Cardiovascular Disease ....................................................................................................................................................       15
    Disease Control Priorities in Developing Countries
    Thomas Gaziano, K. Srinath Reddy, Fred Paccaud, Sue Horton, and Vivek Chaturvedi
3   Respiratory Diseases of Adults ........................................................................................................................................           33
    Disease Control Priorities in Developing Countries
    Frank E. Speizer, Susan Horton, Jane Batt, and Arthur S. Slutsky
4   Prevention of Chronic Disease by Means of Diet and Lifestyle Changes .......................................................................                                      47
    Disease Control Priorities in Developing Countries
    Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, Courtenay Dusenbury, Pekka Puska, and Thomas A. Gaziano
5   The Growing Burden of Risk from High Blood Pressure, Cholesterol, and Bodyweight ...............................................                                                  65
    Disease Control Priorities in Developing Countries
6   Tobacco Addiction ...........................................................................................................................................................     83
    Disease Control Priorities in Developing Countries
    Prabhat Jha, Frank J. Chaloupka, James Moore, Vendhan Gajalakshmi, Prakash C. Gupta, Richard Peck, Samira Asma, and Witold
7   Illicit Opiate Abuse ..........................................................................................................................................................   101
    Disease Control Priorities in Developing Countries
    Wayne Hall, Chris Doran, Louisa Degenhardt, and Donald Shepard
8   Occupational Health .........................................................................................................................................................     127
    Disease Control Priorities in Developing Countries
9   Complementary and Alternative Medicine ......................................................................................................................                     147
    Disease Control Priorities in Developing Countries
                                                                                     Chapter 30

                                         Diabetes: The Pandemic
                                          and Potential Solutions
                                                                                K. M. Venkat Narayan, Ping Zhang, Alka M. Kanaya, Desmond E.
                                                                                Williams, Michael M. Engelgau, Giuseppina Imperatore,
                                                                                and Ambady Ramachandran

NATURE AND DISTRIBUTION OF DIABETES                                             people age 20 to 79 (table 30.1). The prevalence of diabetes
                                                                                was higher in developed countries than in developing coun-
Diabetes is a metabolic disease characterized by hyperglycemia                  tries. In the developing world, the prevalence was highest in
resulting from defects in insulin secretion, insulin action, or                 Europe and Central Asia and lowest in Sub-Saharan Africa.
both (American Diabetes Association 2004).                                      Some of these variations may reflect differences in the age
                                                                                structures and level of urbanization of the various popula-
Classification of Diabetes                                                      tions. By 2025, the worldwide prevalence is projected to be 6.3
                                                                                percent, a 24 percent increase compared with 2003. The
Diabetes takes three major forms. Type 1 diabetes results from                  largest increase in prevalence by 2025 is expected to be in East
destruction of the beta cells in the pancreas, leading to absolute              Asia and the Pacific, and the smallest in Sub-Saharan Africa.
insulin deficiency. It usually occurs in children and young                     In terms of those affected, the biggest increase in the devel-
adults and requires insulin treatment. Type 2 diabetes, which                   oping countries is projected to take place among adults of
accounts for approximately 85 to 95 percent of all diagnosed                    working age.
cases, is usually characterized by insulin resistance in which                      In 2003, 194 million people worldwide ages 20 to 79 had
target tissues do not use insulin properly. A third type of dia-                diabetes, and by 2025, this number is projected to increase to
betes, gestational diabetes, is first recognized during pregnancy.              333 million, a 72 percent increase (table 30.1). The developing
Other rare types of diabetes include those caused by genetic                    world accounted for 141 million people with diabetes (72.5 per-
conditions (for example, maturity-onset diabetes of youths),                    cent of the world total) in 2003. During the same period, the
surgery, drug use, malnutrition, infections, and other illnesses.               number of people with diabetes is projected to double in three
                                                                                of the six developing regions: the Middle East and North Africa,
The Burden of Diabetes                                                          South Asia, and Sub-Saharan Africa.

Diabetes affects persons of all ages and races. The disease                     Diabetes-Related Mortality and Disability. The death rate
reduces both a person’s quality of life and life expectancy and                 of men with diabetes is 1.9 times the rate for men without
imposes a large economic burden on the health care system and                   diabetes, and the rate for women with diabetes is 2.6 times
on families.                                                                    that for women without diabetes (W. L. Lee and others
                                                                                2000). Premature mortality caused by diabetes results in an
Secular Trend and Projections. In 2003, the worldwide                           estimated 12 to 14 years of life lost (Manuel and Schultz
prevalence of diabetes was estimated at 5.1 percent among                       2004; Narayan and others 2003). Cardiovascular disease


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 30.1 Estimated Numbers of People Age 20 to 79 with Diabetes, Mortality, DALYs, and Direct Medical Costs Attributable to
Diabetes, by Regions

                                                                                                                       Direct medical costs,
                                                      Number of people                    Prevalence                   2003 (US$ million)
                                                                                                                                                             Deaths,               adjusted life
                                                      (thousands)                         (percent)
                                                                                                                     Low                 High                2001                  years, 2001
  Region                                              2003              2025            2003           2025          estimate            estimate            (thousands)           (thousands)

  Developing countries                              140,849           264,405            4.5            5.9            12,304               23,127                 757                15,804
     East Asia and the Pacific                        31,363            60,762           2.6            3.9              1,368               2,656                 234                 4,930
     Europe and Central Asia                          25,764            33,141           7.6            9.0              2,884               5,336                  51                 1,375
     Latin America and the Caribbean                  19,026            36,064           6.0            7.8              4,592               8,676                 163                 2,775
     Middle East and North Africa                     10,792            23,391           6.4            7.9              2,347               4,340                  31                   843
     South Asia                                       46,309            94,848           5.9            7.7                840               1,589                 196                 4,433
     Sub-Saharan Africa                                7,595            16,199           2.4            2.8                273                 530                  82                 1,448

  Developed countries                                 53,337            68,345           7.8            9.2           116,365             217,760                  202                 4,192
  World                                             194,186           332,750            5.1            6.3           128,669             240,887                  959                19,996

Source: Number of persons with diabetes, prevalence of diabetes, and direct medical costs of diabetes, International Diabetes Federation 2003b; all other information, WHO 2004.

(CVD) causes up to 65 percent of all deaths in developed                                              Economic Burden of Diabetes
countries of people with diabetes (Geiss, Herman, and Smith                                           Diabetes imposes large economic burdens on national
1995).                                                                                                health care systems and affects both national economies and
   The World Health Organization (WHO) estimates that, in                                             individuals and their families. Direct medical costs include
2001, 959,000 deaths worldwide were caused by diabetes,                                               resources used to treat the disease. Indirect costs include lost
accounting for 1.6 percent of all deaths, and approximately                                           productivity caused by morbidity, disability, and premature
3 percent of all deaths caused by noncommunicable diseases.                                           mortality. Intangible costs refer to the reduced quality of life for
More recent estimates by WHO suggest that the actual num-                                             people with diabetes brought about by stress, pain, and anxiety.
ber may be triple this estimate and that about two-thirds of
these deaths occur in developing countries (WHO 2004).                                                Direct Medical Costs. Good data on the direct medical costs
Within the developing regions, most deaths caused by diabetes                                         of diabetes are not available for most developing countries.
occurred in East Asia and the Pacific and the fewest in Sub-                                          Extrapolation from developed countries suggests that, in 2003,
Saharan Africa (table 30.1).                                                                          the direct costs of diabetes worldwide for people age 20 to 79
   Diabetes-related complications include microvascular dis-                                          totaled at least US$129 billion and may have been as high as
eases (for example, retinopathy, blindness, nephropathy, and                                          US$241 billion (table 30.1). In the developing world, the costs
kidney failure) and macrovascular diseases (coronary heart dis-                                       were highest in Latin America and the Caribbean and lowest in
ease, stroke, peripheral vascular disease, and lower-extremity                                        Sub-Saharan Africa. The direct health care costs of diabetes
amputation). Those complications result in disability. In the                                         range from 2.5 to 15.0 percent of annual health care budgets,
United States, a much higher proportion of people with dia-                                           depending on local prevalence and sophistication of the treat-
betes than of people without diabetes have physical limitations:                                      ments available (International Diabetes Federation 2003b).
66 percent compared with 29 percent (Ryerson and others
2003). Disabilities are even more pronounced among older                                              Indirect and Intangible Costs. In developing countries, the
people (Gregg and others 2000).                                                                       indirect costs of diabetes are at least as high, or even higher,
   The World Health Organization estimated that, in 2001, dia-                                        than the direct medical costs (Barcelo and others 2003).
betes resulted in 19,996,000 disability-adjusted life years                                           Because the largest predicted rise in the number of people with
(DALYs) worldwide. More than 80 percent of the DALYs result-                                          diabetes in the next three decades will be among those in the
ing from diabetes were in developing countries (table 30.1).                                          economically productive ages of 20 to 64 (King, Aubert, and
East Asia and the Pacific had the largest burden, and the Middle                                      Herman 1998), the future indirect costs of diabetes will be even
East and North Africa had the smallest burden. DALYs result-                                          larger than they are now.
ing from diabetes increased by 250 percent worldwide from                                                Diabetes lowers people’s quality of life in many ways,
1990 to 2001 and by 266 percent for low- and middle-income                                            including their physical and social functioning and their
countries (Mathers and others 2000).                                                                  perceived physical and mental well-being. With a value of

592 | Disease Control Priorities in Developing Countries | K. M. Venkat Narayan, Ping Zhang, Alka M. Kanaya, and others

                                                        ©2006 The International Bank for Reconstruction and Development / The World Bank
1 representing the health-related quality of life without illness                indigenous populations and in developing economies (Rowley
and 0 representing death, people with type 2 diabetes had a                      and others 1997; Williams and others 2001). Conversely, in
value of 0.77 in the population of the United Kingdom                            developed countries, those in lower socioeconomic groups
prospective diabetes study (Clarke, Gray, and Holman 2002).                      have a higher risk of obesity and consequently of type 2 diabetes
                                                                                 (Everson and others 2002). Surrogates for socioeconomic sta-
                                                                                 tus, such as level of education attained and income (Paeratakul
Risk Factors for Diabetes                                                        and others 2002; Robbins and others 2001) are inversely asso-
Risk factors for diabetes vary by disease type.                                  ciated with diabetes in high-income countries.

Type 1 Diabetes. Type 1 diabetes is most likely a polygenic dis-
ease, and a number of potential environmental risk factors have                  INTERVENTIONS AND DELIVERY MODES
been implicated—including dietary factors; breastfeeding; initi-
                                                                                 Interventions against diabetes include those for preventing the
ation of bovine milk; infectious agents (for example, enterovirus,
                                                                                 disease, those for detecting the disease in its asymptomatic stage,
rotavirus, and rubella); chemicals; and toxins—but the results
                                                                                 and those for managing the disease to reduce its complications.
have been inconclusive (Akerblom and Knip 1998).

Type 2 Diabetes. The risk for type 2 diabetes is higher in                       Preventing Type 1 Diabetes
monozygotic twins and people with a family history of diabetes                   Not enough scientific evidence is available to indicate that
(Rich 1990). This finding strongly suggests that genetic deter-                  type 1 diabetes can be prevented, although various interven-
minants play a role, but so far few genes have been associated                   tions have been explored. Examples of tested interventions
with type 2 diabetes.                                                            include eliminating or delaying exposure to bovine protein and
    Environmental factors include prenatal factors, obesity,                     using insulin or nicotinamide for people at high risk of devel-
physical inactivity, and dietary and socioeconomic factors                       oping the disease.
(Qiao and others 2004). Exposure to diabetes in utero increases
the risk of developing type 2 diabetes in early adulthood
(Dabelea and others 2000). Disproportionate growth and low                       Preventing Type 2 Diabetes
birthweight increase the risk of developing diabetes and insulin                 Four major trials—in China, Finland, Sweden, and the United
resistance. In the postnatal environment, breastfeeding protects                 States—have demonstrated that intensive lifestyle interventions
against the development of obesity, insulin resistance, and dia-                 involving a combination of diet and physical activity can delay
betes (Pettitt and others 1997; Young and others 2002).                          or prevent diabetes among people at high risk (Eriksson and
    The strongest and most consistent risk factors for diabetes                  Lindgarde 1991; Knowler and others 2002; Pan and others 1997;
and insulin resistance among different populations are obesity                   Tuomilehto and others 2001). In the largest randomized, con-
and weight gain (Haffner 1998): for each unit increase in body                   trolled trial to date, the Diabetes Prevention Program (Knowler
mass index, the risk of diabetes increases by 12 percent (Ford,                  and others 2002), the goals of the intensive lifestyle intervention
Williamson, and Liu 1997). The distribution of fat around the                    were weight loss of 7 percent of baseline bodyweight through
trunk region, or central obesity, is also a strong risk factor for               a low-calorie diet and moderate physical activity for at least
diabetes (Yajnik 2001). Diabetes risk may be reduced by increas-                 150 minutes per week. After 2.8 years of follow-up, the average
ing physical activity. Conversely, a sedentary lifestyle and physi-              weight loss was 4.5 kilograms for those in the lifestyle interven-
cal inactivity are associated with increased risks of developing                 tion group and less than 0.3 kilograms for those in the placebo
diabetes (Hu and others 2003). Some studies report a positive                    group. The lifestyle intervention reduced the incidence of dia-
relationship between dietary fat and diabetes, but specific types                betes by 58 percent.
of fats and carbohydrates may be more important than total fat                       Pharmacological studies of diabetes prevention have been
or carbohydrate intake. Polyunsaturated fats and long-chain                      reviewed in detail elsewhere (Kanaya and Narayan 2003). In
omega-3 fatty acids found in fish oils (Adler and others 1994)                   summary, a variety of specific medications have been tested
may reduce the risk of diabetes, and saturated fats and trans                    (for example, metformin, acarbose, orlistat, troglitazone,
fatty acids may increase the risk of diabetes (Hu, van Dam, and                  angiotensin-converting enzyme [ACE] inhibitors, statins,
Liu 2001). Sugar-sweetened beverages are associated with an                      estrogens, and progestins) and have been found to lower dia-
increased risk of diabetes (Schulze and others 2004). High                       betes incidence, but the expense, side effects, and cumulative
intakes of dietary fiber and of vegetables may reduce the risk of                years of drug intervention are practical concerns. Except for the
diabetes (Fung and others 2002; Stevens and others 2002).                        Diabetes Prevention Program (Knowler and others 2002), no
    Increased affluence and Westernization have been associated                  trial of medication intervention has directly compared the
with an increase in the prevalence of diabetes in many                           effectiveness of a drug to that of lifestyle modification.

                                                                                                                 Diabetes: The Pandemic and Potential Solutions | 593

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
Screening for People with Diabetes or Prediabetes                                                         Managing Diabetes
The benefits of early detection of type 2 diabetes through                                                High-quality evidence exists for the efficacy of several current
screening are not clearly documented, nor is the choice of the                                            treatments in reducing morbidity and mortality in people with
appropriate screening test established. Questionnaires used                                               diabetes. These interventions are summarized in table 30.2.
alone tend to work poorly; biochemical tests alone or in com-                                                 In addition, a review of previous studies (Norris,
bination with assessment of risk factors are a better alternative                                         Engelgau, and Narayan 2001) found positive effects for short
(Engelgau, Narayan, and Herman 2000).                                                                     follow-up (less than six months) of self-management training

Table 30.2 Effectiveness and Cost-Effectiveness of Interventions for Preventing and Treating Diabetes in Developed Countries

                                                                                                                                Quality of        Cost-effectiveness ratio
  Strategy                                                     Benefit                                                          evidencea         (US$/QALY)b
  Preventing diabetes
  • Lifestyle interventions for preventing                     Reduction of 35–58 percent in incidence among                             I        1,100 (Diabetes Prevention Program Research
     type 2 diabetes                                           people at high risk                                                                Group forthcoming)
  • Metformin for preventing type 2 diabetes                   Reduction of 25–31 percent in incidence among                             I        31,200 (Diabetes Prevention Program Research
                                                               people at high risk                                                                Group forthcoming)
  Screening for diabetes
  • Screening for type 2 diabetes in general                   Reduction of 25 percent in microvascular                                 III       73,500 (CDC Diabetes Cost-Effectiveness Study
     population                                                disease                                                                            Group 1998)
  Treating diabetes and its complications
  • Glycemic control in people with HbA1c                      Reduction of 30 percent in microvascular disease                          I        Cost saving (CDC Diabetes Cost-Effectiveness
     greater than 9 percent                                    per 1 percent drop in HbA1c                                                        Study Group 1998)
  • Glycemic control in people with HbA1c                      Reduction of 30 percent in microvascular disease                          I        34,400 (CDC Diabetes Cost-Effectiveness Study
     greater than 8 percent                                    per 1 percent drop in HbA1c                                                        Group 1998; Klonoff and Schwartz 2000)
  • Blood pressure control in people whose                     Reduction of 35 percent in macrovascular and                              I        Cost saving (CDC Diabetes Cost-Effectiveness
     pressure is higher than 160/95 mmHg                       microvascular disease per 10 mmHg drop in                                          Study Group 1998)
                                                               blood pressure
  • Cholesterol control in people with total                   Reduction of 25–55 percent in coronary heart                            II-1       63,200 (CDC Diabetes Cost-Effectiveness Study
     cholesterol greater than 200 milligrams/                  diseases events; 43 percent fall in death rate                                     Group 1998)
  • Smoking cessation with recommended                         16 percent quitting rate                                                  I        12,500 (CDC Diabetes Cost-Effectiveness Study
     guidelines                                                                                                                                   Group 1998)
  • Annual screening for microalbuminuria                      Reduction of 50 percent in nephropathy using                             III       47,400 (Klonoff and Schwartz 2000)
                                                               ACE inhibitors for identified cases
  • Annual eye examinations                                    Reduction of 60 to 70 percent in serious                                  I        6,000 (Klonoff and Schwartz 2000; Vijan, Hofer,
                                                               vision loss                                                                        and Hayward 2000)
  • Foot care in people with high risk of ulcers               Reduction of 50 to 60 percent in serious foot                             I        Cost saving (Ragnarson and Apelqvist 2001)
  • Aspirin use                                                Reduction of 28 percent in myocardial infarctions,                        I        Not available
                                                               reduction of 18 percent in cardiovascular disease
  • ACE inhibitor use in all people with                       Reduction of 42 percent in nephropathy;                                   I        8,800 (Golan, Birkmeyer, and Welch 1999)
     diabetes                                                  22 percent drop in cardiovascular disease
  • Influenza vaccinations among the elderly                   Reduction of 32 percent in hospitalizations;                            II-2       3,100 (Sorensen and others 2004)
     for type 2 diabetes                                       64 percent drop in respiratory conditions and
  • Preconception care for women of                            Reduction of 30 percent in hospital charges and                         II-2       Cost saving (Klonoff and Schwartz 2000)
     reproductive age                                          25 percent in hospital days

Source: Authors.
Note: mmHg millimeters of mercury; QALY quality-adjusted life year.
a. I indicates evidence from at least one randomized, controlled trial; II-1 indicates evidence from a well-designed, controlled trial without randomization; II-2 indicates evidence from cohort or case con-
trol studies; and III indicates opinions of respected authorities (U.S. Preventive Services Task Force 1996).
b. We adjusted cost-effectiveness ratios to 2002 U.S. dollars using the consumer price index for medical care. In cases in which multiple studies evaluated the cost-effectiveness of an intervention, we
report the median cost-effectiveness ratio.

594 | Disease Control Priorities in Developing Countries | K. M. Venkat Narayan, Ping Zhang, Alka M. Kanaya, and others

                                                          ©2006 The International Bank for Reconstruction and Development / The World Bank
on knowledge, frequency, and accuracy of self-monitoring of                      ratios—each weighted by its share (Barcelo and others 2003)—
blood glucose; self-reported dietary habits; and glycemic con-                   for outpatient care, inpatient care, drugs and laboratory tests,
trol. Effects on lipids, physical activity, weight, and blood                    and treatment for diabetic complications. The cost ratio for each
pressure varied.                                                                 cost component was calculated as the cost of medical services or
                                                                                 drugs in the United States divided by the cost of the same serv-
                                                                                 ices or drugs in Latin America and the Caribbean. U.S. data for
COST-EFFECTIVENESS OF INTERVENTIONS                                              medical services and drugs for routine diabetes care, plus treat-
                                                                                 ment cost for diabetes complications, were obtained from a
                                                                                 1998 cost-effectiveness Markov model of the U.S. Centers for
Most of the interventions to prevent and treat diabetes and its                  Disease Control and Prevention (CDC). Data for laboratory
complications significantly affect the use of health services. The               service were obtained from the 2001 Clinical Diagnostic
limitations of clinical trials include their failure in most cases               Laboratory Fee Schedule from the U.S. Centers for Medicare
to capture the entire intervention effect over a lifetime and to                 Services (available from Data for Latin
include all segments of a population to whom the intervention                    America and the Caribbean were obtained from three coun-
may apply. Evaluating the cost-effectiveness of interventions                    tries—Argentina (Gagliardino and others 1993), Brazil (Health
often requires the use of computer simulation models, but data                   Policy Division of the Brazilian Ministry of Health), and Mexico
availability, technical complexity, and resource needs present a                 (Villarreal-Rios and others 2000).
significant barrier to constructing such models for developing                       We applied Mulligan and others’ framework (2003) to esti-
countries. Furthermore, data on interventions are often avail-                   mate the costs of intervention and diabetes care in each devel-
able only from developed countries, and these data are often                     oping region. Assuming that cost estimates are available for one
extrapolated to developing countries.                                            of the regions, this framework allows the development of a rel-
                                                                                 ative cost index for health care services that can then be used to
                                                                                 obtain cost estimates for the other five regions. Using costs esti-
Estimating the Cost-Effectiveness of Interventions                               mated by Mulligan and others (2003), we first estimated three
in Developing Countries                                                          health service indexes, including hospital bed days, outpatient
To assess the cost-effectiveness of interventions in developing                  and inpatient services, and laboratory tests and procedures. We
countries, we updated the results from Klonoff and Schwartz’s                    then combined the three indexes into one overall index for dia-
(2000) comprehensive review by including studies that were                       betes care in accordance with the share of each component in
published up to 2003. Table 30.2 summarizes the cost-                            developing countries (Barcelo and others 2003). Finally, we
effectiveness of interventions for the developed countries,                      estimated the costs of intervention and diabetes care in the
mainly in the United States. The results show that the cost-                     other five developing regions by multiplying the cost of care in
effectiveness of interventions varies greatly—from cost saving                   the Latin America region by the overall regional relative cost
(an intervention is both more effective and less expensive than                  index.
the comparator) to US$73,500 per quality-adjusted life year
(QALY) gained.
    We estimated the cost-effectiveness ratio of diabetes interven-              Ranking Implementation Priorities
tions for the six developing regions shown in table 30.3. We                     We assessed the implementation priority and feasibility of
assumed that the effectiveness of these interventions, as                        interventions, as explained in table 30.3.
measured in QALYs, was the same as in developed countries but
that the cost of interventions and other diabetes care differed                  Level 1 Interventions. All three interventions in this category
between developed and developing countries and also among the                    are cost saving and are also feasible in terms of all four aspects
six developing regions. Using this assumption, we estimated                      considered. The barrier to implementing these interventions
the cost-effectiveness ratio for a developing region as the cost-                may be a short-term hike in intervention costs.
effectiveness ratio in the developed country, mainly represented                    Glycemic control in a population with poor control (hemo-
by the United States, multiplied by the ratio of costs in the devel-             globin A1c greater than 9 percent or another measure of
oping region to the cost in the developed countries, which we                    glucose control in situations where HbA1c tests may be unaf-
calculated as follows. These cost-effectiveness ratios are based on              fordable) is cost saving because the reduction in medical care
costs and benefits over a lifetime, except for preconception care                costs associated with both short-term and long-term complica-
for women of reproductive age.                                                   tions is greater than is the cost of intervention. Glycemic con-
    We estimated that the cost of intervention and other diabetes                trol for people with type 1 diabetes involves insulin use and, for
care in the United States was 8.6 times the cost in Latin America                people with type 2 diabetes, depending on the stage and sever-
and the Caribbean. This cost ratio was an average of four cost                   ity of the disease, consists of diet and physical activity, oral

                                                                                                                 Diabetes: The Pandemic and Potential Solutions | 595

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 30.3 Cost-Effectiveness of Interventions for Preventing and Treating Diabetes and Its Complications in Developing Regions

                                                                                          Cost/QALY (2001 US$)

                                             East Asia                       Latin America Middle East
                                             and                Europe and and the         and                                              Sub-Saharan                                Implementing
  Intervention                               the Pacific        Central Asia Caribbean     North Africa                          South Asia Africa                        Feasibilitya priorityb

  Level 1
  Glycemic control in                        Cost saving        Cost saving         Cost saving             Cost saving          Cost saving       Cost saving                 ++++                   1
  people with HbA1c
  higher than 9 percent
  Blood pressure control in                  Cost saving        Cost saving         Cost saving             Cost saving          Cost saving       Cost saving                 ++++                   1
  people with pressure higher
  than 160/95 mmHg
  Foot care in people with                   Cost saving        Cost saving         Cost saving             Cost saving          Cost saving       Cost saving                 ++++                   1
  a high risk of ulcers

  Level 2
  Preconception care for women              Cost saving         Cost saving         Cost saving             Cost saving          Cost saving       Cost saving                  ++                    2
  of reproductive age
  Lifestyle interventions for                        80                100                   130                   110                   60                  60                 ++                    2
  preventing type 2 diabetes
  Influenza vaccinations among                     220                 290                   360                   310                 180                  160                ++++                   2
  the elderly for type 2 diabetes
  Annual eye examination                           420                 560                   700                   590                 350                  320                 ++                    2
  Smoking cessation                                870               1,170                 1,450                 1,230                 730                  660                 ++                    2
  ACE inhibitor use for people                     620                 830                 1,020                   870                 510                  460                +++                    2
  with diabetes

  Level 3
  Metformin intervention for                     2,180               2,930                 3,630                 3,080               1,820               1,640                  ++                    3
  preventing type 2 diabetes
  Cholesterol control for people                 4,420               5,940                 7,350                 6,240               3,680               3,330                 +++                    3
  with total cholesterol higher
  than 200 milligrams/deciliter
  Intensive glycemic control for                 2,410               3,230                 4,000                 3,400               2,000               1,810                  ++                    3
  people with HbA1c higher
  than 8 percent
  Screening for undiagnosed                      5,140               6,910                 8,550                 7,260               4,280               3,870                  ++                    3
  Annual screening for                           3,310               4,450                 5,510                 4,680               2,760               2,500                  ++                    3

Source: Authors.
a. Feasibility was assessed based on difficulty of reaching the intervention population (the capacity of the health care system to deliver an intervention to the targeted population), technical complexity
(the level of medical technologies or expertise needed for implementing an intervention), capital intensity (the amount of capital required for an intervention), and cultural acceptability (appropriateness
of an intervention in terms of social norms and/or religious beliefs). ++++ indicates feasible for all four aspects, +++ indicates feasible for three of the four, ++ indicates feasible for two of the four, and
+ indicates feasible for one of the four.
b. Implementing priority was assessed by combining the cost-effectiveness of an intervention and its implementation feasibility; 1 represents the highest priority and 3 represents the lowest priority.

glucose-lowering agents, and insulin. Patient education is an                                               For example, the mean HbA1c level for people with diabetes
essential component of these interventions to encourage                                                     in India was 8.9 percent in 1998 (Raheja and others 2001).
patients to comply with medication regimes and to change to                                                 A survey conducted by the International Diabetes Federation
and maintain healthy lifestyles.                                                                            in 1997 (2003b) showed that no country in Africa had 100 per-
   Glucose is generally poorly controlled in people with both                                               cent accessibility to insulin. Ensuring adequate access to
type 1 and type 2 diabetes, mostly because of lack of access to                                             insulin should be an important priority for developing
insulin and other diabetes supplies in developing countries.                                                countries.

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    Blood pressure control for people with diabetes and hyper-                  the prevalence of diabetes in all regions. The expertise
tension reduces the incidence of both microvascular and                         required for the intervention, such as dietitians and exercise
macrovascular diseases. Major medication interventions                          physiologists, and the capacity of health care systems to han-
include an ACE inhibitor, thiazide diuretics, or a beta blocker.                dle the large populations eligible for the intervention may
Blood pressure control is cost saving mainly because of its large               present a barrier to implementing the intervention in many
health benefits and relatively low intervention costs. Even in the              developing countries.
United States, moderate blood pressure control costs less than                     People with diabetes are at higher risk of complications
US$250 per patient per year. Because many blood pressure                        from influenza and pneumococcal infections than those
medications are generic drugs, the costs are much lower in                      without diabetes. Influenza vaccinations are a relatively cost-
developing countries. In addition, the prevalence of people                     effective intervention, mainly because of the low intervention
with poor control of blood pressure may be high in developing                   cost. However, the level of adoption for the intervention would
countries. For example, in Latin America and the Caribbean,                     depend on a country’s ability to deliver the intervention to the
60 percent of people with type 2 diabetes in 2000 had blood                     targeted population.
pressure higher than 140/90 mmHg (Gagliardino, de la Hera                          The detection of proliferative diabetic retinopathy and mac-
and Siri 2001).                                                                 ular edema by dilated eye examination followed by appropriate
    Complications related to foot problems are common among                     laser photocoagulation therapy prevents blindness. Annual
diabetics in developing countries. For example, in India,                       screening and treatment programs for diabetic retinopathy cost
43 percent of diabetes patients had foot-related complications                  US$700 or less per QALY gained in developing countries. The
(Raheja and others 2001). Interventions for foot care are low                   intervention is more cost-effective among older people, those
tech and require little capital. Interventions for foot care in                 who require insulin (Klonoff and Schwartz 2000), or those with
developing countries should include educational programs for                    poor glucose control (Vijan, Hofer, and Hayward 2000). In
patients and professionals (for example, on foot hygiene, treat-                addition, screening less frequently, such as every two years, may
ment of calluses, awareness of functional infections, and care                  be more cost-effective than screening every year (Vijan, Hofer,
for skin injuries); access to appropriate footwear; and multidis-               and Hayward 2000). Eye complications among people with
ciplinary clinics. All three interventions could be cost saving,                diabetes are common in developing countries; for example,
mainly because the cost of the interventions is low and the                     39 percent of people with diabetes in India had eye-related com-
interventions can reduce the risk of foot ulceration and ampu-                  plications (Rajala and others 1998). Although laser treatment is
tation, which are costly. Applying these interventions for high-                an effective intervention, such treatment may not be available in
risk patients, such as those with at least one previous foot ulcer              many developing countries or may be extremely costly.
or amputation, would yield even larger savings (Klonoff and                        ACE inhibitors can lower the blood pressure of those with
Schwartz 2000).                                                                 hypertension and delay the onset or prevent further progres-
                                                                                sion of renal disease for those with diabetes. Compared with
Level 2 Interventions. The six interventions in this category                   screening for microalbuminuria and treating only those who
are either cost saving and not feasible in one or more aspects or               have the condition, offering ACE inhibitors to all people with
cost less than US$1,500 per QALY and are at least moderately                    diabetes was more cost-effective at less than US$1,020 per
feasible. Thus, interventions in this category represent good                   QALY gained. This intervention was more cost-effective among
value for money but may present some difficulties in terms of                   younger people and was sensitive to the cost of drug. Thus,
feasibility.                                                                    lowering the cost of the medication is a key factor for the suc-
   Preconception care among women of reproductive age                           cess of this intervention in developing countries.
includes patient education and intensive glucose management.                       Smoking cessation includes both counseling and using
This intervention reduces short-term hospital costs for both                    medication such as a nicotine patch. Smoking cessation
mothers and infants and improves birth outcomes. However,                       appears to be the least cost-effective among the level 2 inter-
the intervention may not be feasible in some developing                         ventions. However, the benefits of smoking cessation may be
countries because of the resources needed for the intervention                  underestimated because our calculations only took the reduced
and the difficulty of reaching the target population.                           risk of CVD into account (Earnshaw and others 2002). Adding
   The lifestyle intervention for preventing type 2 diabetes                    the health benefits derived from preventing cancer and pul-
costs US$60 to US$130 per QALY over a lifetime, depending                       monary diseases would improve the cost-effectiveness of
on the region. The potential population eligible for a lifestyle                smoking cessation. Considering the high prevalence of smok-
intervention (those with impaired glucose tolerance or                          ing in developing countries, smoking cessation should be a
impaired fasting glucose) is large in developing countries. The                 high-priority intervention, but the availability of the nicotine
International Diabetes Federation (2003b) estimates that the                    patch may be a barrier to implementing this intervention in
prevalence of impaired glucose tolerance was at least as high as                developing countries.

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Level 3 Interventions. The five interventions included in this                           antihypertensive medications—aspirin, statin, and folic acid
category cost at least US$1,640 per QALY but could cost as                               (see also chapter 33). Currently, neither is it available for use,
much as US$8,550 per QALY. Compared with the level 1 and 2                               nor have estimates of its benefits and adverse effects been con-
interventions, those in this category are also less feasible. In                         firmed in a formal, randomized, controlled trial. The idea is
general, depending on cost-effectiveness and feasibility, these                          thus still theoretical. The cost-effectiveness of this hypothetical
interventions may not always be justifiable for all people in                            pill was, however, simulated using a computer model of people
developing countries, given the limited health care resources.                           with newly diagnosed diabetes in the United States (Sorensen
However, these interventions may be reasonable for selected                              and others 2004), and the assessment found that a polypill
subpopulation groups, such as those who can afford them.                                 intervention would cost US$11,000 per QALY gained. The
   Metformin therapy for preventing type 2 diabetes among                                intervention would be cost saving if such a pill cost US$1.28
people at high risk, such as those with prediabetes, is feasible                         or less per day. We estimated that the cost-effectiveness ratio of
because the drug is affordable in many developing countries;                             the polypill ranged from US$560 to US$1,280 per QALY
however, the intervention may not be good value for money.                               gained for the six developing regions. This result was sensitive
Cholesterol control intervention for people with diabetes falls                          to changes in the cost of the intervention, but the intervention
into the same category. The cost-effectiveness of both these                             remained cost-effective within the most likely ranges of its cost
interventions would improve if the costs of the drug could be                            (Sorensen and others 2004). A barrier to this intervention, in
lowered.                                                                                 addition to the feasibility of producing such pill, is that its
   The aim of intensive glucose control is to lower the glucose                          benefits and side effects would still have to be established in a
level of a person with diabetes to a level close to that of a per-                       randomized clinical trial.
son without diabetes. Implementing this intervention is a lower
priority, mainly because of its relatively low cost-effectiveness
in the context of the limited health care resources in develop-                          Cost-Effectiveness of Diabetes Education
ing countries. Although the U.K. Prospective Diabetes Study                              People with diabetes play a central role in managing their dis-
clearly demonstrates that lowering glucose levels can prevent or                         ease. Thus, diabetes education is an integral part of diabetes
delay long-term diabetes complications (UKPDS Group 1998),                               care. The goal of diabetes education is to support the efforts
the marginal return on very intensive glucose control in devel-                          of people with diabetes to understand the nature of their
oping countries was relatively small.                                                    illness and its treatment; to identify emergency health prob-
   Screening for undiagnosed diabetes is a low-priority inter-                           lems at early, reversible stages; to adhere to self-care practices;
vention mainly because of its relatively high cost per QALY.                             and to make necessary changes to their health habits
However, screening for undiagnosed diabetes can be a worth-                              (International Diabetes Federation 2003b). Health providers
while intervention for subpopulation groups, such as those that                          can deliver diabetes education programs in various settings.
have a high prevalence of undiagnosed diabetes. In the United                            Evaluating the effectiveness of health education is challenging
States, for example, screening for undiagnosed diabetes among                            because of the difficulty of separating out its effect from that
African Americans was estimated to be 10 times more cost-                                of other interventions. Nevertheless, a review of literature
effective than screening among other population groups (CDC                              published in the United States suggests that self-management
Diabetes Cost-Effectiveness Study Group 1998). In addition,                              diabetes education may be cost-effective (Klonoff and
screening for undiagnosed diabetes may be a worthwhile inter-                            Schwartz 2000).
vention for patients with risk factors for other chronic diseases,                           Training in diabetes self-management reduces medical
such as hypertension, high lipid profiles, and prediabetes.                              costs for diabetes care in developing countries in the short
   Annual screening for microalbuminuria was a low-priority                              term. A multicenter intervention study in 10 Latin American
intervention because screening added costs with no significant                           countries demonstrated that an education program could
benefits. Treating all persons with diabetes with ACE inhibitors                         reduce the cost of drugs by 62 percent (International Diabetes
was a better treatment option than screening for microalbu-                              Federation 2003b), and another program in Argentina found a
minuria and treating only those who have the condition.                                  reduction in diabetes-related costs of 38 percent (Gagliardino
                                                                                         and Etchegoyen 2001). Because the costs of education pro-
                                                                                         grams are generally low, the intervention may be cost-effective.
Cost-Effectiveness of a Polypill to Prevent CVD                                          Training patients to better manage their diabetes is also
A meta-analysis estimated that a hypothetical polypill could                             feasible because of its low technical complexity, low capital
reduce the risk of CVD by 80 percent among all people over                               requirements, and cultural acceptability. Thus, diabetes educa-
55 or people with diabetes of any age (Wald and Law 2003).                               tion should be a high-priority intervention for all developing
This hypothetical pill is a combination of three half-dose                               regions.

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                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
LESSONS AND EXPERIENCE                                                          had hypertension, 53 percent had high cholesterol, and 45 per-
                                                                                cent had abnormal triglycerides (Gagliardino, de la Hera, and
A number of lessons can be learned from the experiences                         Siri 2001).
in countries where the interventions described have been
                                                                                Quality of Diabetes Care
                                                                                Small, single-site studies indicate that several interventions to
                                                                                improve quality of care at the patient, provider, or system lev-
Data are sparse on community- or population-based strategies                    els are promising (Narayan and others 2004). A systematic
for preventing diabetes along with other chronic diseases such                  review (Renders and others 2001) found that multifaceted pro-
as CVD. Available studies on preventing type 2 diabetes have                    fessional interventions may enhance providers’ performance in
used clinic-based approaches targeted at high-risk groups, and                  managing diabetes care; that organizational interventions
researchers generally agree that type 2 diabetes can be prevent-                involving regularly contacting and tracking patients by means
ed or its onset delayed. Putting these results into practice, how-              of computerized tracking systems or through nurses can also
ever, is fraught with difficulties and unanswered questions,                    improve diabetes management; that patient-oriented interven-
such as the following:                                                          tions can improve patients’ outcomes; and that nurses can play
                                                                                an important role in patient-oriented interventions by educat-
• Who would benefit from diabetes prevention?                                   ing patients and facilitating patients’ adherence to treatment
• How can those who may benefit be identified?                                  regimes. (See also chapter 70.)
• What are the costs and cost-effectiveness of diabetes pre-                       Interventions that could modify providers’ behavior include
  vention at a population level?                                                education as part of more complex interventions that also
• How should results be extrapolated from developed countries                   focus on systems and on the organization of practices—for
  to developing countries, whose priorities and approaches                      example, feedback on performance, reminder systems, consen-
  may be different?                                                             sus development, and clinical practice guidelines. Potential
                                                                                systemic interventions include the use of continuous quality
                                                                                improvement techniques; feedback on performance; physician
Treatment                                                                       incentives for quality; nurses to provide diabetes care (which is
The quality of diabetes care generally remains suboptimal                       typically provided by physicians); computerized reminder sys-
worldwide, regardless of a particular country’s level of devel-                 tems for providers, alone or in combination with a perform-
opment, health care system, or population (Engelgau and oth-                    ance feedback program; patient-tracking or other reminder
ers 2003; Garfield and others 2003). The Costs of Diabetes in                   systems to improve regular follow-up; dedicated blocks of time
Europe—Type 2 study, conducted in eight European countries,                     set aside for diabetes patients in primary care practices; team
found suboptimal diabetes care in each country (Liebl, Mata,                    care; electronic medical record systems; and other methods,
and Eschwege 2002). In the United States, population-based                      such as telephone and mailing reminders, chart stickers, and
surveys in the 1990s among adults age 18 to 75 with diabetes                    flow sheets to prompt both providers and patients.
found that only 63 percent of them had had a dilated eye exam-                     Interventions that empower patients can be successful com-
ination and only 55 percent had had a foot examination with-                    ponents of diabetes programs. A systems-oriented approach
in the past year, 18 percent had poor glycemic control, 42 per-                 using manual or computerized systems that remind patients to
cent had good cholesterol control, and 66 percent had a blood                   make follow-up appointments and that prompt staff members
pressure within the normal range (Saaddine and others 2002).                    to generate reminder cards for patients can improve compli-
   The Diabcare-Asia project was conducted in the late 1990s.                   ance with follow-up and enhance efficiency of office practices.
Results from India, Singapore, and Taiwan (China) found that                    In addition, comprehensive implementation of multiple risk-
in 1998, 32 to 50 percent of the diabetic population had poor                   factor interventions in real-life settings has been shown to
glycemic control (equivalent to HbA1c          8 percent), 43 to                reduce vascular events by more than 50 percent among people
67 percent had high cholesterol (greater than 5.2 millimoles per                with diabetes (Gaede and others 2003).
deciliter), and 47 to 54 percent had an abnormal level of triglyc-                 The Institute of Medicine Committee on Quality of Health
eride (greater than 1.7 millimoles per deciliter) (W. R. Lee and                Care in America (2001) argues strongly that newer systems of
others 2001; Raheja and others 2001). Data from Latin America                   care and newer ways of thinking are needed to tackle complex
and the Caribbean showed that 41 percent of people with type                    diseases such as diabetes. Furthermore, the model of the process
1 diabetes and 57 percent of those with type 2 diabetes had                     of change in a simple mechanical system is woefully inadequate
poor glucose control. Of those with type 2 diabetes, 56 percent                 for dealing with the complex, interactive, and interconnected

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                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
adaptive systems in which diabetes is prevented and treated.                             Medicine Committee on Quality of Health Care in America
Applied research, designed to encompass the system as a whole                            2001).Computer models suitable for assessing cost-effectiveness
and not simply its component parts, can enhance our under-                               and for forecasting the burden in developing countries are need-
standing of complex health care dynamics for chronic diseases                            ed. Operational research aimed at understanding the tradeoffs
(Fraser and Greenhalgh 2001; Plsek and Greenhalgh 2001).                                 and the best mix of resource allocation for diabetes and chronic
                                                                                         disease care in developing countries is also needed.

RESEARCH AND DEVELOPMENT AGENDA                                                          Basic Research

The following subsections discuss the major issues for research                          Further strategic unraveling of the genetic basis of type 2 dia-
and development.                                                                         betes and gene-environment interactions may help explain the
                                                                                         diabetes epidemic and provide better understanding of the
                                                                                         pathophysiology of the disease. It may also may lead to better
                                                                                         prevention and treatment strategies. Understanding the role of
Well-designed community-based studies of primary preven-                                 prenatal influences, especially in developing countries, may
tion for type 2 diabetes are needed, especially as part of multi-                        offer productive opportunities for interventions. Because of the
factorial interventions, in developing countries. Research is also                       increasing occurrence of type 2 diabetes in children, as well as
needed into safer and cheaper drugs to prevent diabetes when                             the role of obesity in accelerating the onset of type 1 diabetes,
lifestyle intervention either is not feasible or has failed. In addi-                    further research into the typology and classification of diabetes
tion, we need to know the long-term effects of diabetes preven-                          is vital. The rapid industrialization and economic development
tion on CVD and other outcomes. More effective and cheaper                               being experienced by several developing countries may make
ways to prevent the major complications of diabetes are also                             research into the role of socioeconomic factors, urban stress,
needed. Other areas also deserving of research include nonin-                            and lifestyle factors on the causation of diabetes productive.
vasive methods for monitoring blood glucose and more effec-
tive and efficient ways of screening for prediabetes, diabetes,
and early diabetes complications. Evidence of the benefits of                            CONCLUSIONS
diabetes education on outcomes is lacking, and organized
research to assess effective components of diabetes education                            A growing diabetes pandemic is unfolding with rapid increases
and their impact on control of risk factors and long-term out-                           in the prevalence of type 2 diabetes. The direct health care costs
comes should be a priority.                                                              of diabetes worldwide amount to 2003 US$129 billion per year.
                                                                                         Estimates indicate that developing countries spend between
Epidemiological and Economics Research                                                   2.5 and 15.0 percent of their annual direct health budgets on
                                                                                         diabetes care, and families with diabetic members spend 15 to
Scant data are available on the future burden of diabetes and its
                                                                                         25 percent of their incomes on diabetes care.
complications in developing countries. Data on trends in and
                                                                                             A whole array of effective interventions to prevent diabetes
the effects of risk factors for diabetes in developing countries—
                                                                                         and its complications is available, and we have attempted to
obesity; birthweight; physical inactivity; television viewing;
                                                                                         assess their potential cost-effectiveness in developing regions.
dietary factors; fast foods; socioeconomic factors; and effects of
                                                                                         Using these estimations and a qualitative assessment of the fea-
urbanization, industrialization, globalization, and stress—are
                                                                                         sibility of implementation, we have prioritized available inter-
also sparse. Low-cost ways to obtain such data in a standardized
                                                                                         ventions into the following three categories:
manner may be worth considering. More data are also needed
on the costs of diabetes, the impact of the disease on quality of
                                                                                         • level 1—cost saving and highly feasible
life, and the cost-effectiveness of various interventions in the
                                                                                         • level 2—cost saving or cost less than US$1,500 per QALY
context of developing countries (International Diabetes
                                                                                           but pose some feasibility challenges
Federation 2003a).
                                                                                         • level 3—cost between US$1,640 and US$8,550 per QALY
                                                                                           and pose significant feasibility challenges.
Health Systems and Operational Research
Greater emphasis on translation research is needed. Well-                                   Table 30.4 presents a summary of all major diabetes inter-
designed and standardized studies of quality of care and out-                            ventions, major health effects of the interventions, and level of
comes will help (TRIAD Study Group 2002). Research aimed at                              implementation priority.
understanding system-level complexity and finding ways to                                   In addition, we propose diabetes education as an essential
deliver chronic disease care that takes such complexity into                             intervention. However, more organized research into the
account is also likely to yield profitable results (Institute of                         precise components of diabetes education and its effect on

600 | Disease Control Priorities in Developing Countries | K. M. Venkat Narayan, Ping Zhang, Alka M. Kanaya, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 30.4 Key Cost-Effective Interventions for Preventing and Treating Diabetes and Its Complications

  Intervention                                Description                                              Applicable population                             Major effect
  Level 1
  • Glycemic control in people with           Insulin, oral glucose-lowering agents, diet              People with diabetes, all ages, HbA1c             Reduction in microvascular disease
     poor control                             and exercise                                             greater than 9 percent
  • Blood pressure control                    Blood pressure control medications                       People with diabetes, hypertensive,               Reduction in macrovascular disease,
                                                                                                       all ages                                          microvascular disease, and mortality
  • Foot care                                 Patient and provider education, foot                     People with diabetes, middle-aged                 Reduction in serious foot diseases and
                                              examination, foot hygiene, and appropriate               or older                                          amputations

  Level 2 b
  • Preconception care for women              Patient self-management                                  Women with diabetes who plan to                   Reduction in HbA1c level and hospital
     of reproductive age                                                                               become pregnant                                   expenses of the mother and baby
  • Lifestyle intervention to prevent Behavioral change, including diet and                            People who are at high risk (for example, Reduction in type 2 diabetes incidence
     diabetes                                 physical activity, to reduce bodyweight                  prediabetes for type 2 diabetes)          by 58 percent
  • Influenza vaccination                     Vaccination                                              Elderly people with diabetes                      Reduction in hospitalizations,
                                                                                                                                                         respiratory conditions, and mortality
  • Detection and treatment of eye            Eye examination to screen for and treat eye              People with diabetes, middle-aged                 Reduction in serious vision loss
     diseases                                 diseases                                                 or older
  • ACE inhibitors                            Angiotensin-converting enzyme medication                 People with diabetes                              Reduction in nephropathy,
                                                                                                                                                         cardiovascular disease, and death
  • Smoking cessation                         Physician counseling and nicotine                        People with diabetes, all ages,                   Increase in quitting rate and reduction
                                              replacement therapy                                      smokers                                           in cardiovascular disease
  Level 3 c
  • Metformin therapy for                     Metformin medication                                     People who are at high risk                       Reduction in type 2 diabetes incidence
     preventing diabetes                                                                               (for example, prediabetes for                     by 33 percent
                                                                                                       type 2 diabetes)
  • Intensive glucose control                 Insulin, oral glucose-lowering agents,                   Diabetes, all ages, with HbA1c less               Reduction in microvascular disease
                                              or both                                                  than 9 percent
  • Lipid control                             Cholesterol-lowering medication                          Diabetes, all ages, with high                     Reduction in cardiovascular disease
                                                                                                       cholesterol                                       events and mortality
  • Screening for microalbuminuria            Screening for microalbuminuria and treating              Diabetes, all ages                                Reduction in kidney diseases
                                              those who test positive
  • Screening for undiagnosed                 Screening for undiagnosed diabetes and                   People who are at high risk for type 2            Reduction in microvascular disease
     diabetes                                 treating those who test positive                         diabetes

  Essential background intervention d
  Diabetes education                          Patient self-management                                  Diabetes, all ages                                Reduction in HbA1c level and better
                                                                                                                                                         compliance with lifestyle changes
  Other promising intervention e
  Polypill                                    Hypothetical pill combining low doses of                 Diabetes, all ages                                Reduction in cardiovascular disease
                                              antihypertensive medication, aspirin, statin,
                                              and folate

Source: Authors.
a. Level 1 interventions are cost saving and highly feasible.
b. Level 2 interventions are cost saving or cost less than US$1,500 per quality-adjusted life year but pose feasibility challenges.
c. Level 3 interventions cost between US$1,640 and US$8,550 per quality-adjusted life year and pose significant feasibility challenges.
d. Diabetes education is the backbone on which many diabetes interventions depend, but empirical data on the effectiveness of diabetes education on outcomes and on the precise components of
diabetes education are still lacking.
e. An intervention that appears promising but needs further research to document its effectiveness and/or safety. The polypill is only a theoretical concept at this time and is not available for

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                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
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©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                     Chapter 33

                                          Cardiovascular Disease
                                                                                Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, Sue Horton,
                                                                                and Vivek Chaturvedi

Cardiovascular disease (CVD) is the number one cause of                         Predominant Cardiovascular Diseases
death worldwide (Mathers and others 2006; Murray and Lopez                      This chapter focuses on the most common causes of CVD
1996; WHO 2002b). CVD covers a wide array of disorders,                         morbidity and mortality:
including diseases of the cardiac muscle and of the vascular sys-
tem supplying the heart, brain, and other vital organs. This                    • ischemic heart disease (IHD)
chapter reviews the epidemiological transition that has made                    • stroke
CVD the world’s leading cause of death, assesses the status of                  • congestive heart failure (CHF).
the transition by region, and indicates regional differences in
the burden of CVD. It also reviews the cost-effectiveness of var-                   These diseases account for at least 80 percent of the burden
ious interventions directed at the most relevant causes of CVD                  of CVD in all income regions, which share many of the same
morbidity and mortality.                                                        common risk factors; accordingly, similar interventions are
                                                                                appropriate. A fourth manifestation, rheumatic heart disease
                                                                                (RHD), which accounts for 3 percent of all disability-adjusted
EPIDEMIOLOGY OF CVD                                                             life years (DALYs) lost as a result of CVD, does not contribute
                                                                                significantly to the overall global burden of CVD. The burden
At the beginning of the 20th century, CVD was responsible for                   of RHD will likely continue to diminish, but it is still an impor-
less than 10 percent of all deaths worldwide, but by 2001 that                  tant inflammatory cause of heart disease in developing coun-
figure was 30 percent. About 80 percent of the global burden of                 tries and accordingly is addressed in this chapter. We do not
CVD death occurs in low- and middle-income countries.                           address many other forms of CVD because of the scope of this
Murray and Lopez (1996) predicted that CVD will be the lead-                    volume; the regional rather than global nature of some inflam-
ing cause of death and disability worldwide by 2020 mainly                      matory diseases, such as Chagas disease; or the congenital
because it will increase in low- and middle-income countries.                   abnormalities or genetically based cardiomyopathies for which
By 2001, CVD had become the leading cause of death in the                       prevention and treatment options remain limited.
developing world, as it has been in the developed world since
the mid 1900s (Mathers and others 2006; WHO 2002a). Nearly                      Ischemic Heart Disease. IHD is the single largest cause of death
50 percent of all deaths in high-income countries and about 28                  in the developed countries and is one of the main contributors
percent of deaths in low- and middle-income countries are the                   to the disease burden in developing countries. The two leading
result of CVD (Mathers and others 2006). Other causes of                        manifestations of IHD are angina and acute myocardial infarc-
death, such as injuries, respiratory infections, nutritional defi-              tion. In 2001, IHD was responsible for 7.3 million deaths and 58
ciencies, and HIV/AIDS, collectively still play a predominant                   million DALYs lost worldwide (WHO 2002b). Seventy-five per-
role in certain regions, but even in those areas CVD is now a                   cent of global deaths and 82 percent of the total DALYs resulting
significant cause of mortality.                                                 from IHD occurred in the low- and middle-income countries.


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank

     ACE inhibitors (angiotensin-converting enzyme                                       Dyslipidemia: a condition marked by abnormal concen-
     inhibitors): a group of antihypertensive drugs that exert                           trations of lipids or lipoproteins in the blood.
     their influence through the renin-angiotensin-aldosterone                           Embolus: a blood clot that moves through the blood-
     system.                                                                             stream until it lodges in a narrowed vessel and blocks
     Antiplatelets: drugs that interfere with the blood’s ability                        circulation.
     to clot.
                                                                                         Endocarditis: inflammation of the lining of the heart and
     Atheroschlerosis: a chronic disease characterized by                                its valves.
     thickening and hardening of the arterial walls.
                                                                                         Hypertension: abnormally high arterial blood pressure.
     Atrial fibrillation: an abnormal rhythm of the heart that
                                                                                         Reperfusion: restoration of the flow of blood to a previ-
     can result in an increased risk of stroke because of the for-
                                                                                         ously ischemic tissue or organ.
     mation of emboli (blood clots) in the heart.
     Beta-blockers: a group of drugs that decrease the heart                             Statins: a group of drugs that inhibit the synthesis of cho-
     rate and force of contractions and lower blood pressure.                            lesterol and promote the production of low-density
                                                                                         lipoprotein (LDL)–binding receptors in the liver, resulting
     Cardiogenic shock: poor tissue perfusion resulting
                                                                                         in a decrease in the level of LDL and a smaller increase in
     from failure of the heart to pump an adequate amount of
                                                                                         the level of high-density lipoprotein (HDL).
                                                                                         Thrombolysis: the breaking up of a blood clot.
     Cardiomyopathy: a disorder of the muscle limiting the
     heart’s function.                                                                   Thrombus: a blood clot that forms inside a blood vessel or
                                                                                         cavity of the heart.
     Chagas disease: a tropical American disease caused by a
     parasitic infection. Chronic symptoms include cardiac                               Transient ischemic attack: transient reduced blood flow
     problems, such as an enlarged heart, altered heart rate or                          to the brain that produces strokelike symptoms but no
     rhythm, heart failure, or cardiac arrest.                                           lasting damage.

    Angina is the characteristic pain of IHD. It is caused by                            Stroke. Stroke is caused by a disruption in the flow of blood to
atherosclerosis leading to stenosis (partial occlusion) of one or                        part of the brain either because of the occlusion of a blood
more coronary arteries. Patients with chronic stable angina                              vessel (ischemic stroke) or the rupture of a blood vessel (hem-
have an average annual mortality of 2 percent or less. Acute                             orrhagic stroke). Many of the same risk factors for IHD apply
myocardial infarction (AMI) is the total occlusion of a major                            to stroke; in addition, atrial fibrillation is an important risk fac-
coronary artery with a complete lack of oxygen and nutrients                             tor for stroke. The annual risk of stroke in patients with non-
leading to cardiac muscle necrosis. AMI is usually diagnosed                             valvular atrial fibrillation is 3 to 5 percent, with 50 percent of
by changes in the electrocardiogram; by elevated serum                                   thromboembolic stroke being attributable to atrial fibrillation
enzymes, such as creatine phosphokinase and troponin T or I;                             (Wolf, Abbott, and Kannel 1991). Chapter 32 discusses the
and by pain similar to that of angina. Thirty-day mortality                              diagnosis and management of the clinical syndromes in greater
after an AMI is high: even with best medical therapy it                                  detail.
remains at about 33 percent, with half the deaths occurring
before the individual reaches the hospital. Even in a hospital                           Congestive Heart Failure. CHF is the end stage of many heart
with a coronary care unit where advanced care options are                                diseases. It is characterized by abnormalities in myocardial func-
available, mortality is still 7 percent. In a hospital without                           tion and neurohormonal regulation resulting in fatigue, fluid
such facilities or therapies, the mortality rate is closer to 30                         retention, and reduced longevity. CHF is caused by pathological
percent. Even though mortality among patients who have                                   processes that affect the heart; IHD and hypertension-related
recovered from an AMI has declined in recent decades,                                    heart disease are the most common etiologies. The risk of
approximately 4 percent of patients who survive initial hospi-                           developing CHF is two times more in hypertensive men and three
talization die in the first year following the event (Antman                             times more in hypertensive women compared with those who are
and others 2004).                                                                        normotensive. CHF is five times more common in those who

646 | Disease Control Priorities in Developing Countries | Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
have had an AMI than in those who have not. The prognosis for                   illness and death. Before 1900, infectious diseases and malnu-
those with established CHF is generally poor and worse than for                 trition were the most common causes of death; however,
those with most malignancies (McMurray and Stewart 2000) or                     primarily because of improved nutrition and public health
AIDS, with a one-year mortality rate as high as 40 percent and a                measures, they have gradually been supplanted in most high-
five-year mortality between 26 and 75 percent.                                  income countries by CVD and cancer. As improvements con-
    The worldwide burden of CHF is substantial and continues                    tinue to spread to developing countries, CVD mortality rates
to rise. Throughout the developed world the prevalence is                       are increasing.
about 2 to 3 percent, with an annual incidence rate of 0.1 to 0.2                   Known as the epidemiological transition, this shift is highly
percent (McMurray and Stewart 2000). However, the incidence                     correlated with changes in personal and collective wealth (the
and prevalence of CHF rise dramatically with age. Prevalence is                 economic transition), social structure (the social transition),
27 per 1,000 population for those older than 65, compared with                  and demographics (the demographic transition). Omran
0.7 per 1,000 for those younger than 50 (McKelvie 2003). CHF                    (1971) provides an excellent model of the epidemiological
occurs more frequently in men, and incidence and mortality                      transition that divides it into three basic ages: pestilence and
differ substantially according to gender and socioeconomic sta-                 famine, receding pandemics, and degenerative and human-
tus. CHF causes 53,000 deaths in the United States each year                    created diseases (table 33.1). Olshansky and Ault (1986) add a
and contributes to another 213,000, and the death rate attrib-                  fourth stage: delayed degenerative diseases.
uted to CHF rose by 155 percent from 1979 to 2001 in the                            The consistent pattern for most high-income countries going
United States (American Heart Association 2002). CHF is the                     through the epidemiological transition has been initially high
first-listed diagnosis in 1 million hospitalizations.                           rates of stroke, mostly hemorrhagic. Only in the third phase,
                                                                                with the presence of increased resources, but coupled with
Rheumatic Heart Disease. RHD is the consequence of an                           increased diabetes and smoking rates and adverse lipid profiles,
acute rheumatic fever (ARF)—that is, a poorly adapted                           do rates of IHD climb. This phase is also accompanied by better
autoimmune response to group A -hemolytic streptococci. It                      control of severe hypertension, reducing the rates of hemor-
affects the connective tissue, mainly the joints and the heart                  rhagic stroke, which is then replaced by ischemic stroke. Most
valves. The most serious complications are valvular stenosis,                   regions appear to be following this pattern and have a predomi-
regurgitation following the valvulitis, or both (Ephrem,                        nance of IHD. The two exceptions are East Asia and the Pacific
Abegaz, and Muhe 1990). RHD is also a predisposing factor for                   and Sub-Saharan Africa. The pattern in East Asia and the Pacific
infective endocarditis, a disease of younger adults, predomi-                   is dominated by China and appears to be a result of China’s stage
nantly males (Koegelenberg and others 2003).                                    in the transition but may also be following a pattern similar to
    According to 2001 estimates, RHD accounts for 338,000                       Japan’s—that is, dominated by more strokes and fewer IHD
deaths per year worldwide, two-thirds of them in Southeast                      deaths—whereas Sub-Saharan Africa is in an earlier phase of the
Asia and the Western Pacific (WHO 2002b). About 12 million                      epidemiological transition.
people in developing countries, most of them children, suffer                       Even though countries tend to enter these stages at different
from RHD (WHO 1995). Steer and others’ (2002) review of                         times, the progression from one stage to the next tends to pro-
developing countries suggests that RHD prevalence in children                   ceed in a predictable manner. The six World Bank regions are
is between 0.7 and 14 per 1,000, with the highest rates in Asia.                at various phases of the epidemiological transition (table 33.1),
RHD and ARF are the most common causes of cardiac disease                       and where development has occurred, it has often been at a
among children in developing countries (Ephrem, Abegaz, and                     more compressed rate than in the high-income countries.
Muhe 1990; Schneider and Bezabih 2001; Steer and others                         Although rates of IHD and stroke fell 2 to 3 percent per year in
2002) and account for almost 10 percent of sudden cardiac                       the high-income countries during the 1970s and 1980s, the rate
deaths (Kaplan 1985).                                                           of decline has since slowed. Overweight and obesity are esca-
    Until the 1950s, ARF accounted for a substantial portion of                 lating at an alarming pace, while rates of type 2 diabetes, hyper-
cardiovascular problems among schoolchildren in developed                       tension, and lipid abnormalities associated with obesity are on
countries, and even though it is now far less common, out-                      the rise. This trend is not unique to the developed countries,
breaks still occur (Carapetis, Currie, and Kaplan 1999),                        however. According to the World Health Organization, world-
suggesting that neither antibiotics nor other public health mea-                wide more than 1 billion adults are overweight and 300 million
sures have been totally effective in controlling ARF.                           are clinically obese. Even more disturbing are increases in
                                                                                childhood obesity that have led to large increases in diabetes
                                                                                and hypertension. If these trends continue, age-adjusted CVD
The Epidemiological Transition                                                  mortality rates could increase in the high-income countries in
Over the past two centuries, the industrial and technological                   the coming years. These trends are discussed in greater detail in
revolutions have resulted in a dramatic shift in the causes of                  chapter 45.

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                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                                                                                                                                              Table 33.1 Stages of the Epidemiological Transition and Its Global Status, by Region

                                                                                                                                                                                                                                                                                                                                   Percentage     Percentage
                                                                                                                                                                                                                                                                                      Life                                         of deaths      of the world’s
                                                                                                                                                                                                                                                                                      expectancy                                   attributable   population
                                                                                                                                                                                                                Stage                          Description                            (years)      Dominant form of CVD            to CVD         in this stage    Regions affected

                                                                                                                                                                                                                Pestilence and famine          Predominance of                            35       RHD, cardiomyopathy caused         5–10              11         Sub-Saharan Africa, parts of all regions excluding
                                                                                                                                                                                                                                               malnutrition and infectious diseases                by infection and malnutrition                                   high-income regions
                                                                                                                                                                                                                Receding pandemics             Improved nutrition and public              50       Rheumatic valvular disease,        15–35             38         South Asia, southern East Asia and the Pacific,
                                                                                                                                                                                                                                               health leads to increase in                         IHD, hemorrhagic stroke                                         parts of Latin America and the Caribbean
                                                                                                                                                                                                                                               chronic diseases, hypertension
                                                                                                                                                                                                                Degenerative and               Increased fat and caloric intake,          60       IHD, stroke (ischemic and             50             35         Europe and Central Asia, northern East Asia and
                                                                                                                                                                                                                human-created                  widespread tobacco use, chronic                     hemorrhagic)                                                    the Pacific, Latin America and the Caribbean,
                                                                                                                                                                                                                diseases                       disease deaths exceed mortality                                                                                     Middle East and North Africa, and urban parts of
                                                                                                                                                                                                                                               from infections and malnutrition                                                                                    most low-income regions (especially India)
                                                                                                                                                                                                                Delayed degenerative           CVD and cancer are leading                  70      IHD, stroke (ischemic and             50             15         High-income countries, parts of Latin America and
                                                                                                                                                                                                                diseases                       causes of morbidity and mortality,                  hemorrhagic), CHF                                               the Caribbean
                                                                                                                                                                                                                                               prevention and treatment avoids
                                                                                                                                                                                                                                               death and delays onset;
                                                                                                                                                                                                                                               age-adjusted CVD declines

                                                                                                                                                                                                              Source: Adapted from Olshanksy and Ault 1986; Omran 1971; WHO 2003b.

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©2006 The International Bank for Reconstruction and Development / The World Bank
Risk Factors                                                                        portion of the world’s population lives in East Asia and the
The risk of developing CVD depends to a large extent on the                         Pacific and South Asia and the incidence of IHD is high in
presence of several risk factors. The major risk factors for CVD                    Europe and Central Asia.
include tobacco use, high blood pressure, high blood glucose,
lipid abnormalities, obesity, and physical inactivity. The global                   East Asia and the Pacific. The status and character of the epi-
variations in CVD rates are related to temporal and regional                        demiological transition across the region reflects the diversity of
variations in these known risk factors. Discussions of the                          economic circumstances in East Asia and the Pacific. Since the
strength of the associations of the various factors with CVD are                    1950s, life expectancy in China has nearly doubled from 37 years
found elsewhere (chapters 30, 44, and 45). Although some risk                       to 71 years (WHO 2003b). Approximately 60 percent of the
factors, such as age, ethnicity, and gender, obviously cannot be                    population still lives outside urban centers, and as is the case in
modified, most of the risk is attributable to lifestyle and behav-                  most developing countries, rates of IHD, stroke, and hyperten-
ioral patterns, which can be changed.                                               sion are higher in urban centers. China appears to be straddling
                                                                                    the second and third stages of a Japanese-style epidemiological
                                                                                    transition, with CVD rates higher than 35 percent, though dom-
BURDEN OF DISEASE                                                                   inated by stroke, not IHD. However, in urban China, the death
CVD is the leading cause of death in all World Bank regions with                    rate from IHD rose by 53 percent from 1988 to 1996.
the exception of Sub-Saharan Africa (figure 33.1), where
HIV/AIDS has emerged as the leading cause of mortality                              Europe and Central Asia. The emerging market economies,
(Mathers and others 2006). Between 1990 and 2020, IHD is                            which consist of the former socialist states of Europe, are
anticipated to increase by 120 percent for women and 137 per-                       largely in the third phase of the epidemiological transition. As
cent for men in developing countries,compared with age-related                      a group, they have the highest rates of CVD mortality in the
increases of 30 to 60 percent in developed countries (Leeder and                    world, similar to those seen in the United States in the 1960s
others 2004). Even though 80 percent of CVD deaths occur in                         when CVD was at its peak. Belarus, Croatia, Kazakhstan,
low- and middle-income countries, the death rates for most                          Romania, and Ukraine have seen significant increases in IHD
regions are still below the rate for high-income countries, which                   death rates (figure 33.2). In the Russian Federation, life
is 320 per 100,000 population annually. The marked exception is                     expectancy for men has dropped precipitously since 1986 from
Europe and Central Asia, which has a rate of 690 CVD deaths per                     71.6 years to about 59 years in 2004, in large part because of
100,000 population.                                                                 CVD. In the Czech Republic, Hungary, Poland, and Slovenia,
                                                                                    age-adjusted CVD rates have been declining. Nevertheless,
Regional Burdens                                                                    CVD rates generally remain higher than in Western Europe.
The majority of the burden occurs in East Asia and the Pacific,
Europe and Central Asia, and South Asia because a large pro-                                Croatia                                                62%            61%

                                                                                       Kazakhstan                                                  56%      36%
Percentage of total deaths
                                                                                           Belarus                                                 53%     30%
                      Cardiovascular diseases       Respiratory infections                 Ukraine                                                49%      38%
60                    Malignant neoplasms           Chronic lung diseases
                                                                                          Romania                                                26% 26%
                      Injuries                      HIV/AIDS
50                                                                                           Japan                                   10%          8%

40                                                                                        Hungary                                          2% 2%

                                                                                            Greece                              15%              11%
                                                                                          Portugal                                   29%          19%
                                                                                     United States                              29%        30%

10                                                                                    Netherlands                              29%     39%

 0                                                                                         Sweden                         40%          43%
               l A nd

                  ric n

                                                                                      Luxembourg                        20%           43%
                 ric d

                ci d

               be nd

              Af ara
              Af an

             Pa an
            ra a

           rib a a


         nt pe

         rth ast

          e ia


        Ca ic
       th As
      Ce uro

                                                                                          Australia                      52%          46%
     No E

     e er






                                                                                          Denmark                        46%          49%                Males      Females


Source: Mathers and others 2006.                                                     Source: Mackay and Mensah 2004.

Figure 33.1 Major Causes of Death in Persons of All Ages in Low-                    Figure 33.2 Percentage Change in Ischemic Heart Disease Death
and Middle-Income Regions                                                           Rates in People Age 35 to 74, 1988–98, Selected Countries

                                                                                                                                                   Cardiovascular Disease | 649

                                     ©2006 The International Bank for Reconstruction and Development / The World Bank
Latin America and the Caribbean. In 2001, CVD accounted                                  disease accounts for the dominance of stroke (Bertrand 1999).
for about 31 percent of all deaths in Latin America and the                              RHD and cardiomyopathies, the latter caused mostly by mal-
Caribbean, but that figure is expected to rise to 38 percent by                          nutrition, various viral illnesses, and parasitic organisms, are
2020 (Murray and Lopez 1996). In recent decades, average life                            also important causes of CVD mortality and morbidity.
expectancy in Latin America and the Caribbean has risen from
51 to 71 years, and the quality of nutrition has improved steadily.                      Social and Economic Impact
At the same time, the region has seen a switch from vegetables as
                                                                                         Leeder and others’ (2004) report highlights the economic
a source of protein to animal protein and an increase in fat
                                                                                         impact of cardiovascular diseases in developing economies,
intake as a percentage of energy. As a whole, the region seems to
                                                                                         which arises largely because working-age adults account for a
be in the third phase, but in South America, some areas are still
                                                                                         high proportion of the CVD burden. Conservative estimates in
in the first phase of the transition.
                                                                                         Brazil, China, India, Mexico, and South Africa indicate that
                                                                                         each year at least 21 million years of future productive life are
Middle East and North Africa. Increasing economic wealth in
                                                                                         lost because of CVD. In South Africa, for example, costs for the
the Middle East and North Africa has been characteristically
                                                                                         direct treatment of CVD were equivalent to 2 to 3 percent of
accompanied by urbanization. The rate of CVD has been
                                                                                         gross domestic product, or roughly 25 percent of all health care
increasing rapidly and is now the leading cause of death,
                                                                                         expenditures (Pestana and others 1996).
accounting for 25 to 45 percent of total deaths. Over the past
                                                                                            Current expenditures in developed countries are indicators
few decades, daily per capita fat consumption has increased in
                                                                                         of possible future expenditure in developing countries. For
most countries in the region, ranging from a 13.6 percent
                                                                                         example, Hodgson and others (2001) estimated that in 2003
increase in Sudan to a 143.3 percent increase in Saudi Arabia
                                                                                         the direct and indirect costs of CVD in the United States would
(Musaiger 2002). IHD is the predominant cause of CVD, with
                                                                                         amount to US$350 billion. They also estimated that in 1998
about three IHD deaths for every stroke death. RHD remains a
                                                                                         Americans spent US$109 billion on hypertension, equivalent to
major cause of morbidity and mortality, but the number of
                                                                                         about 13 percent of the health care budget. Studies are limited
hospitalizations for RHD is declining rapidly.
                                                                                         but suggest that obesity-related diseases are responsible for 2
                                                                                         to 8 percent of all health care expenditures in developed
South Asia. Some regions of India appear to be in the first
phase of the transition, whereas others are in the second or
even the third phase. Nonetheless, India is experiencing an
alarming increase in heart disease, which seems to be linked to
changes in lifestyle and diet, rapid urbanization, and possibly                          COST-EFFECTIVENESS OF INTERVENTIONS
an underlying genetic component. Diabetes is also a major
                                                                                         CVD remains one of the most studied and written about sub-
health issue. India has 31.6 million diabetics, and the number
                                                                                         jects in medicine. As a result, many interventions exist with
is expected to reach 57.2 million by 2025 (Ghaffar, Reddy, and
                                                                                         strong evidence for significant reductions in morbidity and
Singhi 2004). The World Health Organization estimates that,
                                                                                         mortality associated with CVD.
by 2010, 60 percent of the world’s cardiac patients will be in
India. About 50 percent of CVD-related deaths occur among
people younger than 70, compared with about 22 percent in the                            Intervention Effectiveness by Disease
West. Between 2000 and 2030, about 35 percent of all CVD                                 This chapter addresses those interventions believed to have the
deaths in India will occur among those age 35 to 64, compared                            largest effect because they result in large reductions in CVD
with only 12 percent in the United States and 22 percent in                              events, are inexpensive, or the prevalence or incidence of the dis-
China (Leeder and others 2004).                                                          eases to which they are directed is significant. The omission of an
                                                                                         intervention does not imply that it is not cost-effective but rather
Sub-Saharan Africa. In Sub-Saharan Africa, deaths attributa-                             that either it had an effect on a smaller percentage of people or
ble to CVD are projected to more than double in between the                              the chapter was unable to encompass all such interventions.
years 1990 and 2020. Although HIV/AIDS is the leading over-
all cause of death in this region, CVD is the second-leading                             Acute Myocardial Infarction. Treatment of AMI involves
killer and is the first among those over the age of 30. Stroke is                        medical therapies that reduce myocardial oxygen demand and
the dominant form, in keeping with patterns characteristic of                            fatal arrhythmias (beta-blockers), that restore blood flow by
earlier phases of the epidemiological transition. With increas-                          inhibiting platelet aggregation (aspirin), or that dissolve
ing urbanization, levels of average daily physical activity are                          the thrombus occluding the arterial lumen (thrombolytics) or
falling and smoking rates are increasing. Hypertension has                               an invasive intervention with cardiac catheterization and
emerged as a major public health concern, and hypertensive                               angioplasty.

650 | Disease Control Priorities in Developing Countries | Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
    Beta-blockers are used both during and after an AMI.                         luminal coronary angioplasty (PTCA), and PTCA with stents.
Benefits persist for at least 6 years and up to 15 years after the               CABG is the placement of grafts, usually from the saphenous
first AMI. The second Thrombolysis in Myocardial Infarction                      vein or internal mammary artery, to bypass stenosed coronary
trial showed significant benefits when beta-blockers were used                   arteries while maintaining cerebral and peripheral circulation
within two hours of symptoms (Roberts and others 1991).                          by cardiopulmonary bypass. CABG is a major operative proce-
    Aspirin, an antiplatelet agent, and thrombolytic agents, the                 dure requiring appropriate surgical and anesthetic environ-
standard treatments for reopening the artery in AMI, have                        ments and has a perioperative mortality of 1 to 3 percent, with
demonstrated an additive effect in reducing mortality (GISSI                     later complication rates of 15 to 20 percent.
1986), with a benefit irrespective of age, sex, blood pressure,                      Almost 1 million CABGs per year are performed worldwide,
heart rate, or previous history of AMI or diabetes (Fibrinolytic                 with about 519,000 interventions in the United States alone in
Therapy Trialists’ Collaborative Group 1994). The benefits are                   2000 (American Heart Association 2002). The main indication
greater the closer the thrombolytics are given to the time of                    for CABG is for those with left main coronary artery stenosis or
onset, and the risk of bleeding is greater the later they are given.             those with involvement of multiple coronary arteries with
The risk of adverse events following administration of throm-                    reduced left ventricular function, particularly among diabetics.
bolytics is low during the first 24 hours; trials with throm-                    The prevalence estimates of those with left main coronary
bolytics show that the benefits are greatest when they are                       artery stenosis or involvement of three coronary arteries has
administered less than 12 hours after an AMI and preferably                      varied over time, but current estimates range from 7 to 20 per-
less than 6 hours (Antman and others 2004).                                      cent of survivors of myocardial infarction (Kuntz and others
    The invasive alternative to immediate medical reperfusion                    1996; Rogers and others 1991; Topol, Holmes, and Rogers
of an occluded coronary artery is angioplasty or percutaneous                    1991) For these cases, investigators have shown that CABG is
coronary intervention. Its superiority over thrombolysis in                      more beneficial than medical treatment, both in terms of
developed countries remains a matter of debate. Issues that                      symptoms and of mortality (Eagle and others 1999).
remain important in relation to the choice of strategy are over-                     Both developed and developing countries are increasingly
all severity or location of the AMI and the time from symptom                    using PTCA (Denbow and others 1997). The main indications
onset to initiation of treatment. In patients presenting late or                 for its use are low-risk patients with single- or double-vessel
with a high risk of mortality, such as those in cardiogenic                      disease and poor response to medical treatment. The success
shock, percutaneous coronary intervention may be beneficial                      rate of PTCA is more than 95 percent; however, because it has
(Hochman and others 1999). However, as with thrombolytic                         no mortality benefit when compared with medical therapy
agents, the benefits of percutaneous coronary intervention                       or CABG, we did not evaluate new analyses of the cost-
diminish significantly with time between the onset of symp-                      effectiveness of this intervention, but instead provided infor-
toms and the opening of the artery (De Luca and others 2004;                     mation from experience in developed countries. The addition
D. O. Williams 2004).                                                            of stents to PTCA has lead to a decrease in restenosis rates and
    The invasive strategy requires a facility and individual physi-              readmissions to hospitals but shows no change in mortality
cians who conduct enough of the procedures annually to                           compared with medical therapy.
remain proficient. In the absence of these conditions, the
American Heart Association recommends that treatment focus                       Pharmacological Interventions The pharmacological inter-
on thrombolytics (Antman and others 2004). Given either a                        ventions either prevent thrombosis, as does aspirin, or target
lack of facilities and operators for percutaneous interventions                  the individual risk factors, as do the antihypertensives (diuret-
or long distances to such facilities in many developing coun-                    ics, beta-blockers, and ACE inhibitors) or statins targeting
tries, we did not evaluate this procedure.                                       cholesterol. Furthermore, these agents may possibly have addi-
                                                                                 tional properties of reducing the risk of fatal arrhythmias,
Long-Term Management of Existing Vascular Disease. The                           improving repair after AMI (remodeling), or stabilizing the
management of individuals with chronic vascular disease con-                     atherosclerotic plaque.
sists of invasive techniques, pharmacotherapy, lifestyle and                         Overall, the long-term administration of antiplatelet agents
behavioral changes, and rehabilitative measures. It also involves                in those with vascular disease leads to a 25 percent reduction
addressing such issues as adherence to treatment, regular follow-                in the risk of major vascular events: 33 percent for nonfatal
ups to determine compliance and assess risk, and treatment of                    AMI, 25 percent for nonfatal stroke, and 16 percent for any
comorbidities that are likely to have an impact on the progres-                  vascular death. The use of aspirin has produced similar
sion of vascular disease (for instance, renal disease).                          benefits in individuals with IHD or prior stroke. Antiplatelet
                                                                                 treatment in individuals with a previous AMI has been
Invasive Interventions The three most common procedures                          shown to prevent 18 nonfatal myocardial infarctions, 5 nonfa-
are coronary artery bypass graft (CABG), percutaneous trans-                     tal strokes, and 14 vascular deaths for every 1,000 patients

                                                                                                                           Cardiovascular Disease | 651

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
treated for two years (Antithrombotic Trialists’ Collaboration                           brain), the long-term benefits of lowering blood pressure have
2002).                                                                                   been clearly established. Lowering blood pressure reduces the
    The benefits of antiplatelet agents for those with vascular                          overall risk of future stroke by 28 percent and of other vascular
disease far outweigh the risks. The risk of intracranial bleeding                        events and CHF by 26 percent in patients with a history of
increases by nearly 25 percent with the use of antiplatelet                              stroke disease, irrespective of their hypertension status. The
agents, but in absolute terms this risk comes to only one or two                         benefits are even more pronounced for individuals with a his-
intracranial bleeds per 1,000 patients treated per year. The risk                        tory of hemorrhagic stroke. Larger reductions in blood pres-
of major extracranial bleeding, mostly gastrointestinal, also                            sure confer greater benefits, and benefits are present across dif-
increases by 60 percent, or one or two excess events per 1,000                           ferent age groups, genders, and ethnicities and with varying
patients per year.                                                                       comorbid status.
    The most established and commonly used agent is aspirin,                                 Beta-blockers are one of the cornerstones of long-term
although other agents (for example, clopidogrel or ticlopidine)                          treatment of individuals with IHD, especially those with a his-
with similar efficacy but much greater cost are available. Low                           tory of AMI. Long-term use of beta-blockers has been associ-
doses of aspirin—75 to 100 milligrams (mg) per day—are as                                ated with 23 percent relative risk reduction in mortality
beneficial as higher doses.                                                              (Freemantle and others 1999), 25 percent relative risk reduc-
    Lowering LDL and elevating HDL cholesterol levels is one                             tion in nonfatal myocardial infarction, and 30 percent relative
of the cornerstones of treatment of cardiovascular disease,                              risk reduction in sudden cardiac death (Yusuf and others
and investigators have suggested that suboptimal levels of                               1985). The benefits are larger for those at highest risk of sus-
cholesterol contribute to almost two-thirds of the global car-                           taining a vascular event in the future and are present across all
diovascular risk (WHO 2002b). Although the usual target of                               age groups and sexes. Furthermore, beta-blockers provide clear
lipid-lowering therapy has been lowering total or LDL choles-                            benefits in patients with chronic stable angina, where they pro-
terol, medical experts are increasingly recognizing the impor-                           vide symptom relief as well as reductions in vascular events
tance of increasing HDL cholesterol and lowering triglyceride                            (Heidenreich and others 1999).
levels, especially in high-risk individuals, such as those with                              ACE inhibitors have proved invaluable in preventing cardio-
diabetes or metabolic syndrome, as well as in ethnic popula-                             vascular events and CHF in those with IHD. The extent to
tions like Southeast Asians.                                                             which the benefits conferred by their use are caused by their
    Recent evidence has demonstrated that the relationship                               ability to lower blood pressure or by their other properties,
between cholesterol levels and vascular events is continuous                             such as cardiac remodeling and neurohormonal modulation, is
and occurs at much lower cholesterol thresholds than previ-                              not clear. Long-term use of ACE inhibitors in those with a his-
ously believed. The clinical trials have consistently demon-                             tory of myocardial infarction and in other individuals at high
strated a 25 to 30 percent reduction in the risk of cardiovascu-                         risk of vascular disease reduces vascular mortality by 25 percent
lar morbidity and mortality. Furthermore, the evidence                                   and other nonfatal events, such as recurrent myocardial infarc-
suggests that more aggressive reductions in cholesterol have                             tion, revascularization, hospitalization, progression or new
higher benefits than mild or moderate reductions (Cannon and                             onset of CHF, and stroke (Teo and others 2002). In those with
others 2004; Knatterud and others 2000). No increased risk of                            asymptomatic or symptomatic left ventricular dysfunction
cancers appears to exist, as was previously believed, although a                         after myocardial infarction, ACE inhibitors reduce the risk of a
small increase exists in the risk of inflammation of noncardiac                          variety of vascular endpoints by 20 to 26 percent. Similarly, the
muscle (myopathy) (Pfeffer and others 2002).                                             use of ACE inhibitors even in those with no evident left ven-
    As with cholesterol, the relationship between blood pressure                         tricular dysfunction confers a 21 percent reduction in risk for
and vascular events is continuous and is discussed further in                            major coronary events (Dagenais and others 2001), 32 percent
chapter 45. Even patients with presumed “normal” blood pres-                             for stroke (Bosch and others 2002), and 20 to 22 percent for
sure and prior vascular disease benefit from lowering blood                              composite vascular outcomes (Fox 2003).
pressure (Nissen and others 2004), confirming earlier evidence
that individuals with a history of AMI who have lower blood                              Nonpharmacological Interventions Cessation of smoking
pressure are less likely to have future vascular events.                                 and dietary modifications are important goals of secondary
Furthermore, investigators have established mortality and mor-                           prevention of CVD. Cardiac rehabilitation, including exercise,
bidity benefits for several specific classes of drugs to reduce                          is useful for a wide range of patients with IHD and reduces
blood pressure in patients with vascular disease, namely,                                future vascular events by about 15 percent. Exercise alone
beta-blockers, calcium-channel blockers, and ACE inhibitors                              reduces vascular mortality by 24 percent and vascular end-
(Fox 2003).                                                                              points by 15 percent (Jolliffe and others 2000). Results of trials
    In patients with a prior history of stroke or transient                              for psychological interventions targeted at stress, depression,
ischemic attack (transient occlusion of artery supplying the                             low social support, and so on have been conflicting.

652 | Disease Control Priorities in Developing Countries | Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Congestive Heart Failure. Diuretics are standard therapy for                     Linking Costs and Effectiveness in Developing Countries
CHF, with the loop and thiazide diuretics most commonly                          Few intervention trials have been carried out solely in develop-
used. Diuretics provide relief of symptoms more rapidly than                     ing countries, but investigators have extrapolated estimates of
any other CHF medication because they are the only drugs                         cost-effectiveness ratios for the developing world in general
that can adequately control the fluid retention associated with                  based on changes in key input prices (Goldman and others
CHF. Using spironolactone, a neurohormonal antagonist,                           1991); however, this process is limited by the fact that both the
together with a diuretic decreased the risk of mortality by 30                   underlying epidemiology and the costs can differ significantly
percent and of hospitalization by 35 percent, compared with                      across and within countries and regions. Thus, our results
a placebo in patients with severely advanced heart failure                       reflect models that used prices and epidemiological data for
(Pitt and others 1999); however, this combination requires                       World Bank regions where applicable. Intervention effects were,
intensive monitoring of electrolytes and testing to follow                       however, based on systematic reviews of randomized trials or
patients and thus was not included in our cost-effectiveness                     meta-analyses in developed countries. Until intervention trials
analyses.                                                                        are conducted in developing countries, this option remains the
    Investigators have shown that ACE inhibitors reduce risks                    best for evaluating the cost-effectiveness of various interven-
related to a variety of endpoints, including mortality, hospital-                tions in the developing regions. In cases in which models for dis-
ization, major coronary events, deterioration of symptoms, and                   eases in selected regions were not developed, we present results
progression from asymptomatic to symptomatic left ventricu-                      of cost-effectiveness analyses from high-income countries.
lar dysfunction, by 25 to 33 percent. The benefit is conferred                       We used estimates of life expectancy for the model from
irrespective of the etiology of systolic failure; begins soon after              data supplied by the volume editors. The model includes only
the start of treatment; persists over the long term; and is inde-                the costs related to the intervention itself and to CVD events
pendent of age, sex, and baseline use of other medications.                      and their sequelae. Costs include personnel salaries, health care
Furthermore, the use of ACE inhibitors has proved to be highly                   visits, diagnostic tests, and hospital stays as provided by the vol-
cost-effective in developed countries.                                           ume editors. Our analysis does not include indirect costs, such
    Beta-blockers improve symptoms, decrease hospitalization                     as those arising from lost work time or family assistance. Drug
and deterioration of heart function, and improve mortality.                      costs are from McFayden (2003). All are in U.S. dollars unless
They should be used even when the patient becomes asympto-                       otherwise specified. Disability weights were taken from
matic. Beta-blockers are beneficial at all stages of CHF, reduc-                 Mathers and others (2006).
ing the morbidity and mortality associated with CHF by 25 to
33 percent. Because most patients with CHF die of sudden car-                    Ischemic Heart Disease.
diac death, the protective effects of beta-blockers are probably
related to their antiarrhythmic properties.                                      Acute Myocardial Infarction We evaluated four incremental
    Digitalis decreases hospitalization rates in individuals with                strategies for the treatment of AMI and compared them with
CHF but has no effect on vascular or total mortality (Digitalis                  a strategy of no treatment as a base case. The four treatment
Investigation Group 1997). Given that it also has a narrow                       strategies were aspirin (162.5 mg per day for 30 days); aspirin
therapeutic-toxic window and requires careful monitoring, its                    and atenolol (100 mg per day for 30 days); aspirin, atenolol, and
role in standard treatment for CHF has diminished and has not                    streptokinase (1.5 million units); and aspirin, atenolol, and tis-
been included in our cost-effectiveness analyses.                                sue plasminogen activator (100 mg accelerated regimen). Doses
                                                                                 for the aspirin and streptokinase were those used by the Second
Rheumatic Heart Disease. The management of patients                              International Study of Infarct Survival Collaborative Group
with ARF includes providing antistreptococcal treatment,                         (ISIS-2 Collaborative Group 1988), the atenolol regimen was
managing clinical manifestations, and screening children. In                     that of the First International Study of Infarct Survival (ISIS-1
the acute stage, all patients with ARF should be treated as if                   Collaborative Group 1986), and the tissue plasminogen activa-
they have a group A streptococcal infection—that is, with a                      tor dosing was that used in the Global Use of Strategies to Open
10-day course of penicillin. Anti-inflammatory agents                            Occluded Coronary Arteries (GUSTO)–I trial (GUSTO
provide symptomatic relief during ARF but do not prevent                         Investigators 1993). The relative risk of dying from AMI was
RHD. Secondary prophylaxis prevents colonization of the                          reduced for all patients receiving the medications. Patients
upper respiratory tract and consists of penicillin or sulfadiazine               receiving the thrombolytics faced increased risks of major
for the first five years (and for life for patients with valvular                bleeds and hemorrhagic strokes. Because the effectiveness of
heart disease). Noncompliance is frequent, reaching rates                        streptokinase diminishes over time, we carried out two further
as high as one-third of patients (Bassili and others 2000).                      sensitivity analyses to compare its use for patients over and
Tertiary treatment entails surgery for valve replacement or                      under the age of 75 and for patients who receive the intervention
valvuloplasty.                                                                   sooner or later than six hours after the onset of symptoms.

                                                                                                                             Cardiovascular Disease | 653

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
    Table 33.2 presents incremental cost-effectiveness ratios                            able in developed countries; however, given that hospital facil-
(ICERs) for each therapy by region. The incremental cost per                             ities may not be available to most patients in many developing
DALY averted was less than US$25 for all six regions for the                             regions, we undertook two separate analyses, one with hospital
aspirin and aspirin plus atenolol interventions; US$634 to                               costs and one without.
US$734 for aspirin, atenolol, and streptokinase; and slightly                                In a setting where hospitals are available, a combination of
less than US$16,000 for aspirin, atenolol, and tissue plasmino-                          aspirin and atenolol dominated no therapy and was cost saving
gen activator. Minor variations occurred between regions                                 in all regions (table 33.2). The ICERs for the addition of
because of small differences in follow-up care costs. The results                        enalapril ranged from US$660 per DALY in Sub-Saharan Africa
for an analysis that evaluated ICERs as cost per life year saved                         to US$866 per DALY in Europe and Central Asia. The combi-
showed no significant differences.                                                       nation of all four medications ranged from US$1,720 per
    Table 33.3 displays the results of the secondary analysis for                        DALY to US$2,026 per DALY. For CABG the costs per DALY
streptokinase and tissue plasminogen activator. Giving the                               ranged from about US$24,000 to more than US$72,000.
streptokinase sooner than six hours following onset reduces the                          Despite having similar benefits as aspirin and atenolol in rela-
incremental cost per DALY to less than US$440 compared with                              tion to mortality, enalapril and lovastatin demonstrated higher
more than US$1,300 if given after six hours. Similar effects are                         per DALY costs because of the added costs of monitoring renal
seen when streptokinase is given to those under 75 compared                              and liver function, respectively, as is required for these two
with those 75 years or older.                                                            medications.
    According to meta-analyses, nitroglycerin has a modest                                   When we assumed that hospitals were not readily available
effect on mortality in AMI: a 3 percent reduction. However,                              (table 33.2), no therapy combination was cost saving compared
given that it can have profound effects on blood pressure that                           with no therapy. The combination of aspirin and atenolol was
could limit the use of beta-blockers that confer more signifi-                           the next best strategy, with ICERs ranging from US$386 per
cant benefits, its use should be limited to patients with ongoing                        DALY in South Asia to US$545 per DALY in Latin America and
ischemic pain and systolic blood pressures greater than 90 mil-                          the Caribbean. The addition of enalapril increased the range of
limeters of mercury who do not have ongoing right ventricu-                              ICERs to US$783 per DALY to US$1,111 per DALY, and the
lar infarction. When modeled, it had a reasonable cost-                                  addition of lovastatin increased them still further. CABG was
effectiveness ratio of US$70 per life year saved, but we did not                         not evaluated because of the underlying assumption that hos-
include the analysis in the incremental analysis because of the                          pitals were not available.
blood pressure effects of the multiple agents.                                               Table 33.4 shows the number of events prevented with the
                                                                                         four-drug combination medical therapy compared with no
Secondary Prevention Four medical therapies—aspirin, beta-                               therapy and the additional number of events averted
blockers, statins, and ACE inhibitors—have been the mainstay                             with CABG compared with the four-drug combination. The
of treatment for those with IHD in the developed world. To                               medical regimen alone would prevent some 2,000 CVD deaths,
evaluate the best medical intervention, we used incremental                              about 4,000 myocardial infarctions, and approximately 200
cost-effectiveness analysis to examine the 15 different possible                         strokes per million persons treated in each region. The use of
combinations of the four standard medical therapies. The four                            CABG in addition to the medical regimen would prevent an
therapies were 75 to 100 mg per day of aspirin, 100 mg per day                           additional 65–70 deaths, nearly 300 myocardial infarctions, and
of atenolol, 10 mg per day of enalapril, and 40 mg per day of                            up to 30 strokes per million population.
lovastatin. In addition, CABG surgery provides an invasive
option that gives added mortality benefit when compared with                             Congestive Heart Failure. The interventions examined for
conventional medical therapy in patients with certain anatom-                            CHF were the addition of the ACE inhibitor enalapril, the beta-
ical obstructions in coronary circulation. Thus, we evaluated                            blocker metoprolol, or both to a baseline of diuretic treatment.
CABG in addition to all four medications for those with left                             As for the IHD interventions, we performed separate analyses
main coronary artery disease or with three-vessel coronary                               for each assumption of whether or not hospital facilities would
artery disease and reduced left ventricular function. Because                            be available. For the model of treatment for CHF assuming
these therapies also have significant effects on the incidence of                        hospitalization (table 33.2), the addition of enalapril is cost sav-
stroke, we included the effect on DALYs and costs for stroke in                          ing and the ICER for the addition of metoprolol ranges from
the analyses.                                                                            US$124 to US$219 per DALY depending on the region. When
    In addition to the mortality benefits demonstrated by trials                         the availability of hospitals is limited (table 33.2), the enalapril
of the individual medications or surgery, they also resulted in                          plus diuretics strategy is no longer cost saving, but it costs only
significant reductions in hospitalizations in developed coun-                            US$31 per DALY or less, and the ICER for enalapril, metopro-
tries. The cost savings from these reduced hospitalizations                              lol, and diuretics increases only to about US$275 per DALY.
make the cost-effectiveness of such interventions quite favor-                           These figures are probably underestimates of the cost per

654 | Disease Control Priorities in Developing Countries | Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                                                  Table 33.2 ICERs for Treatment Compared with No Treatment, by Region

                                                                                                                                                                                                                                                                                                                                                                 and beta-
                                                                                                                                                                                                                                                                                                                                                                 for CHF
                                                                                                                                                                                                                                                                                                                                           ACE inhibitors        compared with
                                                                                                                                                                                                                                                                                                                                           and beta-blockers     baseline of
                                                                                                                                                                                                                                                                                          Medical therapy and                              for CHF compared      diuretics,
                                                                                                                                                            Medical therapy for                                     Medical therapy and CABG for IHD                                      CABG for IHD compared                            with baseline         limited
                                                                                                                                                            AMI compared with                                       compared with baseline of no treatment,                               with baseline of no treatment,                   of diuretics,         hospital
                                                                                                                                                            baseline of no treatment                                hospital access                                                       limited hospital access                          hospital access       access

                                                                                                                                                                             ASA            ASA, BB,                             ASA, BB,           ASA, BB,                                           ASA, BB,           ASA, BB,                       ACEI,          ACEI,

                                                                                                                    Region                      ASA         ASA, BB          BB, SK         TPA               ASA, BB            ACEI               ACEI, Statin         CABG         ASA, BB          ACEI               Statin           ACEI          MET     ACEI   MET

                                                                                                                    East Asia and                 13             15            672            15,867          Cost saving             781               1,914            33,846           461                942           2,220           Cost saving    189     27      274
                                                                                                                    the Pacific
                                                                                                                    Europe and                    19             21            722            15,878          Cost saving             866               2,026            47,942           530             1,097            2,470           Cost saving    144     30      275
                                                                                                                    Central Asia
                                                                                                                    Latin America and             20             22            734            15,887          Cost saving             821               1,942            62,426           545             1,111            2,497           Cost saving    124     31      275
                                                                                                                    the Caribbean
                                                                                                                    Middle East and               17             20            715            15,893          Cost saving             672               1,686            72,345           527                996           2,305           Cost saving    128     29      275

©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                                                    North Africa
                                                                                                                    South Asia                      9            11            638            15,860          Cost saving             715               1,819            24,040           386                828           2,034           Cost saving    219     25      273
                                                                                                                    Sub-Saharan                     9            11            634            15,862          Cost saving             660               1,720            26,813           389                783           1,955           Cost saving    218     25      273

                                                                                                                  Source: Authors’ calculations.
                                                                                                                  ASA aspirin, BB atenolol, SK streptokinase, TPA tissue plasminogen activator, ACEI enalapril, Statin lovastatin, MET metoprolol.
                                                                                                                  Note: The intervention in the first column of each set of strategies is compared with the baseline; each successive intervention for each set of strategies is compared with the intervention immediately to its left.

                                                                                   Cardiovascular Disease | 655
Table 33.3 Sensitivity Analyses: Effect of Time to Treatment                                           may be cost-effective. Secondary prevention using benzathine
and Age on Use of Thrombolytics in AMI (All Regions                                                    penicillin injections is cost-saving according to Strasser (1985)
Combined)                                                                                              and should be considered for all developing countries with the
                                          SKa (US$/DALY)                   TPAa (US$/DALY)             infrastructure to perform the required follow-up.

  Time to thrombolysis
        6 hours                                    374–437                         15,800              Cost-Effectiveness Analyses in High-Income Countries
     6–12 hours                              1,300–1,440                           15,700              Table 33.5 summarizes the results of cost-effectiveness analyses
  Age at treatment                                                                                     for CVD interventions in high-income countries. These results
        75                                         559–650                         14,800              include analyses that are similar to ours. The differences are
     75 or older                             1,260–1,350                           21,000              that they reflect costs and treatment patterns in the high-
                                                                                                       income countries studied, mostly the United States. Costs in
Source: Authors’ calculations.
SK streptokinase; TPA tissue plasminogen activator.                                                    developing countries are roughly one-fifth of those in devel-
a. In addition to aspirin and atenolol.                                                                oped countries (but closer to one-third in Latin America and
                                                                                                       approaching one-half in South Africa). However, where
DALY, given some loss in the mortality benefit for the hospital-                                       patented drugs are involved and patent laws are enforced, the
ization that the model does not capture.                                                               costs may be much closer to U.S. levels.
                                                                                                           Because the cost-effectiveness studies have been undertaken
Rheumatic Heart Disease. For RHD, except in epidemics, sec-                                            largely in the United States, the results do not always readily
ondary prevention is more effective than primary prevention.                                           transfer to developing countries. In some U.S. studies, the
Primary prevention by means of antibiotic treatment of strep-                                          alternative procedure considered is medical management; such
tococcus infections of the pharynx is not highly cost-effective in                                     facilities simply may not exist in developing countries.
endemic situations, given that only 10 to 20 percent of such                                           Similarly, interventions that are cost saving in the United States
infections are from streptococcus, less than 3 percent of these                                        may not be cost saving in developing countries but may well be
will evolve into rheumatic fever, and only a proportion of these                                       cost-effective in terms of cost per DALY saved. Furthermore,
continue on to RHD (Strasser 1985). The development of a                                               the cost-effectiveness analyses reflect morbidity and mortality
rapid antigen test for diagnosing group A streptococcal pharyn-                                        rates in developed countries.
gitis may make primary prevention more cost-effective (Majeed                                              Interventions that Kupersmith and others (1995) classify as
and others 1993). Similarly, in an epidemic in which the pro-                                          highly cost-effective in the United States (less than US$20,000
portion of infections from streptococcus is higher or the rate of                                      per life year saved or quality-adjusted life year saved) may be
progression to rheumatic fever is higher, primary prevention                                           cost-effective in many developing countries. Interventions that

Table 33.4 Number of Deaths and CVD Events Prevented by the Use of a Four-Component Medical Regimen and CABG per
100,000 Myocardial Infarction Survivors over 10 Years, by Region

                                     Number of events prevented with four-component                                       Number of incremental events prevented with
                                     medical regimen compared with no therapya                                            CABG compared with medical therapy

                                   IHD                Stroke           Myocardial                                                                   Myocardial
                                   deaths             deaths           infarctions          Strokes            IHD deaths           Stroke deaths   infarctions     Strokes
  Region                           averted            averted          prevented            prevented          averted              averted         prevented       prevented

  East Asia and                      1,900              104                4,077                209                  79                   11           248              22
  the Pacific
  Europe and                         1,990               89                3,964                179                  83                     1          294              7
  Central Asia
  Latin America and                  1,913               83                4,040                118                  62                     4          258              18
  the Caribbean
  Middle East and                    1,908               95                4,294                118                  62                     1          296              22
  North Africa
  South Asia                         1,930               97                4,043                122                  34                     2          275              30
  Sub-Saharan Africa                 1,909               91                4,233                173                  69                   12           254              1

Source: Authors’ calculations.
a. Aspirin, atenolol, enalapril, and lovastatin.

656 | Disease Control Priorities in Developing Countries | Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, and others

                                                              ©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                                                  Table 33.5 Cost-Effectiveness Analyses for CVD Interventions in High-Income Countries

                                                                                                                    Intervention                                              Alternative                 Cost-effectiveness                                                            Source

                                                                                                                    Lovastatin, 20 mg/day                                     Diet                        Cost saving (males age 45–54); US$4,700/life year saved (females age 45–54)   Goldman and others 1991a
                                                                                                                    Defibrillators in emergency vehicles                      No defibrillators           US$47 to US$551/life year saved; up to US$2,600 in rural areas                Jermyn 2000; Ornato and others 1988;
                                                                                                                                                                                                                                                                                        Rowley, Garner, and Hampton 1990b
                                                                                                                    Propranolol for postmyocardial                            No beta-blockers            US$2,400 for high-risk patients; US$23,400 for low-risk patients              Goldman and others 1988 a
                                                                                                                    infarction (beta-blocker)
                                                                                                                    CABG for left main disease                                Medical management          US$2,700 to US$6,700/life year saved                                          Weinstein and Stason 1982;b A. Williams 1985a
                                                                                                                    PTCA (men age 55 with                                     Medical management          US$6,400 to US$8,800/life year saved (US$28,000 to US$132,000 for             Wong and others 1990b
                                                                                                                    severe angina)                                                                        mild angina)
                                                                                                                    Primary angioplasty                                       No intervention after AMI   US$12,000/quality-adjusted life year                                          Parmley 1999
                                                                                                                    Three-vessel CABG                                         Medical management          US$14,000/life year saved                                                     Weinstein and Stason 1982
                                                                                                                    Streptokinase (reperfusion), with                         No intervention after AMI   US$15,000/quality-adjusted life year                                          Parmley 1999
                                                                                                                    PTCA available
                                                                                                                    Tissue plasminogen activator (AMI)                        Steptokinase                US$33,500/life year saved                                                     Lorenzoni and others 1998
                                                                                                                    Primary stenting, one-vessel, men                         PTCA                        US$32,000/life year saved                                                     Cohen and others 1993
                                                                                                                    over age 55

                                                                                                                    Three-vessel CABG for severe angina                       PTCA                        US$41,000/life year saved                                                     Wong and others 1990b
                                                                                                                    Two-vessel CABG                                           Medical management          US$33,000 to US$90,000/life year saved                                        Weinstein and Stason 1982; A. Williams 1985
                                                                                                                    Angiography for coronary artery disease                   CABG                        US$45,000/quality-adjusted life year                                          Doubilet, McNeil, and Weinstein 1985a

                                                                                                                    Anticoagulants (warfarin) for chronic                     Aspirin                     Warfarin dominates for high-risk patients; US$10,000/quality-adjusted life    Gage, Cardinalli, and Owens 1998c
                                                                                                                    nonvascular atrial fibrillation                                                       year for medium-risk patients; US$462,000/quality-adjusted life year for
                                                                                                                                                                                                          low-risk patients
                                                                                                                    Anticoagulants for mitral stenosis                        No anticoagulants           US$5,500/quality-adjusted life year                                           Eckman, Levine, and Pauker 1992c
                                                                                                                    and atrial fibrillation

©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                                                    Carotid endarterectomy                                    Aspirin                     US$5,100 to US$51,000/life year saved                                         Kuntz and Kent 1996; Matchar, Pauk, and
                                                                                                                    (symptomatic patients)                                                                                                                                              Lipscomb 1996c
                                                                                                                    Cardiac transplant                                        No transplant               US$54,000/life year saved                                                     Evans 1986a

                                                                                                                    Implantable cardioverter-defibrillator                    Medical management          US$28,000/life year saved                                                     King, Aubert, and Herman 1998; Kuppermann and
                                                                                                                    for cardiac arrest (long term)                                                                                                                                      others 1990

                                                                                                                    Benzathine penicillin injections                          No injections               Cost saving                                                                   Strasser 1985

                                                                                                                  Source: Authors.
                                                                                                                  Note: All costs have been converted to 2001 U.S. dollars.
                                                                                                                  a. Surveyed in Kupersmith and others 1995.
                                                                                                                  b. Surveyed in Tengs and others 1995.

                                                                                   Cardiovascular Disease | 657
                                                                                                                  c. Surveyed in Holloway and others 1999.
Kupersmith and others (1995) classify as cost-effective in                               Primary Prevention
the United States (US$20,000 to US$40,000 per life year saved                            Because the control of many cardiovascular risk factors is
or quality-adjusted life year saved) are probably borderline                             strongly related to the legislative environment—for example,
cost-effective for developing countries. Interventions that                              that pertaining to tobacco use or nutrition—the design and
Kupersmith and others (1995) classify as borderline, expensive,                          implementation of appropriate laws and regulations is likely to
or very expensive in the United States are unlikely to merit                             increase in developing countries. However, any such initiatives
public funding in developing countries.                                                  need to be monitored and systematically evaluated, especially
   Thus, medical interventions that are likely to be cost-                               to estimate the magnitude of the reduction achieved.
effective in developing countries include benzathine penicillin                              Another area of research is the assessment of chemoprophy-
injections as secondary prevention for those who have had                                laxis in primary prevention. Multidrug combinations such
rheumatic fever (usually for five years); ACE inhibitors for                             as the hypothetical “polypill” are likely to be the first practical
CHF; and various drugs (beta-blockers, off-patent statins) for                           initiative of a long list of important innovations. Both the
long-term care following a myocardial infarction, confirming                             efficacy and the effectiveness of new interventions in primary
our earlier analyses. Other therapies that are probably cost-                            prevention should be evaluated as a matter of urgency, because
effective but that we did not analyze include antithrombotic                             no results of large-scale clinical trials in developing countries
agents (aspirin, heparin) to prevent venous thromboembolism;                             are as yet available.
anticoagulants for medium- and high-risk nonvalvular atrial
fibrillation (stroke); and anticoagulants for mitral stenosis and
atrial fibrillation (stroke).                                                            Health Services
   Selected invasive interventions that might possibly be cost-                          Capacity building—more specifically, education and training—
effective for CVD in certain developing countries include pace-                          of health care workers in developing countries, is a major issue
maker implants for atrioventricular heart block, primary                                 for the future, along with critical evaluations of the perform-
angioplasty for acute myocardial infarction, and reperfusion                             ance of health workers. Such evaluations should compare vari-
with streptokinase. Of course, the ability to undertake these                            ous capacity-building strategies; for instance, they could com-
interventions assumes a cost-effective infrastructure for diag-                          pare the delivery of simplified regimens of care by community
nosis and referral and an adequate volume of cases. For exam-                            health workers versus delivery of care by trained health profes-
ple, the American Heart Association recommends acute angio-                              sionals.
plasty in centers where the physician conducts at least 75 such                             The dissemination of innovations deserves special attention
procedures each year and the hospital conducts at least 200 per                          in a context of scarce resources (Berwick 2003). The transfer of
year. For stroke, carotid endarterectomy is potentially cost-                            technologies to developing countries should be made on cost-
effective for symptomatic patients compared with aspirin                                 effectiveness criteria, which implies analysis conducted in the
alone, again in an environment with an adequate volume of                                specific situation of developing countries—for example, cost-
cases. Cost-effectiveness is much lower for asymptomatic cases.                          effectiveness for thrombolytics in a developing country might
   Interventions that rank as cost-effective for heart disease in                        be much worse than in the United States if getting to a hospi-
the U.S. context and that are borderline cost-effective in devel-                        tal on time is a problem. Sensitivity analysis of the cost-
oping countries include implantable cardioverter-defibrillator                           effectiveness of surgical and medical interventions in develop-
for cardiac arrest, primary stenting for single-vessel disease (the                      ing countries is also needed.
study was for men over age 55), CABG for two-vessel disease,                                Furthermore, the appropriate incentives for technological
and angiography for patients with a high probability of coro-                            changes in health care should be investigated (McClellan and
nary artery disease.                                                                     Kessler 1999). This line of research includes analyses of the
                                                                                         pricing of technologies (including drugs) or of new designs for
RESEARCH AND DEVELOPMENT                                                                 services, such as point-of-care devices for use by community
                                                                                         health workers.
Even though most of the interventions currently available                                   The long period of incubation of CVD opens up opportu-
appear to be expensive and complex for developing countries,                             nities for extensive screening based on preclinical signs and
the demand for effective care for cardiovascular diseases will                           biomarkers. However, strong lines of research are needed to
exert major pressure on health systems in coming decades.                                secure effective and safe screening programs and should
Increased use of these procedures is already documented in                               include opportunistic screening for places where visits to
China and India (Murray and Lopez 1994, 1997; Unger 1999).                               health centers are limited.
In this context, cardiovascular research should be concentrated                             Finally, all assessments made in relation to health services
in the fields of primary prevention, health services, clinical                           research should take into account the costs related to scaling up
guidelines, clinical research, and epidemiology.                                         any procedure evaluated.

658 | Disease Control Priorities in Developing Countries | Thomas A. Gaziano, K. Srinath Reddy, Fred Paccaud, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Clinical Guidelines                                                               Epidemiological Research
The diffusion of health technologies usually leads to a widen-                    A basic task of epidemiological research is to assess geographic
ing of the clinical indication beyond the evidence-based scope                    and secular trends in the distribution of risk factors. Of special
of the intervention (PTCA is a classic example) (Dravik 1998),                    relevance is the movement from regional to country levels and
corresponding to a decrease not only in the procedure’s                           the trend within a country. The impact of poor health status in
efficacy, but also in its effectiveness (Anderson and Lomas                       early life should be assessed from the impact of poor fetal
1988; Blustein 1993). Several studies suggest that overuse and                    health to the consequence of multiple childhood infections on
underuse tend to coexist in the same community and that                           the risk for CVD. Because of the scarce availability of resources,
even severe scarcity of resources does not protect against                        the development and maintenance of health care should be
overuse of cardiological interventions, at least among certain                    supported by a comprehensive information system. Simple,
segments of the population (Joorabchi 1979; Soumerai and                          affordable health information systems are preferable along the
others 1997).                                                                     lines of the framework developed by the World Health
    The consequences of such trends are more dramatic in                          Organization.
developing than developed countries. Therefore, the introduc-
tion of costly care should be accompanied by a corresponding
                                                                                  CONCLUSIONS: PITFALLS AND PROMISES
effort in relation to the provision of formal education to
providers and prescribers, complemented by the development                        A global CVD epidemic is rapidly evolving, and the burden of
of clinical guidelines aimed at avoiding both the overuse and                     disease is shifting. Twice as many deaths from CVD now occur in
the underuse of procedures.                                                       developing as in developed countries. The vast majority of CVD
    Clinical guidelines are already numerous, but all have been                   can be attributed to conventional risk factors. Even in Sub-
established in affluent countries. A new, specific effort should                  Saharan Africa, high blood pressure, high cholesterol, extensive
be made in developing countries to address local issues, such as                  tobacco and alcohol use, and low vegetable and fruit consump-
problems related to the availability of procedures or drugs or to                 tion are already among the top risk factors for disease. Because of
accessibility of services, and the development and maintenance                    the time lag associated with CVD risk factors, especially in chil-
of these guidelines should follow best available standards.                       dren, the full effect of exposure to these factors will be seen only
                                                                                  in the future. Information from more than 100 countries shows
Clinical Research                                                                 that more 13- to 15-year-olds smoke than ever before, and stud-
                                                                                  ies show that obesity levels in children are increasing markedly in
In most situations, health care innovations should be intro-
                                                                                  countries as diverse as Brazil, China, India, and almost all island
duced as experimental interventions to permit proper moni-
                                                                                  states (Leeder and others 2004). Populationwide efforts now to
toring and evaluation. These experiments do not have to
                                                                                  reduce risk factors through multiple economic and educational
address the efficacy of the procedure (many innovations will
                                                                                  policies and programs will reap savings later in medical and
already have been tested), but rather issues pertaining to their
                                                                                  other direct costs as well as indirectly in terms of improved qual-
effectiveness and efficiency in the specific context of developing
                                                                                  ity of life and economic productivity.
    Another reason for the experimental approach is the rapid-
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                                                                                     Chapter 35

                          Respiratory Diseases of Adults
                                                                                Frank E. Speizer, Susan Horton, Jane Batt, and Arthur S. Slutsky

Adult respiratory diseases in the developing world are a major                  for each decade of life, whereas rates of death from tuber-
burden in terms of morbidity and mortality and, particularly as                 culosis remain relatively constant. Notably, acute respiratory
related to chronic respiratory disease, are of increasing concern               diseases—in addition to tuberculosis—remain major concerns
(Murray and Lopez 1996). For many years, the leading cause of                   among adults with AIDS.
adult respiratory disease mortality has been tuberculosis, which                    The diagnosis of pneumonia varies according to the patient’s
still kills far more people than it should, given the increased                 access to medical care. Often the diagnosis is made simply on
efficacy of treatment and preventive regimens (see chapter 16).                 the basis of cough and fever. For patients with access to a hospi-
However, the burden of other acute and chronic adult respira-                   tal, the likelihood of obtaining a chest x-ray increases; generally
tory diseases, which is the focus of this chapter, has been rising              the infection is bacteriologically confirmed only in the most
throughout the world. These diseases fall into four categories:                 sophisticated medical centers. The natural history of pneumo-
acute diseases, such as pneumonia and influenza; chronic                        nia without antibiotic treatment varies with the etiologic agent
diseases, such as chronic obstructive pulmonary disease                         and the patient’s underlying comorbid conditions and age.
(COPD) and asthma; occupational lung diseases, such as byssi-                   Mortality resulting from these lower respiratory diseases is
nosis, asbestosis, and coal worker’s pneumoconiosis; and other                  approximately 10-fold higher in people age 60 to 69 than in
parenchymal lung diseases, such as immune-related lung                          people age 15 to 59 (WHO 2000). Comorbid conditions, mal-
diseases. Lung cancer, tuberculosis, and AIDS-related lung dis-                 nutrition, low socioeconomic status, and cigarette smoking
eases are dealt with in chapters 29, 16, and 18, respectively.                  each play a role in increasing the incidence of disease and wors-
                                                                                ening the prognosis, both with and without treatment.
ACUTE DISEASES: PNEUMONIA AND INFLUENZA                                             From studies conducted in the developed world, it would be
                                                                                reasonable to conclude that common antibiotics for pneumo-
Obtaining figures on the incidence and burden of pneumonia                      nias that occur outside a hospital setting would effectively
and influenza in adults throughout the developing world has                     reduce days lost from work and, in the absence of other morbid
been surprisingly difficult. Much of the research and surveil-                  conditions, mortality. The few studies in which sputum speci-
lance has been directed toward the pediatric age group (see                     mens have been cultured suggest that Streptococcus pneumoniae
chapter 25). In 2000, fatal lower respiratory infections, as a                  is found in between 40 and 50 percent of the cases. Gram-
class that represents serious pneumonia and influenza, were                     negative organisms or mixed infections are often isolated, and
reported as the cause of 120 deaths per million men and                         thus, the use of broad-spectrum antibiotics is warranted (Hooi,
76 deaths per million women worldwide for the 15 to 59 age                      Looi, and Ng 2001; Hui and others 1993; Lieberman and others
group (WHO 2000). For both sexes in this age group, this sta-                   1996). As would be expected, increased use of antibiotics
tistic represents approximately one-third of the deaths caused                  has resulted in increased resistance to common antibiotics. In
by tuberculosis. However, for the age groups over 60, rates                     addition, 10 to 15 percent of these cases may be tuberculosis
of death from lower respiratory disease more than double                        (Dolin, Raviglione, and Kochi 1994).


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
   Scott and others (2000) suggested that, despite the similarity                         the elderly are at greater risk of suffering from complications
of the mortality rates for hospital-treated pneumonia in devel-                           from influenza. Those criteria, along with the adequacy of sup-
oping and developed countries, there are important differences                            ply, form the basis for choosing who should be considered for
in the age distributions. The median age at death among                                   vaccination each year. Because the symptoms of influenza can
Kenyan adults was 33 years, in contrast to more than 65 years                             be quite similar to those of bacterial pneumonia, influenza may
in more developed countries. Many patients in developing                                  often be misdiagnosed as pneumonia. Generally, influenza is
countries present late in the course of the disease. Often they                           more self-limiting than pneumonia, although the infectivity
die before an appropriate diagnostic workup can be completed,                             and transmission of influenza from person to person can be
thus leading to an underestimate of case-fatality rates.                                  substantial. The current threat of H5N1 influenza has resulted
   Signs and symptoms of influenza can vary from trivial to                               in increased human and avian surveillance and preparations
explosive. Although the disease is usually self-limiting, it can                          for a possible pandemic (box 35.1).
result in both severe incapacity and, when not properly treated,                             The recent 2003 outbreak of severe acute respiratory syn-
potentially fatal secondary pneumonia. Clearly, patients with                             drome (SARS; see chapter 53) emphasizes the importance of
comorbid conditions, the very young, pregnant women, and                                  accurate and open surveillance and a coordinated response in

     Box 35.1

     H5N1 Influenza

     Clearly, of even greater concern is the potential for a new                          sources, it is not clear how effective these control measures
     influenza A pandemic, as occurred in 1918 and more                                   have been. Although these efforts were thought to help
     recently in 1958 and 1968, from a newly altered strain of                            control the spread of the virus, permanent ecological
     avian influenza. With each additional bird-to-human case,                            reservoirs appear to have become established in wild fowl
     modest genetic mutation or re-assortment increases the                               and domestic chickens over a relatively broad region of
     chance for the avian virus to be altered to become estab-                            Southeast Asia. WHO authorities have expressed concern
     lished and virulent in mammalian species. This may result                            about the finding that migratory birds that are infected
     in the establishment of sustained transmission among                                 with H5N1 but are relatively asymptomatic have spread
     humans. While the pandemics of 1958 and 1968 were                                    viable viruses over large regions with subsequent infection
     together responsible for approximately 3 million deaths,                             in domestic poultry. Furthermore, more recently there has
     mostly in the very young, the elderly, and in those with co-                         been evidence of disease in wild and zoo mammals as well
     morbid conditions, the 1918 episode is believed to have                              as isolated cases of infection in domestic cats. Recent
     caused over 40 million deaths, mostly in the age group 15                            reports from Vietnam include two cases in humans
     to 35 years. This potential for greatly increased mortality                          infected through the consumption of uncooked duck
     among such a robust population has fueled recent concern                             blood. Further investigation of possible person-to-person
     (WHO 2005a).                                                                         transmission is underway. Recently, WHO (2005b) stated,
         This concern has become more immediate with the                                  “The possible spread of H5N1 avian influenza to poultry
     identification of a sub-strain of influenza A, H5N1, first                           in additional countries cannot be ruled out. WHO recom-
     identified in 1997 in Hong Kong when it jumped from                                  mends heightened surveillance for outbreaks in poultry
     poultry to humans and killed six of 18 infected people.                              and die-offs in migratory birds, and rapid introduction of
     Virtually all of the original cases were believed to have                            containment measures, as recommended by FAO and OIE.
     been bird-to-human transmission. Since that time there                               Heightened vigilance for cases of respiratory disease in
     have been a few hundred serologically confirmed cases in                             persons with a history of exposure to infected poultry is
     Cambodia, Indonesia, Thailand, and Vietnam, with high                                also recommended in countries with known poultry out-
     case fatality but no sustained evidence of ongoing human-                            breaks. The provision of clinical specimens and viruses,
     to-human transmission (WHO 2005b).                                                   from humans and animals, to WHO and OIE/FAO refer-
         The H5N1 strain is highly pathogenic among poultry.                              ence laboratories allows studies that contribute to the
     During 2003–2004 it resulted in outbreaks in 8 countries                             assessment of pandemic risk and helps ensure that work
     in Asia, with over 100 million birds dying from disease or                           towards vaccine development stays on course.”
     being culled. More recently, though an additional 150 mil-                              Humans have little natural immunity to the H5N1
     lion birds have been culled, because much of the develop-                            viruses. Thus, in contrast to the usual influenza epidemics,
     ing world’s poultry economy depends on rural backyard                                which affect the very young, elderly, and those with

682 | Disease Control Priorities in Developing Countries | Frank E. Speizer, Susan Horton, Jane Batt, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
      comorbid conditions, virtually the entire population in an                                       Given the lack of natural immunity, there is considerable
      exposed community is at risk. In human cases of avian                                            concern that even if adequate vaccines were available, distri-
      influenza, following the initial respiratory infection,                                          bution on a worldwide basis would be limited by economic
      mortality results from two distinct processes. One process                                       considerations as well as distribution problems in the devel-
      begins with relatively rapid onset of respiratory distress                                       oping world. Efforts are underway to identify the genetic
      from hypoxia associated with ARDS.a The alternative                                              make-up of the strains of H5N1 that will yield the most
      process results from secondary bacterial infection with a                                        effective vaccines and to produce such vaccines in a cost-
      variety of organisms. In the documented H5N1 influenza                                           effective manner. Testing H5N1 vaccines based on recently
      infections in humans, respiratory symptoms are most                                              identified viruses in normal healthy volunteers suggests the
      prominent. However, in one case of encephalitis in a child                                       immunologic response may be adequate, but several
      from Vietnam, H5N1 influenza virus was identified in                                             months of production would be necessary to produce ade-
      cerebrospinal fluid and fecal matter, and in throat and                                          quate supplies for one region, let alone for worldwide distri-
      serum samples. Isolates from several cases were resistant                                        bution. Stockpiles of effective antiviral medications are
      to two commonly used antiviral medications (amantadine                                           being generated in some countries. In the interim, WHO
      and rimantadine), while two other antiviral medications                                          has encouraged the rapid reporting of cases and the estab-
      (oseltamivir and zanamivir) still appear to be effective.                                        lishment of procedures for better public health intervention
          There is no way to predict the outcome of these ongoing                                      strategies before and during a pandemic (WHO 2005c).
      events. What seems evident is that if human-to-human                                             Many countries have developed pandemic influenza pre-
      transmission becomes established, a pandemic will follow.                                        paredness plans in anticipation of such an event.
      Source: Authors.
      a. ARDS is defined as Acute Respiratory Distress Syndrome resulting from multiple causes, the most likely in this situation being an immunological reaction to the virus.

Table 35.1 Public Health Measures in the SARS Episode, 2003

  Procedure                                       Comment

  1. Isolation of patients                        Isolate rapidly after onset of symptoms.
  2. Quarantine of contacts                       Usually at home, but separate from patients. When in contact with unexposed subjects, wear masks and avoid public
                                                  transportation and visits to crowded places.
  3. Education                                    Reduce delay between onset of symptoms and isolation. In endemic areas, get subject to monitor temperature daily. Use
                                                  fever hotlines, fever evaluation clinics.
  4. Thermal screening                            Monitor temperature of travelers from endemic areas (not proven effective).
  5. Increased social distance                    Cancel mass gatherings. Close schools, theaters, public facilities. Require use of masks in public settings.
  6. Disinfection                                 Practice frequent hand washing. Use aerosol disinfectant agents.
  7. Travel advisories                            Postpone unessential travel. Screen travelers at entry and exit (not proven effective). Distribute health notices to travelers.

Source: Data compiled and summarized from Bell 2004.

controlling the spread of newly active influenza strains. The                                         part of the reason the epidemic was contained as promptly as it
potential for global spread and the occurrence of worldwide                                           was (see table 35.1). However, because of the high case-fatality
epidemics of influenza (presumed to be transmitted to humans                                          rate, the disease caused significant disruption throughout the
from domesticated or wild animals and then through close                                              world.
proximity to humans with symptomatic disease—generally to
caregivers) points out the importance of continued surveil-
lance for such episodes (Low and McGeer 2004). The lessons                                            Economic Impact of Influenza and Cost-Effectiveness
learned from the SARS epidemic reinforce the importance of                                            of Interventions in the Developed World
proven traditional public health measures, such as finding and                                        Influenza is common in developed countries. Annually, it
isolating cases, quarantining close contacts, and improving                                           affects 10 to 20 percent of the U.S. population (Lee and others
infection control practices (Bell 2004). Those methods, along                                         2002); those affected experience on average a loss of 2.8
with several other, less traditional efforts, were presumed to be                                     workdays per episode. Those over 65 years of age are more

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                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
susceptible to complications, increased costs of hospitaliza-                             annual burden of influenza in the tropics from data on such
tion, and even death. The cost of outbreaks can be large. The                             occasional and severe outbreaks. Because many areas (for
costs of the 1996–97 epidemic in Germany were estimated                                   example, Sub-Saharan Africa) do not have surveillance centers,
at US$1,045 million, and the annual costs of outbreaks at                                 not enough is known at this point to make policy recommen-
US$11 million to US$18 million (WHO 2002a).                                               dations. There are also no readily available estimates of the
    For those over age 65, many countries encourage preventive                            cost-effectiveness of influenza vaccination in those environ-
vaccinations annually, on the basis of studies suggesting that                            ments. (For further discussion of the role of vaccination, see
vaccination (either opportunistic or in a campaign) is cost-                              chapter 20.)
effective in elderly populations (for example, see the model of
Scuffham and West 2002). Given a good antigenic match, inac-
tivated influenza vaccines prevent laboratory-confirmed illness                           CHRONIC RESPIRATORY DISEASES:
in 70 to 90 percent of healthy adult vaccine recipients (WHO
                                                                                          NATURE, CAUSES, AND BURDEN
2002a). Vaccination is less costly than chemoprophylaxis (with
ion-channel inhibitors such as amantadine and rimantadine,                                COPD and asthma have very different diagnoses and causes;
or with neuraminidase inhibitors such as zanamivir and                                    hence, they are discussed in separate sections. However, the
oseltamivir) or early treatment with the same drugs. In both                              treatments for these different chronic respiratory diseases share
the institutionalized and the healthy elderly, vaccination sub-                           similarities, and that discussion is therefore combined. One of
stantially reduces overall mortality from influenza (by 40 to                             the difficulties in defining COPD on a worldwide basis is that
68 percent).                                                                              three distinct levels are used, depending on the sophistication
    The cost-effectiveness of vaccination for healthy working-                            of the health care system in the country where the patient is
age adults, taking into account workdays lost, is a matter of                             being evaluated:
debate. Demicheli and others (2000) concluded that the most
cost-effective option for healthy adults age 14 to 60 was to take                         • Chronic bronchitis with and without obstruction, which may
no action. However, these authors include only medical costs in                             be part of the COPD diagnosis, is defined by the presence of
their calculations. Postma and others (2002) reviewed 11 stud-                              chronic cough and phlegm for three months per year for
ies. Only one shows cost savings on the basis of medical costs                              two or more years and is generally assessed by standardized
alone, but nine of them implied cost savings from vaccination                               questionnaires.
if the value of lost work is included. Because of differences in                          • Obstructive airways disease is often assessed by reduced pul-
costs and health care usage patterns, data on cost savings in                               monary function as measured by simple spirometry and the
developed countries cannot be helpfully extrapolated to devel-                              presence of a reduced ratio of the forced expiratory volume
oping countries.                                                                            in one second (FEV1) divided by the vital capacity (VC).
                                                                                          • For emphysema, which is also part of the syndrome of
                                                                                            COPD, pulmonary function (changes in lung volume and
Economic Impact of Influenza in the Developing World                                        reduced diffusion capacity), x-ray evidence of bullae forma-
In Hong Kong, China (where there is a milder year-round pat-                                tion, hyperinflation of the chest, and (with the use of high-
tern of infection, little influenza-related mortality, and low                              resolution CT scanning) the presence of characteristic
reported work losses), a model suggested that vaccination was                               changes in lung architecture all may contribute to the
not cost saving, even if targeted to the elderly (Fitzner and                               diagnosis.
others 2001). The only case for vaccination was if it controlled
the emergence of highly virulent strains and prevented trans-                                 What is apparent is that not all these diagnostic procedures
mission to the rest of the world. According to the World Health                           are applied equally, particularly in the developing world; thus,
Organization (WHO), much less is known about the impact of                                COPD may be seriously underreported. The 1998 Workshop
influenza in the developing world. However, in the tropics,                               Report by the WHO and the National Institutes of Health
where viral transmission normally continues year-round,                                   (NIH) on “Global Strategy for the Diagnosis, Management,
influenza outbreaks tend to have high attack and case-fatality                            and Prevention of COPD,” developed as part of the Global
rates. For example, during an influenza outbreak in                                       Initiative for Chronic Obstructive Lung Disease (GOLD 2001),
Madagascar in 2002, more than 27,000 cases were reported                                  uses an international standard for defining the level of obstruc-
within three months and 800 deaths occurred despite rapid                                 tion from COPD. This strategy should improve worldwide
intervention. An investigation of this outbreak, coordinated by                           estimates. This standard definition will still require the use of
WHO, found that health consequences were severe in poorly                                 equipment that measures pulmonary function (Buist 2002).
nourished populations with limited access to adequate health                              Over the next several years, as the price and distribution of this
care (WHO 2002b). It is not possible to extrapolate the exact                             equipment becomes more favorable and as more groups

684 | Disease Control Priorities in Developing Countries | Frank E. Speizer, Susan Horton, Jane Batt, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
                                a. Males                                             Rates per million people
Percent                                                                              25,000
       15–29         30–44   45–59      60–69          70–79          80
                               Age group                                                  0
                                                                                                 15–29        30–44     45–59     60–69       70–79        80
                               b. Females                                                                                  Age group
                                                                                                                        Males     Females
                                                                                     Source: WHO 2000.

 8                                                                                  Figure 35.2 COPD by Age and Sex, Worldwide


                                                                                    reduced mortality from COPD, presumably through a mecha-
                                                                                    nism that results in a modest improvement in pulmonary
 0                                                                                  function that appears to be related primarily to the extent of
       15–29         30–44   45–59      60–69          70–79          80
                               Age group                                            chronic bronchitis and mucus hypersecretion (Scanlon and
                                                                                    others 2000; Speizer and others 1989). Within a few years of
      COPD          Asthma   Other respiratory diseases         Tuberculosis
                                                                                    stopping smoking, smokers’ rate of decline of pulmonary func-
Source: WHO 2000.                                                                   tion (that is, FEV1) returns to the rate found in nonsmokers,
                                                                                    although little of the lost pulmonary function is regained
Figure 35.1 Chronic Respiratory Diseases DALYs as a Percentage of
                                                                                    (Fletcher and others 1976). Similar effects are seen in the
World Totals
                                                                                    developing world. However, because smoking is far less
                                                                                    prevalent in developing countries, especially among women,
                                                                                    other exposures are related to the development of disease (see
undertake the training in its use and in the interpretation of                      also chapter 46). One of the most important exposures, partic-
results from the tests, diagnostic uniformity will improve.                         ularly for women, is to unvented coal-fired cooking stoves,
Unfortunately, as pointed out by Aït-Khaled, Enarson, and                           starting during childhood and continuing into adult life (see
Bousquet (2001), the applicability of these guidelines has not                      chapter 42).
been effectively tested in developing countries.                                        Because the interventions and treatments for COPD overlap
    In adults, COPD dominates all other chronic respiratory                         with those for asthma, they will be treated together.
diseases in accounting for 2 percent to more than 10 percent                            The diagnosis of asthma has been debated for centuries.
of lost disability-adjusted life years (DALYs) on a worldwide                       Health care providers can generally agree on the diagnosis in
basis. Its incidence increases dramatically with age (fig-                          the individual patient who is wheezing and in whom other eti-
ures 35.1a and 35.1b). Of note, mortality from COPD is low                          ologic factors are ruled out. They would also agree on the def-
before age 45. Over age 45, death rates increase from 50 to 200                     inition of the disease as an inflammatory response in the
per 10,000 individuals and are consistent across age groups in                      airways that results in variable and generally reversible airflow
men and women, with the exception of death rates in women                           obstruction with or without treatment. However, depending
over age 80, which exceed those in men in that age group                            on the training of health care providers, the nature of surveil-
(figure 35.2).                                                                      lance, the characteristics of a given community, and the par-
    Much of COPD in the developed world is related to cigarette                     ticular environment of the community, the accuracy of the
smoking, and there is no question that progression of the dis-                      estimate of the prevalence of asthma in a community may vary
ease is related to the number of cigarettes smoked and the years                    much more. The reported prevalence of the disease may be
of smoking. Smoking cessation has been associated with                              based on no more than an answer to this question: “Has a

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                                     ©2006 The International Bank for Reconstruction and Development / The World Bank
provider ever told you that you (or your child) has had                                   Economic Impact of Asthma in the Developing World
asthma?” The response to this question has been validated in a                            Data for developing countries are much scarcer. For Estonia,
number of studies. In contrast, the diagnosis may depend on                               Kiivet and others (2001, cited in Lee and Weiss 2002) estimated
examination of the patient’s chest, physiological testing,                                the direct annual costs of asthma to be US$104 per year per
responsiveness to provocative stimuli to the airways, and                                 asthma patient, equivalent to 1.4 percent of direct health care
specific response to therapy. Thus, estimates of community                                costs. In Singapore, medical costs for asthma constitute 1.3 per-
burden from asthma may depend on the threshold used in                                    cent of total health care costs (Chew, Goh, and Lee 1999, cited
making the diagnosis.                                                                     in WHO 2001).
   Despite variations in diagnostic criteria, worldwide esti-                                 One study (Aït-Khaled, Enarson, and Bousquet 2001, cited
mates of the asthma burden among adults have generally                                    in Weiss and Sullivan 2001) found that asthma drugs cost
come from surveys within selected communities. In contrast                                between 3.8 and 25 percent of the patient’s monthly income in
to other adult respiratory diseases, the prevalence of asthma is                          24 developing countries in Asia and Africa. K. R. Smith (2000)
relatively low (figures 35.1a and 35.1b). In adults, the DALYs                            estimates the burden of respiratory disease in India that is
for asthma are at a peak of about 2 percent of the total world-                           attributable to indoor air pollution (only a fraction of all respi-
wide in people age 15 to 29, and they decline in each older age                           ratory disease) as 1.6 billion to 2 billion sick days per year. Of
group. This pattern is also reflected in mortality rates, with the                        that total, asthma is responsible for about one-third, acute res-
highest rates occurring in young people and equal rates in                                piratory infection is responsible for about one-third, and the
men and women about age 60. After age 60, reported rates of                               remainder is attributable to COPD, tuberculosis, and ischemic
death caused by asthma in men begin to exceed those in                                    heart disease. Asthma and COPD combined account for 44 per-
women, and both become substantial. That shift reflects pri-                              cent of the burden.
marily either increasingly questionable diagnostic accuracy or
misclassification of other obstructive respiratory diseases such
as COPD.                                                                                  Cost Effectiveness of Interventions for COPD and Asthma
                                                                                          in Developed Countries
                                                                                          Five recent overviews of the economics of chronic respiratory
Economic Impact of Asthma and COPD                                                        disease, COPD, and asthma (Friedmann and Hilleman 2001;
in the Developed World                                                                    Lee and Weiss 2002; Ruchlin and Dasbach 2001; Sullivan and
In the United Kingdom (where asthma rates are particularly                                Weiss 2001; Weiss and Sullivan 2001), in addition to many indi-
high), respiratory disease accounts for 6.5 percent of hospital                           vidual studies, focus on developed countries.1 Only a limited
admissions. Fifteen percent of the working population report                              number of studies use cost- or quality-adjusted life years
work-limiting health problems caused by respiratory disease,                              (QALYs) saved as the outcome (others use life years saved).
and 18.3 million workdays were lost to asthma problems in                                 (Studies focusing on intermediate health outcomes and on cost
1995–96 (Chung and others 2002).                                                          minimization are not discussed here.) In general, costs in
   In the Netherlands, annual costs associated with asthma                                developing countries would be about 20 percent of those
and COPD (direct and indirect) were estimated to exceed                                   reported here, according to detailed unit cost data by region
US$500 million for a population of about 14 million (data for                             from WHO-CHOICE (Choosing Interventions That Are Cost-
the 1980s). Asthma or COPD was responsible for 3 percent of                               Effective) and on comparisons of respiratory drug prices from
absenteeism caused by illness, and asthma was also the main                               online pharmacies in the United States and from the
reason for absence from school among children age 4 to 12                                 International Drug Price Indicator Guide (
(Rutten–van Mölken and others 1992).                                                      The exceptions are interventions involving nondiscounted
   In the United States in the early 1990s, health care costs                             drugs that are still under strictly enforced patents, for which the
attributable to respiratory disease were US$11 billion (about                             costs in developing countries would be closer to those in the
2 percent of total health care costs), and an estimated 3 million                         United States. Table 35.2 summarizes the results.
workdays and 10 million schooldays were lost to respiratory                                   Inhaled salbutamol (short-acting beta-2 agonist) is the first
disease (Stoloff, Poinsett-Holmes, and Dorinsky 2002).                                    line of treatment for both intermittent asthma (daytime symp-
   Another survey (Weiss and Sullivan 2001) estimated the                                 toms less than once per week, nocturnal symptoms less than
costs of asthma in 1991 US dollars for four developed countries                           twice per month, and normal spirometry between episodes)
(Australia, Sweden, the United Kingdom, and the United                                    and COPD (mild to severe) in both developed and developing
States) and one state (New South Wales in Australia). Per                                 countries. This treatment became standard practice beginning
patient costs of asthma ranged from US$326 (Australia) to                                 in the 1970s, so there are no cost-effectiveness studies of salbu-
US$1,315 (Sweden) annually, with direct costs accounting, in                              tamol compared with placebo. This medical intervention is
most cases, for more than half of total costs.                                            likely the most cost-effective one, but it is still likely to cost

686 | Disease Control Priorities in Developing Countries | Frank E. Speizer, Susan Horton, Jane Batt, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 35.2 Cost-Effectiveness of Interventions for Asthma and COPD in 2001

  Reference                                   Intervention                                       Alternative                        Cost-effectiveness

  Authors’ estimates                          Inhaled ipratropium bromide                        Placebo                            US$6,700–US$8,900/QALY for moderate COPD
  Paltiel and others 2001                     Quick relieversa and inhaled                       Quick relievers only               US$13,900/QALY in adults with mild to moderate
                                              corticosteroids                                                                       asthma: US$10,600 for moderate only
  Van den Boom and others 2001                Inhaled corticosteroid                             Placebo                            US$13,400/QALY COPD treatment
                                              (fluticasone propionate)
  Akins and O’Malley 2000                     A-1 antitrypsin augmentation therapy               Standard careb                     US$14,400/QALY, severely deficient individuals
  Hay and Robin 1991,                         A-1 antitrypsin augmentation therapy               Standard careb                     US$45,000–US$215,000/life year, depends on age,
  in Ruchlin and Dasbach 2001                                                                                                       efficacy, and so forth

  Toevs, Kaplan, and Atkins 1984,             Education and exercise program                     Exercise program only              US$71,500/QALY
  in Ruchlin and Dasbach 2001

  Long-term oxygen
  Authors’ estimate                           Home oxygen therapy for COPD                       No oxygen                          US$19,000/life year (US$26,700–US$38,000/QALY)

  Mechanical ventilation
  Schmidt and others 1983, in                 Mechanical ventilation                             Standard hospital carec            US$6,400–US$23,600/life year (COPD, asthma, cardiac
  Rutten–van Mölken                                                                              (excluding ventilation)            patients) excluding physician costs
  Anon and others 1999 in                     Mechanical ventilation in                          Standard hospital carec            US$35,000–US$60,700/QALY
  Ruchlin and Dasbach 2001                    intensive care unit, asthma,                       (excluding ventilation)
                                              and COPD patients

  Al and others 1998, in                      Lung transplant in end-stage disease               No transplant                      US$464,000/QALY
  Ruchlin and Dasbach 2001
  Ramsey and others 1995,                     Lung transplant in those eligible                  No transplant                      US$238,200/QALY
  in Ruchlin and Dasbach 2001

a. Quick relievers refer to rapid-acting bronchodilators (for example, salbutamol) that act to relieve bronchoconstriction and accompanying acute symptoms of wheeze, chest tightness, and cough.
b. Standard care includes medical management (ipratropium bromide, beta-2 agonist, steroid) and home oxygen as needed.
c. Standard care includes medical management and oxygen.

some thousands of dollars per life year saved in the United                                            COPD. The cost per QALY is likely to be lower for severe asth-
States.                                                                                                ma, but ethical considerations render random controlled trials
    The next line of treatment currently recommended for                                               unfeasible.
developing countries is inhaled corticosteroids (for example,                                              No cost-effectiveness study could be found for ipratropium
beclomethasone) for mild to severe persistent asthma (disease                                          bromide compared with placebo. We estimate that the cost per
ranging from daytime symptoms greater than once per week,                                              QALY saved would be between one-half and two-thirds of that
nocturnal symptoms more than twice a month, and normal                                                 for a new-generation inhaled steroid such as fluticasone
spirometry between episodes to daily frequent symptoms asso-                                           propionate. This estimate, which is based on the relative cost
ciated with severe obstruction) and inhaled ipratropium bro-                                           of the two drugs in the United States and assumes similar
mide for COPD. Both first-generation corticosteroids and ipra-                                         effectiveness of the two drugs, would put the cost of ipratro-
tropium bromide are off patent. However, as pointed out by                                             pium bromide between US$6,700 and US$8,900 per QALY.
Chan-Yeung and others (2004), the use of corticosteroids either                                            Most of the other interventions summarized in table 35.2
intermittently or chronically is commonly recommended in                                               have a higher cost per QALY. For individuals who develop
developed countries, where the background level of tuberculo-                                          COPD related to a severe deficiency in alpha-1 antitrypsin,
sis among patients is considerably lower. In developing coun-                                          alpha-1 antitrypsin therapy is sometimes considered, at a cost
tries with higher tuberculosis rates, corticosteroids must be                                          of between US$45,000 and US$215,000 per life year.2 The use
used with greater caution.                                                                             of long-acting beta-2 agonists and leukotriene modifiers is now
    Inhaled steroids cost about US$13,900 per QALY for mild                                            an accepted and integrated component of the treatment of
to moderate asthma or when used in early treatment of                                                  moderate to severe asthma in the developed world. However,

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                                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
the cost savings for the developing world are difficult to                                pressure ventilation, where it is feasible, is less costly than inva-
demonstrate because the endpoints of studies using those                                  sive mechanical ventilation for specific indications. Finally,
drugs are often changes in spirometric testing, improved                                  costs of lung transplants are at a level scarcely affordable even
quality-of-life measures, steroid-sparing effects, or altered                             in developed countries; Al and others (1998, cited in Ruchlin
hospital admission rates.                                                                 and Dasbach 2001) estimated costs at US$464,000 per QALY,
    Likewise, oral or intravenous steroids play a crucial role in                         and Ramsey and others (1995, cited in Ruchlin and Dasbach
the treatment of acute exacerbations in both asthma and COPD,                             2001) estimated costs at US$238,000 per QALY (in 2000 U.S.
but endpoint assessments in studies typically address decreases                           dollars).
in the duration of hospital stays and increases in the use of                                All those interventions compare unfavorably with the cost-
emergency department facilities, which result in decreases in                             effectiveness of smoking prevention for preventing COPD
health costs in the developed world. Oral steroids are inexpen-                           (discussed in chapter 46). Smoking prevention is one of the
sive, even by standards in developing countries, and in the short                         most cost-effective health interventions that exists, and there is
term might appear to be cost-effective, but they are associated                           a strong case for moving resources from expensive curative
with major medium- to long-term consequences and are not                                  interventions to that intervention. Likewise, prevention of
recommended as standard therapy.                                                          COPD by switching the cooking source from unventilated
    Educational programs tend to be cost saving in developed                              stoves that burn biomass to either improved stoves or kerosene
countries, where uncontrolled exacerbations are extremely                                 stoves is more cost-effective than treatment (see chapter 42).
costly in terms of hospital care (six such programs are surveyed
in Van Mölken and others 1992 and one in Ruchlin and
Dasbach 2001). Similarly, exercise rehabilitation programs (six                           Cost-Effectiveness of Interventions for COPD and Asthma
surveyed in Ruchlin and Dasbach 2001) can also be cost sav-                               in Developing Countries
ing. WHO (2001) has commented on cost savings achieved by                                 It is difficult to transfer the costs per QALY saved in developed
education programs for asthma from four different U.S. stud-                              countries to developing countries. The cost of patented drugs
ies. Only one of these studies addressed cost per well year,                              in developing countries should be the same as that in devel-
which was estimated at US$71,500 in 2001 (Toevs, Kaplan, and                              oped countries, whereas the costs of education and of the time
Atkins 1984, cited in Ruchlin and Dasbach 2001). However,                                 of medical personnel should be substantially lower (on the
there are likely to be monetary savings from fewer workdays                               order of 20 percent of U.S. levels). In practice, the costs of off-
lost, which are not factored into this analysis.                                          patent drugs also vary considerably. Beclomethasone dipropi-
    WHO (2001) surveyed one self-management training pro-                                 onate (one of the older, off-patent inhaled steroids) is available
gram for chronic asthma in India (Ghosh and others 1998),                                 for about US$15 per 200-dose inhaler in Canada in online
which resulted in improvements in health status, reduced use                              pharmacies but is quoted at US$1 to US$3 by agencies and
of emergency departments and hospitals, and savings on health                             suppliers on the International Drug Price Indicator Guide
costs. Sudre and others (1999) pointed out that studies of edu-                           ( A similar price difference exists for salbu-
cation programs tend not to provide a good description of the                             tamol inhalers. Hence, the most cost-effective therapies in
actual program content and that a more systematic description                             developed countries (inhaled salbutamol and first-generation
of these interventions needs to be promoted to replicate best                             corticosteroids for asthma and ipratropium bromide for
practice.                                                                                 COPD) are also likely to be cost-effective in the wealthier devel-
    Long-term oxygen therapy is a life-prolonging intervention                            oping countries—or more broadly if inexpensive drug supplies
in advanced stages of COPD. Recent studies do not quantify the                            are available. Those drugs are likely to be particularly cost-
cost per QALY but instead compare different methods of oxy-                               effective for those with severe and moderately severe asthma or
gen delivery (cylinder or concentrator). These authors’ crude                             COPD but less cost-effective for those with mild disease.
estimate for long-term oxygen use is US$19,000 per life year                              Recent practice suggests that a combination of long-acting beta
saved.3 If the quality-of-life scores of patients on long-term                            agonists and inhaled corticosteroids can control moderate to
oxygen were 0.8 or 0.6, the cost per QALY would be US$22,750                              severe disease more rapidly. However, to make this form of
or US$31,700, respectively. (K. J. Smith and Pesce 1994, cited in                         therapy cost-effective, the patient needs to be reevaluated to
the Harvard Catalogue of Preference Scores, assign a median                               determine whether one or the other drug can be removed.
score of 0.4 to quality of life for patients with severe COPD                             Because of cost considerations, that may not be feasible in the
with high supportive care needs and poor functional status.)                              developing world.
    In hospitals, mechanical ventilation in the intensive care                                Once control has been obtained, education alone appears to
unit has been estimated to cost US$35,000 to US$60,700 per                                be ineffective when only respiratory outcomes are considered
QALY in 2001 (Anon and others 1999, cited in Ruchlin and                                  (although education on the benefits of exercise has other health
Dasbach 2001). Studies suggest that noninvasive positive                                  benefits: see chapter 44 on lifestyles). However, education

688 | Disease Control Priorities in Developing Countries | Frank E. Speizer, Susan Horton, Jane Batt, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
addressing the appropriate use of medication is extremely                           There are few reliable estimates of the global burden of
important, particularly in developing countries, where timely                   occupation-related respiratory diseases. Because of the lack of
emergency care for severe exacerbations may not be readily                      systematic surveillance in most developing countries, the few
available. Although the cost of educational efforts would be                    published estimates of occupation-related respiratory diseases
expected to be considerably lower in developing countries, this                 have relied on selected studies involving particular industries
area requires more systematic research.                                         that investigators have had unique opportunities to explore.
    Long-term oxygen is also an option for high-income house-                   For example, Trapido and others (1996) conducted a survey in
holds in middle-income developing countries. The costs are                      a relatively small group of former mineworkers and found that
likely to be lower than in developed countries. In Brazil the                   approximately 55 percent had pneumoconiosis with or without
monthly cost for supplemental home oxygen therapy is close                      tuberculosis. They estimated that about 25 percent of migrant
to US$150 (Sant’Anna and others 2003), compared with                            and former mineworkers in South African gold mines with
US$400 per month paid by Medicare, which would bring the                        15 to 25 years of exposure had occupational lung diseases.
cost-effectiveness to US$7,000 per life year by these authors’                  Loewenson (1999) pointed out the difficulties in making
crude estimates, or between US$8,750 and US$11,700 per QALY.                    assessments of occupational risk throughout the African coun-
Publicly funded systems are unlikely to be able to pay this rate,               tries and suggested a series of methodological issues that need
although private insurers and wealthy households might pay                      to be considered.
because such therapy prolongs life.                                                 Leigh and others (1999) estimated the global burden of dis-
    The other interventions in table 35.2 are likely to be too                  eases related to occupational factors at 4.2 million to 10.0 mil-
expensive for most developing countries to use at present.                      lion cases per year. If one subtracts the rates for established
                                                                                market economy countries, the total burden for the rest of the
OCCUPATIONAL LUNG DISEASE AND OTHER                                             world is approximately 3.4 million to 9.1 million cases per year.
                                                                                Using limited data and applying rates from individual nations
                                                                                and regional groups of countries, the authors made an indirect
Although occupational lung diseases are often considered dis-                   calculation for the expected number of cases of occupation-
eases of the industrial world, they are occurring with increased                related diseases globally. Figure 35.3 summarizes their esti-
frequency in the developing world, where guidelines for worker                  mates for pneumoconiosis and other chronic respiratory dis-
safety are generally more lax or nonexistent. In addition,                      eases by age and gender. Notably, these two categories of disease
because of increased migration from rural areas to more                         account for approximately 30 percent of all occupational dis-
urbanized centers and the transfer of major manufacturing                       eases. The prevalence of these diseases increases with age and is
activities from the developed market economy countries to the                   higher among men.
less developed countries, the number of employees with
potentially harmful occupational exposures has increased
exponentially in the past 30 years. The general discussion of
occupation-related diseases is reviewed in chapter 60. We focus                  Rates per million people
here on specific occupation-related lung diseases.                               2,500
   Occupational lung diseases are, for the most part, charac-
terized as related to particular occupational exposures and                      2,000
generally fall into two broad pathophysiological types. One
type may result in pulmonary fibrosis, which is manifested by                    1,500
restricted lung volume and decreased diffusion capacity on
pulmonary function testing and increased interstitial pul-                       1,000
monary markings on chest x-ray. Certain occupational lung
diseases, such as silicosis, are complicated by a substantially                    500
increased risk of tuberculosis, which contributes to the overall
burden of respiratory disease in the developing world. The                           0
second pattern of occupational lung disease is that of obstruc-                                 0–14                15–44               45–59            60
                                                                                                                            Age group
tive airways disease, which may be reversible (occupational
asthma) or irreversible (chronic bronchitis with or without                                                           Males        Females
obstruction or emphysema or COPD), in which the chest x-
                                                                                 Source: Leigh and others 1999.
ray often is negative and the diagnosis is dependent largely on
reported histories of exposures, symptoms, and pulmonary                         Figure 35.3 Estimated Combined Pneumoconiosis and Other
function testing.                                                                Occupation-Related Chronic Respiratory Diseases

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                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
    Asbestosis and asbestos-related cancers present a particular                          immunologically related pulmonary diseases most often asso-
problem in developing countries. Asbestosis can manifest both                             ciated with environmental exposures to specific inhaled anti-
as other interstitial lung disease, as described above, and as                            gens or interstitial inflammation and fibrosis, often of
obstructive airways disease. In addition, occupational expo-                              unknown origin. In the developing world, little systematic
sure is associated with the occurrence of lung cancer, and                                work has been done on these diseases to assess incidence or
according to studies in developed countries, the rate of occur-                           prevalence. These conditions probably occur considerably less
rence is synergistically associated with smoking. Because the                             frequently than asthma and COPD. However, they are likely
cost of health care compensation in the developed world                                   to have a higher prevalence in developing countries than is
exceeds the potential profit from mining and manufacturing                                reported in the developed world simply because of the pre-
of asbestos products, much of the industry has moved to the                               sumed associations with exposures to organic dusts and the
developing world.                                                                         increased prevalence of malnutrition (see chapter 56), both of
    LaDou (2004) has recently summarized the status of the                                which are likely to occur in more rural and less developed areas
potential for reducing occupational exposure on a worldwide                               of the world.
basis and suggests that upward of 10 million lives will be lost if                            See chapters 16, 18, and 29 for interventions for tuberculo-
the current lack of controls and continued increases in mining                            sis, AIDS-related lung disease, and lung cancer, respectively.
and manufacturing are not changed. In 2000, more than 2 mil-                              Managing immunologic and fibrotic respiratory diseases with
lion tons of asbestos products were produced, whereas 25 years                            medication is extremely difficult and expensive. Therapeutic
earlier the total production was 350,000 tons each year. Except                           trials often fail, presumably because the treatments are not
for the Russian Federation and Canada, virtually all the larger                           aimed at a particular antigen. The most effective way of manag-
producers are in the developing world, where the recognition                              ing these respiratory diseases is to reduce exposure to the
and reporting of health effects are less well established. The                            inciting agents, an approach that hinges on two strong prem-
likelihood of reversing this trend and developing an interna-                             ises, which are not always applicable in the developed world.
tional ban on asbestos use is small, particularly because it is the                       First, the disease must be recognized as related to a common
nations that produce more asbestos products that are, in fact,                            environmental contaminant encountered in an occupational or
increasing consumption.                                                                   avocational exposure—for example, exposure to thermophilic
    The economic burden of occupational lung diseases is sur-                             actinomycetes in moldy hay or sugarcane results in farmer’s
prisingly difficult to document. Most developed countries and                             lung, and exposure to bird feathers or droppings results in bird
some developing countries (for example, South Africa) have                                fancier’s disease. Second, community resources must be directed
legislation protecting workers from exposure and compensat-                               toward educating the public about the importance of limiting
ing those who have contracted chronic conditions. In the                                  exposure to these agents.
United States, compensation payments from the Social Security
Administration and the Department of Labor for black lung
disease totaled US$1.6 billion in 1996 (NIOSH 1999). Data                                 GENERAL APPROACH TO LOWERING RISK
exist on compensation for claims for various occupational lung
                                                                                          OF ADULT RESPIRATORY DISEASE
diseases for the United States and the European Union coun-
tries. However, claims data represent only a small fraction of                            Although interventions of various sorts are indicated for each
the true economic cost (for example, not all workers make                                 of the disease categories discussed, these interventions are often
claims; compensation payments lag considerably). For the                                  costly and sometimes ineffective in lowering or preventing pre-
United States, the annual costs of complying with the revised                             mature mortality. Thus, from an operational perspective, it is
respirator standards for 1993 were US$111 million for about                               important to consider preventive and therapeutic strategies that
5 million workers needing to use a respirator (presumably                                 will have greater societal effect than will the management of the
these costs of prevention were far lower than the economic cost                           manifestations of diseases as they arise in individuals. This
of unprotected work) (OSHA 1998). The primary treatment                                   approach applies to acute diseases (vaccination schemes to
for affected workers is to remove them from the inciting expo-                            reduce the burden of influenza, in contrast to individual man-
sures. (See chapter 60 for discussion of preventive strategies                            agement of community-acquired pneumonia) and chronic dis-
that need to be considered to reduce the risk of occupational                             eases (smoking prevention and reduction programs, compared
disease.)                                                                                 with availability of routine asthma medication). Primary pre-
    Some of the other major classes of adult respiratory diseases                         vention strategies should include efforts by multiple agencies of
are discussed in other chapters: tuberculosis, in chapter 16;                             government and the community coming together to establish
AIDS-related lung disease, in chapter 18; and lung cancer, in                             appropriate priorities for action. Four sources of exposure
chapter 29. Other diseases that have been studied, particularly                           stand out: tobacco smoke, indoor smoke, outdoor air pollu-
in the developed world, include the hypersensitivity or                                   tants, and occupational exposure (see chapters 46, 42, 43,

690 | Disease Control Priorities in Developing Countries | Frank E. Speizer, Susan Horton, Jane Batt, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
and 60, respectively). Of these, the most pressing and cost-                     nities for research that go beyond the primary prevention that
effective is a cohesive policy to control tobacco smoking.                       would result from better smoking control policies. Because not
    In conjunction with the International Union against                          all smokers are at increased risk, the interaction of smoking
Tuberculosis and Lung Disease (IUATLD) and selected univer-                      with nutritional status (including micronutrient status), with
sities and health institutions in various countries, WHO is                      genetic factors that determine susceptibility, and with respira-
developing the Practical Approach to Lung Health (PAL, previ-                    tory infections may act as a precursor of susceptibility to envi-
ously known as the Adult Lung Health Initiative). The program                    ronmental (ambient or occupational) pollution and personal
is focused on improving primary care services, as well as appro-                 (smoking) pollution. Similarly, the role of immunologic stim-
priate referral to secondary health care facilities, for individuals             ulation or immunocompetence needs further exploration as it
with tuberculosis, acute respiratory infections (especially pneu-                relates to the development of asthma. Synergies between the
monia), asthma, and COPD. Four countries (Chile, Morocco,                        conditions discussed in this chapter and other infections (par-
Nepal, and South Africa) are serving as the pilot implementa-                    ticularly tuberculosis, but possibly others) may be especially
tion sites (WHO 2003).                                                           important in the developing world. Finally, specific environ-
    In Chile, where respiratory symptoms account for one-third                   mental conditions—such as altitude, heat and cold stress, and
of primary health care visits, a respiratory disease program was                 increased ambient pollution from rapid urbanization—and
initiated in 2001 as part of ongoing efforts to strengthen pri-                  their effects on asthma and COPD should be explored.
mary health care. The pilot program was implemented in 15                            Acute respiratory infections, specifically bacterial pneumo-
centers. Standard formats are used to devise scores to deter-                    nia, have not been addressed nearly as well for adults as they
mine follow-up for asthma and COPD. Sentinel centers are                         have been for children. For example, simple data on the preva-
used to provide epidemiologic information. Influenza immu-                       lence of infecting organisms, typical susceptibilities, the ability
nization coverage of the elderly and at-risk population has                      to train ancillary workers in clinical diagnosis, and the correla-
reached 85 percent (WHO 2003).                                                   tion of clinical assessment with verified disease would be help-
    In Morocco, survey work done before establishing a PAL                       ful in establishing the feasibility of assessment and treatment at
strategy showed that 31 percent of patients who consult                          home versus at a clinic or hospital, specifically in the develop-
primary health care centers present with respiratory symp-                       ing world. Common etiologic agents in North America are
toms. Of those patients, 85 percent have acute respiratory                       common elsewhere; therefore, treatment of disease would be
infections, 14 percent have chronic conditions, and 1 percent                    relatively inexpensive. Most community-acquired acute disease
have tuberculosis. In Mexico, an IUATLD study implementing                       responds relatively well. Certainly, penicillin should be recom-
asthma control measures was shown to be cost-effective.                          mended as a first-line drug for community-acquired pneumo-
Control of asthma improved, and the majority of patients                         nia. Educating local healers on the importance of initiating
experienced a decrease in the severity of asthma. The cost of                    treatment earlier in the course of disease would translate into
asthma management decreased because of lower costs for                           savings with respect to decreased days of work lost and reduced
emergency services and hospitalizations (WHO 2003).                              case-fatality rates. Follow-up monitoring and the development
                                                                                 of hospital-based bacteriologic testing should be expanded to
                                                                                 identify and control for the emergence of resistant bacterial
                                                                                     Studies of asthma in the developed world have been exten-
One of the difficulties in quantifying the burden of respiratory                 sive and of extremely high quality but are directed specifically
diseases in adults is the inability to apply uniform methods of                  toward the health care structures in which they are tested.
diagnosis across economies in which sophisticated diagnostic                     Specific cost-effectiveness studies in the developing world
procedures are possible, let alone across less developed                         should be done to see, for example, whether a focus on disease
economies. The problems relate in part to differences in the                     education and modification of risk factors in addition to med-
language describing the same symptoms, levels of registration                    ications outweighs simple administration of medications (with
of census and disease reporting, availability of diagnostic pro-                 instructions on use). In the developed world, there is no ques-
cedures, and reluctance to make accurate estimates because of                    tion that an approach that is multitiered and involves multiple
the cost of intervention strategies. Furthermore, unless controls                health care providers is the best, but we still do not have
on cigarette smoking are initiated, little progress in stemming                  concrete evidence of where monies are best spent in the devel-
the increasing burden of chronic respiratory diseases can be                     oping world. Another possible fruitful area of research is on
expected.                                                                        education programs. Most of the literature relates to education
   There are still a number of unanswered questions related to                   programs for specific entities (for example, “asthma triggers”)
COPD, which remains the dominant respiratory disease in                          and their costs in developed countries. Education programs
adults. The developing world provides some unique opportu-                       in developing countries that are multidimensional (smoking

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                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
cessation, indoor air quality, vaccination) are likely to be rela-                        Chung, F., N. Barnes, M. Allen, R. Angus, P. Corris, A. Knox, and others.
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                                                                                              Respiratory Medicine 96: 963–75.
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©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                    Chapter 44

      Prevention of Chronic Disease by Means
                 of Diet and Lifestyle Changes
                                                                                Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, Courtenay
                                                                                Dusenbury, Pekka Puska, and Thomas A. Gaziano

Coronary artery disease (CAD), ischemic stroke, diabetes, and                   facilities, an outcome that is not surprising, because their rates
some specific cancers, which until recently were common only                    have historically been extremely low in developing countries
in high-income countries, are now becoming the dominant                         with few medical facilities. However, preventing these diseases
sources of morbidity and mortality worldwide (WHO 2002).                        will require changes in behaviors related to smoking, physical
In addition, rates of cancers and cardiovascular disease (CVD)                  activity, and diet; investments in education, food policies, and
among migrants from low-risk to high-risk countries almost                      urban physical infrastructure are needed to support and
always increase dramatically. In traditional African societies,                 encourage these changes (see box 44.1).
for example, CAD is virtually nonexistent, but rates among
African Americans are similar to those among Caucasian
Americans. These striking changes in rates within countries                     CHRONIC DISEASE PREVENTION
over time and among migrating populations indicate that the
primary determinants of these diseases are not genetic but                      In this section, we briefly review dietary and lifestyle changes
environmental factors, including diet and lifestyle. Thus, con-                 that reduce the incidence of chronic disease. The potential
siderable research has been aimed at identifying modifiable                     magnitude of benefit is also discussed.
determinants of chronic diseases.
    Prospective epidemiological studies, some randomized pre-
vention trials, and many short-term studies of intermediate                     Recommended Lifestyle Changes
endpoints such as blood pressure and lipids have revealed a                     Specific changes in diet and lifestyle and likely benefits are
good deal about the specific dietary and lifestyle determinants                 summarized in table 44.1. These relationships and supporting
of major chronic diseases. Most of these studies have been con-                 evidence are summarized here.
ducted in Western countries, in part because of the historical
importance of these diseases in the West, but also because they                 Avoid Tobacco Use. Avoidance of smoking by preventing
have the most developed research infrastructure. A general                      initiation or by cessation for those who already smoke is the
conclusion is that reducing identified, modifiable dietary and                  single most important way to prevent CVD and cancer (chap-
lifestyle risk factors could prevent most cases of CAD, stroke,                 ter 46). Avoiding the use of smokeless tobacco will also prevent
diabetes, and many cancers among high-income populations                        a good deal of oral cancer.
(Willett 2002). These findings are profoundly important,
because they indicate that these diseases are not inevitable con-               Maintain a Healthy Weight. Obesity is increasing rapidly
sequences of a modern society. Furthermore, low rates of these                  worldwide (chapter 45). Even though obesity—a body mass
diseases can be attained without drugs or expensive medical                     index (BMI) of 30 or greater—has received more attention


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
      Box 44.1

      The Insulin Resistance Syndrome

      In recent years, researchers have recognized the insulin                                           most direct causes are overweight and inactivity, but
      resistance syndrome (also known as the metabolic syn-                                              dietary factors contribute. Genetic factors, which are
      drome) as a common contributing factor to the develop-                                             probably beneficial during periods of food shortages, also
      ment of diabetes, CAD, and some cancers. The syndrome                                              play a role. Recent evidence indicates that the populations
      is characterized by increased waist circumference, low                                             of Asia, Latin America, and probably Africa are particu-
      HDL (high-density lipoprotein) cholesterol, high levels of                                         larly susceptible (Dickinson and others 2002; Harris and
      triglycerides, hypertension, and glucose intolerance. The                                          others 1998).

Table 44.1 Convincing and Probable Relationships between Dietary and Lifestyle Factors and Chronic Diseases

  Dietary and                               Type 2                        Dental                                          Birth               Metabolic                Sexual
  lifestyle factors                CVD      diabetes        Cancer        disease       Fracture       Cataract           defects   Obesity   syndrome    Depression   dysfunction

  Avoid smoking

  Pursue physical activity

  Avoid overweight


  Consume healthy
  types of fatsa

  Eat plenty of fruits and

  Replace refined grains
  with whole grains

  Limit sugar intakeb

  Limit excessive calories

  Limit sodium intake

Source: Authors’ summary of a review by the WHO and FAO 2003; Bacon and others 2003; Fox 1999; IARC 2002.
Note: Bold convincing; Standard probable relation; ↑ increase in risk; ↓ decrease in risk.
a. Replace trans and saturated fats with mono- and polyunsaturated fats, including a regular source of N-3 fatty acids.
b. Includes limiting sugar-based beverages.

than overweight, overweight (BMI of 25 to 30) is typically even                                         experience elevated mortality from cancers of the colon, breast
more prevalent and also confers elevated risks of many dis-                                             (postmenopausal), kidney, endometrium, and other sites
eases. For example, overweight people experience a two- to                                              (Calle and others 2003).
threefold elevation in the risks of CAD and hypertension and a                                             Many people with a BMI of less than 25 have gained sub-
more than tenfold increase in the risk of type 2 diabetes com-                                          stantial weight since they were young adults and are also at
pared with lean individuals (BMI less than 23) (Willett, Dietz,                                         increased risk of these diseases, even though they are not
and Colditz 1999). Both overweight and obese people also                                                technically overweight (Willett, Dietz, and Colditz 1999). For

834 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                         ©2006 The International Bank for Reconstruction and Development / The World Bank
example, in rural China, where the average BMI was less than                      Aspects of the food supply unrelated to its macronutrient
21 for both men and women, F. B. Hu and others (2000) found                    composition are also likely to be contributing to the global rise
that the prevalence of hypertension was nearly five times                      in obesity. Inexpensive food energy from refined grains, sugar,
greater for those with a BMI of approximately 25 than for the                  and vegetable oils has become extremely plentiful in most
leanest people. Because many Asians are experiencing adverse                   countries. Food manufacturers and suppliers use carefully
consequences of excess body fat with a BMI of less than 25, the                researched methods to make products based on these cheap
definition of overweight for Asia has recently been expanded to                ingredients maximally convenient and attractive.
include a BMI of 23 to 25 (WHO 2000). For most people,
unless obviously malnourished as an adolescent or young                        Maintain Daily Physical Activity and Limit Television
adult, bodyweight should ideally not increase by more than 2                   Watching. Contemporary life in developed nations has
or 3 kilograms after age 20 to maintain optimal health (Willett,               markedly reduced people’s opportunities to expend energy,
Dietz, and Colditz 1999). Thus, a desirable weight for most                    whether in moving from place to place, in the work environ-
people should be within the BMI range of 18.5 to 25.0, and                     ment, or at home (Koplan and Dietz 1999). Dramatic
preferably less than 23.                                                       reductions in physical activity are also occurring in developing
   Additional valuable information can be obtained by meas-                    countries because of urbanization, increased availability of
uring waist circumference, which reflects abdominal fat accu-                  motorized transportation to replace walking and bicycle riding,
mulation. In many studies, waist circumference is a strong                     and mechanization of labor. However, regular physical activity
predictor of CAD, stroke, and type 2 diabetes, even after con-                 is a key element in weight control and prevention of obesity
trolling for BMI (Willett, Dietz, and Colditz 1999). A waist                   (IARC 2002; Swinburn and others 2004). For example, among
circumference of approximately 100 centimeters for men and                     middle-aged West African women, more walking was asso-
88 centimeters for women has been used as the criterion for                    ciated with a three-unit lower BMI (Sobngwi, Gautier, and
the upper limit of the healthy range in the United States, but                 Mbanya 2003), and in China, car owners are 80 percent more
for many people this extent of abdominal fat would be far                      likely to be obese (Hu 2002).
above optimal. Because abdominal circumference is easily                           In addition to its key role in maintaining a healthy weight,
assessed, even where scales may not be available, further work                 regular physical activity reduces the risk of CAD, stroke, type 2
to develop locally appropriate criteria could be worthwhile. In                diabetes, colon and breast cancer, osteoporotic fractures,
the meantime, increases of more than 5 centimeters can be                      osteoarthritis, depression, and erectile dysfunction (table 44.1).
used as a basis for recommending changes in activity patterns                  Important health benefits have even been associated with walk-
and diet.                                                                      ing for half an hour per day, but greater reductions in risk are
   Views about the causes of obesity and ways to prevent or                    seen with longer durations of physical activity and more
reduce it have been controversial. Diets low in fat and high in                intense activity.
carbohydrates were believed to limit caloric intake sponta-                        The number of hours of television watched per day is asso-
neously and thus to control adiposity, but such diets have not                 ciated with increased obesity rates among both children and
reduced bodyweight in trials that have lasted for a year or more               adults (Hernandez and others 1999; Ruangdaraganon and
(Willett and Leibel 2002). Some researchers have suggested that                others 2002) and with a higher risk of type 2 diabetes and gall-
diets with a high energy density, referring to the amount of                   stones (F. B. Hu and others 2001; Leitzmann and others 1999).
energy per volume, offer an alternative explanation for the                    This association is likely attributable both to reduced physical
observed increases in obesity (Swinburn and others 2004), but                  activity and to increased consumption of foods and beverages
long-term studies have not examined this theory. Sugar-                        high in calories, which are typically those promoted on televi-
sweetened beverages contribute significantly to the overcon-                   sion. Decreases in television watching reduce weight
sumption of calories, in part because calories in fluid form                   (Robinson 1999), and the American Academy of Pediatrics
appear to be poorly regulated by the body (E. A. Bell, Roe, and                recommends a maximum of two hours of television watching
Rolls 2003). In children, an increase in soda consumption of                   per day.
one serving per day was associated with an odds ratio of 1.6 for
incidence of obesity (Ludwig, Peterson, and Gortmaker 2001),                   Eat a Healthy Diet. Medical experts have long recognized the
and in a randomized trial, replacement of a standard soda with                 effects of diet on the risk of CVD, but the relationship between
a zero-calorie diet soda was associated with significant weight                diet and many other conditions, including specific cancers, dia-
loss (Raben and others 2002). Reductions in dietary fiber and                  betes, cataracts, macular degeneration, cholelithiasis, renal
increases in the dietary glycemic load (large amounts of rapidly               stones, dental disease, and birth defects, have been documented
absorbed carbohydrates from refined starches and sugar) may                    more recently. The following list discusses six aspects of diet
also contribute to obesity (Ebbeling and others 2003; Swinburn                 for which strong evidence indicates important health implica-
and others 2004).                                                              tions (table 44.1). These goals are consistent with a detailed

                                                                                       Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 835

                                ©2006 The International Bank for Reconstruction and Development / The World Bank
2003 World Health Organization (WHO) report (WHO and                                          of fruits and vegetables is low. For example, in northern
FAO 2003).                                                                                    China, approximately half the adult population is deficient
                                                                                              in folic acid (Hao and others 2003).
• Replace saturated and trans fats with unsaturated fats,                                 •   Consume cereal products in their whole-grain, high-fiber
  including sources of omega-3 fatty acids. Replacing saturated                               form. Consuming grains in a whole-grain, high-fiber form
  fats with unsaturated fats will reduce the risk of CAD (F. B.                               has double benefits. First, consumption of fiber from cereal
  Hu and Willett 2002; Institute of Medicine 2002; WHO and                                    products has consistently been associated with lower risks of
  FAO 2003) by reducing serum low-density lipoprotein                                         CAD and type 2 diabetes (F. B. Hu, van Dam, and Liu 2001;
  (LDL) cholesterol. Also, polyunsaturated fats (including the                                F. B. Hu and Willett 2002), which may be because of both
  long-chain omega-3 fish oils and probably alpha-linoleic                                    the fiber itself and the vitamins and minerals naturally pres-
  acid, the primary plant omega-3 fatty acid) can prevent                                     ent in whole grains. High consumption of refined starches
  ventricular arrhythmias and thereby reduce fatal CAD. In a                                  exacerbates the metabolic syndrome and is associated with
  case-control study in Costa Rica, where fish intake was                                     higher risks of CAD (F. B. Hu and Willett 2002) and type 2
  extremely low, the risk of myocardial infarction was 80 per-                                diabetes (F. B. Hu, van Dam, and Liu 2001). Second, higher
  cent lower in those with the highest alpha-linoleic acid                                    consumption of dietary fiber also appears to facilitate
  intake (Baylin and others 2003). Intakes of omega-3 fatty                                   weight control (Swinburn and others 2004) and helps pre-
  acids are suboptimal in many populations, particularly if                                   vent constipation.
  fish intake is low and the primary oils consumed are low in                             •   Limit consumption of sugar and sugar-based beverages. Sugar
  omega-3 fatty acids (for example, partially hydrogenated                                    (free sugars refined from sugarcane or sugar beets and high-
  soybean, corn, sunflower, or palm oil). These findings                                      fructose corn sweeteners) has no nutritional value except for
  have major implications, because changes in the type of oil                                 calories and, thus, has negative health implications for those
  used for food preparation are often quite feasible and not                                  at risk of overweight. Furthermore, sugar contributes to the
  expensive.                                                                                  dietary glycemic load, which exacerbates the metabolic syn-
      Trans fatty acids produced by the partial hydrogenation                                 drome and is related to the risk of diabetes and CAD (F. B.
  of vegetable oils have uniquely adverse effects on blood                                    Hu, van Dam, and Liu 2001; F. B. Hu and Willett 2002;
  lipids (F. B. Hu and Willett 2002; Institute of Medicine                                    Schulze and others 2004). WHO has suggested an upper
  2002) and increase risks of CAD (F. B. Hu and Willett                                       limit of 10 percent of energy from sugar, but lower intakes
  2002); on a gram-for-gram basis, both the effects on blood                                  are usually desirable because of the adverse metabolic effects
  lipids and the relationship with CAD risk are considerably                                  and empty calories.
  more adverse than for saturated fat. In many developing                                 •   Limit excessive caloric intake from any source. Given the
  countries, trans fat consumption is high because partially                                  importance of obesity and overweight in the causation of
  hydrogenated soybean oil is among the cheapest fats avail-                                  many chronic diseases, avoiding excessive consumption
  able. In South Asia, vegetable ghee, which has largely                                      of energy from any source is fundamentally important.
  replaced traditional ghee, contains approximately 50 per-                                   Because calories consumed as beverages are less well-
  cent trans fatty acids (Ascherio and others 1996).                                          regulated than calories from solid food, limiting the con-
  Independent of other risk factors, higher intakes of trans fat                              sumption of sugar-sweetened beverages is particularly
  and lower intakes of polyunsaturated fat increase risk of                                   important.
  type 2 diabetes (F. B. Hu, van Dam, and Liu 2001).                                      •   Limit sodium intake. The principle justification for limiting
• Ensure generous consumption of fruits and vegetables and ade-                               sodium is its effect on blood pressure, a major risk factor
  quate folic acid intake. Strong evidence indicates that high                                for stroke and coronary disease (chapter 33). WHO has
  intakes of fruits and vegetables will reduce the risk of CAD                                suggested an upper limit of 1.7 grams of sodium per day
  and stroke (Conlin 1999). Some of this benefit is mediated                                  (5 grams of salt per day) (WHO and FAO 2003).
  by higher intakes of potassium, but folic acid probably also
  plays a role (F. B. Hu and Willett 2002). Supplementation
  with folic acid reduces the risk of neural tube defect preg-
  nancies. Substantial evidence also suggests that low folic                              Potential of Dietary and Lifestyle Factors to Prevent
  acid intake is associated with greater risk of colon—and                                Chronic Diseases
  possibly breast—cancer and that use of multiple vitamins                                Several lines of evidence indicate that realistic modifications of
  containing folic acid reduces the risk of these cancers                                 diet and lifestyle can prevent most CAD, stroke, diabetes, colon
  (Giovannucci 2002). Findings relating folic acid intake to                              cancer, and smoking-related cancers. Less progress has been
  CVD and some cancers have major implications for many                                   made in identifying practically modifiable causes of breast and
  parts of the developing world. In many areas, consumption                               prostate cancers.

836 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
    Box 44.2

    Success in Finland

    Finland provides one of the best-documented examples                        cant improvements were documented in smoking, choles-
    of a community intervention. In 1972, Finland had the                       terol, and blood pressure. By 1992, CVD mortality rates
    world’s highest CVD mortality rate. Planners examined                       for men age 35 to 64 had dropped by 57 percent. The pro-
    the policy and environmental factors contributing to CVD                    gram was so successful that it was expanded to include
    and sought appropriate changes, such as increased avail-                    other lifestyle-related diseases. Twenty years later, major
    ability of low-fat dairy products, antismoking legislation,                 reductions in CVD risk-factor levels, morbidity, and mor-
    and improved school meals. They used the media; schools;                    tality were attributed to the project. Recent data show a
    worksites; and spokespersons from sports, education, and                    75 percent decrease in CVD mortality (Puska and others
    agriculture to educate residents. After five years, signifi-                1998).

    One line of evidence is based on declines in CAD in coun-                  INTERVENTIONS
tries that have implemented preventive programs. Rates of
CAD mortality have been cut in half in several high-income                     Interventions aimed at changing diet and lifestyle factors
countries, including Australia, the United Kingdom, and the                    include educating individuals, changing the environment,
United States. The most dramatic example is that of Finland                    modifying the food supply, undertaking community interven-
(box 44.2).                                                                    tions, and implementing economic policies. In most cases,
    Other evidence derives from randomized intervention                        quantifying the effects of the intervention is difficult, because
studies. These often have serious limitations for estimating the               behavioral changes may take many years and synergies are
potential magnitude of benefits, because typically only one or                 potentially important but hard to estimate in formal studies.
a few factors are modified, durations are usually only a few                   Substantial nihilism often exists regarding the ability to
years, and noncompliance with lifestyle change is often sub-                   change populations’ diets or behaviors, but major changes are
stantial. Nevertheless, some examples are illustrative of the                  possible over extended periods of time. For example, per
potential benefit. In two randomized studies among adults                      capita egg consumption in the United States decreased from
at high risk of type 2 diabetes, those assigned to a program                   approximately 420 to 270 per year between 1940 and 1990
emphasizing dietary changes, weight loss, and physical activity                following recommendations for preventing CAD (though in
experienced only half the risk of incident diabetes (Knowler                   reality, the evidence for benefits was meager). Similarly, the
and others 2002; Tuomilehto and others 2001). The Lyon                         prevalence of smoking, despite its being a physically addictive
Heart Study, conducted among those with existing heart dis-                    behavior, halved among men in the United States between
ease, found a Mediterranean-type diet high in omega-3 fatty                    1965 and 2000. Because changing behaviors related to diet and
acids reduced recurrent infarction by 70 percent compared                      lifestyle require sustained efforts, long-term persistence is
with an American Heart Association diet (de Lorgeril and                       needed. However, opportunities exist that do not require indi-
others 1994).                                                                  vidual behavior changes, and these can lead to more rapid
    A third approach is to estimate the percentage of disease                  benefits.
that is potentially preventable by reducing multiple behavioral
risk factors using prospective cohort studies. Among U.S.                      Educational Interventions
adults, more than 90 percent of type 2 diabetes, 80 percent                    Efforts to change diets, physical activity patterns, and other
of CAD, 70 percent of stroke, and 70 percent of colon cancer                   aspects of lifestyle have traditionally attempted to educate indi-
are potentially preventable by a combination of nonsmoking,                    viduals through schools, health care providers, worksites, and
avoidance of overweight, moderate physical activity, healthy                   general media. These efforts will continue to play an important
diet, and moderate alcohol consumption (Willett 2002).                         role, but they can be strongly reinforced by policy and environ-
    Collectively, these findings indicate that the low rates of                mental changes.
these diseases suggested by international comparisons and time
trends are attainable by realistic, moderate changes that are                  School-Based Programs. School-based programs include the
compatible with 21st-century lifestyles.                                       roles of nutrition and physical activity in maintaining physical

                                                                                       Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 837

                                ©2006 The International Bank for Reconstruction and Development / The World Bank
     Box 44.3

     The Planet Health Program

     Planet Health, developed for middle school students, in                              education complement the classroom lessons. Teacher
     the United States, has an immediate goal of reducing tele-                           training, student self-assessment using graphs, and stu-
     vision viewing time with the long-range goal of prevent-                             dent reflection about enjoyable activities that could
     ing unhealthy weight gain (Gortmaker and others 1999).                               replace at least a portion of the time they spend watching
     Teachers incorporate messages about reducing television                              television are key elements. This program has reduced tel-
     watching, nutrition, and increasing fitness into mathe-                              evision watching and weight in girls (Gortmaker and oth-
     matics, social studies, science, and language arts lessons.                          ers 1999). Because the program is integrated into existing
     Fitness units and periodic “FitChecks” during physical                               classes, its cost is minimal.

     Box 44.4

     Live for Life®
     Johnson & Johnson introduced Live for Life in 1979 with                              were offered US$500 in benefit credits for participation.
     the goal of making its employees the healthiest in the                               The program included routine health risk assessment,
     world (Bly, Jones, and Richardson 1986). In 1993, the                                health promotion after recovery from a medical event, and
     company integrated its health and wellness program with                              support when returning to work after a major illness. Even
     its disability management, employee assistance, and occu-                            though the intervention program had little effect on body-
     pational medicine programs. Instead of using physicians                              weight, physical fitness did increase. By the end of the
     and nurses to treat symptoms, the combined program                                   third year, savings to the company were more than
     sought to use a variety of health professionals to change                            US$400 per year per employee.
     individual behavior and improve health status. Employees

and mental health (box 44.3). School food services should pro-                            programs during breaks or after work; improving the physical
vide healthy meals, both because they directly affect health and                          environment to promote activity; and providing healthier
because they provide a special opportunity to teach by exam-                              foods in cafeterias (box 44.4). Worksite health promotion can
ple. In many countries, school-based physical education                                   result in a positive return on investment through lower health
remains a significant source of physical activity for young peo-                          costs and fewer sick days.
ple. In China, 72 percent of children age 6 to 18 engage in mod-
erate to vigorous physical activity for a median of 90 to 100 min-                        Interventions by Health Care Providers. Controlled inter-
utes per week (Tudor-Locke and others 2003). Maintaining                                  vention trials for smoking cessation and physical activity have
these programs should be a high priority because they have                                shown that physician counseling, especially when accompanied
likely contributed to the historically low rates of obesity in such                       by supporting written material, can be efficacious in modifying
countries.                                                                                behavior. Studies of dietary counseling by physicians indicate
                                                                                          that even brief messages about nutrition can influence behav-
Worksite Interventions. Worksite interventions can effi-                                  ior and that the magnitude of the effect is related to the inten-
ciently include a wide variety of health promotion activities                             sity of the intervention (Pignone and others 2003). Identifying
because workers spend a large portion of their waking hours                               patients who are overweight or obese, or who are gaining
and eat a large percentage of their food there. Interventions can                         weight but are not yet overweight, is an initial step in prevent-
include educating employees; screening them for behavioral                                ing and treating overweight. However, many physicians are not
risk factors; offering incentive programs to walk, ride a bicycle,                        well trained to measure and calculate BMI and identify weight
or take public transportation to work; offering exercise                                  problems.

838 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
    Box 44.5

    Reducing Automobile Use in Brazil

    Curitiba, Brazil, provides an example of the benefits of a                   are used to quickly and efficiently transport individuals
    strategy that reduces automobile use and increases use of                    from residential neighborhoods to express bus lines. These
    public transportation. In 1965, city planners adopted a                      bus lines run almost every 90 seconds and can carry up to
    master plan that promoted development along designated                       270 passengers each. Compared with other Brazilian cities
    corridors along with a bus system so efficient that it has                   of its size, Curitiba uses 30 percent less gasoline per capita,
    virtually eliminated the need for automobiles. Minibuses                     and its air pollution is among the lowest in the nation.

Transportation Policy and Environmental Design                                  developed to discourage private automobile use and to
Transportation policies and the design of urban environments                    promote public transportation, walking, and bicycling (see
are fundamental determinants of physical activity and there-                    box 44.5). Singapore has long been in the lead in relation to
fore influence the risks of obesity and other chronic diseases.                 such efforts: a combination of limiting the number of licenses
Countries can take a number of steps to make positive changes.                  issued, implementing a vehicle quota system, and introducing
                                                                                a road pricing system has limited personal car ownership and
Limit the Role of Automobiles. In wealthy countries, the                        congestion throughout the country. Other nations and regions
automobile has strongly influenced the trend toward low-                        are now enacting similar road pricing systems or congestion
density, automobile-based suburban developments, many built                     taxes. For example, London’s congestion charging system levies
without sidewalks. These sprawling settlements tend to have                     a fee of approximately US$8 per day for cars entering central
few services within walking distance and are usually not linked                 London. Since its inception in 2003, the charge has reduced
to public transporationt. Dependence on automobiles affects                     congestion in the city and is expected to channel funds back
physical activity, because those who use public transportation                  into the city’s transportation facilities.
tend to walk more. In a prospective study in eight provinces in                    Unfortunately some countries, particularly China, have
China, 14 percent of households acquired a car between 1889                     taken a different approach to their future transportation needs.
and 1997, and the likelihood of men becoming obese during                       Government initiatives that encourage families to buy automo-
the same period was twice as great in households that acquired                  biles include lowering taxes, simplifying registration proce-
a car than in those that did not (A. C. Bell, Ge, and Popkin                    dures, and allowing foreign financing. In Beijing alone, resi-
2002).                                                                          dents purchased 400,000 cars in 2003.
   National policies strongly influence automobile use and
dependency. In the United States, low taxes on gasoline, free                   Promote Walking and Bicycle Riding. Walking or cycling for
parking, and wide streets encourage car ownership: almost                       transportation and leisure are effective and practical means of
92 percent of U.S. households own at least one car, and 59 per-                 engaging in physical activity and are still the most common
cent own two or more cars (Pucher and Dijkstra 2003). In                        ways to travel in many developing countries. In Bangkok and
contrast, in most of Western Europe, narrow streets, limited                    Manila, only 25 percent of travel is by car, motorcycle, or taxi,
parking, and high gasoline prices make the costs of automobile                  compared with 75 percent by public transportation or walking
use almost double those in the United States (Pucher and                        (Pendakur 2000). In Madras, India, only 8 percent of the pop-
Dijkstra 2003). As a result, Europeans walk or bike more and                    ulation travels by private, motorized transportation; 22 per-
use their cars approximately 50 percent less than their                         cent of people walk; 20 percent bike; and the rest use public
American counterparts. Investment in roads rather than in                       transportation (Pendakur 2000). In China, approximately
public transportation creates a vicious cycle: poor public trans-               90 percent of the urban population walks or rides a bicycle to
portation systems lead to more dependency on the automobile.                    work, shopping, or school each day (G. Hu and others 2002).
   As car use grows, injuries and deaths associated with auto-                  Walking or biking is more likely to be prevalent in smaller
mobile accidents also grow. In China, the number of four-                       cities—that is, those with 1 million to 5 million people—than
wheeled vehicles increased from about 60,000 to more than                       in larger ones.
50 million between 1951 and 1999, and traffic fatalities                            Bicycle riding and walking are also important for children’s
increased from about 6,000 to more than 413,000 (S. Y. Wang                     health. Most American children do not walk or bike to school,
and others 2003). Many innovative strategies have been                          even when distances are short (box 44.6). In contrast, almost

                                                                                        Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 839

                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
     Box 44.6

     Walking and Cycling to School

     One of the most effective ways to promote walking and                                walking routes and proposed solutions for problem areas.
     cycling is through local schools. The Safe Routes to School                          The program also sponsors walk- and bike-to-school days,
     program (, estab-                                frequent-rider contests, and other promotional events
     lished in Marin County, California, is a private-public                              (Staunton, Hubsmith, and Kallins 2003).
     partnership that created a citywide map of safe biking and

90 percent of Chinese children under 12 walk or ride a bicycle                            linked to decreases in mental health and social capital
to school (Hu 2002).                                                                      (Frumkin 2002) as well as anger and frustration over long com-
   In many areas, the shift toward private car use has not yet                            mutes (Surface Transportation Policy Project 1999). Sprawl
begun and can perhaps be forestalled by policies that benefit                             adversely affects the elderly in particular because they are
walkers and cyclists rather than drivers. Such policies include                           unable to walk to places of interest and many cannot drive.
implementing road designs that promote a safe and well-lit                                Such isolation does not promote good physical or mental
environment for walking and cycling, including traffic-calming                            health.
measures to reduce automobile speeds.                                                         The so-called smart growth movement has resulted from
   Many Western European countries have taken steps to                                    concerns about urban sprawl and unsustainable development
increase safety for cyclists and walkers. In Germany and the                              and is encouraging governments worldwide to rethink how
Netherlands, bike paths serve as travel routes, not just weekend                          they develop new areas and redevelop older suburbs and cities.
recreational destinations as they do in the United States. The                            Smart growth principles include mixing land uses, using com-
former countries have invested heavily in bike paths and have                             pact building designs, including a range of transportation and
also created extensive car-free areas in cities, with well-lit side-                      housing choices, building walker-friendly neighborhoods in
walks, clearly marked crosswalks, and pedestrian islands that                             attractive communities with a distinctive sense of place, and
have improved safety. Both countries have increased the num-                              implementing a philosophy of directing development toward
ber of bicycle-friendly streets (on which cars are permitted but                          existing communities and the preservation of open space
bicycles have the right of way) and have created systems to sep-                          (Office of the Administrator 2001) (box 44.7).
arate streams of traffic, including cars, pedestrians, and bicy-                              The involvement of public health practitioners in trans-
cles. A meta-analysis of selected traffic-calming studies in many                         portation planning and building design is becoming more
countries reported reductions in traffic speed, accidents,                                common. In Edinburgh, a health impact assessment conducted
injuries, and fatalities and an increase in bicycle use and walk-                         on proposed options for transportation policy showed the
ing (Bunn and others 2003).                                                               effects of specific choices on both affluent members of the
                                                                                          community and the poor. Its recommendations, now adopted,
Design Cities and Towns to Promote Health. Handy and                                      included new spending on pedestrian safety, a citywide bicycle
others’ (2002) comprehensive assessment of recent research on                             network, more greenways and park-and-ride programs, and
urban planning concludes that a combination of urban design,                              more rail transportation or bus services. Priorities are to bene-
land-use patterns, and transportation systems that promotes                               fit pedestrians first, cyclists second, public transportation users
walking and bicycling will help create active, healthier, and                             third, freight and delivery people fourth, and car users last.
more livable communities. In densely developed cities that                                Establishing criteria for building design can also lead to
have been built around public transportation rather than away                             increases in physical activity. For example, increasing signage
from it, individuals are much more likely to take public transit,                         promoting stair use, as well as the attractiveness of the facilities
walk, or bicycle than in other areas and to weigh less and be less                        themselves, encourages people to use the stairs (Boutelle and
likely to suffer from hypertension (Ewing, Schieber, and Zegeer                           others 2001) (box 44.8).
2003; Lopez 2004; Saelens, Sallis, and Frank 2003).
    Those living in walker-friendly neighborhoods also appear
to be more mentally healthy and are more likely to know their                             Improved Food Supply
neighbors, to be socially active, and to participate in the politi-                       People’s diets can be enhanced by improving the food supply.
cal process (Leyden 2003). In contrast, urban sprawl has been                             The usual position of the food industry is that it simply

840 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
    Box 44.7

    Enhancing Urban Life in the Republic of Korea

    In Seoul, the government is managing growth by creating                     the balance of employment away from one centralized
    six satellite communities with high-rise residential build-                 location to provide a more regional balance. Major
    ings outside the city center. These communities are                         expressways are being removed to create parks, sidewalks,
    intended to become new job-creation centers and to shift                    and bikeways (

    Box 44.8

    Promoting Physical Activity in Brazil

    One successful example of increasing activity is Agita São                  message is displayed on electricity bills and stickers, and it
    Paulo, a multilevel physical activity initiative designed for               is touted by radio stations and other media outlets.
    the 34 million citizens of Brazil’s São Paulo state (Matsudo                    After four years, 55.7 percent of those surveyed had
    and others 2002). The program was launched in 1996 to                       heard about Agita, 37 percent knew its purpose, and those
    increase the public’s knowledge of the benefits of exercise                 who knew of the program’s purpose were more likely to be
    and expand participation in physical fitness activities by                  active. Agita appears to have played a role in increasing
    encouraging people to do 30 minutes of moderate activity                    activity in the region (Matsudo and others 2002). It is
    at least five times a week. As elsewhere, program designers                 closely linked to a national program to promote healthy
    perceived a lack of time as the major factor preventing                     diets and active lifestyles by nutritional content labeling,
    daily exercise. They chose three settings as places to pro-                 promotion of healthy diets in schools, communication of
    mote activity: home (gardening, chores, avoidance of tele-                  guidelines for healthy eating, and encouragement of inno-
    vision watching); transportation (walking, taking the                       vative community-based initiatives (Coitinho, Monteiro,
    stairs); and leisure time (dancing). Agitol, a prescription                 and Popkin 2002).
    for exercise, was developed for physicians to dispense. Its

provides whatever consumers demand, but this argument is                       Drug Administration announced that food manufacturers had
misleading, because the industry spends more than US$12 bil-                   to include trans fatty acid content on the standard food label.
lion annually to influence consumer choices just within the                    Following imposition of this requirement, several large food
United States and many times this amount globally. Much of                     companies said that they would reduce or eliminate trans fats,
this sum goes to promote foods with adverse health effects, and                and many more are planning to do so (U.S. Food and Drug
children are primary targets.                                                  Administration 2003). In Mauritius, the government required
                                                                               a change in the commonly used cooking oil from mostly palm
Improving Processing and Manufacturing. Altering the                           oil to soybean oil, which changed people’s fatty acid intake and
manufacturing process can rapidly and effectively improve                      reduced their serum cholesterol levels (Uusitalo and others
diets because such action does not require the slow process of                 1996). Changes in types of fat can often be almost invisible and
behavioral change. One example is eliminating the partial                      inexpensive. Omega-3 fatty acid intakes can be increased by
hydrogenation of vegetable oils, which destroys essential                      incorporating oils from rapeseed, mustard, or soybean into
omega-3 fatty acids and creates trans fatty acids. European                    manufactured foods, cooking oils sold for use at home, or both.
manufacturers have largely eliminated trans fatty acids from                   Selective breeding and genetic engineering provide alternative
their food supply by altering production methods.                              ways to improve the healthfulness of oils by modifying their
   Regulations can facilitate changes in manufacturing directly                fatty acid composition.
or indirectly by providing an incentive for manufacturers to                       When the consumption of processed food is high, a reduc-
change their processes. For example, in 2003, the U.S. Food and                tion in salt consumption will usually require changes at the

                                                                                       Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 841

                                ©2006 The International Bank for Reconstruction and Development / The World Bank
manufacturing level, because processed food is a major salt                                  Another strategy is to protect consumers from aggressive
source. If the salt content of foods is reduced gradually, the                            marketing of unhealthy foods. Producers spend billions of dol-
change is imperceptible to consumers. Coordination among                                  lars a year encouraging children to consume foods that are
manufacturers or government regulation is needed; otherwise                               detrimental to their health. Manufacturers and fast-food chains
producers whose foods are lower in salt may be placed at a dis-                           personify food products with cartoon characters; display food
advantage. Unfortunately, good examples are not available.                                brands on toys; and issue “educational” card games that subvert
Another example of improved processing would be to reduce                                 children’s natural gift for play, story telling, and make believe.
the refining of grain products, which can be done in small,                               The willingness to limit advertising depends on a country’s
almost invisible decrements.                                                              political culture, but the public clearly distinguishes between
                                                                                          advertising aimed at adults and that targeted at children. For
Fortifying Food. Food fortification has eliminated iodine                                 example, in the United States, 46 percent of adults surveyed
deficiency, pellagra, and beriberi in much of the world. In                               supported restrictions on advertising to children (Blendon
regions where iodine deficiency remains a serious problem,                                2002). Restrictions can range from banning advertising to
fortification should be a high priority. Folic acid intake is sub-                        children to limiting the types of products that advertisers may
optimal in many regions of both developing and developed                                  promote to this audience.
countries. Fortifying foods with folic acid is extremely inex-
pensive and could substantially reduce the rates of several                               Initiatives at the Community Level
chronic diseases. Grain products—such as flour, rice, and                                 Nations and regions can promote a variety of initiatives to
pasta—are usually the best foods to fortify, and in many coun-                            encourage greater physical activity and better nutrition. These
tries, they are already being fortified with other B vitamins.                            initiatives are likely to be most effective when they are multi-
Since 1998, grain products in the United States have been                                 faceted and coordinated and when they are developed with the
fortified with folic acid, which has almost eliminated folate                             active involvement of individuals and organizations within
deficiency, and rates of neural tube defect pregnancies have                              communities (Puska and others 1998).
declined by about 19 percent (Honein and others 2001). Where                                 Many countries are undertaking efforts to educate their
intakes of vitamins B12 and B6 are also low and contribute to                             populations about healthy lifestyles. In the Islamic Republic of
elevations of homocysteine, as among vegetarian populations                               Iran, the Isfahan Healthy Heart Program, a WHO collaborating
in India, simultaneous fortification of food with these vitamins                          center for research and training for CVD control, prevention,
should be considered. The effects of fortification on reducing                            and rehabilitation for cardiac patients, has developed a com-
CVD are not considered proven, but the potential benefits are                             prehensive, integrated community intervention that involves
huge; therefore, intervention trials to evaluate the effects of                           schools, worksites, health care facilities, food services, urban
fortification should be a high priority.                                                  planners, and the media. Physical activity is promoted by
                                                                                          creating safe routes for walking and bicycle riding and
Increasing the Availability and Reducing the Cost of Healthy                              by organizing recreational walking that involves entire families
Foods. Policies regarding the production, importation, distri-                            (
bution, and sale of specific foods can influence their cost and                              South Africa’s Community Health Intervention Pro-
availability. Policies may be directed at the focus of agricultur-                        gramme, a partnership between an insurance company and an
al research and the types of production promoted by extension                             academic institution, has created programs targeted to specific
services. Policies often promote grains, dairy products, sugar,                           age groups, including children and older adults. The program’s
and beef, whereas those that encourage the production and                                 twice-weekly classes have reduced blood pressure and increased
consumption of fruits, vegetables, nuts, legumes, whole grains,                           strength and balance (Lambert, Bohlmann, and Kolbe-
and healthy oils would tend to enhance rather than reduce                                 Alexander 2001) (box 44.9).
health.                                                                                      Singapore’s Fit and Trim Program uses a multidisciplinary
                                                                                          approach to increase physical activity and healthy diets among
                                                                                          schoolchildren. Between 1992 and 2000, the rate of obesity
Promoting Healthy Food Choices and Limiting Aggressive
                                                                                          declined by 13.1 to 16.6 percent for children age 11 to 12 and
Marketing to Children. Almost every national effort to
                                                                                          15 to 16 (Toh, Cutter, and Chew 2002) (box 44.10 outlines the
improve nutrition incorporates the promotion of healthy food
                                                                                          national program for adults).
choices, such as fruits, vegetables, and legumes. Ideally, such
efforts are coordinated among government groups, retailers,
professional groups, and nonprofit organizations, and invest-                             Economic Policies
ment in such efforts should include the careful testing and                               Economic policies can have important effects on behavior and
refining of social-marketing strategies.                                                  choices, and these policies have been particularly useful in

842 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
    Box 44.9

    A Comprehensive Intervention Approach in South Africa

    The Coronary Risk Factor Study in South Africa (Rossouw                     results showed an improvement in the community risk
    and others 1993) tested community interventions at dif-                     factor profile for CAD in the intervention communities,
    ferent levels of intensity in two communities with a third                  especially in relation to blood pressure, smoking, and over-
    control community. The target population was Caucasian                      all risk. The results indicate no additional benefit of the
    South Africans. Interventions included direct media cam-                    personal intervention for high-risk individuals beyond that
    paigns, public health messages delivered in a variety of ways,              already offered by the mass media program. Estimated per
    and home mailings. Also included were community acti-                       capita costs of the heavy intervention program were roughly
    vities, such as fun walks, public meetings, involvement of                  four times as much as for the mild intervention program
    community-based organizations, free screening for blood                     (US$22 per capita compared with US$5 per capita), and the
    pressure, small-group personal interventions, and encour-                   low-intervention community received almost the same
    agement of food substitution in stores and restaurants. The                 level of benefits as the high-intervention community.

    Box 44.10

    The Singapore National Healthy Lifestyle Program

    Because CVD and cancer had become the major causes of                           In a follow-up survey after six years, cigarette smoking
    death in Singapore, the government adopted the National                      had decreased from 34 to 27 percent among men, the pro-
    Healthy Lifestyle Program in 1992 (Cutter, Tan, and Chew                     portion of adults who exercised regularly had increased
    2001). This coordinated, multisectoral approach involved                     from 14 to 17 percent, and the prevalence of obesity was
    government ministries, health professionals, employers,                      stable. However, hypertension and high LDL cholesterol
    unions, and community organizations. The program                             levels had increased modestly. From 1991 to 1999, the age-
    aimed at improving the social and physical environment so                    standardized incidence of myocardial infarction declined
    as to promote healthy living. Healthy diets, regular physi-                  from 98.2 to 83.0 per 100,000 residents (Mak and others
    cal exercise, and nonsmoking were emphasized. The pro-                       2003) and age-standardized mortality from CAD
    gram used the mass media; legislative measures to discour-                   decreased from 60.8 to 47.2 per 100,000 residents.
    age smoking; and widespread school, workplace, and com-
    munity health promotion packages.

reducing the prevalence of smoking (see chapter 46). Policies                     and those high in trans fats. Legislation can make this
that could influence diet and physical activity deserve careful                   distinction, providing a modest economic incentive for
consideration because they are rarely neutral and often support                   healthier choices and at the same time conveying important
unhealthy behaviors. Consider the following examples:                             nutritional messages (see chapter 11).
                                                                                • Use of individual automobiles is often subsidized by build-
• Subsidies can favor the consumption of less healthy foods,                      ing and maintaining highways, providing inexpensive
  such as sugar, refined grains, beef, and high-fat dairy prod-                   parking, and imposing low taxes on petroleum products
  ucts as opposed to fruits, vegetables, whole grains, nuts,                      that do not fully reflect their societal and environmental
  legumes, and fish. Poland provides a striking example of                        costs. Increasing taxes on petroleum products and subsidiz-
  how changes in subsidies can affect health (box 44.11).                         ing public transportation could have an important effect on
  Governments often subsidize foods indirectly by sheltering                      choice of transportation modality, which as noted earlier,
  them from sales taxes in the recognition that they are essen-                   has major effects on health.
  tial; however, this logic should not extend to foods with                     • Walking, riding bicycles, and using public transportation
  adverse health effects, such as sugar-sweetened beverages                       can be promoted by economic policies that, in addition

                                                                                        Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 843

                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
     Box 44.11

     Poland: A Dramatic Decline in Heart Disease

     After Poland’s transition to a democratic government                                                  Risk of Coronary Heart Disease
                                                                                                  According to Polyunsaturated to Saturated Fat Ratio
     in the early 1990s, the government removed large sub-
     sidies for butter and lard, and consumption of nonhy-                           Rate ratio for coronary heart                          Rate ratio for coronary heart
     drogenated vegetable fat increased rapidly (Zatonski,                           disease in Nurses’ Health Study                         disease mortality in Poland
     McMichael, and Powles 1998). The ratio of dietary
     polyunsaturated to saturated fat increased from 0.33                                                1990      1992
     in 1990 to 0.56 in 1999, and during this period mor-
     tality rates from CAD dropped by 28 percent (data                                                                                    1994
                                                                                     0.8                                                          1996
     provided by W. Zatonski). Changes in smoking and in
     the consumption of fruits and vegetables probably                                                                                                                    0.7
     played a minor role in this decrease (see figure).



                                                                                                               0.33                                       0.56
                                                                                            0.2           0.3          0.4           0.5           0.6
                                                                                                      Dietary polyunsaturated to saturated fat ratio

                                                                                     Notes: Squares represent data for Poland from 1990 to 1999. Circles are for deciles of
                                                                                     polyunsaturated fat to saturated fat and for risk of coronary heart disease in the Nurses’
                                                                                     Health Study (Hu 1999), which closely predict the observed changes in Poland.

    to providing better infrastructure, include discounts on                               Reducing Saturated Fat Content. In the base case, assuming a
    transportation fares, provide secure bicycle parking, and                              3 percent drop in cholesterol and a US$6 per person cost of the
    reduce health insurance premiums.                                                      intervention, averting one disability-adjusted life year (DALY)
                                                                                           would cost as little as US$1,865 in South Asia and as much as
COST-EFFECTIVENESS OF INTERVENTIONS                                                        US$4,012 in the Middle East and North Africa. The interven-
                                                                                           tion’s effectiveness could be increased by replacing part of the
Only a few studies have described interventions for lifestyle                              saturated fat with polyunsaturated fat, which has additional
diseases in developing countries.                                                          beneficial effects mediated by mechanisms other than LDL
                                                                                           cholesterol (see tables 44.2 and 44.3).
Modeling Likely Interventions
Primary targets for reducing lifestyle diseases include changing                           Replacing Dietary Trans Fat from Partial Hydrogenation
the fat composition of the diet, limiting sodium intake, and                               with Polyunsaturated Fat. We could not use the model for
engaging in regular physical activity.                                                     saturated fat to estimate the effects of replacing trans fat with
   Using available data, we calculated a range of estimates                                polyunsaturated fat because only a small part of the benefit is
under given assumptions for the cost-effectiveness of replacing                            attributable to reducing LDL cholesterol (F. B. Hu and Willett
dietary saturated fat with monounsaturated fat, replacing                                  2002). Trans fats also adversely affect high-density lipoprotein
trans fat with polyunsaturated fat, and reducing salt intake. An                           (HDL) cholesterol, triglycerides, endothelial function, and
increase in moderate physical activity by three to five hours per                          inflammatory markers. In addition, increases in polyunsatu-
week is considered likely to lower the risk of many diseases, but                          rated fat (assuming a mix of N-6 and omega-3 fatty acids) will
data to model the cost-effectiveness of this intervention are not                          reduce LDL cholesterol, insulin resistance, and probably fatal
currently available. For further details of methods and assump-                            cardiac arrhythmias.
tions underlying the analyses presented here, see the Web site                                In calculations that are based only on the adverse effects on
version of this book.                                                                      LDL and HDL, replacing 2 percent of the energy from trans fat

844 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 44.2 Incremental Cost-Effectiveness Ratios, Selected Interventions, by Region
(US$/DALY averted)

                                                                                                      Substituting 2 percent of energy from
                                                                                                       trans fat with polyunsaturated fat

                                                Media campaign                 7 percent CAD reduction                          40 percent CAD reduction             Reducing salt
                                                to reduce                    Intervention      Intervention                 Intervention      Intervention           content by means
                                                saturated fat                cost of           cost of                      cost of           cost of                of legislation plus
  Region                                        content                      US$0.50/adulta    US$6.00/adult                US$0.50/adulta    US$6.00/adult          public education

  East Asia and the Pacific                             2,769                         73                     1,583            Cost saving              227                  2,056
  Europe and Central Asia                               2,929                         65                     1,670            Cost saving              228                  2,170
  Latin America and the Caribbean                       3,297                         40                     1,865            Cost saving              225                  2,476
  Middle East and North Africa                          4,012                         25                     2,259            Cost saving              252                  3,056
  South Asia                                            1,865                         38                     1,014            Cost saving              138                  1,325
  Sub-Saharan Africa                                    2,356                         53                     1,344            Cost saving              184                  1,766

Source: Authors’ calculations.
a. Based on the U.S. Food and Drug Administration’s analysis of the costs of the intervention in the United States.

Table 44.3 Two-Way Sensitivity Analysis of the Costs of the                                               was estimated to have only a modest effect on consumer
Intervention to Reduce Saturated Fat Content and of the                                                   behavior, as noted earlier, it is having a major effect on manu-
Relative Risk Reduction in CAD Events, South Asia                                                         facturers’ behavior.
(US$/DALY averted)
                                                                                                              The potential for reducing CVD rates by replacing trans fats
  Relative risk                                                                                           with polyunsaturated fats will depend on the diets of specific
                                                    Cost per individual
  reduction in CAD                                                                                        populations. Whereas the intake of trans fat is low in China, it
  events (percent)                   US$0.25                   US$3.00              US$6.00a              is likely to be high in parts of India, Pakistan, and other Asian
  10                                 Cost saving                   318                     680            countries because of the extraordinarily high content in com-
    5                                Cost saving                   680                 1,403              monly used cooking fats.
   4b                                Cost saving                   911                 1,865                  Table 44.2 presents the results of a cost-effectiveness analysis
    1                                     258                    3,572                 7,188              assuming the two different estimates for CAD reduction: 7 per-
                                                                                                          cent and 40 percent. We used costs of US$0.50 per adult per year,
Source: Authors’ calculations.
                                                                                                          which was the maximal cost in the U.S. Food and Drug
a. Threshold analysis reveals that at the base assumption of US$6 for the intervention, no level in
the range of assumed CAD reduction is cost saving.                                                        Administration analysis, and of US$6.00 per adult per year using
b. Threshold analysis reveals that at a cost below US$0.36 per individual and a 4 percent                 traditional health education approaches. The lower estimate—
reduction in CAD (base assumption), the intervention is cost saving.
                                                                                                          or one even lower—is possible because trans fat can be elimi-
                                                                                                          nated at the source rather than depending entirely on changes in
with polyunsaturated fat was estimated to reduce CAD by 7                                                 individual behavior. With the lower cost, the smaller effect esti-
to 8 percent (Grundy 1992; Willett and Ascherio 1994).                                                    mate leads to a cost-effectiveness ratio of between US$25 and
Epidemiological studies, which include the contributions of                                               US$73 per DALY averted, depending on the region, and with the
the additional causal pathways, suggest a much greater reduc-                                             higher-effect estimate, the intervention can be cost saving.
tion, from about 25 to 40 percent (F. B. Hu and others 1997;
Oomen and others 2001). Another likely benefit is a reduction                                             Reducing the Salt Content of Manufactured Foods through
in the incidence of type 2 diabetes: estimates indicate that the                                          Legislation and an Accompanying Education Campaign.
same 2 percent reduction would reduce incidence by 40 percent                                             Table 44.2 shows the base-case cost-effectiveness of a legislated
(Salmeron and others 2001).                                                                               reduction in salt content. The intervention appears to be rela-
   Because voluntary action by industry (as has nearly been                                               tively cost-effective, with a cost per DALY averted of US$1,325
achieved in the Netherlands) or by regulation (as occurred in                                             in South Asia to US$3,056 in the Middle East and North Africa.
Denmark) can eliminate partially hydrogenated fat from the                                                Those regional variations are attributable to differing risk pro-
diet, this initiative does not require consumer education, and                                            files across regions as well as to price differentials for the costs
the costs can be extremely low. In an analysis required before                                            of treating disease sequelae.
implementing food labeling, the U.S. Food and Drug                                                            The actual blood pressure reduction from lower salt con-
Administration (2003) estimated that trans fat labeling would                                             sumption could vary from the base-case assumption, as could
be highly cost-effective. Even though the effect of labeling itself                                       the costs of the education campaign. Table 44.4 shows the

                                                                                                                  Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 845

                                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 44.4 Two-Way Sensitivity Analysis of the Costs of the                                            and without risk factors for noncommunicable diseases (phys-
Intervention to Reduce Salt Content and Its Effectiveness,                                             ical activity, BMI, and smoking status) and find that a healthi-
South Asia                                                                                             er lifestyle of physical activity three times per week, a moderate
(US$/DALY averted)
                                                                                                       BMI, and nonsmoking status reduce health care costs by
  Blood pressure                                                                                       49 percent compared with an unhealthy lifestyle.
                                                           Cost per individual
  reduction (millimeters
  of mercury)                                  US$1a                  US$3                 US$6        Cost-Effectiveness of Community-Based Interventions
  4                                                 9                   308                  608       Populationwide and community-based interventions appear to
  3                                               49                    448                  847       be cost-effective if they reach large populations, address high-
  2b                                             129                    727                1,326       mortality and high-morbidity diseases, and are multipronged
  1                                              368                  1,565                2,761       and integrated efforts. The full costs of achieving changes in
Source: Authors’ calculations.
                                                                                                       behavior and policy are often complex and difficult to estimate.
a. Threshold analysis reveals that at a cost of US$1 per individual, a blood pressure reduction        Interventions may yield additional spinoff benefits. For
would have to be greater than 5 millimeters of mercury for the intervention to be cost saving. At
                                                                                                       instance, decisions to reduce children’s television viewing could
the base-case assumption of a cost of US$6 for the intervention, there is no cost saving threshold
level of reduction.                                                                                    easily improve school outcomes as well as reduce childhood
b. Threshold analysis reveals that at a cost of less than US$0.47 per individual the intervention is   obesity. Similarly, increasing walking and bicycle riding for
                                                                                                       transportation could reduce air pollution.

results of lower costs of the education campaign and higher or
                                                                                                       RESEARCH AND DEVELOPMENT PRIORITIES
lower effects of the intervention on blood pressure. These
results may argue for initial efforts to focus on reductions in the                                    A number of research and development priorities have been
use of salt during the manufacturing process with no public                                            identified:
education campaign. The cost-effectiveness of such a change is
high and could be augmented with a public education cam-                                               • Conduct randomized trials of the use of folic acid and
paign only if needed to support the legislated change. At lower                                          alpha-linoleic acid to prevent CAD in developing countries.
implementation costs, the intervention is highly cost-effective,                                         These interventions cost little, and the potential benefits are
even with half the assumed effect on blood pressure.                                                     large and rapid.
                                                                                                       • Develop prospective cohort studies of dietary and lifestyle
Adopting Physical Activity Interventions. Even though                                                    factors in developing and transition countries to refine the
health experts believe that physical activity interventions are                                          understanding of risk factors in those contexts. To date,
effective in reducing the risk of lifestyle diseases, no studies of                                      almost all such studies have taken place in Europe and
their cost-effectiveness are available from developing countries.                                        North America.
If people walk voluntarily (the model assumes no opportunity                                           • Develop surveillance systems for chronic diseases and for
cost), a net economic benefit would accrue to all segments of                                            major risk factors, such as obesity, in developing countries.
the U.S. population. If we project the economic benefits to the                                        • Develop additional multifaceted, community-based
entire U.S. population and assume 25 percent compliance by                                               demonstration programs in developing countries to docu-
the sedentary population, the voluntary program would gener-                                             ment the feasibility of lifestyle changes and to learn more
ate US$6.8 billion in savings (in 2001 U.S. dollars).                                                    about effective strategies.
                                                                                                       • Conduct detailed cost-effectiveness analyses of various pre-
                                                                                                         vention strategies to modify dietary and lifestyle factors.
Aggregate Costs of Obesity and Unhealthy Lifestyles
A series of U.S. studies appears to confirm that the avoidable
costs of chronic diseases are substantial, although many devel-
                                                                                                       RECOMMENDED PRIORITY INTERVENTIONS
oping countries have not yet experienced the full demands on
their health sectors resulting from these conditions. Colditz                                          An overall objective is to develop comprehensive national and
(1999) estimates that obesity is responsible for 7 percent of all                                      local plans that take advantage of every opportunity to encour-
U.S. direct health care costs and that inactivity is responsible for                                   age and promote healthy eating and active living. These plans
an additional 2.4 percent of all health care costs. Indirect costs                                     would involve health care providers; worksites; schools; media;
associated with obesity and inactivity account for another                                             urban planners; all levels of food production, processing, and
5 percent of health care costs. Pronk and others (1999) assess                                         preparation; and governments. The goal is cultural change
the difference in health care costs between adult patients with                                        in the direction of healthy living. An important element in

846 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                          ©2006 The International Bank for Reconstruction and Development / The World Bank
cultural change is national leadership by individuals and by                      º Implement folic acid fortification if folic acid intake is
professional organizations. Specific interventions will depend                       low.
on local physical and cultural conditions and should be based                     º Ensure that health providers regularly weigh both chil-
on careful analysis of existing dietary and activity patterns and                    dren and adult patients, track their weights over time,
their determinants; however, the following interventions can be                      and provide counseling regarding diet and activity if
considered (specific interventions for control of smoking are                        they are already overweight or if unhealthy weight gain is
discussed elsewhere):                                                                occurring during adulthood. Those activities should be
                                                                                     integrated with programs that address undernutrition.
• Physical activity:                                                                 Health care providers should be encouraged to set a
  º Develop transportation policies and a physical environ-                          good example by not smoking, by exercising regularly,
     ment to promote walking and riding bicycles. This inter-                        and by eating healthy diets.
     vention includes constructing sidewalks and protected                        º Promote healthy foods at worksite food services.
     bicycle paths and lanes that are attractive, safe, well-                        Worksites can also promote physical activity by provid-
     lighted, and functional with regard to destinations.                            ing financial incentives for using public transportation
  º Adopt policies that promote livable, walker-friendly                             or riding bicycles (and by not subsidizing automobiles
     communities that include parks and are centered around                          by providing free parking). Providing areas for exercise
     access to public transportation.                                                during work breaks and showers may be useful.
  º Encourage the use of public transportation and discour-                       º Set standards that restrict the promotion of foods high
     age overdependence on private automobiles.                                      in sugar, refined starch, and saturated and trans fats to
  º Promote the use of stairs. Building codes can require the                        children on television and elsewhere.
     inclusion of accessible and attractive stairways.                            º Set national standards for the amount of sodium in
• Healthy diets:                                                                     processed foods.
  º Develop comprehensive school programs that integrate                        • National campaigns:
     nutrition into core curricula and healthy nutrition into                     º Invest in developing locally appropriate health messages
     school food services. Regional or national standards to                         related to diet, physical activity, and weight control. This
     promote healthy eating should be developed for school                           effort is best done in cooperation with government agen-
     food services. Programs should also aim at limiting                             cies, nongovernmental organizations, and professional
     television watching, in part by promoting attractive                            organizations so that consistent messages can be used on
     alternatives.                                                                   television and radio; at health care settings, schools, and
  º Work with the agriculture sector and food industries to                          worksites; and elsewhere. This effort should use the best
     replace unhealthy fats with healthy fats, including ade-                        social-marketing techniques available, with messages
     quate amounts of omega-3 fatty acids. This goal can be                          continuously evaluated for effectiveness.
     achieved through a combination of education, regula-                         º Develop a sustainable surveillance system that monitors
     tion, and incentives. Specific actions will depend on local                     weight and height, physical activity, and key dietary
     sources of fat and on regional production and distribu-                         variables.
     tion. For example, in areas where palm oil is dominant,
     research could focus on developing strains that are lower                     Implementation of the recommended policies to promote
     in saturated fat and higher in unsaturated fat through                     health and well-being is often not straightforward because of
     selective breeding or genetic alteration. Labeling require-                opposition by powerful and well-funded political and economic
     ments or regulation can be used to discourage or elimi-                    forces, such as those involved in the tobacco, automobile, food,
     nate the use of partially hydrogenated vegetable oils and                  and oil industries (Nestle 2002). The solutions will depend on a
     to promote the use of nonhydrogenated unsaturated oils                     country’s specific political landscape. However, experiences in
     instead.                                                                   many countries indicate that alliances of public interest groups,
  º Require clear labeling of energy content for all packaged                   professional organizations, and motivated individuals can over-
     foods, including fast food.                                                come such powerful interests. Strategies should start with sound
  º Use tax policies to encourage the consumption of                            science and can use a mix of mass media, lobbying efforts, and
     healthier foods. For example, high-sugar sodas could be                    lawsuits. Also, the food industry is far from monolithic, and ele-
     fully taxed and not subsidized in the same way as health-                  ments can often be identified whose interests coincide with
     ier foods.                                                                 health promotion, which can create valuable partnerships. As an
  º Emphasize the production and consumption of healthy                         example, the willingness of some margarine manufacturers to
     food products in agriculture support and extension                         invest in developing products free of trans fatty acids greatly
     programs.                                                                  helped the effort to reduce these fats, because these producers

                                                                                        Prevention of Chronic Disease by Means of Diet and Lifestyle Changes | 847

                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
then became proponents for labeling the trans fat content of                                  Studied Cohort of U.S. Adults.” New England Journal of Medicine 348:
foods. Protection of children can be a powerful lever because of                              1625–38.

almost universal concern about their welfare and the recogni-                             Coitinho, D., C. A. Monteiro, and B. M. Popkin. 2002. “What Brazil Is
                                                                                             Doing to Promote Healthy Diets and Active Lifestyles.” Public Health
tion that they cannot be responsible for the long-term conse-                                Nutrition 5: 263–67.
quences of their diet and lifestyle choices.                                              Colditz, G. A. 1999. “Economic Costs of Obesity and Inactivity.” Medicine
                                                                                             Science and Sports Exercise 31: S663–67.
                                                                                          Conlin, P. R. 1999. “The Dietary Approaches to Stop Hypertension (Dash)
CONCLUSIONS                                                                                 Clinical Trial: Implications for Lifestyle Modifications in the Treatment
                                                                                            of Hypertensive Patients.” Cardiology Review 7: 284–88.
Many of the ongoing diet and lifestyle interventions in low-
                                                                                          Cutter, J., B. Y. Tan, and S. K. Chew. 2001. “Levels of Cardiovascular Disease
and middle-income countries are relatively recent, and few                                   Risk Factors in Singapore Following a National Intervention
have documented reductions in the rates of major chronic dis-                                Programme.” Bulletin of the World Health Organization 79: 908–15.
eases. However, the successes of Finland, Singapore, and many                             de Lorgeril, M., S. Renaud, N. Mamelle, P. Salen, J. L. Martin, I. Monjaud,
other high-income countries in reducing rates of CAD, stroke,                                and others. 1994. “Mediterranean Alpha-Linolenic Acid–Rich Diet in
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efits will emerge in the developing countries.                                            Dickinson, S., S. Colagiuri, E. Faramus, P. Petocz, and J. C. Brand-Miller.
                                                                                             2002. “Postprandial Hyperglycemia and Insulin Sensitivity Differ
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                                                                                          Ebbeling, C. B., M. M. Leidig, K. B. Sinclair, J. P. Hangen, and D. S.
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this manuscript.                                                                             Adolescent Obesity.” Archives of Pediatric and Adolescent Medicine 157:
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850 | Disease Control Priorities in Developing Countries | Walter C. Willett, Jeffrey P. Koplan, Rachel Nugent, and others

                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                     Chapter 45

                    The Growing Burden of Risk from
                    High Blood Pressure, Cholesterol,
                                    and Bodyweight
                                                                                Anthony Rodgers, Carlene M. M. Lawes,
                                                                                Thomas Gaziano, and Theo Vos

High blood pressure, cholesterol, and bodyweight are responsi-                  investments.Another approach is an evolution of the individual-
ble for a large and increasing proportion of the global burden of               based strategy in which treatments are targeted to those at high
disease. Although historically these risks have been regarded as                absolute risk of cardiovascular disease (CVD) rather than those
“Western,” their impact is now recognized as global: they are                   with single risk-factor levels above traditional thresholds, such
already leading causes of disease in middle-income countries                    as hypertension or obesity (Jackson and others 1993). Such an
and of emerging importance in low-income countries                              approach appears to be highly cost-effective, with the potential
(Ezzati and others 2004; WHO 2002). This chapter presents an                    to substantially reduce CVD rates when combined with popu-
evidenced-based review of the impact of high blood pressure,                    lationwide interventions (Murray and others 2003).
cholesterol, and bodyweight; the cost-effectiveness of relevant
interventions; and the economic benefits of interventions. The
chapter focuses on personal interventions—that is, those that                   EPIDEMIOLOGY
are mediated largely by interpersonal actions and take place at
the individual level. As such, the chapter should be considered                 Elevated blood pressure, cholesterol, and bodyweight are all
as complementary to chapter 44 on lifestyles, which addresses                   established risk factors for CVD and, in the case of body-
populationwide interventions.                                                   weight, for other diseases, such as diabetes, certain cancers,
   Prevention strategies have been broadly classified as indi-                  and osteoarthritis. The associations between blood pressure
vidual based (also known as high risk) or population based                      (Asia Pacific Cohort Studies Collaboration 1999, 2003a;
(Rose 1985). The former typically involve screening to detect                   Prospective Studies Collaboration 2002); cholesterol (Asia
individuals above a certain threshold level of an individual risk               Pacific Cohort Studies Collaboration 2003b; Law, Wald, and
factor—for example, people with hypertension—followed by                        Thompson 1994; Prospective Studies Collaboration 1995);
personal interventions for those individuals. In contrast, the                  and body mass index (BMI) (Asia Pacific Cohort Studies
population-based approach aims at lowering mean risk-factor                     Collaboration 2004; Willett and others 1995) and CVD are
levels and shifting the population distribution of exposure in                  direct and continuous from relatively low levels, indicating that
a favorable direction (Rose 1985). One example would be by                      optimal levels are about 115/75 millimeters of mercury
reducing salt content in manufactured foods, thereby lowering                   (mmHg), 3.8 millimoles per liter (mmol/l), and 21 kilograms
blood pressure levels on a populationwide basis. Such an                        per square meter (kg/m2), respectively (figure 45.1).
approach has the potential to produce large and lasting changes                    Although some studies suggest J- or U-shaped associations
in disease incidence but requires substantial sociopolitical                    (Calle and others 1999; Cruickshank 1994; D’Agostino and


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
                     a. Blood pressure                                            b. Cholesterol                                      c. Body mass index
    Relative risk of coronary heart disease               Relative risk of coronary heart disease                      Relative risk of coronary heart disease
    4.0                                                   4.0                                                          4.0

    2.0                                                   2.0                                                          2.0

    1.0                                                   1.0                                                          1.0
                                 Hypertension                                                     Hyper-                                                 Obesity

    0.5                                                   0.5                                                          0.5
          110    120 130 140 150 160 170                            4.0       5.0       6.0      7.0          8.0            16    20    24     28      32         36
                Systolic blood pressure (mmHg)                              Total cholesterol (mmol/l)                             Body mass index (kg/m2)

    Figure 45.1 Continuous Risks of Blood Pressure, Cholesterol, and Body Mass and Coronary Heart Disease Risk

others 1991; Farnett and others 1991; Field and others 2001; Iso                        12 percent lower stroke and IHD risk and an approximately
and others 1989; Kannel, D’Agostino, and Silbershatz 1997;                              20 to 30 percent lower diabetes risk.
Stewart 1979; Troiano and others 1996), low levels of these risk
factors are unlikely to cause CVD. Rather, such associations
more likely reflect incipient disease, which itself produces                            BURDEN OF THE DISEASE, CONDITION,
both a fall in risk-factor levels and an increase in CVD risk                           OR RISK FACTOR
(Alderman 1996; Flack and others 1995; MacMahon and others                              Epidemiological data on blood pressure, cholesterol, and body-
1997; Manson, Willett, and Stampfer 1995; Neaton and                                    weight levels are predominantly available from developed
Wentworth 1992; Sleight 1997a, 1997b; Stevens and others                                countries; however, evidence indicates that these risk factors
1998). No trial evidence points to a J-curve association for                            are important and increasing in many other countries. Surveys
blood pressure, despite including patients with below average                           in developing countries suggest increases in these risks occur
blood pressure (Hansson and others 1999; McMurray and                                   early in the path to industrialization (Bobak and others 1997;
McInnes 1992; Pfeffer 1993; Staessen and others 1997).                                  Evans and others 2001; Suh 2001; Wu and others 1996). Good
    The continuous associations between blood pressure, cho-                            evidence also documents risk-factor levels rising after people
lesterol, and bodyweight and CVD demonstrate the lack of a                              migrate to more urbanized settings (Poulter and Sever 1994) in
biological justification for current threshold levels, such as                          Africa (Poulter 1999; Poulter, Khaw, and Sever 1988), China
those that define hypertension. Indeed, most of the disease                             (He, Klag, and others 1991; He, Tell, and others 1991), and the
burden resulting from these three risk factors occurs in the                            Pacific islands (Joseph and others 1983; Salmond and others
large majority of the population with nonoptimal levels but                             1985; Salmond, Prior, and Wessen 1989). The World Health
without hypertension, hypercholesterolemia, or obesity. Hence,                          Organization’s Global Burden of Disease study demonstrated
this chapter avoids those terms and instead uses high blood                             that CVD was a leading cause of death in many regions and
pressure, high cholesterol, and high bodyweight, defined as                             that most adults in developed and developing countries have
nonoptimal levels of these risk factors (that is, over 115/75                           nonoptimal blood pressure, cholesterol, and bodyweight levels
mmHg, 3.8 mmol/l, or 21 kg/m2, respectively).                                           (Ezzati and others 2004; WHO 2002). Indeed, even using
    The strength of the proportional associations of these risk                         traditional cutoff points, these risk factors are prevalent: of 140
factors with CVD is similar for most population subgroups.                              subgroups defined by age, sex, and region, 45 percent had a
Although they attenuate with age, they remain strong and                                mean SBP equal to or greater than 140 mmHg, 25 percent
positive in the oldest age groups. Overall, in middle-aged                              had mean cholesterol levels over 5.5mmol/l, and 45 percent had
populations, a 10 mmHg lower systolic blood pressure (SBP) is
                                                                                        mean BMI levels of at least 25 kg/m2.
associated with a roughly 30 to 40 percent lower stroke risk
and 20 to 25 percent lower ischemic heart disease (IHD) risk, a
1 mmol/l lower cholesterol level is associated with about a 15                          Health Burden
to 20 percent lower stroke risk and 20 to 25 percent lower                              The Global Burden of Disease study assessed the burden attrib-
IHD risk, and a 2 kg/m2 lower BMI is associated with an 8 to                            utable to nonoptimal levels of these risks (table 45.1) (Ezzati

852 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

                                               ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 45.1 Global Burden of Disease Attributable to Nonoptimal Blood Pressure, Cholesterol, and BMI by Region, 2000

                                                       High-mortality                                Low-mortality                                Developed
  Condition                                            developing countriesa                         developing countriesb                        countriesc                       World total

  Attributable deaths (thousands)
  Blood pressure                                                   1,969                                         2,205                                 2,966                      7,140 (12.8%)
  Cholesterol                                                      1,405                                           849                                 2,161                       4,415 (7.9%)
  BMI                                                                 399                                          775                                 1,417                       2,591 (4.6%)

  Attributable DALYs (thousands)
  Blood pressure                                                  20,630                                       20,277                                 23,363                     64,270 (4.4%)
  Cholesterol                                                     15,602                                         8,609                                16,227                     40,438 (2.8%)
  BMI                                                              6,408                                       11,115                                 15,892                     33,415 (2.3%)

Sources: Ezzati and others 2004; WHO 2002b.
Note: The burden of disease estimated to be attributable to nonoptimal blood pressure (mean SBP 115 mmHg), cholesterol (mean 3.8 mmol/l), and body mass index (mean 21 kg/m2) in 2000.
A, B, C and D designations in specific notes below are as follows: A very low child mortality and very low adult mortality; B low child mortality and low adult mortality; C low child mortality and
high adult mortality; D high child mortality and high adult mortality; E high child mortality and very high adult mortality.
a. The high-mortality developing countries include those in Africa, America D, the Eastern Mediterranean D, and Southeast Asia D.
b. The low-mortality developing countries include those in America B, Eastern Mediterranean B, Southeast Asia B, and the Western Pacific B.
c. The developed countries include those in America A, Europe, and the Western Pacific A.

and others 2004; WHO 2002). The burden for blood pressure                                            burden can be attributed to those risks. In addition, more than
was related to deaths and disability-adjusted life years (DALYs)                                     three-quarters of type 2 diabetes is caused by high bodyweight
from IHD, stroke, hypertensive disease, and other CVD; end-                                          (Ezzati and others 2004; WHO 2002). Hence the economic
points for cholesterol included IHD and stroke; and endpoints                                        impact of nonoptimal levels of those risks will be at least two-
for BMI were IHD, stroke, hypertensive disease, diabetes,                                            thirds that due to CVD and diabetes. A recent report high-
certain cancers, and osteoarthritis. Globally, 7.1 million deaths                                    lighted the economic impact of CVD in developing economies,
were attributed to high blood pressure in 2000, 4.4 million to                                       noting that a high proportion of the CVD burden occurs
high cholesterol, and 2.6 million to high BMI. This burden was                                       among adults of working age (Leeder and others 2004). In
shared approximately equally among the sexes. A large fraction                                       Brazil, China, India, Mexico, and South Africa, conservative
occurred in middle age, especially in developing countries, and
this factor, together with the frequently debilitating nature of
nonfatal CVD, accounted for a large number of DALYs.                                                                                                                 Cardiovascular
   More of the DALY burden was experienced in developing
countries than in developed countries, reflecting the large pop-
ulations in developing countries and their already high risk-
factor levels. In all regions, most CVD is attributable to the                                                           Systolic blood              Cholesterol over
combined effects of high blood pressure, cholesterol, and body-                                                          pressure over                 3.8 mmol/l
                                                                                                                           115 mmHg                       28%
weight levels (figure 45.2).                                                                                                  45%
   Table 45.2 shows the burden resulting from the overlapping
or multicausal etiology of diseases. Analyses of the combined
impact of these and other major cardiovascular risks indicate                                                                             Body mass index
                                                                                                                                              21 kg/m2
that the joint contribution of established risks is responsible for                                                                            15%
83 to 89 percent of the IHD burden and 70 to 76 percent of the
stroke burden worldwide (Ezzati and others 2003; Ezzati and
others 2004).                                                                                        Source: Ezzati and others 2004; WHO 2002.
                                                                                                     Note: Individual and joint contributions of high blood pressure, cholesterol, and body
                                                                                                     weight to global cardiovascular burden are shown, with the size of each circle
                                                                                                     proportional to the size of burden (as measured in DALYs) (WHO 2002). The percentages
Financial Burden                                                                                     indicate the attributable burden for each risk factor, and the overlap shows disease
                                                                                                     caused by joint or mediated effects.
The economic impact of high blood pressure, cholesterol, and
bodyweight levels can be estimated indirectly using the forego-                                      Figure 45.2 Global CVD Burden Caused by High Blood Pressure,
ing data—namely, that more than two-thirds of the CVD                                                Cholesterol, and Bodyweight

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                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 45.2 Individual and Joint Contributions of Seven Selected Risk Factors to the Burden of CVD by Region

                              Percentage of the                              Population attributable fractions for individual              Overall population
  Disease                     regional disease burden                        risk factors (percentages)                                    attributable fraction (percent)

  High-mortality developing countries
  Stroke                                    1.6                               High blood pressure (56), high cholesterol (18),                          65–71
                                                                              high BMI (7), low fruit and vegetable intake (12),
                                                                              physical inactivity (6), tobacco (7), alcohol (2)
  IHD                                       3.0                               High blood pressure (44), high cholesterol (54),                          80–87
                                                                              high BMI (11), low fruit and vegetable intake (33),
                                                                              physical inactivity (21), tobacco (8), alcohol (4)

  Low-mortality developing countries
  Stroke                                    4.7                               High blood pressure (58), high cholesterol (13),                          67–74
                                                                              high BMI (11), low fruit and vegetable intake (10),
                                                                              physical inactivity (5), tobacco (8), alcohol (7)
  IHD                                       3.2                               High blood pressure (45), high cholesterol (48),                          79–87
                                                                              high BMI (22), low fruit and vegetable intake (31),
                                                                              physical inactivity (22), tobacco (8), alcohol (3)

  Developed countries
  Stroke                                    6.0                               High blood pressure (72), high cholesterol (27),                          81–86
                                                                              high BMI (23), low fruit and vegetable intake (12),
                                                                              physical inactivity (9), tobacco (22), alcohol (0)
  IHD                                       9.4                               High blood pressure (58), high cholesterol (63),                          89–93
                                                                              high BMI (33), low fruit and vegetable intake (28),
                                                                              physical inactivity (22), tobacco (22), alcohol ( 0.2)

  Stroke                                    3.1                               High blood pressure (62), high cholesterol (18),                          70–76
                                                                              high BMI (13), low fruit and vegetable intake (11),
                                                                              physical inactivity (7), tobacco (12), alcohol (4)
  IHD                                       4.0                               High blood pressure (49), high cholesterol (56),                          83–89
                                                                              high BMI (21), low fruit and vegetable intake (31),
                                                                              physical inactivity (22), tobacco (12), alcohol (2)

Source: Ezzati and others 2003.
Note: See notes to table 45.1 for a breakdown of the regional groupings.

estimates indicated that at least 21 million years of future pro-                                for 2 to 8 percent of all health care expenditures in developed
ductive life are lost because of CVD each year. Although no                                      countries. For example, in 1991, 2.5 percent of health care costs
detailed data exist on the direct economic burden of the indi-                                   in New Zealand were attributable to obesity (Swinburn and
vidual risk factors, the costs of CVD treatment in developing                                    others 1997), and in 1996, US$22 billion was attributed to obe-
countries are significant. In South Africa, for example, 2 to                                    sity-related CVD in the United States, equivalent to 17 percent
3 percent of gross domestic product was devoted to the direct                                    of CVD-related health expenditures (G. Wang and others 2002).
treatment of CVD, or roughly 25 percent of all health care
expenditures (Pestana and others 1996). For many middle-
income countries, high body mass is already an important                                         INTERVENTIONS
cause of health inequities (Monteiro and others 2004).
    Current expenditure in developed countries provides an                                       Data on the choice of interventions for blood pressure, choles-
indication of possible future expenditure in developing coun-                                    terol, and bodyweight and their effectiveness are now presented.
tries. For example, estimated direct and indirect costs of CVD
in the United States were US$350 billion in 2003. In 1998,
US$109 billion was spent on hypertension, or about 13 percent                                    Choice and Classification of Interventions
of the health care budget (Hodgson and Cai 2001). Studies are                                    A variety of population-based and personal interventions
limited but suggest that obesity-related diseases are responsible                                could potentially be used to address the risks associated with

854 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

                                                        ©2006 The International Bank for Reconstruction and Development / The World Bank
high blood pressure, cholesterol, and bodyweight. Of the per-                    chapter discusses the cost-effectiveness of efforts to manage
sonal interventions discussed in this section—lifestyle and                      those without previous CVD, and chapter 33 reviews the man-
dietary, pharmacological, and surgical interventions—two                         agement of those with known vascular disease. A unifying sys-
main strategies exist for choosing whom to treat: those above                    tem targeting treatments at those at highest risk, either with
certain threshold values of single risk-factor levels and those                  CVD or multiple risk factors, is likely to be highly cost-effective
above certain values of absolute cardiovascular (or global) risk,                because more than 75 percent of events occur in the 5 to 10
which is determined by the levels of multiple factors.                           percent of people with CVD or specific clusters of risk factors
    Targeting treatments by levels of a single risk factor (such as              (Haq and others 1999; Tosteson and others 1997).
hypertension) does not effectively focus on overall risk of                         The limitations of the individual-risk-factor approach,
developing CVD, which is mainly determined by the net effects                    together with increasing evidence that the thresholds do not
of other risk factors. For example, the predicted 10-year CVD                    have any biological justification, have motivated the adoption
risk for someone with an SBP of 140/90 mmHg can vary from                        of strategies that take other risk factors into account. Although
5 to 50 percent depending on the number of concomitant risk                      the most complete way of doing so is using the absolute-risk
factors. The number of people who would need to be treated to                    strategy outlined earlier, one intermediate strategy involves
prevent an event can therefore vary by an order of magnitude,                    lowering the thresholds of blood pressure or lipid levels at
even if they have the same blood pressure levels. Thus, a treat-                 which treatment is initiated if one or more additional CVD
ment strategy based only on individual risk-factor levels is                     risk factors, such as diabetes, are present (Chobanian and
likely to result in high-risk patients being undertreated and                    others 2003).
many patients at relatively low risk being treated with little
absolute benefit, which is unlikely to be the best allocation of
scarce health care resources.                                                    Intervention Effectiveness
    The absolute-risk strategy was developed in New Zealand                      This section summarizes data on the effectiveness of popula-
(Jackson and others 1993) and has been adopted extensively                       tion-based interventions and personal interventions (lifestyle
elsewhere, for example, by the British Hypertension Society                      and dietary interventions and pharmacological and surgical
(Ramsay and others 1999) and the Joint Task Force of European                    interventions). The studies concerned have mainly been con-
and other Societies on Coronary Prevention (Wood and others                      ducted in developed countries.
1998). The absolute CVD risk is estimated using risk assess-
ments such as the Framingham risk function (Anderson and                         Population-Based Interventions. Investigators have under-
others 1991) or the Prospective Cardiovascular Munster Study                     taken a variety of population-based community intervention
score (Assmann, Cullen, and Schulte 2002) on the basis of the                    studies, mostly in developed countries in the 1970s and 1980s
number and severity of CVD risk factors. Targeting treatments                    (for further details see chapter 44). These studies have tended
at those at high absolute risk rather than those above arbitrary                 to be multifactorial projects testing whether comprehensive
thresholds ensures a favorable ratio of benefits to risks. It can be             community programs could produce favorable changes in such
expected to reduce events in the large proportion of people who                  risk factors as bodyweight, cholesterol, and blood pressure and
are, for example, nonhypertensive but who still have nonopti-                    in CVD morbidity and mortality (Schooler and others 1997).
mal blood pressure (Rose 1981). Combinations of personal                         In general, they included a combination of populationwide
interventions targeted at those at high absolute risk also have                  and individual interventions, including messages disseminated
the potential of being highly cost-effective.                                    through local associations, sports clubs, the media, and food
    The simplest indicator of high absolute risk is established                  associations; healthy food options at restaurants and worksite
CVD, principally myocardial infarction, angina, stroke, or tran-                 cafeterias; food labeling at supermarkets; face-to-face commu-
sient ischemic attack. For example, without preventive treat-                    nication at meetings and distribution of educational materials;
ment, people who have had a myocardial infarction face an                        smoking restrictions; and competitions to develop healthy
annual risk of death from coronary heart disease of about                        food. Except in Finland, the projects had mixed results,
5 percent (Law, Watt, and Wald 2002). That risk persists                         although many demonstrated significant effects with respect to
indefinitely—probably for the rest of a person’s life—and                        individual components of the interventions. The limitations of
varies little with age or sex.                                                   many of the projects include inability to detect small but
    However, many individuals with no history of CVD are at                      potentially important changes in risk factors, short duration of
similar elevated risk for future CVD as a result of constellations               intervention and follow-up, and issues with outcome measures.
of elevated risks. Thus, the distinction between primary                         Some have also suggested that those trials with less favorable
and secondary prevention is somewhat artificial and could                        results may have lacked adequate community support and
lead to undertreatment of many high-risk individuals. While                      public policy initiatives (Feinleib 1996; Mittelmark and others
recognizing that the distinction is somewhat arbitrary, this                     1993; Schooler and others 1997; Susser 1995).

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                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
   A number of population-based interventions have also                                 salt intake lowers blood pressure, with larger blood pressure
taken place in developing countries, including the following:                           reductions in the elderly and in those with higher initial blood
                                                                                        pressure levels (Law, Frost, and Wald 1991; Whelton and others
• In China, the Tianjin Project showed a significant reduction                          1998). An increase in daily fruit and vegetable intake may also
  in sodium intake in men after three years of intervention,                            lower blood pressure, and when combined with an increase in
  and after five years, the prevalence rates of both hyperten-                          low-fat dairy products and a reduction in saturated and total
  sion and obesity decreased among 45- to 65-year-olds                                  fat, may lower blood pressure even more (Appel and others
  (Schooler and others 1997).                                                           1997). Weight reduction lowers blood pressure in proportion
• In Chile, the Mirame Project was a three-year intervention                            to the amount of weight lost (Whelton and others 1998), and
  program designed to provide and evaluate strategies to pro-                           physical activity appears to lower blood pressure in a way that
  mote healthy lifestyles among schoolchildren and their fam-                           may be independent of weight loss. High levels of alcohol
  ilies. Nissinen, Berrios, and Puska (2001) report a significant                       intake are associated with blood pressure elevation, which is
  positive effect on some risk factors for the intervention                             reversible by reducing intake (Kaplan 1995).
  schools.                                                                                  Dietary approaches to lowering total cholesterol and low-
• In Mauritius, government-led initiatives resulted in a                                density lipoprotein (LDL) cholesterol typically involve reduced
  change in the composition of cooking oil from mostly palm                             intake of dietary fats, particularly saturated fats. Evidence sug-
  oil, which is high in saturated fatty acids, to wholly soybean                        gests a dose-response relationship between saturated fatty acid
  oil, which is high in unsaturated fatty acids. From 1987 to                           intake and LDL cholesterol levels (NCEP Expert Panel 2002).
  1992, total cholesterol concentrations fell significantly, and                        Plant sterols and stanols have recently been incorporated into
  the estimated intake of saturated fatty acids decreased, with                         foods such as margarine and can reduce LDL cholesterol
  much of this finding reportedly resulting from the change in                          by about 10 percent; however, this approach is currently rela-
  cooking oil (Uusitalo and others 1996).                                               tively expensive (Law 2000). Dietary advice may also suggest
                                                                                        increasing the intake of viscous fiber—for instance, in the
   An effective populationwide intervention draws together                              form of cereal grains, fruits, and vegetables—because these
different kinds of feasible activities that combined produce a                          dietary sources may enhance the lowering of LDL cholesterol.
synergistic effect (Nissinen, Berrios, and Puska 2001; Puska                            Maintaining bodyweight in the desirable range and engaging in
1999). Even though the projects and trials were undertaken in a                         moderate physical activity complement these dietary strategies
range of different communities and used a variety of methods                            (NCEP Expert Panel 2002).
and interventions, several common themes emerge. Some of                                    Increases in obesity have been related to declines in energy
the important elements of a successful program that enables                             expenditure (for example, reductions in physical activity and
individuals to adopt healthier lifestyles include the following:                        adoption of a more sedentary lifestyle) and a higher intake of
                                                                                        energy-dense but micronutrient-poor foods, such as most
• clear responsibility for coordinating prevention efforts, with                        processed foods (WHO 2003b). A variety of trials have recorded
  credible agencies with good communication methods carry-                              beneficial health effects, with weight reduction achieved by a
  ing out long-term education programs                                                  combination of interventions (NHLBI Obesity Education
• intersectoral collaboration, with multiple messages sourced                           Initiative Expert Panel 1998). These interventions include
  from different organizations, including health sector enti-                           dietary counseling and therapy that involves a decrease in daily
  ties, nonhealth government agencies, schools, workplaces,                             caloric intake and a reduction in saturated fats and total fats.
  religious organizations, and voluntary agencies                                       An increase in physical activity is an important component of
• collaboration with the food industry to ensure the availabil-                         weight-loss therapy. Behavioral strategies revolving around
  ity of reasonably priced healthier food options, with food                            self-monitoring of eating habits, stress management, problem
  labeling that presents relevant information in a clear, reli-                         solving, and social support may also complement these
  able, and standardized format                                                         approaches. Overall, however, the effects of lifestyle modifica-
• realistic multiyear time frames.                                                      tions to reduce weight and maintain the weight loss are rela-
                                                                                        tively poor, with many reports finding that weight returns to
Lifestyle and Dietary Personal Interventions. Many guide-                               baseline levels after several years.
lines have concluded that lifestyle modifications, such as weight
loss, healthy diet (such as one rich in potassium and low in                            Pharmacological and Surgical Personal Interventions.
sodium), physical activity, and moderate alcohol consumption                            Randomized trials have shown that medications to lower blood
are effective in reducing blood pressure (see, for example,                             pressure effectively reduce the risk of stroke, IHD, and heart fail-
Chobanian and others 2003). Trials indicate that a reduction of                         ure. Results from meta-analyses of more than 40 different trials

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                                               ©2006 The International Bank for Reconstruction and Development / The World Bank
published in 2003 included about 210,000 participants and                           In clinical trials of statins, the relative risk reduction in car-
more than 8,000 stroke and 11,000 IHD events (Blood Pressure                    diovascular events is similar at all levels of baseline cholesterol,
Lowering Treatment Trialists’ Collaboration 2003; Fox and                       extending to levels below 5 mmol/l total cholesterol, and is also
EUROPA Investigators 2003; Law, Wald, and Rudnicka 2003;                        consistent among patients who are and are not taking concur-
Lawes and others 2004; Pepine and others 2003). The trials may                  rent blood pressure lowering and other medications (Heart
be broadly classified into three groups: (a) drug versus placebo                Protection Study Collaborative Group 2002). Similar findings
trials, (b) more intensive regimens to lower blood pressure ver-                are observed with treatments to lower blood pressure (Progress
sus less intensive regimens, and (c) drug versus drug trials.                   Collaborative Group 2001), indicating that these treatment
    The drug versus placebo trials achieved the greatest reduc-                 effects are independent. This finding is plausible, because they
tions in blood pressure, and a dose-response relationship was                   act through different mechanisms and because observational
apparent between blood pressure reduction and reduced risk of                   studies do not suggest a large interaction (Neaton and
stroke. Overall, the trials indicated that a 10 mmHg reduction                  Wentworth 1992).
in SBP would result in a 32 percent reduction in stroke risk and                    The benefits of lowering blood pressure and cholesterol are
a 14 percent relative reduction in IHD risk. This finding is con-               achieved surprisingly rapidly: for most outcomes,risk appears to
sistent with the size of associations observed in cohort studies.               be fully reversed within 6 to 18 months of beginning treatment.
    Clear evidence indicates that all the major drug classes have               For example,individuals with cholesterol lowered in the past two
similar effects on the risk of stroke and coronary heart disease                or more years are at approximately the same coronary heart dis-
per mmHg reduction in blood pressure (Blood Pressure                            ease risk as otherwise identical individuals whose cholesterol has
Lowering Treatment Trialists’ Collaboration 2003; Lawes and                     been at that level for decades (Law, Wald, and Thompson 1994).
others 2004). The only clear evidence of clinically important,                      Pharmacological agents for weight loss that have been sub-
class-specific effects are with agents that block the renin-                    ject to randomized controlled trials include dexfenfluramine,
angiotensin system, which reduce diabetes incidence by about                    sibutramine, orlistat, and phentermine/fenfluramine (although
one-quarter, and with calcium channel blockers, which reduce                    the last has been withdrawn because of a reported association
heart failure less than other agents (although this result may be               between the drugs and valvular heart disease). Overall, trials
partly caused by misclassification, because a known side effect                 suggest only modest weight-loss effects, with an average net
of calcium channel blockers is ankle edema, which is a diag-                    weight loss of 1.5 kg after eight weeks and 2 to 3 kg after one
nostic component of heart failure). Because all agents lower                    year (NHLBI Obesity Education Initiative Expert Panel 1998).
blood pressure by about the same modest amount and because                      A systematic review of orlistat trials indicated a pooled net
their effects on blood pressure are additive (Law and others                    weight loss of 1.2 kg at 12 weeks, 2.9 to 3.4 kg at one year, and
2003), the key issue seems to be which combinations of two or                   2.5 to 2.4 kg at two years (O’Meara and others 2001). Results of
more drugs should be provided and how long-term adherence                       a systematic review of trials assessing sibutramine were similar
can be maximized.                                                               (O’Meara and others 2002), with fewer data available on long-
    Over the past three decades, numerous trials have assessed                  term sustained weight loss.
the effect of different cholesterol-lowering interventions (Law,                    Investigators have also undertaken several randomized con-
Wald, and Rudnicka 2003; Law, Wald, and Thompson 1994).                         trolled trials to assess the effects of different surgical interven-
The placebo-controlled trials can be broadly classified into                    tions, generally in individuals with a BMI equal to or greater
those testing fibrates, statins, and other interventions (mostly                than 35 or 40 kg/m2. Weight loss resulting from gastric bypass
dietary interventions, but also some other interventions such as                varied from 50 to 100 kg six months to a year following surgery
resins and niacin). The statins are the most effective in lower-                (NHLBI Obesity Education Initiative Expert Panel 1998).
ing total and LDL cholesterol, with reductions of more than                     Overall, several trials suggest that surgery resulted in about
1 mmol/l in most trials. A good correlation has been found                      23 to 37 kg more weight loss than conventional treatment and
between reduction in total cholesterol and relative risk reduc-                 that this loss was maintained for eight years (Clegg and others
tion. This finding suggests, as for trials investigating blood                  2002). Furthermore, gastric bypass surgery appears to be more
pressure lowering, that even though some drugs are more                         beneficial than gastroplasty or jejunoileal bypass.
effective in achieving greater reductions in risk factors, their                    In relation to compliance and adherence with pharmacolog-
effect on disease outcomes is similar per unit reduction of                     ical therapy, population surveys have demonstrated that, even
cholesterol. Overall, a 1 mmol/l reduction in total cholesterol is              in industrial countries, high blood pressure is either untreated
associated with a 21 percent relative risk reduction in IHD and                 or inadequately controlled in about 70 to 75 percent of patients
a 17 percent reduction in risk of stroke. Again, this finding is                and that adherence to medications among patients suffering
consistent with the epidemiology, with the proviso that the vast                from chronic disease is only about 50 percent (WHO 2003a).
majority of strokes in clinical trials were ischemic.                           The extent of poor adherence is likely to be even greater in

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                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
developing countries given the relative lack of health services                         COST-EFFECTIVENESS OF INTERVENTIONS
and inequities in access. Pharmacotherapy faces a variety of
potential barriers, including the symptomless nature of the                             Costs include expenditures required to identify and treat risk
conditions, a lack of knowledge or denial of risk, the compli-                          factors as well as expenditures for treating CVD when it is not
cated nature of drug regimens, the risk of side effects (real and                       prevented. Where possible, this chapter deals with the separate
perceived), and the costs of treatment.                                                 sources of costs for several reasons. First, the costs for identify-
    Health providers may use multiple strategies to increase                            ing those requiring treatment vary significantly by level of eco-
compliance and adherence. Patient-centered interventions                                nomic development and by urban versus rural location. In
include involving individuals in the decision-making process;                           many situations in developing countries, such costs will make
providing individualized patient education and disease coun-                            most or all forms of screening beyond a determination of CVD
seling and adapting treatment to patients’ lifestyles; simplifying                      history unaffordable. Second, in some countries, such as India,
dosing schedules; providing drug information leaflets, medica-                          that are large producers of generic drugs, prices are reported to
tion charts, and special reminder packaging for medications;                            be lower than in most other drug-producing or -importing
holding group sessions for education and family-oriented dis-                           countries. Third, this approach allows researchers and policy
ease management therapies; and implementing automated                                   makers to understand the constituent costs so that they can
telephone assessment and self-care education calls with nurse                           examine where cost reductions may be most beneficial. Fourth,
follow-up (Haynes and others 2003).                                                     it clarifies what expenditures may be required as a result of
    Strategies may also aim to increase physician adherence, and                        changes in decisions about the treatment of risk factors. Finally,
interventions may include the use of guidelines, peer review                            many people in developing countries do not have access to
and audit, and prompts to remind physicians to review risks                             hospitals for acute management of CVD events. Nonetheless,
and medications (Ebrahim 1998; NCEP Expert Panel 2002).                                 increased expenditure on treating risk factors may lead to
These strategies obviously do not address issues pertaining to                          significant reductions in the costs of treating subsequent CVD
resources and access in poor countries.                                                 events for many countries. Ultimately, the net effect is reflected
    Several trials and overviews have attempted to assess the                           in cost-effectiveness analyses. Unless otherwise stated, costs are
value of different interventions to improve compliance and                              in 2001 U.S. dollars.
adherence; however, issues have arisen in connection with the                               The costs of personal interventions include the costs of
generalizability of the interventions, the low statistical power                        patient screening (identifying high-risk patients), drugs and
in many trials, the lack of description of all parts of interven-                       their acquisition, clinic visits, health care workers’ time, labora-
tions, and the assessment of complex interventions without                              tory tests, and travel. Annual drug costs for medications to
assessment of the separate effects of the intervention compo-                           lower blood pressure and cholesterol vary widely by country
nents. Haynes and others’ (2003) systematic review concludes                            and depend on whether generics are available and used. For
that, overall, no single approach to improving adherence can be                         example, according to the International Drug Price Indicator
recommended. Simpler treatment regimens can sometimes                                   Guide (Management Sciences for Health 2004), annual costs in
improve adherence and treatment outcomes for both short-                                2002 of generic 40 mg lovastatin ranged from US$14 in
and long-term treatments. Several complex strategies,                                   Barbados to US$217 in Costa Rica, and on-patent statins can
including combinations of more thorough patient instructions                            cost almost a US$1,000 a year in the United States. Because
and counseling, easier access to care, reminders, close follow-                         drug costs vary by up to two orders of magnitude across coun-
up, supervised self-monitoring, family therapy, and rewards for                         tries, results of cost-effectiveness analyses are particularly
success can improve adherence and treatment outcomes in                                 sensitive to their input prices. Table 45.3 presents some
some patients. However, even the most effective interventions                           sample prices. The costs of these medications have dropped
did not lead to large improvements in adherence or treatment                            considerably in recent years, and now the annual costs for
outcomes and were relatively resource intensive. By contrast,                           hydrochlorothiazide (25 mg), atenolol (50 mg), and captopril
Connor, Rafter, and Rodgers’s (2004) systematic review indi-                            (50 mg), are US$2, US$4, and US$9, respectively (Management
cates improved adherence and clinical outcomes with fixed-                              Sciences for Health 2004). Statins will become increasingly
dose combination treatment or unit-of-use packaging.                                    affordable as simvastatin joins lovastatin in coming off patent
    Few good, evidence-based strategies to improve obesity                              (2006 in the United States and already off patent in Germany
management are currently available, although reminder                                   and the United Kingdom).
systems, brief training interventions, shared care, inpatient                               The estimated number of visits to manage high blood pres-
care, and dietitian-led treatments may all be worth further                             sure and cholesterol, under traditional paradigms, ranges from
investigation (Harvey and others 2003). Thus, a clear need for                          two to six per year at costs ranging from US$3 to US$20 per
innovations still exists to help people follow medication                               visit across the six regions assessed, but note that generally
prescriptions as well as dietary and lifestyle advice.                                  many fewer tests and less follow-up is required with a strategy

858 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

                                               ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 45.3 Annual Costs of Selected Cardiovascular Medications

  Medication                                    United States (2002 US$)a                           Average international price (2002 US$)                    Projected polypillb

  Beta-blocker                                              32–365                                                     3–15                                            n.a.
  Diuretic                                                   6–37                                                      1–3                                             n.a.
  Statin                                                   180–864                                                    11–147                                           n.a.
  Aspirin                                                    2                                                         1–6                                             n.a.
  Angiotensin-converting                                    65–365                                                     1–19                                            n.a.
  enzyme inhibitor
  Total                                                    285–1,633                                                  17–190                                          20–40

Sources: U.S. prices: Murray 2004; international prices: Management Sciences for Health 2004.
n.a. not applicable.
a. Based on average wholesale prices.
b. Based on a moderate increase from the sum of the lowest-cost generic components.

based on absolute risk. Diagnostic testing for cholesterol in the                                    nity intervention that expects a 4 percent reduction in total
United States using a general laboratory is reimbursed at US$6                                       serum cholesterol and costs US$5 per person annually targeted
for total cholesterol, US$16 for a complete lipoprotein choles-                                      would save more than US$2 billion over 25 years of the pro-
terol fractionation analysis, and US$6 for triglycerides (Xact                                       gram. When the North Karelia (Puska 1999) estimates were
Medicare Services 2003). Point-of-care one-step enzymatic                                            used in a cost-effectiveness analysis in the United States
strips that require only a few drops of blood from a finger                                          (Tosteson and others 1997), the cost-effectiveness ratios ranged
stick and that can process total cholesterol in minutes cost less                                    from being cost saving to US$88,000 (in 1985 U.S. dollars) per
than US$3 per test (Greenland and others 1987). A basic                                              life year saved, depending on the percentage reduction in cho-
metabolic panel for those on diuretics or for measuring renal                                        lesterol (1 to 4 percent).
function is US$12. The costs attributed to patient time and
travel for visits have not been estimated for many countries,
but they were recently estimated at US$12 to US$26 per visit                                         Personal Interventions to Lower Blood Pressure or
in the United States, depending on age and sex (Prosser and                                          Cholesterol in Developed Countries
others 2000).                                                                                        A common finding of cost-effectiveness analyses of primary
    A review of studies to date highlights several issues regard-                                    prevention of CVD by means of lowering blood pressure and
ing cost-effectiveness analyses, including the significant varia-                                    cholesterol is the wide variability in cost-effectiveness
tions in terms of calculations of cost per life year saved. The two                                  ratios, depending on underlying risk, age, and costs of medica-
most important aspects of the cost-effectiveness of any primary                                      tions. For personal interventions using drug treatment for
intervention are the future risk for CVD of the population                                           lowering blood pressure and cholesterol levels, no single cost-
treated and the costs of the medications.                                                            effectiveness analysis adequately summarizes experience in the
                                                                                                     developed countries. Collectively, the studies evaluating
                                                                                                     hypertension treatment in Australia, New Zealand, the United
Population-Based Interventions                                                                       States, and the Scandinavian countries suggest a range of cost-
Given the strong association between CVD and high blood                                              effectiveness ratios from US$4,600 to more than US$100,000
pressure, cholesterol, and body mass, most guidelines for those                                      per life year gained when applied to the entire adult population
risk factors begin by recommending lifestyle modifications.                                          without further risk stratification (Kupersmith and others
Although these benefits can lead to changes in risk factors, their                                   1995). Compared with the entire population, for those at high
effect on CVD events is not well documented. However, on the                                         risk with diastolic blood pressures over 105 mmHg and older
basis of assumptions about cholesterol and blood pressure                                            than 45, hypertension treatment can cost as little as a few hun-
reduction from population-based lifestyle education programs                                         dred dollars per life year gained or can even be cost saving
and given the relatively low cost of the interventions—US$5 to                                       (Johannesson and others 1991).
US$17 per person per year (Tosteson and others 1997)—the                                                 Investigators have reported that primary prevention with
cost-effectiveness of such programs may be reasonable.                                               cholesterol-reducing medications is less attractive overall than
However, the cost-effectiveness ratios of these interventions                                        other interventions, such as hypertension treatment, from a
were sensitive to the cost of the intervention as well as to the                                     cost-effectiveness perspective, although once again this finding
expected reduction in the risk factor. For example, a commu-                                         is likely to differ considerably now that statins are off patent.

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                                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
Reported cost-effectiveness ratios have ranged from US$10,000                           both hypertension and increased cholesterol with all three med-
to US$2 million per life year gained (Hay, Yu, and Ashraf 1999),                        ications. Finally, the effects of combination treatment with a
whereas dietary interventions for cholesterol reduction are more                        beta-blocker, diuretic, statin, and aspirin were modeled for four
favorable, with ratios of around US$2, 000 per quality-adjusted                         groups defined on the basis of absolute risk (10-year probability
life year (QALY) (Prosser and others 2000). For cholesterol treat-                      of a cardiovascular event of 5, 15, 25, or 35 percent).
ment, Prosser and others (2000) find cost-effectiveness ratios of                           Intervention effects were based on systematic reviews of
US$50,000 per QALY for on-patent statins among those at high-                           randomized trials or meta-analyses. Population health effects
est risk (high cholesterol levels and multiple risk factors) and up                     caused by the interventions were based on stochastically simu-
to US$1.4 million per QALY among low-risk females when com-                             lating populations on the basis of age, sex, and risk factor dis-
pared with dietary strategy alone. The cost per life year gained in                     tribution of smoking, hypertension, cholesterol, BMI, and
the primary prevention trial of the West of Scotland Coronary                           smoking in the 14 subregions, both with and without the vari-
Prevention Study among high-risk individuals treated with                               ous treatments to determine the effect. The effects of the inter-
pravastatin was about US$30,000 (Caro and others 1997). Using                           vention were then translated into DALYs using a standard mul-
the same criteria, Downs and others (1998) find that the cost per                       tistate modeling tool. Costs include both program-level costs
life year saved in the Air Force/Texas Coronary Atherosclerosis                         (media, training, and administration) and patient-level costs
Prevention Study cohort with average cholesterol levels was                             (medicines, health care visits, diagnostic tests). All costs were
more than US$100,000.In general,younger and older age groups                            based on a standard ingredients approach and on regional esti-
tend to have the least favorable cost-effectiveness ratios. For                         mations. The costs of CVD events were not included.
younger groups, this finding probably reflects their overall lower                          The results are summarized in table 45.4. The incremental
risk and the many years of treatment required before realizing a                        cost-effectiveness ratios for the strategy assessing absolute risk
benefit. For the elderly, high cost-effectiveness ratios may reflect                    and using the triple combination of beta-blocker, statin, and
other competing causes of death and the delay of up two                                 aspirin with or without the addition of health education and salt
years between treatment and benefit seen in most primary pre-                           legislation ranged from US$138 per DALY saved (absolute risk
vention trials.                                                                         greater than 35 percent) in the Africa E region to US$4,319 per
                                                                                        DALY saved (absolute risk greater than 5 percent) in the Latin
                                                                                        America and the Caribbean B region. These estimates are in
Personal Interventions to Lower Blood Pressure or                                       international or purchasing-power parity dollars (see chapter 15
Cholesterol in Developing Countries                                                     for an explanation). Table 45.4 also shows the approximate
No trials of blood pressure, cholesterol, or body mass lowering                         equivalent costs in U.S. dollars and explains the conversion
have been conducted solely in developing countries. As a result,                        from the WHO-CHOICE estimates. The nonpersonal interven-
we have derived assessments of cost-effectiveness by extrapo-                           tions, including efforts to reduce salt intake in processed foods,
lating from results in developed countries presented earlier.                           were less costly than the personal interventions. Personal
Goldman and others (1991) report that a decline in the cost of                          interventions based on treatment guidelines were cost-
lovastatin by 40 percent, once generic, would result in a roughly                       effective; however, when the strategies for treating high choles-
30 percent reduction in the cost-effectiveness ratio. However,                          terol or hypertension were compared with the absolute-risk
this finding does not take into account that both the underly-                          approach, they were not favorable and were dominated by the
ing epidemiology and the costs can be quite different across                            latter, meaning that the absolute-risk approach of treating those
and within countries and regions.                                                       with a greater than 35 percent risk averted more DALYs and cost
    Murray and others (2003) compare 17 nonpersonal and per-                            less than either the blood pressure or cholesterol strategies. For
sonal health service interventions or combinations of interven-                         an example of a country-specific analysis, see box 45.1.
tions in the 14 epidemiological subregions defined by the                                   Several recent publications have suggested that combination
World Health Organization (WHO) as part of its Choosing                                 treatments of medications to lower blood pressure, statin,
Interventions That Are Cost-Effective (WHO-CHOICE) initia-                              aspirin, and perhaps other agents such as folate could more
tive. The nonpersonal interventions included health education                           than halve cardiovascular risk (Wald and Law 2003; WHO
through the mass media and legislative efforts to reduce salt                           2002; Yusuf 2002). This suggestion is especially relevant for
intake, improve blood pressure generally, and reduce cholesterol                        developing countries, given that suitable components are all
and obesity levels. The personal interventions included treat-                          now off patent. Good evidence indicates that single-pill combi-
ment with statins of those above two different cholesterol-level                        nations increase adherence to drug regimens (Connor, Rafter,
thresholds (greater than 6.2 mmol/l or greater than 5.7 mmol/l),                        and Rodgers 2004) and reduce supply and transport costs. We
treatment with beta-blockers and diuretics of those above two                           used a Markov model to evaluate the cost-effectiveness of such
different hypertension thresholds (greater than 160 mmHg or                             a hypothetical pill or combination packaging of the individual
greater than 140 mmHg), and treatment of individuals with                               medications. We modeled the effect of a pill that included half

860 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

                                               ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 45.4 Comparison of the Cost-Effectiveness of Absolute Risk with Treatment According to Either Blood Pressure or Lipid
Targets Alone in Addition to Population-Based Strategies, Selected WHO Regions

                                                                                                                                                             Incremental cost-effectiveness
                                                                                                                                                             ratio (cost/DALY saved)a

  Region                                              Strategy                                                   Risk (percent)                           International $                            US$
  Africa E                                            Prevention (SL and/or HE)                                                                             Dominated
                                                      Targeted risk factors                                                                                 Dominatedb
                                                      Absolute risk (TRI)                                                35                                       138                                  42
                                                                                                                         25                                       778                                 295
                                                                                                                         15                                     1,445                                 639

  Latin America and the                               Prevention (SL)                                                                                             127                                  65
  Caribbean B                                         Prevention (SL         HE)                                                                                  145                                  74
                                                      Targeted risk factorsc                                                                                Dominatedb
                                                      Absolute riskd (TRI           SL   HE)                             35                                       286                                 178
                                                                                                                         25                                     1,598                              1,058
                                                                                                                         15                                     2,391                              1,664
                                                                                                                          5                                     4,319                              3,075

  Southeast Asia B                                    Prevention (SL)                                                                                               70                                 18
                                                      Prevention (SL         HE)                                                                                  127                                  32
                                                      Targeted risk factorsc                                                                                Dominatedb
                                                      Absolute risk (TRI            SL   HE)                             35                                       301                                 133
                                                                                                                         25                                     1,197                                 578
                                                                                                                         15                                     2,094                              1,120
                                                                                                                          5                                     3,952                              2,233

  Western Pacific B                                   Prevention (SL)                                                                                               97                                 18
                                                      Targeted risk factorsc                                                                                Dominatedb
                                                      Absolute riskd (TRI           SL   HE)                             35                                     1,124                                 423
                                                                                                                         25                                     1,278                                 564
                                                                                                                         15                                     2,092                              1,042
                                                                                                                          5                                     4,028                              2,135

Source: Murray and others 2003.
B low child mortality and low adult mortality; E high child mortality and very high adult mortality; HE health education through the mass media to reduce cholesterol; SL legislation to
decrease the salt content of processed foods, including appropriate labeling and enforcement; TRI treatment with aspirin, beta-blockers, and a statin.
a. Costs of prevention and nondrug costs for treatment according to absolute risk are converted at an estimated regional average ratio of exchange rate to purchasing-power parity rate; drug costs are
not converted, assuming drugs to be imported at world prices. The share of drug costs in total treatment cost, as a function of risk, is taken from the estimates for India in table 45.6 and assumed to be
the same for all regions.
b. Dominated strategies were both less effective and more costly than comparator strategies.
c. Treating SBP greater than 140 mmHg or 160 mmHg or total cholesterol greater than 5.7 mmol/l or 6.2 mmol/l (220 or 240 mg/dlL).
d. Risk refers to 10-year risk of CVD greater than or equal to the number listed.

of the standard doses of hydrochlorothiazide, atenolol, lisino-                                          fits seen from a societal perspective and with the intervention
pril, lovastatin, and aspirin on overall morbidity and mortality                                         run for 10 years. We calculated estimates for one representative
in treating those without prior CVD. We did not include folate                                           country from each region where demographic and risk factor
because no randomized trials had shown that it reduced CVD                                               data existed. Unlike the WHO-CHOICE analysis, this analysis
events at the time of the analysis. The assumptions of the rela-                                         separated use of the intervention according to those with and
tive risk reductions were based on those of Wald and Law                                                 without established CVD. Table 45.5 presents the results.
(2003). The strategies compared were for treating various high-                                              Table 45.6 shows the breakdown of events averted and costs
risk populations (absolute risk for CVD greater than 15, 25, and                                         for India. Even though the absolute numbers differ for other
35 percent over 10 years. We applied the model to a population                                           countries, the relative differences between the different groups
of 1 million adults over the age of 35, with the costs and bene-                                         receiving the “polypill” compared with the groups not receiving

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                                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
      Box 45.1

      Example of Country-Specific Analysis: South Africa

      In another analysis, researchers (Gaziano 2001) compared                                             than 40 percent had an incremental cost-effectiveness ratio
      the approach based on absolute risk with blood pressure                                              of US$700 per QALY gained compared with no treatment.
      guidelines in South Africa. The analysis used country-                                               The absolute risk of CVD greater than 30, 20, and 15 per-
      specific epidemiology and, where available, applied local                                            cent had larger and increasing cost-effectiveness ratios.
      cost data. The study compared six strategies for initiating                                          Treatments based on the 1995 South African guidelines and
      drug treatment—two different blood pressure levels                                                   the Joint National Commission VI guidelines were both
      (160/95 mmHg and 140/90 mmHg) and four different                                                     more costly and resulted in fewer QALY gains than the 15
      levels of absolute CVD risk over 10 years (40, 30, 20, and                                           percent absolute-risk strategy and were therefore domi-
      15 percent)—to a strategy of no treatment. The method-                                               nated by the less costly absolute-risk treatment strategies.
      ology differed from the WHO-CHOICE study because of                                                     Furthermore, the results showed that the cost-
      the availability of local data. Data on diabetes prevalence                                          effectiveness ratios were quite sensitive to the costs of
      were included to further refine risk estimates. Also the                                             treatment for hypertension, especially medication costs.
      actual mix of medications was used to assess costs with                                              Further analysis revealed a threshold point for an annual
      actual current drug-use patterns, which included the use                                             treatment cost of US$53. Below this threshold, the 40 per-
      of some nongeneric medications.                                                                      cent absolute-risk strategy cost less and increased the
         The table displays the results. The four absolute-risk                                            number of life years gained compared with the no pri-
      strategies had the four lowest incremental cost-effectiveness                                        mary prevention strategy and is therefore cost saving. In
      ratios.The strategy of initiating antihypertensive therapy for                                       South Africa, annual treatment with diuretics and beta-
      those individuals with a predicted 10-year CVD risk greater                                          blockers could be provided for less than US$40.

      Incremental Cost-Effectiveness Ratios for Selected Hypertension Management Strategies over 10 Years, South Africa

                                                                                                                                       Incremental cost-effectiveness ratioa

         Treatment                                                                                                           US$/QALY                                   US$/life year savedb

         No treatment                                                                                                            n.a.                                               n.a.
         Absolute risk of CVD 40 percent                                                                                         700                                                900
         Absolute risk of CVD 30 percent                                                                                       1,600                                              2,100
         Absolute risk of CVD 20 percent                                                                                       4,900                                              6,700
         Absolute risk of CVD 15 percent                                                                                      11,000                                             18,000
         Target level 160/95 mmHg (1995 South African guidelines)c                                                          Dominatedd                                         Dominatedd
         Target level 140/90 mmHg (Joint National Commission VI guidelines)                                                 Dominatedd                                         Dominatedd

      Source: Gaziano and others 2005.
      n.a. not applicable.
      a. Each strategy’s costs and effects are compared with those of the preceding less costly strategy.
      b. Total and incremental life years not shown.
      c. Compared with an absolute risk of CVD greater than 15 percent because the 1995 South African guidelines are dominated by the former.
      d. A dominated strategy is one that is both more expensive and less effective than the preceding strategy to which it is compared.

Table 45.5 Incremental Cost-Effectiveness Ratios of a Multidrug Regimen by World Bank Region Compared with a Baseline of
No Drug Treatment (2001 US$/DALY)

  Region                                                       35 percent risk                          25 percent risk                          15 percent risk                      5 percent risk

  East Asia and the Pacific                                            830                                     1,440                                    2,320                               3,820
  Europe and Central Asia                                              940                                     1,450                                    1,960                               3,620
  Latin America and the Caribbean                                      920                                     1,470                                    2,420                               3,740
  Middle East and North Africa                                         720                                     1,290                                    2,190                               4,030
  South Asia                                                           670                                     1,250                                    1,932                               3,020
  Sub-Saharan Africa                                                   610                                     1,170                                    1,920                               2,960

Source: Authors’ calculations.
Note: The regimen includes aspirin, a beta-blocker, a thiazide diuretic, an angiotensin-converting enzyme inhibitor, and a statin. The risk refers to a 10-year risk of CVD.

862 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

                                                           ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 45.6 Polypill Cost-Effectiveness Estimates for a Population of 1 Million Adults at Varying Levels of Risk for CVD Treated
for 10 Years in India

                                                                                                                   Absolute risk of a CVD event over 10 years

                                                                     Comparison with                     35                    25                15                  5
  Costs and effects                                                  no polypill                       percent               percent           percent             percent

  Total cost (2001 US$ millions)                                             23.5                          34.5                   51.4           92.2                205.2
  Profile of total costs
  Percentage attributable to inpatient stay                                  12.0                           6.0                    3.0            1.0                  0.3
  Percentage attributable to ambulatory care                                   0                           29.0                   40.0           49.0                 54.0
  Percentage attributable to labor                                           75.0                          36.0                   21.0            9.0                  2.0
  Percentage attributable to pharmaceuticals                                   0                           23.0                   31.0           38.0                 42.0
  Percentage attributable to laboratory expenses                             12.0                           6.0                    3.0            1.0                  0.0
  Number of myocardial infarction cases averted                               n.a.                      10,200                   14,400        21,300                31,800
  Number of stroke cases averted                                              n.a.                        5,200                   7,000        12,400                19,600
  Number of coronary heart disease deaths averted                             n.a.                      10,500                   13,500        19,600                25,900
  Number of stroke deaths averted                                             n.a.                        5,900                   7,500        10,500                14,200
  Number of life years saved                                                  n.a.                      39,000                   51,000        67,000                98,000
  Number of DALYs gained                                                      n.a.                      41,000                   57,000        86,000              134,000
  Incremental cost-effectiveness (US$/DALY)                                   n.a.                          300                    990           1,500                2,430

Source: Authors’ calculations.
n.a. not applicable.
a. Each strategy compared with no polypill.

it are similar for all countries. Although the total costs for treat-                        Distributional and Equity Consequences
ing lower-risk patients increase, so do the benefits, and the                                Failing to translate available evidence from industrial countries
overall incremental cost-effectiveness ratio remains relatively                              about CVD prevention strategies into practicable solutions for
favorable. The proportion of costs shifts away from those                                    developing countries would have clear equity implications,
attributable to hospital care when no primary prevention is ini-                             especially when CVD is a large and growing problem in devel-
tiated to costs attributable to ambulatory care and pharmaceu-                               oping countries and when safe and effective interventions that
ticals when more lower-risk patients are treated.                                            were once extremely expensive are now available for a few cents
                                                                                             a day. Because access to cardiovascular health care in develop-
Interventions to Reduce Bodyweight                                                           ing countries often depends on patients’ ability to pay, the poor
No large-scale randomized trials of weight reduction as an iso-                              would stand to benefit the most from a low-cost intervention
lated intervention are available on which to base estimates of                               such as a polypill.
the benefits of weight loss in lowering the risk of coronary                                     Some see CVD as exclusively a disease of the affluent in
heart disease. Thus, costs per life year saved would have to be                              developing countries; however, in many developing coun-
modeled to project benefits. In one such analysis, a school-                                 tries, the transition of CVD to becoming a disease of the
based educational program to reduce obesity among middle                                     poor has already begun—a transition already seen in devel-
school students reported a cost of US$4,300 per QALY (L.                                     oped countries around the world. A recent analysis of the
Wang and others 2003). However, this analysis assumed that                                   distribution of major cardiovascular risks by poverty levels
the weight loss would be maintained throughout adulthood,                                    has shown that many cardiovascular risks already affect the
but the high relapse rates found in weight reduction studies                                 poor in the world’s poorest countries (Ezzati and others 2004;
do not bear out this assumption (Serdula and others 1999).                                   WHO 2002). Combating the trend requires highly effective,
Further research is needed to evaluate the benefits of                                       low-cost solutions relevant for most or all of those at risk in
weight reduction in relation to reducing CVD events and the                                  developing countries, in contrast to the investments in high-
long-term sustainability of weight loss before reliable cost-                                tech treatment interventions that have commonly occurred to
effectiveness estimates can be made.                                                         date.

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                                              ©2006 The International Bank for Reconstruction and Development / The World Bank
ECONOMIC BENEFITS OF INTERVENTION                                                           new paradigm and its advantages over traditional para-
                                                                                            digms, such as hypertension treatment. One barrier to
In the cost-effectiveness analyses, most of the gains are reported                          adopting preventive therapy based on absolute risk has
in cost savings either from particular interventions, such as                               been its relative complexity compared with dichotomous
decreased hospitalizations resulting from the improved combi-                               diagnosis-based strategies, such as hypertension–no
nation therapy of the polypill, or from a more efficient means                              hypertension.
of screening those at highest risk through an absolute-risk                               º Develop simple methods for predicting absolute risk
approach. Those who do not die from the sequelae of poorly                                  using straightforward, inexpensive, direct measures, such
controlled risk factors for CVD suffer from serious chronic ill-                            as physical examination, clinical history, and on-site tests.
ness, such as stroke and congestive heart failure. Those chronic                            These methods would likely involve low-cost algorithms
diseases can result in significant impairments, thereby prevent-                            completed by a multipurpose health care worker involv-
ing those affected from continuing to work and sometimes also                               ing, for example, the collection of data on age, sex, tobacco
requiring the services of other family members, who them-                                   use, blood pressure, waist circumference, and urine
selves end up having to leave the workforce. Further losses                                 dipstick results. The development of different levels of
resulting from disability include the loss of wages for major                               screening protocol may also be needed in certain settings.
wage earners and their families and the state’s losses in terms of                        º Calibrate existing algorithms for different disease rates
disability compensation. Leeder and others (2004) estimate                                  and cardiovascular profiles in developing countries.
that in 2000 the cost of CVD disability payments in South                                 º Develop treatment algorithms that can easily be adopted
Africa equaled US$70 million.                                                               in resource-poor settings by, for example, multipurpose
   However, many other indirect economic gains or losses are                                health care workers.
not included in the economic analysis, such as gains or losses in                         º Develop methods for predicting absolute risk on the
productivity. Leeder and others (2004) report that, at current                              basis of the probability of lost healthy life years as well as
CVD mortality rates, the potential productive years of life lost                            the probability of a clinical event. This strategy could
(defined as those years between the ages of 35 and 64) will                                 mean developing an index of healthy life years at risk
nearly double by 2030. Those later adult working years are par-                             from a cardiovascular event in the next five years, which
ticularly important, given the many years of investment in skills                           would require taking case fatalities into consideration
through formal education and experience that would be lost.                                 and discounting. A major barrier to adopting a strategy
Preventing CVD would therefore improve the size and skills of                               based on absolute risk has been the absence of a time-
the workforce and would therefore aid economic development.                                 based measure and, hence, the equal value placed on pre-
For those reasons, the Commission for Macroeconomics and                                    venting an event at a young and at an old age.
Health has recommended that any intervention that costs less                            • Develop and evaluate combination treatments:
than triple a country’s per capita gross domestic product be                              º Carry out new research on the ideal combinations for
regarded as cost-effective (WHO 2001). Many of the combina-                                 different patient groups and populations at different
tion cardiovascular preventive approaches outlined in this                                  stages of the health transition. Local initiatives would be
chapter comfortably satisfy that criterion.                                                 needed to determine the ideal combination of medica-
                                                                                            tions based principally on cost, tolerability, and ability to
RESEARCH AND DEVELOPMENT AGENDA                                                             lower risk-factor levels. One default set of interventions
                                                                                            could be an angiotensin-converting enzyme inhibitor
The cost-effectiveness data reviewed in this chapter indicate that                          (for example, enalapril or lisinopril); a diuretic (such as
the best use of resources for personal-level interventions for                              hydrochlorothiazide or chlothalidone); a statin (for
preventing CVD mediated by high blood pressure, cholesterol,                                instance, simvastatin or lovastatin); and low-dose
and bodyweight would be combination medications targeted to                                 aspirin.
those at high absolute risk. This strategy represents a consider-                         º Measure the potential costs and benefits of adding other
able departure from existing paradigms, such as hypertension                                active agents, such as vitamins or diabetic medications.
treatment. Research and development is therefore required in                              º Quantify the extent of improved access, acceptability,
several areas to develop, implement, and evaluate this strategy.                            and tolerability for people with symptomatic vascular
This research could include several themes as follows:                                      disease who have established indications for those
• Refine absolute risk-based treatment in developing country                              º Evaluate the benefits and costs in developing countries
  settings:                                                                                 with large-scale clinical trials and demonstration
  º Evaluate optimal communications to the public and to                                    projects, both among patients who have established
     health professionals that explain the rationale for this                               indications (compared with usual care) and among those

864 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

                                               ©2006 The International Bank for Reconstruction and Development / The World Bank
     who do not have clear indications but are still at high risk               REFERENCES
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868 | Disease Control Priorities in Developing Countries | Anthony Rodgers, Carlene M. M. Lawes, Thomas Gaziano, and others

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                                                                                     Chapter 46

                                                        Tobacco Addiction
                                                                                Prabhat Jha, Frank J. Chaloupka, James Moore, Vendhan
                                                                                Gajalakshmi, Prakash C. Gupta, Richard Peck, Samira Asma,
                                                                                and Witold Zatonski

Cigarette smoking and other forms of tobacco use impose a                       on the uniquely addictive properties of nicotine. A review of the
large and growing global public health burden. Worldwide,                       effectiveness of tobacco-control policies in reducing tobacco ini-
tobacco use is estimated to kill about 5 million people annually,               tiation and in increasing cessation follows. A cost-effectiveness
accounting for 1 in every 5 male deaths and 1 in 20 female                      analysis of these interventions is provided. Finally, the con-
deaths of those over age 30. On current smoking patterns,                       straints to implementing tobacco-control policies are discussed.
annual tobacco deaths will rise to 10 million by 2030. The 21st
century is likely to see 1 billion tobacco deaths, most of them                 SMOKING TRENDS
in low-income countries. In contrast, the 20th century saw
100 million tobacco deaths, most of them in Western countries                   Tobacco use, in both smoked and nonsmoked forms, is com-
and the former socialist economies.                                             mon worldwide. This chapter focuses on smoked tobacco,
    Hundreds of millions of premature tobacco deaths could                      chiefly cigarettes and bidis (tobacco hand rolled in the leaf of
be avoided if effective interventions were widely applied in                    another plant, temburi, which is popular in India and parts of
low- and middle-income countries. Numerous studies from                         Southeast Asia), because smoked tobacco is more common—
high-income countries and a growing number from low- and                        accounting for about 65 to 85 percent of all tobacco produced
middle-income countries provide robust evidence that tobacco                    worldwide (WHO 1997)—and causes more disease and more
tax increases, timely dissemination of information about the                    diverse types of disease than does oral tobacco use.
health risks of smoking, restrictions on smoking in public and
workplaces, comprehensive bans on advertising and promo-                        Prevalence
tion, and increased access to cessation therapies are effective in              A systematic review of 139 studies on adult smoking prevalence
reducing tobacco use and its consequences. Cessation by the                     (Jha and others 2002) found that more than 1.1 billion people
1.1 billion current smokers is central to meaningful reductions                 worldwide smoke, with about 82 percent of smokers residing
in tobacco deaths over the next five decades. New analyses pre-                 in low- and middle-income countries. Table 46.1 provides an
sented here find that higher tobacco taxes could prevent 3 mil-                 update of these estimates for the population in 2000. Globally,
lion tobacco deaths by 2030 among smokers alive today.                          male smoking far exceeds female smoking, with a smaller gen-
Reduced uptake of smoking by children would yield benefits                      der difference in high-income countries. Smoking prevalence is
chiefly after 2050. Price and non-price interventions are, for the              highest in Europe and Central Asia, where 35 percent of all
most part, highly cost-effective.                                               adults are smokers.
    This chapter begins with an overview of smoking trends and                     While overall smoking prevalence continues to increase in
tobacco’s health consequences, followed by a discussion of the                  many low- and middle-income countries, many high-income
economic rationale for government intervention, with a focus                    countries have witnessed decreases, most clearly in men. A


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 46.1 Estimated Smoking Prevalence (by Gender) and Number of Smokers, 15 Years of Age and Older, 2000

                                                           Smoking prevalence (percent)                                            Total smokers

  World Bank region                               Males                 Females                  Overall                Millions      Percentage of all smokers

  East Asia and the Pacific                         63                       5                     34                      429                     38
  Europe and Central Asia                           56                     17                      35                      122                     11
  Latin America and the Caribbean                   40                     24                      32                       98                     9
  Middle East and North Africa                      36                       5                     21                       37                     3
  South Asia                                        32                       6                     20                      178                     15
  Sub-Saharan Africa                                29                       8                     18                       56                     6
  Low- and middle-income economies                  49                       8                     29                      920                     82
  High-income economies                             37                     21                      29                      202                     18

Source: Authors.

study in 36 mostly Western countries, from early 1980 to the                             health and population policy. Thus, the salient aspects of
mid 1990s, suggested that the decrease in smoking prevalence                             tobacco epidemiology are outlined in this section.
observed among men was caused by the higher prevalence in
younger age groups of those who have never smoked. Among                                 Key Messages for the Individual Smoker
women, there was little overall change in smoking prevalence                             More than 50 years of epidemiology on smoking-related dis-
because the increasing prevalence of smokers in younger                                  eases have led to three key messages for individual smokers
cohorts counterbalanced increasing cessation in older age                                worldwide (Doll and others 2004; Peto and others 2003).
groups (Molarius and others 2001).
                                                                                         • The eventual risk of death from smoking is high, with about
Cessation                                                                                  one-half to two-thirds of long-term smokers eventually
Ex-smoking rates are a good measure of cessation at a popula-                              being killed by their addiction.
tion level. In some high-income countries, the prevalence rates                          • These deaths involve a substantial number of life years for-
of ex-smokers have increased over the past two to three                                    gone. About half of all tobacco deaths occur at ages 35 to 69,
decades. For example, in the United Kingdom, smoking preva-                                resulting in the loss of about 20 to 25 years of life, compared
lence among males over age 30 fell from 70 percent in the 1950s                            with the life expectancy of nonsmokers.
to 30 percent in 2000; female smoking prevalence fell from 40                            • Cessation works: those adults who quit before middle age
to 20 percent over the same period. Much of the decrease arose                             avoid almost all the excess hazards of continued smoking.
from cessation. Today, two times as many ex-smokers as smok-
ers exist among those age 50 or over. Currently, 30 percent of                               Worldwide, about 80 percent of deaths among the 2.7 bil-
the U.K. male population is made up of former smokers (Peto                              lion adults over age 30 involve vascular, respiratory, or neoplas-
and others 2000). Polish male cessation rates have also                                  tic disease. Smoking is associated with an increase in the
increased, partly because of control programs. One of every                              frequency of many of these diseases, although important dif-
four adult Polish males described himself as an ex-smoker                                ferences exist between and across populations. The following
(Zatonski and Jha 2000). In contrast, the prevalence of male ex-                         discussion focuses on the consequences of smoking on adult
smokers in most developing countries is low: 10 percent in                               mortality. Detailed epidemiological reviews of worldwide mor-
Vietnam, 5 percent in India, and 2 percent in China (Jha and                             tality from smoking are found elsewhere (C. Gajalakshmi and
others 2002). Even those low figures may be falsely elevated                             others 2000; V. Gajalakshmi and others 2003; Gupta and Mehta
because they include people who quit because either they were                            2000; Liu and others 1998; Niu and others 1998; Peto and
too ill to continue or they had early symptoms of tobacco-                               others 1994).
related illness (Martinson and others 2003).
                                                                                         Current Mortality and Disability from Smoking

HEALTH CONSEQUENCES OF SMOKING                                                           Recent updates of indirect estimates of global tobacco mortality
                                                                                         (Ezzati and Lopez 2003; M. Ezzati, personal communication,
The health consequences of smoking are often assumed to be                               November 2004) indicate that in 2000, 5.0 million premature
widely understood. In fact, ignorance of the magnitude of                                deaths were caused by tobacco. About half (2.6 million) of
tobacco hazards is widespread in terms of both individual                                those deaths were in low-income countries. Males accounted

870 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 46.2 Tobacco Mortality and Total DALYs by Gender, 2000

                                                                                     Tobacco deaths                                                                Total DALYs

  World Bank region                                                    Males                                Females                                 Males                               Females

  East Asia and the Pacific                                               829                                   274                                 13,116                               4,128
  Europe and Central Asia                                                 754                                   161                                 12,407                               2,686
  Latin America and the Caribbean                                         177                                    97                                  2,789                               1,613
  Middle East and North Africa                                             97                                    28                                  1,676                                 554
  South Asia                                                              768                                   187                                 12,397                               3,285
  Sub-Saharan Africa                                                      105                                    66                                  1,659                               1,091
  Low- and middle-income economies                                      2,730                                   813                                 44,044                              13,357
  High-income economies                                                   929                                   548                                 12,304                               6,866
  World                                                                 3,659                                 1,361                                 56,347                              20,222

Source: Ezzati and Lopez 2003; Mathers and others 2006.
Note: The terms high-income and former socialist economies as used in the text correspond roughly to high-income and Europe and Central Asia regions using the World Bank classification. Low-income
countries corresponds roughly to East Asia and the Pacific, Latin America and the Caribbean, Middle East and North Africa, South Asia, and Sub-Saharan Africa.

for 3.7 million deaths, or 72 percent of all tobacco deaths.                                         1990. Similarly, a large increase in female lung cancer at young
About 60 percent of male and 40 percent of female tobacco                                            ages was avoided in the United Kingdom, but female lung cancer
deaths were of middle-aged persons (ages 35 to 69).                                                  at young ages continues to rise in France.
   In high-income countries and former socialist economies,                                              Future increases in tobacco deaths worldwide are expected
the 1 million middle-aged male tobacco deaths were largely                                           to arise from increased smoking by males in developing coun-
composed of cardiovascular disease (0.45 million) and lung                                           tries and by women worldwide. Such increases are a product of
cancer (0.21 million). In contrast, in low-income countries, the                                     population growth and increased age-specific tobacco mortali-
leading causes of death among the 1.3 million male tobacco                                           ty rates, the latter relating to both smoking duration and the
deaths were cardiovascular disease (0.4 million), chronic                                            amount of tobacco smoked. Peto and others (1994) have made
obstructive pulmonary disease (0.2 million), other respiratory                                       the following calculation: if the proportion of young people
disease (chiefly tuberculosis, 0.2 million), and lung cancer                                         taking up smoking continues to be about half of men and one-
(0.18 million). The specific numbers of deaths from tobacco                                          tenth of young women, there will be about 30 million new
and of total disability-adjusted life years (DALYs) by gender                                        long-term smokers each year. As previously noted, epidemio-
and World Bank region are shown in table 46.2. Disability esti-                                      logical studies in developed and developing countries suggest
mates are not discussed here; however, disability is highly cor-                                     that half of these smokers will eventually die from smoking.
related with mortality in most settings.                                                             However, if we conservatively assume that “only” about one-
                                                                                                     third of smokers die as a result of smoking, then smoking will
Past and Future Trends in Mortality                                                                  eventually kill about 10 million people a year. Thus, for the
In high-income and former socialist economies with more                                              25-year period from 2000 to 2025, there would be about 150
complete and reliable mortality statistics, one can measure                                          million tobacco deaths, or about 6 million deaths per year on
the effects of increased smoking prevalence and subsequent                                           average; from 2025 to 2050, there would be about 300 million
decreases that have been observed among large numbers of                                             tobacco deaths, or about 12 million deaths per year.
adults. These changes are best documented by examining lung                                              Further estimations are more uncertain, but current smok-
cancer mortality rates among young adults because lung cancer                                        ing trends and projected population growth indicate that from
is not often misclassified with other causes of death at young                                       2050 to 2100 there will be an additional 500 million tobacco
ages and it is almost entirely attributable to smoking.                                              deaths. These projections for the next three to four decades are
                                                                                                     comparable to retrospective and early prospective epidemiolog-
Age-Standardized Lung Cancer Mortality Rates                                                         ical studies in China (Liu and others 1998; Niu and others 1998),
Age-standardized male lung cancer rates at ages 35 to 44 per                                         which suggest that annual tobacco deaths will rise to 1 million
100,000 men in the United Kingdom had fallen from 18 in 1950 to                                      before 2010 and to 2 million by 2025, when the young adult
4 by 2000. In contrast, comparable French male lung cancer rates                                     smokers of today reach old age. Similarly, results from a large
show the reverse pattern (Peto and others 2003; figure 46.1). In                                     retrospective study in India suggest that 1 million annual deaths
France,the increase in smoking occurred some decades later than                                      can be expected from male smokers by 2025 (V. Gajalakshmi
in the United Kingdom, and declines in smoking began only after                                      and others 2003). With other populations in Asia, Eastern

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                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
                                 a. United Kingdom                                                                                   b. France

Death rate/100,000 men, age standardized a                                                  Death rate/100,000 men, age standardized a

18                                                                                          18

16                                                                                          16

14                                    Males                                                 14                                                   Males
12                                                                                          12

10                                                                                          10

 8                                                                                           8

 6                                                                                           6

 4                                      Females                                              4
 2                                                                                           2

 0                                                                                           0
  1950           1960            1970             1980           1990            2000         1950            1960            1970               1980         1990            2000
Source: Peto and others 2003.
a. Mean of annual rates in component five-year age groups (35–39, 40–44).

Figure 46.1 Changes in Lung Cancer Mortality at Age 35 to 44 in the United Kingdom and France, 1950–99

Europe, Latin America, the Middle East, and (less certainly)                               Tobacco deaths (million)
Sub-Saharan Africa showing similar growth in population and                                                                                                                   520
                                                                                           500                                                                                500
age-specific tobacco death rates, the estimate of some 450 mil-
lion tobacco deaths over the next five decades appears plausible.
Almost all of these deaths will be among current smokers.                                  400

Benefits of Cessation
Current tobacco mortality statistics reflect past smoking behav-                           200
ior, given the long delay between the onset of smoking and                                                                                              190
the development of disease. The prevention of a substantial
proportion of these tobacco deaths before 2050 requires adult
cessation. For example, halving the per capita adult consump-
tion of tobacco by 2020 (akin to the declines in adult smoking                                0
                                                                                               1950                    2000                        2025                   2050
in the United Kingdom) would avert about 180 million tobacco
deaths. Continuing to reduce the percentage of children who                                              Baseline                           If proportion of young adults
start to smoke will prevent many deaths, but its main effect will                                        If adult consumption               taking up smoking halves
                                                                                                         halves by 2020                     by 2020
be on mortality rates in 2050 and beyond (figure 46.2; Jha and
Chaloupka 2000a; Peto and Lopez 2001).                                                     Source: Jha and Chaloupka 2000a; Peto and Lopez 2001.
    Substantial evidence indicates that smoking cessation                                  Note: Peto and others (1994) estimate 60 million tobacco deaths between 1950 and 2000
                                                                                           in industrial countries. This figure estimates an additional 10 million tobacco deaths
reduces the risk of death from tobacco-related diseases. Among                             between 1990 and 2000 in developing countries. The figure also assumes no tobacco
doctors in the United Kingdom, those who quit smoking before                               deaths before 1990 in developing countries and minimal tobacco deaths worldwide
                                                                                           before 1950. Projections for deaths from 2000 to 2050 are based on Peto and Lopez (2001).
the onset of major disease avoided most of the excess hazards
of smoking (Doll and others 2004). The benefits of quitting                                Figure 46.2 Tobacco Deaths in the Next 50 Years under Current
were largest in those who quit before middle age (between ages                             Smoking Patterns
25 and 34 years) but were still significant in those who quit later
(between ages 45 and 54 years).                                                            have never smoked. In the United Kingdom, among those
    Cessation before middle age avoids more than 90 percent                                who stopped smoking, the risk of lung cancer fell steeply with
of the lung cancer risk attributable to tobacco, with quitters                             time since cessation. For men who stopped at ages 60, 50, 40,
possessing a pattern of survival similar to that of persons who                            and 30, the cumulative risks of lung cancer by age 75 were

872 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
  Lung cancer mortality (percent)                                                      • The addictive nature of tobacco is underappreciated and
                                                                                         poorly understood. Although general awareness of risks is
  15                                                            smoking                  better in high-income countries, many people still underes-
                                                                                         timate tobacco’s danger relative to other health risks, and
                                                                                         many smokers fail to fully internalize these risks (Weinstein
  10                                                                                   • Smokers may impose costs on others from passive tobacco
                                                                                         smoke or, more controversially, from higher health care
                                                                                         costs (Lightwood and others 2000; Warner 2003).
                                                                Stopped age 50
   5                                                                                      The reader is referred to more detailed discussions on the
                                                                                       welfare economics of tobacco (Barnum 1994; Jha and others
                                                                Stopped age 30         2000; Peck and others 2000; Warner and others 1995; and
                                                                Never smoked           several background papers in the Disease Control Priorities
                                                                                       Project Working Paper Series). We discuss nicotine addiction
       45                55              65                75
                                  Age                                                  because this newer evidence has profound implications for
                                                                                       explaining smoking behavior and for devising control policies.
  Source: Peto and others 2000.

Figure 46.3 Stopping Works: Cumulative Risk of Lung Cancer
                                                                                       Nicotine Addiction
Mortality in U.K. Males, 1990 rates
                                                                                       Before the landmark 1988 U.S. Surgeon General’s report, which
                                                                                       suggested that cigarettes and other forms of tobacco are addic-
                                                                                       tive and that nicotine is the major agent in tobacco responsible
10 percent, 6 percent, 3 percent, and 2 percent, respectively
                                                                                       for addiction, the prevailing view was that tobacco use was
(Peto and others 2000; figure 46.3). These results have been
                                                                                       largely a voluntary behavior or personal choice (Koop 2003).
supported by a recent multicenter study of men in four
                                                                                       Since that time, clinicians, behavioral scientists, researchers,
European countries; for men who quit smoking at age 40, the
                                                                                       and public health experts have increasingly recognized manu-
study found that the excess lung cancer risk avoided was
                                                                                       factured tobacco products as some of the most addictive and
85 percent, 91 percent, and 80 percent in the United Kingdom,
                                                                                       deadly dependence-producing substances available. Although
Germany, and Italy, respectively (Crispo and others 2004).
                                                                                       numerous factors have been identified that can contribute to
Smoking cessation is uncommon in most developing countries,
                                                                                       the reinforcement of the smoking habit—for example, the syn-
but some evidence exists that, among Chinese men, quitting
                                                                                       ergistic and independent effects of other compounds in tobacco
also reduces the risks of total and vascular mortality (Lam and
                                                                                       smoke (such as tar and acetaldehyde) or the sensory and envi-
others 2002).
                                                                                       ronmental stimuli associated with smoking (such as tobacco
                                                                                       advertising)—little debate exists that nicotine is a significant
                                                                                       contributor to the development and maintenance of the smok-
RATIONALE FOR GOVERNMENT INTERVENTION                                                  ing habit (Markou and Henningfield 2003). In most aspects of
                                                                                       dependence, nicotine is on par with other powerfully addictive
In addition to the public health burden caused by tobacco,
                                                                                       drugs, such as heroin and cocaine. Newer evidence has con-
an economic rationale exists for government to intervene to
                                                                                       verged on the following key points.
reduce tobacco use:

• Consumers have inadequate information about the health                               Biological Aspects. Nicotine is a psychoactive drug that trig-
  consequences of tobacco use (Jha and others 2000; Warner                             gers a cascade of neurobiological events in the reward areas of
  and others 1995). Specifically, the decision to initiate smok-                       the brain and throughout the body that can, in turn, act in con-
  ing is made primarily by youths, whose ability to make fully                         cert to reinforce tobacco use (Markou and Henningfield 2003).
  informed, appropriately forward-looking decisions is                                 Even a short-term exposure to nicotine has been shown to
  questioned by society in many different contexts (minimum                            induce long-lasting changes of the excitatory input into the
  ages for drinking, driving, and voting, for instance). In                            brain’s reward system, which may be an important early step in
  industrial countries, about 80 percent of adult smokers                              the path to addiction (Laviolette and van der Kooy 2004).
  begin smoking before age 20. Even if children and young                              Notably, in some experimental models, if nicotine’s neurobio-
  adults have information on future risks, they tend to dis-                           logical effects are blocked pharmacologically, or if nicotine is
  count that future risk greatly.                                                      removed from cigarette smoke, smoking eventually ceases

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                                        ©2006 The International Bank for Reconstruction and Development / The World Bank
(Jarvis 2004). The overwhelming property of nicotine that                                smoking choices, the net economic costs of tobacco are pro-
leads to its frequent use is the occurrence of nicotine with-                            foundly negative (Barnum 1994; Peck and others 2000). While
drawal, for which cigarette smoke provides rapid relief. Though                          some of the methods for such costing have been disputed,
each individual differs greatly in his or her sensitivity to nico-                       newer economic evidence supports the idea that widespread
tine dependence, evidence suggests that most adults are sus-                             hazards of tobacco use lead to major economic costs. Jamison,
ceptible to the biological effects of nicotine and tobacco                               Lau, and Wang (2005) have outlined that male survival explains
(Picciotto 2003).                                                                        income growth independent of changes in physical capital,
                                                                                         education, fertility, economic openness, and technical progress.
Psychological Aspects. In addition to the unique neurobiolo-                             Thus, if adult male survival in the former socialist economies
gy of nicotine, the ready availability of tobacco influences the                         of Europe had been that of high-income countries, annual
uptake of smoking as well as the development and mainte-                                 growth rates over the past three decades would have been about
nance of dependence. With illicit drugs, legal and social barri-                         1.4 percent rather than 1 percent, making 1990 per capita
ers constantly test a user’s drive to consume the drug. In                               income about 12 percent higher, or an absolute value of
contrast, a smoker is presented with nearly ubiquitous                                   US$140 billion. The chief determinant of the mortality gap
opportunities and frequent cues to both purchase and use                                 between the former socialist economies and high-income
tobacco because of mass marketing and promotion of tobacco                               countries from 1960 to 1990 is smoking (Peto and others 1994;
(Shiffman and West 2003). Young people, who are attracted                                Zatonski and Jha 2000). More recent economic studies that
to many risk behaviors, such as fast driving or binge drinking,                          have put a value on “statistical life” suggest that smoking cessa-
do not “learn” from early smoking in the way that most young                             tion generates huge benefits. For example, Murphy and Topel
people become safer drivers and moderate drinkers as adults                              (2003) find that in the United States, the value of reduced mor-
(Jha and others 2000; O’Malley, Bachman, and Johnston 1988).                             tality from all causes between 1970 and 1998 amounted to
                                                                                         US$2.6 trillion per year, or half of gross domestic product
Economics. The traditional economic formulation of costs                                 (GDP) growth during the period. Fully US$1.1 trillion per year
and benefits tends not to take into account the unique proper-                           arose from reduced heart disease, of which at least one-third
ties of addiction (see Chaloupka, Tauras, and Grossman 2000                              was from reduced smoking and saturated fat in diets (Cutler
for a review). Newer models have begun to incorporate factors                            and Kadiyala 2003; see chapter 15 for a fuller discussion on the
such as lack of information, regret, and addiction itself. One                           economic benefits of disease control).
key innovation by Gruber and Koszegi (2001, 2002) permits
smokers to be time inconsistent, meaning that, given prefer-                             INTERVENTIONS TO REDUCE DEMAND
ences, smokers would make different decisions at different
                                                                                         FOR TOBACCO
points in time. This approach, now widely used within the new
field of behavioral economics, admits conflict between what                              Numerous studies, mostly from high-income countries, have
smokers would like for themselves today and what they would                              examined the effect of interventions aimed at reducing the
like for themselves in the future.                                                       demand for tobacco products on smoking and other kinds of
                                                                                         tobacco use. The small but growing number of studies from
Implications for Control Programs. These newer economic                                  low- and middle-income countries provide useful lessons
models have several implications for control programs. First is                          about differences in the effect of these interventions between
the need for much more aggressive tobacco taxation to deter                              these countries and high-income countries. The following is a
the development of tobacco smoking. Estimates suggest that,                              review of the effect of price and non-price interventions in
in the United States, optimal taxation taking into account                               reducing demand for smoking, including a discussion of each
smoking initiation and nicotine addiction would be at least                              intervention’s effect on initiation and cessation. A more com-
US$1 higher per pack (Gruber 2003; Gruber and Koszegi 2002;                              plete study of the effectiveness of various interventions is avail-
Gruber and Mullainathan 2002). The second implication is                                 able elsewhere (Jha and Chaloupka 2000b).
that the usual assumption that higher taxes reduce the welfare
or satisfaction of continuing smokers may not be true. Higher                            Tobacco Taxation
taxes enhance welfare by acting like an external control device                          Nearly all governments tax tobacco products. However, signifi-
over the time-inconsistent preferences of smokers, which                                 cant differences exist across countries in levels of tobacco taxa-
would reduce the likelihood of smoking initiation.                                       tion. Some of these taxes are specific or per unit taxes; others
    The third implication is that the overall economic benefits                          are expressed as a percentage of wholesale or retail prices (ad
of tobacco control, taking into account addiction, are likely to                         valorem taxes). As illustrated in figure 46.4, taxes tend to be
be substantially positive. Earlier cost-benefit analyses have                            absolutely higher and account for a greater share of the retail
shown that if even modest costs are assigned to uninformed                               price (two-thirds or more) in high-income countries. In

874 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Average price or tax per pack (US$)                 Percentage of tax share          to 13 percent shorter smoking duration or a 3.4 percent higher
3.5                                                                          80      probability of cessation.
                                                                                         Many recent studies from the United States have used
3.0                                                                          70
                                                                                     individual-level data to explore differences in the price elastic-
                                                                             60      ity of cigarette demand by age, with a particular emphasis on
                                                                                     youth and young adults (Chaloupka, Hu, and others 2000; U.S.
2.0                                                                                  DHHS 2000). Given that most smoking behavior becomes
                                                                             40      firmly established during teenage years and young adulthood,
                                                                             30      interventions that are effective in preventing smoking initiation
1.0                                                                                  and the transition to regular, addicted smoking will have sig-
                                                                                     nificant long-term public health benefits. Estimates from these
0.5                                                                          10      recent studies conclude that an inverse relationship exists
                                                                                     between price elasticity and age, with estimates for youth price
  0                                                                          0
       High-income    Upper-middle- Lower-middle-          Low-income                elasticity of demand up to three times those obtained for adults
        countries        income        income               countries                (Gruber 2003; Ross, Chaloupka, and Wakefield 2001). Several
                        countries     countries
                                                                                     recent studies have begun to explore the differential effect of
                     Average price             Percentage                            cigarette prices on youth smoking uptake, concluding that
                     Average tax               of tax share
                                                                                     higher cigarette prices are particularly effective in preventing
Source: Authors.                                                                     young smokers from moving beyond experimentation into
                                                                                     regular, addicted smoking (Emery, White, and Pierce 2001;
Figure 46.4 Average Cigarette Price, Tax, and Percentage of Tax                      Ross, Chaloupka, and Wakefield 2001).
Share per Pack, by Income Group, 1996                                                    In the United Kingdom and the United States, increases in
                                                                                     the price of cigarettes have had the greatest effect on smoking
low- and middle-income countries, taxes are generally much                           among the lowest-income and least educated populations
lower and account for less than half of the final price of ciga-                     (CDC 1994; Townsend, Roderick, and Cooper 1998).
rettes. In the United States, federal and state excise taxes on cig-                 Furthermore, it was estimated that smokers in U.S. households
arettes were one-third lower, in real terms, in 1995 than their                      below median income level are four times more responsive to
peak level of the mid 1960s. However, taxes rose sharply over the                    price increases than smokers in households above median
next eight years and stood at US$1.12 per pack as of 2002.                           income level. In general, estimates of price elasticity for low-
    Well over 100 studies from high-income countries clearly                         and middle-income countries are about double those esti-
demonstrate that increases in taxes on cigarettes and other                          mated for high-income countries, implying that significant
tobacco products lead to significant reductions in cigarette                         increases in tobacco taxes in these countries would be effective
smoking and other tobacco use (Chaloupka, Hu, and others                             in reducing tobacco use.
2000). These reductions reflect the combination of increased
smoking cessation, reduced relapse, lower smoking initiation,
and decreased consumption among continuing tobacco users.                            Restrictions on Smoking
    Studies from Canada, the United Kingdom, the United                              Over the past three decades, as the quantity and quality of
States, and many other high-income countries generally esti-                         information about the health consequences of exposure to
mate that the price elasticity of cigarette demand ranges from                       passive smoking have increased, many governments, especially
   0.25 to 0.50, indicating that a 10 percent increase in                            in high-income countries, have enacted legislation restricting
cigarette prices will reduce overall cigarette smoking by 2.5 to                     smoking in a variety of public places and private worksites. In
5.0 percent (Chaloupka, Hu, and others 2000; U.S. DHHS                               addition, increased awareness of the consequences of passive
2000). Estimates from a limited number of studies from low-                          smoke exposure, particularly to children, has led many work-
and middle-income countries suggest a greater price elasticity                       places and households to adopt voluntary restrictions on
of 0.8 in such countries. Recent studies using survey data                           smoking. Although the intent of those restrictions is to reduce
have concluded that half or more of the effect of price on over-                     nonsmokers’ exposure to passive tobacco smoke, the policies
all cigarette demand results from reducing the number of cur-                        also reduce smokers’ opportunities to smoke. Additional
rent smokers (CDC 1994; Wasserman and others 1991). Higher                           reductions in smoking, especially among youths, will result
taxes increase both the number of attempts at quitting smok-                         from the changes in social norms that are introduced by adopt-
ing and the success of those attempts (Tauras 1999; Tauras and                       ing these policies (U.S. DHHS 1994).
Chaloupka 2003). A study in the United States (Taurus 1999)                             In Western populations, comprehensive restrictions on
suggested that a 10 percent increase in price would result in 11                     cigarette smoking have been estimated to reduce population

                                                                                                                                   Tobacco Addiction | 875

                                      ©2006 The International Bank for Reconstruction and Development / The World Bank
smoking rates by 5 to 15 percent (see review by Woolery, Asma,                           spent US$12.5 billion on advertising and promotion in the
and Sharp 2000) and can also lead to changes in social norms                             United States alone, the highest spending level reported to date
regarding smoking behavior, especially among youths. As with                             (U.S. Federal Trade Commission 2004). Tobacco advertising
higher taxes, these restrictions reduce both the prevalence of                           efforts worldwide include traditional forms of advertising on
smoking and cigarette consumption among current smokers.                                 television, radio, and billboards and in magazines and newspa-
Smoking bans in workplaces generally reduce the quantity of                              pers as well as favorable product placement; price-related
cigarettes smoked by 5 to 25 percent and reduce prevalence                               promotions, such as coupons and multipack discounts; and
rates by up to 20 percent (Levy, Friend, and Polishchuk 2001).                           sponsorship of highly visible sporting and cultural events.
No-smoking policies were most effective when strong social                                   Numerous econometric studies, largely from the United
norms against smoking helped make smoking restrictions self-                             Kingdom and the United States, have explored the relationship
enforcing.                                                                               between cigarette advertising and promotional expenditure
                                                                                         and cigarette demand. In general, these studies have resulted in
Health Information and Counteradvertising                                                mixed findings, with most studies concluding that advertising
The 1962 report by the British Royal College of Physicians and                           has a small positive effect on demand (Chaloupka, Hu, and
the 1964 U.S. Surgeon General’s Report were landmark tobacco-                            others 2000; Townsend 1993). However, critics of these studies
control events in high-income countries. These publications                              note that econometric methods, which estimate the effect of a
resulted in the first widespread press coverage of the scientific                        marginal change in advertising expenditures on smoking, are
links between smoking and lung cancer. The reports were fol-                             ill suited for studying the effect of advertising (Chaloupka,
lowed, in many countries, by policies requiring health warning                           Hu, and others 2000; U.S. Federal Trade Commission 2004;
labels on tobacco products, which were later extended to                                 Townsend 1993). Approaches used by other disciplines, includ-
tobacco advertising.                                                                     ing survey research and experiments that assess reactions to
   Research from high-income countries indicates that these                              and recall of cigarette advertising, do support the hypothesis
initial reports and the publicity that followed about the health                         that increases in cigarette advertising and promotion directly
consequences of smoking led to significant reductions in con-                            and indirectly increase cigarette demand and smoking initia-
sumption, with initial declines of between 4 and 9 percent and                           tion (U.S. DHHS 1994; U.K. Department of Health 1992).
longer-term cumulative declines of 15 to 30 percent (Kenkel                              These studies conclude that cigarette advertising is effective in
and Chen 2000; Townsend 1993). Efforts to disseminate infor-                             getting and retaining children’s attention, with the strength
mation about the risks of smoking and of other tobacco use in                            of the association strongly correlated with current smoking
low- and middle-income countries have led to similar declines                            behavior, smoking initiation, and smoking intentions.
in tobacco use in those countries (Kenkel and Chen 2000). In                                 Comprehensive advertising and promotion bans on ciga-
addition, mass media antismoking campaigns, in many cases                                rettes provide more direct evidence on the effect of advertising
funded by earmarked tobacco taxes, have generated reductions                             these products (Saffer 2000). One study using data from
in cigarette smoking and other tobacco use (Kenkel and Chen                              22 high-income countries for the period 1970 through 1992
2000; Saffer 2000). Decreases in smoking prevalence were                                 provides strong evidence that comprehensive bans on cigarette
largest in Western countries, where the public is constantly and                         advertising and promotion led to significant reductions in cig-
consistently reminded of the dangers of smoking by extensive                             arette smoking. The study predicts that a comprehensive set
coverage of issues related to tobacco in the news media                                  of tobacco advertising bans in high-income countries could
(Molarius and others 2001).                                                              reduce tobacco consumption by more than 6 percent, taking
   In many low- and middle-income countries, a lack of aware-                            into account price and non-price control interventions (Saffer
ness continues to exist about the risks of mortality and disease                         and Chaloupka 2000). However, the study concludes that par-
posed by smoking. For example, a national survey in China in                             tial bans have little effect on smoking behavior, given that the
1996 found that 61 percent of smokers thought that tobacco                               tobacco industry can shift its resources from banned media to
did them “little or no harm” (Chinese Academy of Preventive                              other media that are not banned.
Medicine 1997). In high-income countries, smokers are aware
of the risks, but a recent review of psychological studies found
that few smokers judge the size of these risks to be higher and                          Smoking Cessation Treatments
more established than do nonsmokers, and that smokers min-                               Near-term reductions in smoking-related mortality depend
imize the personal relevance of these risks (Weinstein 1998).                            heavily on smoking cessation. Numerous behavioral smoking
                                                                                         cessation treatments are available, including self-help manuals,
Bans on Advertising and Promotion                                                        community-based programs, and minimal or intensive clinical
Cigarettes are among the most heavily advertised and pro-                                interventions (U.S. DHHS 2000). In clinical settings,
moted products in the world. In 2002, cigarette companies                                pharmacological treatments, including nicotine replacement

876 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
therapies (NRT) and bupropion, have become much more                            ment of antismuggling laws, and stronger penalties for those
widely available in recent years in high-income countries                       caught violating these laws (Joossens and others 2000). Recent
through deregulation of some NRT from prescription to over-                     analysis suggests that, even in the presence of smuggling,
the-counter status (Novotny and others 2000; U.S. DHHS                          tax increases will reduce consumption and increase revenue
2000). The evidence is strong and consistent that pharmaco-                     (Merriman, Yurekli, and Chaloupka 2000).
logical treatments significantly improve the likelihood of quit-                    In contrast to the effectiveness of demand-side interven-
ting, with success rates two to three times those when pharma-                  tions, there is much less evidence that interventions aimed at
cological treatments are not used (Novotny and others 2000;                     reducing the supply of tobacco products are as effective in
Raw, McNeill, and West 1999; U.S. DHHS 2000). The effective-                    reducing cigarette smoking (Jha and Chaloupka 1999, 2000a).
ness of all commercially available NRT seems to be largely                      The U.S. experience provides mixed evidence about the effec-
independent of the duration of therapy, the setting in which                    tiveness of limiting youth access to tobacco products in reduc-
the therapy is provided, regulatory status (over-the-counter                    ing youth tobacco use (U.S. DHHS 2000; Woolery, Asma, and
versus prescribed therapy), and the type of provider (Novotny                   Sharp 2000). In addition, the effective implementation
and others 2000). Over-the-counter NRT without physician                        and enforcement of these policies may require infrastructure
oversight have been used in many countries for a number of                      and resources that do not exist in many low- and middle-
years with good success.                                                        income countries. A preliminary discussion is occurring in
   Although NRT are successful in treating nicotine addic-                      Canada about reducing its number of retail outlets for tobacco
tion, the markets for NRT and other pharmacological thera-                      from the current 65,000. Neither the effect of such a move nor
pies are more highly regulated and less affordable than are                     its enforcement costs are well known. Crop substitution and
nicotine-containing tobacco products. Recent evidence indi-                     diversification programs are often proposed as a means of
cates that the demand for NRT is related to economic factors,                   reducing the supply of tobacco. However, little evidence exists
including price (Tauras and Chaloupka 2003). Policies that                      that such programs would significantly reduce the supply of
decrease the cost of NRT and increase availability—such as                      tobacco, given that the incentives for growing tobacco tend to
mandating private health insurance coverage of NRT, includ-                     attract new farmers who would replace those who abandon
ing such coverage in public health insurance programs, and                      tobacco farming (Jacobs and others 2000). Similarly, direct
subsidizing NRT for uninsured or underinsured individuals—                      prohibition of tobacco production is not likely to be politically
would likely lead to substantial increases in the use of these                  feasible, effective, or economically optimal. Finally, although
products. Given the demonstrated efficacy of NRT in treating                    trade liberalization has contributed to increases in tobacco use
smoking, these policies could generate significant increases in                 (particularly in low- and middle-income countries), restric-
smoking cessation.                                                              tions on trade in tobacco and tobacco products that violate
                                                                                international trade agreements or draw retaliatory measures
                                                                                (or both) may be more harmful (Taylor and others 2000).
The key intervention on the supply side is the control of smug-                 EFFECTIVENESS AND COST-EFFECTIVENESS
gling. Recent estimates suggest that 6 to 8 percent of cigarettes               OF TOBACCO-CONTROL INTERVENTIONS
consumed globally are smuggled (Merriman, Yurekli, and
                                                                                Using a static model of the cohort of smokers alive in 2000, we
Chaloupka 2000). Of note, the tobacco industry itself has an
                                                                                estimate the number of deaths attributable to smoking over the
economic incentive to smuggle, in part to increase market share
                                                                                next few decades that could be averted by (a) price increases,
and decrease tax rates (Joossens and others 2000; Merriman,
                                                                                (b) NRT, and (c) a package of non-price interventions other
Yurekli, and Chaloupka 2000). Although differences in taxes
                                                                                than NRT. Cost-effectiveness of these policy interventions was
and prices across countries create a motive for smuggling, a
                                                                                calculated by weighing the approximate public sector costs
recent analysis comparing the degree of corruption in individ-
                                                                                against the years of healthy life saved, measured in DALYs. The
ual countries with price and tax levels found that corruption
                                                                                details of an earlier version of this model have been published
within countries is a stronger predictor of smuggling than is
                                                                                previously (Ranson and others 2002).
price (Merriman, Yurekli, and Chaloupka 2000). Several gov-
ernments are adopting policies aimed at controlling smuggling.
In addition to harmonizing price differentials between coun-
tries, effective measures include prominent tax stamps and                      Results of Model Projections
warning labels in local languages, better methods for tracking                  The following is an updated analysis, using higher price
cigarettes through the distribution chain, aggressive enforce-                  increases and a greater effectiveness for NRT than did the

                                                                                                                             Tobacco Addiction | 877

                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 46.3 Reductions in Future Tobacco Deaths among Smokers Alive in 2000 from Price Increases of 10 Percent, 33 Percent,
50 Percent, and 70 Percent by World Bank Region

                                                                                                   Reduction in number of deaths (millions)

                                                                          10 percent                33 percent                 50 percent          70 percent
                                                                          price increase            price increase             price increase      price increase
  World Bank region                      deaths (millions)               Low          High         Low          High          Low        High     Low        High

  East Asia and the Pacific                      173                      2.9          8.7           9.6         27.5          14.5      37.5     20.3        46.2
  (percent)                                                               (1.7)        (5.0)        (5.5)       (15.9)         (8.4)     (21.7)   (11.7)     (26.8)
  Europe and Central Asia                         51                      0.9          2.6           2.8          8.1              4.3   11.2      6.0        13.8
  (percent)                                                               (1.7)        (5.1)        (5.6)       (16.0)         (8.5)     (22.0)   (11.8)     (27.2)
  Latin America and the Caribbean                 40                      0.7          2.1           2.3          6.7              3.5    9.5      4.9        11.6
  (percent)                                                               (1.8)        (5.3)        (5.8)       (16.8)         (8.8)     (23.7)   (12.3)     (29.1)
  Middle East and North Africa                    13                      0.2          0.7           0.8          2.2              1.2    3.1      1.6         3.8
  (percent)                                                               (1.7)        (5.2)        (5.8)       (16.6)         (8.7)     (23.2)   (12.2)     (28.5)
  South Asia                                      62                      0.9          2.6           2.9          8.5              4.4   12.5      6.2        16.0
  (percent)                                                               (2.4)        (8.6)        (9.5)       (27.7)        (14.3)     (40.6)   (20.1)       (52)
  Sub-Saharan Africa                              23                      0.4          1.1           1.3          3.7              1.9    5.5      2.7         6.6
  (percent)                                                               (1.6)        (4.9)        (5.4)       (15.9)         (8.2)     (23.6)   (11.5)     (28.5)
  Low- and middle-income countries               362                      6.0         17.9         19.7          56.8          29.8      79.2     41.7        98.2
  (percent)                                                               (1.6)        (4.9)        (5.4)       (15.7)         (8.2)     (21.9)   (11.5)     (27.1)
  High-income countries                           81                      0.6          2.6           2.1          8.5              3.2   12.2      4.5        16.2
  (percent)                                                               (0.8)        (3.2)        (2.6)       (10.6)         (4.0)     (15.1)    (5.6)     (20.0)
  World                                          443                      6.6         20.5         21.8          65.3          33.0      91.5     46.2       114.3
  (percent)                                                               (1.5)        (4.6)        (4.9)       (14.7)         (7.5)     (20.7)   (10.4)     (25.8)

Source: Authors’ calculations.

original (Ranson and others 2002). This analysis is conservative                         Africa, recent tax increases have doubled the real price of ciga-
in its assumptions about effectiveness and generous in its                               rettes (Guindon, Tobin, and Yach 2002).
assumptions about the costs of tobacco control.
                                                                                         Potential Effect of Nicotine Replacement Therapies.
Potential Effect of Price Increases. With a price increase of                            Provision of NRT with an effectiveness of 1 percent is predicted
33 percent, the model predicts that 22 million to 65 million                             to result in the avoidance of about 3.5 million smoking-
smoking-attributable deaths will be averted worldwide, which                             attributable deaths (table 46.4). NRT of 5 percent effectiveness
is approximately equivalent to 5 to 15 percent of all smoking-                           would have about five times the effect. Again, low- and middle-
attributable deaths expected among those who smoke in 2000                               income countries would account for roughly 80 percent of
(see table 46.3). Low- and middle-income countries account                               the averted deaths. The relative effect of NRT (of 2.5 percent
for about 90 percent of averted deaths. East Asia and the Pacific                        effectiveness) on deaths averted is 2 to 3 percent among indi-
alone will account for roughly 40 percent of averted deaths.                             viduals age 15 to 59 and lower among those age 60 and older
Total smoking-attributable deaths averted worldwide range                                (results not shown).
from 33 million to 92 million for a 50 percent price increase
and 46 million to 114 million for a 70 percent price increase. A                         Potential Effect of Non-price Interventions Other Than NRT.
70 percent price increase would avert 10 to 26 percent of all                            A package of non-price interventions, other than NRT, that
smoking-attributable deaths worldwide.                                                   decreases the prevalence of smoking by 2 percent is predicted
    Of the tobacco-related deaths that would be averted by a                             to prevent about 7 million smoking-attributable deaths (more
price increase, 80 percent would be male, reflecting the higher                          than 1.6 percent of all smoking-attributable deaths among
overall prevalence of smoking in men. The greatest relative                              those who smoked in 2000; see table 46.4). A package of inter-
effect of a price increase on deaths averted is among younger                            ventions that decreases the prevalence of smoking by 10 per-
cohorts. Note that these projections use conservative price                              cent would have an effect five times greater. Low- and middle-
increases. In certain countries, such as Poland and South                                income countries would account for approximately four-fifths

878 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 46.4 Reductions in Future Tobacco Deaths among Smokers Alive in 2000 from Price Increases of 33 Percent, Increased
NRT Use, and a Package of Non-price Measures by World Bank Region

                                                                                              Reduction in number of deaths (millions)

                                                                                                                                                  Non-price intervention
                                                                      33 percent price increase                   NRT effectiveness               effectiveness
  World Bank region                  deaths (millions)            Low elasticity       High elasticity        1 percent          5 percent       2 percent       10 percent

  East Asia and the Pacific                  173                        9.6                  27.5                  1.4               6.9              2.8           13.8
  (percent)                                                             (5.5)                (15.9)               (0.8)             (4.0)            (1.6)          (8.0)
  Europe and Central Asia                     51                        2.8                   8.1                  0.4               2.1              0.8            4.1
  (percent)                                                             (5.6)                (16.0)               (0.8)             (4.0)            (1.6)          (8.1)
  Latin America and the Caribbean             40                        2.3                   6.7                  0.3               1.7              0.7            3.4
  (percent)                                                             (5.8)                (16.8)               (0.8)             (4.2)            (1.7)          (8.5)
  Middle East and North Africa                13                        0.8                   2.2                  0.11              0.6              0.2            1.1
  (percent)                                                             (5.8)                (16.6)               (0.8)             (4.2)            (1.7)          (8.4)
  South Asia                                  62                        2.9                   8.5                  0.4               2.2              0.9            4.3
  (percent)                                                             (9.5)                (27.7)               (1.4)             (7.2)            (2.8)         (13.9)
  Sub-Saharan Africa                          23                        1.3                   3.7                  0.2               0.9              0.4            1.8
  (percent)                                                             (5.4)                (15.9)               (0.8)             (4.0)            (1.6)          (7.9)
  Low- and middle-income countries           362                       19.7                  56.8                  2.9              14.3              5.7           28.6
  (percent)                                                             (5.4)                (15.7)               (0.8)             (4.0)            (1.6)          (7.9)
  High-income countries                       81                        2.1                   8.5                  0.6               3.1              1.2            6.1
  (percent)                                                             (2.6)                (10.6)               (0.8)             (3.8)            (1.5)          (7.6)
  World                                      443                       21.8                  65.3                  3.5              17.4              6.9           34.7
  (percent)                                                             (4.9)                (14.8)               (0.8)             (3.9)            (1.6)          (7.8)

Source: Authors.

of quitters and averted deaths. The greatest relative effect of                        Tobacco deaths (millions)
non-price interventions on deaths averted would be among                                                                                                             443
younger cohorts.                                                                       400                                                                           408
   Figure 46.5 summarizes the potential effect of a set of                                   Death year 2030: 10 million                                             377
                                                                                                  deaths per year
independent tobacco-control interventions, using 33 and                                                                                                              328
70 percent price increases (using a high elasticity of 1.2 for                         300
low- and middle-income regions and 0.8 for high-income                                                7 million deaths
                                                                                                         per year
regions), a 5 percent effectiveness of NRT, and a 10 percent
reduction from non-price interventions other than NRT. In
this cohort of smokers alive in 2000, approximately 443 mil-
lion are expected to die in the next 50 years in the absence                           100
of interventions. A substantial fraction of these tobacco
deaths are avoidable with interventions. Price increases have
the greatest effect on tobacco mortality, with the most                                  0
aggressive price increase of 70 percent having the potential                              2000            2010            2020        2030          2040          2050

to avert almost one-quarter of all tobacco deaths. Even a                                           Baseline                                 33 percent price increase
modest price increase of 33 percent could potentially                                               NRT with 5 percent                       70 percent price increase
prevent 66 million tobacco deaths over the course of the                                            effectiveness
                                                                                                    Non-price interventions
next 50 years. Although NRT and other non-price interven-                                           with 10 percent reduction
tions are less effective than price increases, they can still
avert a substantial number of tobacco deaths (18 million                               Source: Authors.
                                                                                       Note: Price increases assume a high price elasticity (–1.2 for low- and
and 35 million deaths, respectively). The greatest effect of                           middle-income countries and –0.8 for high-income countries).
these tobacco-control interventions would occur after 2010,
but a substantial number of deaths could be avoided even                               Figure 46.5 Potential Effect of Tax Increases, NRT, and Non-price
before then.                                                                           Interventions on Tobacco Mortality, 2000–50

                                                                                                                                                      Tobacco Addiction | 879

                                       ©2006 The International Bank for Reconstruction and Development / The World Bank
   Note that no attempt has been made in this analysis to                                highly sensitive to the actual price of the NRT. NRT with a price
examine the effect of combining the various packages of inter-                           of US$25 have a cost-effectiveness of US$75 per DALY com-
ventions (for example, price increases with NRT, or NRT and                              pared with US$329 for an NRT price of US$150 (data not
other non-price interventions). A number of studies have com-                            shown).
pared the effect of price and non-price interventions; few                                   For a given set of assumptions, the variation in the cost-
empirical attempts have been made to assess how these inter-                             effectiveness of each intervention between low- and middle-
ventions might interact. Although price increases have been                              income regions is relatively small and sensitive to the discount
found in this analysis to be the most cost-effective antismoking                         rate (data not shown). All three interventions are most cost-
intervention, policy makers should use both price and non-                               effective in South Asia and Sub-Saharan Africa. The difference
price interventions to counter smoking. Non-price measures                               between low- and middle-income countries and high-income
may be required to affect the most heavily dependent smokers,                            countries is more pronounced. For NRT, the cost per year of
for whom medical and social support in stopping will be nec-                             healthy life gained is 3 to 10 times higher in high-income coun-
essary. Furthermore, these non-price measures may be effective                           tries than elsewhere. For non-price interventions other than
in increasing social acceptance and support of tobacco price                             NRT, the cost in high-income countries is 22 times higher, and
increases.                                                                               for price increases, almost 42 times higher. Of note, the esti-
                                                                                         mates of cost-effectiveness are given as wide ranges,which reflect
Cost-Effectiveness of Antismoking Interventions. In general,                             the range of assumptions used.
price increases are found to be the most cost-effective anti-                                For price increases, the high-end estimates are roughly 25
smoking intervention. A 33 percent price increase (our base                              times the low-end estimates, and this difference is consistent
case scenario) could be achieved for a cost of US$13 to US$195                           among the regions. For NRT, the high-end estimates are 2.5 to
per DALY saved globally, or US$3 to US$42 in low-income                                  10 times the low-end estimates, varying among the regions. For
countries and US$85 to US$1,773 in high-income countries.                                non-price interventions other than NRT, the high-end esti-
Wider access to NRT could be achieved for between US$75 and                              mates are 20 times the low-end estimates, and this difference is
US$1,250 per DALY saved, depending on which assumptions                                  consistent among the regions.
are used. Non-price interventions other than NRT could be                                    The cost-effectiveness results can be compared against exist-
implemented for between US$233 and US$2,916 per DALY                                     ing studies only for high-income countries because of a lack
saved (table 46.5). Thus, NRT and other non-price measures                               of studies situated elsewhere. Our estimates of deaths avoided
are slightly less cost-effective than price increases but remain                         for a 10 percent price increase are conservative compared with
cost-effective in many settings. The cost-effectiveness of NRT is                        those of Moore (1996) and Warner (1986).

Table 46.5 Range of Cost-Effectiveness Values for Price Increase, NRT, and Non-price Interventions, 2000
(2002 U.S. dollars per DALY saved)

                                                                                                                   NRT with                   Non-price interventions
                                                                               33 percent price                    effectiveness of           with effectiveness of
                                                                               increase                            1 to 5 percent             2 to 10 percent
                                          smoking-attributable            Low-end           High-end          Low-end              High-end   Low-end       High-end
  World Bank region                       deaths (millions)               estimate          estimate          estimate             estimate   estimate      estimate

  East Asia and the Pacific                       173                          2                30                65                 864         40           498
  Europe and Central Asia                          51                          3                42                45                 633         55           685
  Latin America and the Caribbean                  40                          6                85                53                 812        109          1,361
  Middle East and North Africa                     13                          6                89                47                 750        115          1,432
  South Asia                                       62                          2                27                54                 716         34           431
  Sub-Saharan Africa                               23                          2                26                42                 570         33           417
  Low- and middle-income countries                362                          3                42                55                 761         54           674
  High-income countries                            81                        85              1,773              175                3,781       1,166        14,572
  World                                           443                        13                195                75               1,250        233          2,916

Source: Authors.

880 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
COMPREHENSIVE TOBACCO-CONTROL                                                            use and in improving public health (Farrelly, Pechacek, and
PROGRAMS                                                                                 Chaloupka 2003; Townsend, Roderick, and Cooper 1998; U.S.
                                                                                         DHHS 1994). In California, for example, the state’s compre-
In recent years, several governments, mostly in high-income                              hensive tobacco-control program has produced a rate of
countries, have adopted comprehensive programs to reduce                                 decline in tobacco use double that seen in the rest of the United
tobacco use, often funded by earmarked tobacco tax revenues.                             States.
The programs generally have similar goals for reducing tobacco                              The cost of implementing control programs is low.
use:                                                                                     Table 46.6 provides the estimated total costs of implementing
                                                                                         price and NRT interventions by World Bank region. Current
•    preventing initiation among youths and young adults                                 estimates of the costs of implementing a comprehensive
•    promoting cessation among all smokers                                               tobacco-control program range from US$2.50 to US$10 per
•    reducing exposure to passive tobacco smoke                                          capita in the United States. The U.S. Centers for Disease
•    identifying and eliminating disparities among population                            Control and Prevention recommends spending US$6 to US$16
     subgroups (U.S. DHHS 1994).                                                         per capita for a comprehensive tobacco-control program in the
                                                                                         United States (CDC 1999). Canadian spending on tobacco-
   Furthermore, the programs have one or more of four key                                control programs was approximately US$1.70 per capita in
components: community interventions engaging a diverse set                               1996 (Pechmann, Dixon, and Layne 1998). At the highest rec-
of local organizations; countermarketing and health informa-                             ommended spending level (US$16 per capita) in the United
tion campaigns; program policies and regulations (such as                                States, annual funding for a comprehensive tobacco program
taxes, restrictions on smoking, bans on tobacco advertising,                             would equal only 0.9 percent of U.S. public spending, per
and access to better cessation treatments); and surveillance and                         capita, on health.
evaluation of potential issues, such as smuggling (U.S. DHHS                                Evidence from the United States demonstrates that states
1994). Programs have placed differing emphasis on these four                             with the greatest prevalence of smoking have a greater marginal
components, with substantial diversity among the types of                                effect with their tobacco-control spending, suggesting that the
activities supported within each component. Disaggregating                               potential gains from modest investments in comprehensive
current tobacco-control program spending reveals that the                                tobacco-control measures are large. Each US$10 spent per
greatest effect can be achieved through a focus on macro-level                           capita on tobacco control annually has resulted in a 55 percent
changes, such as policy change. Recent analyses from the                                 reduction (variation of 20 to 70 percent) in per capita cigarette
United Kingdom and United States clearly indicate that these                             consumption (Tauras and others 2005). In the United States,
comprehensive efforts have been successful in reducing tobacco                           US$10 translates into 0.03 percent of per capita GDP in 2003.

Table 46.6 Estimated Cost of Price Intervention and NRT Programs
(2002 U.S. dollars)

                                                                                                                       Cost of NRT (US$25 to US$150) (millions)

                                                                                                                 To treat 1 percent of          To treat 5 percent of
                                                              Cost for price increase (millions)                 current smokers                current smokers

                                                          Low-end estimate          High-end estimate
    World Bank region                  GDP (billions)     (0.02 percent GDP)        (0.05 percent GDP)        US$25      US$50       US$150   US$25    US$50      US$150

    East Asia and the Pacific              1,802                   360                         901             1,079         2,158    6,474    5,395   10,791     32,372
    Europe and Central Asia                1,136                   227                         568               318          635     1,906    1,588    3,176      9,529
    Latin America and the Caribbean        1,673                   335                         836               250          500     1,500    1,250    2,500      7,499
    Middle East and North Africa             694                   139                         347                84          169      506      422       843      2,530
    South Asia                               655                   131                         327             2,312         1,926    3,853   11,558    2,312      1,926
    Sub-Saharan Africa                       319                    64                         159               868          723     1,447    4,340      868       723
    Low- and middle-income countries       6,279                 1,256                       3,138             4,911         6,111   15,686   24,553   20,490     54,579
    High-income countries                 25,992                 5,198                     12,996              3,034         2,529   10,114   15,172    3,034      2,529
    World                                 32,271                 6,454                     16,134              7,945         8,640   25,800   39,725   23,524     57,108

Source: Authors.

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                                          ©2006 The International Bank for Reconstruction and Development / The World Bank
CONSTRAINTS TO EFFECTIVE                                                                 or “dead-weight losses” from earmarking tobacco taxes are
TOBACCO-CONTROL POLICIES                                                                 minimal (Hu, Xu, and Keeler 1998). Furthermore, earmarking
                                                                                         tobacco taxes can be justified if governments use the funds to
Although substantial evidence exists concerning the effective-                           benefit those who pay (the benefits principle), provide assured
ness of numerous policy interventions to reduce tobacco use,                             funding for tobacco-control policies and programs, and secure
the use of these interventions globally is uneven and limited                            public support for new or higher tobacco taxes. Earmarked
(see a more formal analysis in Chaloupka and others 2001).                               taxes also have a political function in that they help concentrate
World Bank data reveal that ample room exists to increase                                political winners of tobacco control and thus influence policy.
tobacco taxes. In 1995, the average percentage of all govern-                            Earmarked funds that support broad health and social services
ment revenue derived from tobacco tax was 0.63 percent.                                  (such as other disease programs) broaden the political and civil
Middle-income countries averaged 0.51 percent of govern-                                 society support base for tobacco control. In Australia, broad
ment revenue from tobacco taxes, while lower-income coun-                                political support from the Ministries of Sports and Education
tries averaged only 0.42 percent. An increase in cigarette taxes                         helped convince the Ministry of Finance that raising tobacco
of 10 percent globally would raise cigarette tax revenues by                             taxes was possible. Indeed, after an earmarked tax was passed,
nearly 7 percent, with relatively larger increases in revenues                           the Ministry of Finance went on to raise tobacco taxes further
in high-income countries and smaller increases in revenues in                            without earmarking (Galbally 1997). Additionally, targeting
low- and middle-income countries (Sunley, Yurekli, and                                   revenue from tobacco taxes to other health programs for the
Chaloupka 2000). Despite this evidence, price increases have                             poorest socioeconomic groups could produce double health
been underused. Guindon, Tobin, and Yach (2002) studied 80                               gains—reduced tobacco consumption combined with
countries and found that the real price of tobacco, adjusted for                         increased access to and use of health services. In China, a
purchasing power, fell in most developing countries from 1990                            10 percent increase in cigarette taxes would decrease consump-
to 2000.                                                                                 tion by 5 percent and would increase government revenue by
    Why does so much variation exist in tobacco-control                                  5 percent. The increased earnings could finance a package of
policies? The political economy of tobacco control has been                              essential health services for one-third of China’s poorest
inadequately studied. A few plausible areas of interest are out-                         100 million citizens in 1990 (Saxenian and McGreevey 1996).
lined here. First, the recognition of tobacco as a major health                             Finally, a key pillar in tobacco control that can help over-
hazard appears to be the impetus for most of the tobacco-                                come some of these constraints is the Framework Convention
control policies in many high-income countries. Some evi-                                on Tobacco Control (FCTC). The World Health Assembly
dence shows that improved national capacity and local needs                              of the World Health Organization adopted the FCTC in
assessment could increase the likelihood that tobacco-control                            May 2003. It consists of a series of negotiated protocols within
measures will be adopted. For example, econometric analyses                              a general framework. The first three protocols are negotiations
in South Africa geared to local policy requirements substantially                        covering smuggling, advertising, and treatment of tobacco
increased the willingness of the government to implement                                 addiction. Countries agreeing to the negotiated protocols are to
tobacco-control policies (Abedian and others 1998). Second,                              adopt appropriate legislation and, if necessary, implement the
tobacco-control budgets are only a fraction of what is required.                         appropriate measures. As of February 2005, 168 countries had
Funding is needed not so much to implement programs as to                                signed the FCTC, 57 had ratified it, and it had come into force
fight off tobacco industry tactics and to build popular support                          on February 27, 2005.
for control. Third, the most obvious constraint to tobacco
control is political opposition, which is difficult to quantify.
Opposition from the tobacco industry is well organized and
well funded (Pollock 1996).
    A key tool for addressing political opposition is earmarking                         Worldwide, only two large and growing causes of death exist.
tobacco taxes. Earmarking has been successfully used in several                          One is HIV-1 infection, and the other is tobacco. On current
countries, including Australia, Finland, Nepal, and Thailand.                            consumption patterns, about 1 billion people in the 21st
Of the 48 countries currently in the World Health                                        century will be killed by their addiction to tobacco. Strong
Organization’s European region, 12 earmark taxes for tobacco                             evidence shows that tobacco tax increases, the dissemination
control and other public health measures. The average level of                           of information about health risks from smoking, restrictions
allocation is less than 1 percent of total tax revenue (WHO                              on smoking in public places and workplaces, comprehensive
2002). Earmarking does introduce clear restrictions and ineffi-                          bans on advertising and promotion, and increased access to
ciencies on public finance, and for this reason alone most                               cessation therapies are effective both in reducing tobacco use
macroeconomists do not favor earmarking, no matter how                                   and in improving the health of populations. Despite this
worthy the cause. However, analysis suggests that the efficiency                         evidence, these policies, especially higher taxes, have been

882 | Disease Control Priorities in Developing Countries | Prabhat Jha, Frank J. Chaloupka, James Moore, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
applied aggressively only in a few high-income countries, cov-                         Ezzati, M., and A. D. Lopez. 2003. “Estimates of Global Mortality
ering a small proportion of the world’s smokers. Limited                                   Attributable to Smoking in 2000.” Lancet 362 (9387): 847–52.
                                                                                       Farrelly, M. C., T. F. Pechacek, and F. J. Chaloupka. 2003. “The Impact of
implementation of effective tobacco control in developing
                                                                                           Tobacco Control Program Expenditures on Aggregate Cigarette Sales:
countries is due to political constraints as well as the lack of                           1981–2000.” Journal of Health Economics 22 (5): 843–59.
awareness of the unique effectiveness and cost-effectiveness                           Gajalakshmi, C. K., P. Jha, K. Ranson, and S. Nguyen. 2000. “Global
of these interventions.                                                                    Patterns of Smoking and Smoking-Attributable Mortality.” In Tobacco
                                                                                           Control in Developing Countries, ed. P. Jha and F. J. Chaloupka. Oxford,
                                                                                           U.K.: Oxford University Press.
ACKNOWLEDGMENTS                                                                        Gajalakshmi, V., R. Peto, T. S. Kanaka, and P. Jha. 2003. “Smoking and
                                                                                           Mortality from Tuberculosis and Other Diseases in India:
                                                                                           Retrospective Study of 43,000 Adult Male Deaths and 35,000
We thank Allison Gilbert for help with the cost-effectiveness                              Controls.” Lancet 362 (9883): 507–15.
analyses and Hellen Gelband, Andra Ghent, and Dhirendra                                Galbally, R. L. 1997. “Health-Promoting Environments: Who Will Miss
Sinha for comments.                                                                        Out?” Australia and New Zealand Journal of Public Health 21 (4 Spec.
                                                                                           No.): 429–30.
                                                                                       Gruber, J. 2003. “Government Policy toward Smoking: A New View from
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©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                    Chapter 48

                                                      Illicit Opiate Abuse
                                                                               Wayne Hall, Chris Doran, Louisa Degenhardt, and Donald Shepard

Illicit drugs are those banned by international drug control                   disease control priorities for illicit opioid dependence, because
treaties. They include cannabis products (for example, mari-                   dependent users account for most of the illicit opioids con-
juana, hashish, and bhang); stimulant drugs (such as cocaine                   sumed and experience most of the harm such dependence
and methamphetamine); so-called dance-party drugs (such as                     causes (W. Hall, Degenhardt, and Lynskey 1999).
3, 4-methylenedioxymethamphetamine, also known as ecstasy
or MDMA); and illicit opioids (for instance, heroin and
opium) and diverted pharmaceutical opioids (such as                            NATURE, CAUSES, AND HEALTH CONSEQUENCES
buprenorphine, methadone, and morphine) (see annex 48.A).
                                                                               OF ILLICIT OPIOID USE
    Worldwide, 185 million people were estimated to have used
illicit drugs during 1998–2002 (UNODC 2004; UNODCCP                            Before considering interventions, we briefly summarize what is
2002). Cannabis was the most widely used illicit drug, with                    known about the antecedents, causes, and health consequences
146.2 million users in 2002, or 3.7 percent of the global                      of illicit opioid use.
population over age 15. The stimulant drugs were the next
most widely used illicit drugs: 29.6 million people worldwide
used amphetamines; 13.3 million used cocaine; and 8.3 million                  Antecedents of Heroin Use
used ecstasy. An estimated 15.3 million, or 0.4 percent of the                 Law enforcement efforts to reduce the availability of heroin
world population age 15 to 64, used illicit opioids; more than                 aim to increase its price, deter illicit drug use, and promote
half used heroin and the remainder used opium or diverted                      social values that discourage heroin use (Fergusson, Horwood,
pharmaceutical opioids. Illicit opioids continue to be the major               and Lynskey 1998; Hawkins, Catalano, and Miller 1992;
illicit drug problem in most regions of the world in terms of                  Newcomb and Bentler 1988). These gains may be at the cost of
impact on public health and public order (UNODC 2004).                         increasing harm among the minority who use opioids despite
    Even though cannabis use accounts for about 80 percent of                  the prohibition—for example, by encouraging injecting use as
illicit drug use worldwide, the mortality and morbidity attrib-                the most efficient way to use an expensive drug and increasing
utable to its use are not well understood, even in developed                   needle sharing because clean injecting equipment is not freely
countries (W. Hall and Pacula 2003; Macleod and others 2004;                   available (Rhodes and others 2003; Strathdee and others 2003).
WHO Programme on Substance Abuse 1997). The same is true                          Two aspects of the family environment are associated with
of the morbidity and mortality attributable to cocaine and                     increased rates of both licit and illicit drug use in young people
amphetamine-type stimulants (Macleod and others 2004).                         in developed countries. The first is exposure to a disadvantaged
Dance-party drugs have been used for too short a time in most                  home environment, with parental conflict and poor discipline
developed societies to enable a good assessment of their poten-                and supervision; the second is exposure to parents’ and sib-
tial for harm (Boot, McGregor, and Hall 2000; Macleod and                      lings’ use of alcohol and other drugs (Hawkins, Catalano, and
others 2004). The remainder of this chapter is concerned with                  Miller 1992). In developed countries, children who perform


                                ©2006 The International Bank for Reconstruction and Development / The World Bank
poorly in school because of impulsive or problem behavior and                                 2. withdrawal, as manifested by either of the following:
those who are early users of alcohol and other drugs are most                                    a. the characteristic withdrawal syndrome for the
likely to use illicit opioids (Fergusson, Horwood, and Swain-                                        substance
Campbell 2002). Affiliation with drug-using peers is a risk fac-                                 b. the same (or closely related) substance is taken to relieve
                                                                                                     or avoid withdrawal symptoms;
tor for drug use that operates independently of individual and
                                                                                              3. the substance is often taken in larger amounts or over a
family risk factors (Fergusson, Horwood, and Lynskey 1998;
                                                                                                 longer period than was intended;
Hawkins, Catalano, and Miller 1992).
                                                                                              4. there is a persistent desire or unsuccessful efforts to cut
                                                                                                 down or control substance use;
                                                                                              5. a great deal of time is spent in activities necessary to obtain
Health Consequences of Heroin Use
                                                                                                 the substance (e.g., visiting multiple doctors, driving long
The following sections describe the major health consequences                                    distances), use the substance (e.g., chain smoking), or
of heroin use. They include dependence, increased mortality                                      recover from its effects;
and morbidity attributable to drug overdoses, and bloodborne                                  6. important social, occupational, or recreational activities are
viruses.                                                                                         given up or reduced because of substance use;
                                                                                              7. the substance use is continued despite knowledge of having
Heroin Dependence. In household surveys, 1 to 2 percent of                                       a persistent or recurrent physical or psychological problem
                                                                                                 that is likely to have been caused or exacerbated by the
adults in Australia, the United States, and Europe report using
heroin at some time in their lives (Australian Institute of
Health and Welfare 1999; EMCDDA 2002; SAMHSA 2002).
The highest rates are typically among adults age 20 to 29. Self-                             Indirect estimation methods suggest that in Australia, the
reported heroin use in population surveys probably underesti-                            United Kingdom, and the European Union fewer than 1 per-
mates rates of use because heroin users are undersampled and                             cent of adults age 15 to 54 are heroin dependent (EMCDDA
those who are sampled underreport their use (W. Hall, Lynskey,                           2002; W. Hall and others 2000). Research in the United States
and Degenhardt 1999).                                                                    indicates that dependent heroin users who seek treatment or
   In developed countries, one in four of those who report                               who come to the attention of the legal system may use heroin
heroin use become dependent on it (Anthony, Warner, and                                  for decades (Goldstein and Herrera 1995; Hser, Anglin, and
Kessler 1994). People who are heroin dependent continue to                               Powers 1993), with periods of use punctuated by abstinence
use heroin in the face of problems that they know (or believe)                           (Bruneau and others 2004; Galai and others 2003), drug treat-
to be caused by its use. These problems include being arrested                           ment, and imprisonment (Gerstein and Harwood 1990). When
or imprisoned, having interpersonal and family problems,                                 periods of abstinence are included, dependent heroin users use
catching infectious diseases, and suffering from drug over-                              heroin daily for 40 to 60 percent of the 20 years that they typi-
doses. Many heroin users who seek treatment have typically                               cally are addicts (Ball, Shaffer, and Nurco 1983; Maddux and
been daily heroin injectors, although in Europe (EMCDDA                                  Desmond 1992).
2002), North America (Office of National Drug Control Policy                                 Illicit opioid use increased in Asia, Europe, and Oceania
2001), and parts of Asia, illicit opioid users also smoke or                             and, to a lesser extent, in Africa and South America in the
“chase” the drug (inhale the fumes released when heroin is                               1990s, but it has stabilized or declined since 2000 (UNODC
heated) (UNODC 2004).                                                                    2004). Most illicit opioid users (7.8 million) live in Asian coun-
   The American Psychiatric Association defines drug depend-                             tries that surround the major opium-producing countries,
ence as “a cluster of cognitive, behavioral, and physiologic                             Afghanistan and Myanmar. Europe accounts for about 25 per-
symptoms indicating that the individual continues use of the                             cent of illicit opioid use (4 million users or 0.8 percent of the
substance despite significant substance-related problems”                                adult population age 15 to 64). Two-thirds of users are in
(American Psychiatric Association 1994, 176). In the fourth                              Eastern Europe, which reported large increases in illicit opioid
edition of the association’s Diagnostic and Statistical Manual of                        use during the second half of the 1990s (Atlani and others
Mental Disorders (1994,), a diagnosis of substance dependence                            2000; Hamers and Downs 2003; Kelly and Amirkhanian 2003;
requires that three or more of the following occur together:                             Rhodes and others 1999; Uuskula and others 2002).
                                                                                             Illicit opioid use stabilized in much of Asia between 2000 and
    At any time in the same 12-month period:                                             2002 (UNODC 2004) as a result of decreased opium production
    1. tolerance, as defined by either of the following:                                 after the rapid expansion during the 1990s (Dorabjee and
       a. need for markedly increased amounts of the substance                           Samson 2000; Reid and Crofts 2000). After 2000, India and
           to achieve intoxication or desired effect                                     Pakistan reported stabilizing rates of illicit opioid use but
       b. markedly diminished effect with continued use of the                           increased injection of pharmaceutical opiates (Ahmed and
           same amount of the substance;                                                 others 2003; Dorabjee and Samson 2000; Strathdee and others

908 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
2003). China has reported a steady rate of growth in illicit opiate              account for 25 to 33 percent of deaths of young adult males
use in its southern and northern provinces (Beyrer 2003; Beyrer                  (EMCDDA 2002).
and others 2000; Yu and others 1998) and a 15-fold increase in
the number of registered opioid addicts between 1990 and 2002,                   Economic Costs of Illicit Opioid Use. In Canada, Xie and
bringing the total to about 1 million (UNODC 2004).                              others (1996) calculate the costs of illicit drugs as 0.2 percent
   Oceania experienced a marked rise in heroin use in the late                   of gross domestic product (GDP). In Australia, Collins and
1990s, largely driven by a dramatic increase in the availability of              Lapsley (1996) estimate the economic costs of illicit drug abuse
heroin in Australia (Darke, Topp, and others 2002; W. Hall,                      at 2 percent of GDP.
Degenhardt, and Lynskey 1999). In late 2000, an abrupt heroin
shortage resulted in a large reduction in fatal and nonfatal
overdoses (Day and others 2004; Degenhardt, Day, and Hall                        CONTRIBUTION OF OPIOID DEPENDENCE
                                                                                 TO THE GLOBAL BURDEN OF DISEASE
Mortality, Morbidity, and Heroin Dependence. In developed                        Degenhardt, Hall, and others (2004) estimate the contribution
countries, dependent heroin users have an increased risk of                      of illicit opioid dependence to the global burden of disease
premature death from drug overdoses, violence, suicide,                          using data on deaths caused by opioid and other drug over-
and alcohol-related causes (Darke and Ross 2002; Goldstein                       doses, suicides and accidents, and HIV/AIDS. When estimates
and Herrera 1995; Vlahov and others 2004). Heroin users                          of morbidity attributable to illicit drug use were added in, illicit
treated before the HIV epidemic were 13 times more likely to                     opioid use accounted for 0.7 percent of global disability-
die prematurely than their peers (Hulse and others 1999), with                   adjusted life years (DALYs) in 2000 (WHO 2003).
opioid overdose the most frequent cause of death (W. Hall,                           These estimates suggest that illicit opioid use is a significant
Degenhardt, and Lynskey 1999). In countries with a high                          global cause of premature mortality and disability among
prevalence of HIV infection, AIDS is a major cause of prema-                     young adults. Even so, they probably underestimate the disease
ture death among drug users (EMCDDA 2002; UNAIDS and                             burden attributable to illicit opioids, because they omit differ-
WHO 2002). Fatal opioid overdose deaths increased in many                        ences across subregions in the quality of data on causes of mor-
developed countries during the 1990s before declining after                      tality and estimates of mortality and morbidity attributable to
2000 (UNODC 2004).                                                               hepatitis and violence (Degenhardt, Hall, and others 2004).
   In parts of Asia, Eastern Europe, and the United States, the
sharing of contaminated injecting equipment accounts for a
substantial proportion of new HIV infections (EMCDDA                             INTERVENTIONS FOR ILLICIT OPIOID
2002; UNAIDS and WHO 2002; UNODC 2004). Injecting
opioid use has been a major driver of HIV epidemics in China
(Yu and others 1998), Myanmar (Beyrer and others 2000), the                      Methods adopted to control the problems arising from illicit
Russian Federation and former Soviet republics (Hamers and                       opioid dependence include source-country control; interdic-
Downs 2003), and Vietnam (Beyrer and others 2000; Hien                           tion of supply into end-use countries; enforcement by the
and others 2001).                                                                police force and the criminal justice system of legal prohibi-
   The prevalence of infection with hepatitis B and C viruses                    tions on the supply, possession, and use of opioids; treatment
among injecting drug users is greater than 60 percent in                         of those who are opioid dependent, both voluntarily and under
Australia (National Centre in HIV Epidemiology and Clinical                      legal coercion from the criminal justice system; school-based
Research 1998), Canada (Fischer and others 2004), China                          and mass media preventive educational programs; and regula-
(Ruan and others 2004), the United States (Fuller and others                     tory policies restricting the prescription of opioids (Manski,
2004), and the European Union (EMCDDA 2002). Chronic                             Pepper, and Petrie 2001).
infection occurs in 75 percent of infections, and 3 to 11 percent
of chronic hepatitis C virus carriers develop liver cirrhosis
within 20 years (Hepatitis C Virus Projections Working Group                     Prevention of Heroin Use
1998).                                                                           Countries use a variety of interventions in attempts to prevent
   Heroin-related deaths primarily occur among young adults                      the initiation of use of illicit drugs such as cannabis (Manski,
and account for a large number of life years lost in developed                   Pepper, and Petrie 2001; Spooner and Hall 2002), in the belief
societies. In Australia in 1996, for example, such deaths                        that early initiation of cannabis use leads to an increased
accounted for 2.2 percent of life years lost, with each death                    risk of using illicit opioids (Fergusson, Horwood, and
accounting for 22 years of life lost (Mathers, Vos, and                          Swain-Campbell 2002). These interventions include legal pro-
Stephenson 1999). In Scotland and Spain, opiate-related deaths                   hibitions on the manufacture, sale, and use of opioid drugs

                                                                                                                                Illicit Opiate Abuse | 909

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
for nonmedical purposes; enforcement of these sanctions by                               others 2000; Kimber and others 2003). Supervised injecting
law enforcement officials by means of fines and imprisonment;                            facilities have been introduced in Germany, the Netherlands,
and enforcement of restrictions on medically prescribed opi-                             and Switzerland (Dolan and others 2000; Kimber and others
oids to prevent their diversion (Manski, Pepper, and Petrie                              2003), but their effect on overdose deaths has not been rigor-
2001). Preventive measures also include mass media and                                   ously evaluated to date. A supervised injecting facility was eval-
school-based educational campaigns about the health risks of                             uated in Australia, but the evaluation was limited by the con-
opioid and other illicit drug use (Spooner and Hall 2002). It is                         current onset of a heroin shortage that resulted in a 40 percent
unclear how effective these interventions are in preventing                              decline in overdose deaths (Kaldor and others 2003).
cannabis use and even less clear whether they reduce the initia-                            A fourth strategy is to increase methadone maintenance
tion of opioids (Caulkins and others 1999; Manski, Pepper, and                           among older, high-risk opioid-dependent people, because indi-
Petrie 2001).                                                                            viduals enrolled in methadone maintenance treatment (MMT)
   The most popular interventions against illicit opioid use in                          are substantially less likely to suffer from a fatal overdose
many developed societies have been the interdiction of drug                              (Caplehorn and others 1994; Gearing and Schweitzer 1974;
supply and the enforcement of legal sanctions against the pos-                           Langendam and others 2001).
session, use, and sale of opioid drugs (Manski, Pepper, and
Petrie 2001). As a consequence, imprisonment is the most com-
mon intervention to which many illicit opioid users have been                            Treatment Interventions for Dependent Opioid Users
exposed (Gerstein and Harwood 1990). In Asia and Eastern                                 The range of treatment interventions includes voluntary pro-
Europe, high rates of imprisonment of drug users have been a                             grams such as detoxification, abstinence-oriented treatments,
factor in HIV transmission, because drug users engage in high-                           and oral Methadone maintenance treatment, as well as invol-
risk injecting while imprisoned (Beyrer and others 2000).                                untary options imposed by criminal justice systems.

                                                                                         Detoxification. Detoxification is supervised withdrawal from
Interventions to Reduce Heroin-Related Harm                                              a drug of dependence that attempts to minimize withdrawal
The most effective intervention to reduce bloodborne virus                               symptoms. It is not a treatment for heroin dependence; it
infection arising from illicit injecting of opioids and other                            provides a respite from opioid use and may be a prelude to
drugs is the provision of clean injecting equipment to reduce                            abstinence-based treatment (Mattick and Hall 1996).
users’ risks of contracting or transmitting bloodborne viruses.                             Naltrexone is a longer-acting opiate antagonist than nalox-
This intervention has been widely supported in most developed                            one; it can be used to accelerate the opioid withdrawal process.
countries, but it has been incompletely adopted in developing                            Ultra-rapid opioid detoxification accelerates withdrawal by
countries that have problems with the concept of facilitating                            giving the patient naltrexone under general anesthetic. There is
the injection of illicit drugs (UNAIDS and WHO 2002). Vac-                               no evidence that accelerated withdrawal in itself reduces the
cinations are available against hepatitis B but not hepatitis C.                         high rate of relapse to heroin use in the absence of further
These important interventions are covered in chapter 18.                                 treatment (W. Hall and Mattick 2000).
    A number of strategies can potentially reduce deaths from
opioid overdoses (Darke and Hall 2003; Sporer 2003). First,                              Abstinence-Oriented Treatments. Abstinence-oriented treat-
injecting drug users can be educated about the dangers of com-                           ments aim to achieve enduring abstinence from all opioid
bining the use of opioids with alcohol and benzodiazepines                               drugs by providing some type of intervention after withdrawal
(McGregor and others 2001), both of which heighten the risk                              to reduce the high rate of relapse to opioids (Mattick and Hall
of a fatal opioid overdose (Darke and Zador 1996; Warner-                                1996). The interventions may include social and psychological
Smith and others 2001). Heroin users also need to be discour-                            support only or such support supplemented by pharmacologi-
aged from injecting in the streets or alone, thereby denying                             cal methods.
themselves assistance in the event of an overdose. These inter-                             Residential treatment in therapeutic communities and out-
ventions have yet to be evaluated.                                                       patient drug counseling may entail encouraging patients to
    A second strategy is to encourage drug users who witness                             become involved in self-help groups such as Narcotics
overdoses to seek medical assistance and to use simple resusci-                          Anonymous. These approaches share a commitment to achiev-
tation techniques until help arrives. A more controversial                               ing abstinence from all opioids, using group and psychological
option is to distribute the opioid antagonist naloxone to high-                          interventions to help dependent heroin users remain abstinent.
risk heroin users (Darke and Hall 1997; Strang and others                                Therapeutic communities and drug counseling are usually pro-
1996). Neither of these interventions has been evaluated.                                vided through specialist addiction or mental health services.
    A third strategy is to provide supervised injecting facilities                       The former are residential, and the latter are provided on an
in areas with high rates of injecting opioid use (Dolan and                              outpatient basis.

910 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
    No randomized controlled trials of therapeutic communi-                     of injected heroin, allowing the individual to take advantage of
ties or outpatient drug counseling have been carried out.                       psychotherapeutic and rehabilitative services.
Observational studies in the United Kingdom (Gossop,                                Every one of the small number of randomized controlled
Marsden, and Stewart 1998; Gossop and others 1997) and the                      trials of MMT compared with placebo or no treatment has
United States (Hubbard and others 1989; Simpson and Sells                       produced positive results (W. Hall, Ward, and Mattick 1998;
1982) have found that therapeutic communities and drug                          Mattick and others 2003). Large observational studies show
counseling were less successful than MMT in attracting and                      that MMT decreases heroin use and criminal activity and
retaining dependent heroin users, but they substantially                        reduces HIV transmission while patients remain in treatment
reduced heroin use and crime among those who remained in                        (Gerstein and Harwood 1990; Simpson and Sells 1990; Ward,
treatment for at least three months (Gerstein and Harwood                       Hall, and Mattick 1998). MMT is the best-supported form of
1990; Gossop, Marsden, and Stewart 1998; Gossop and others                      opioid maintenance treatment (Farre and others 2002; Marsch
1997). Some evidence indicated that therapeutic communities                     1998; Mattick and others 2003).
may be more effective if they are used in combination with                          Buprenorphine is a mixed agonist-antagonist that also
legal coercion to ensure that heroin users are retained in treat-               blocks the effects of heroin. When given in high doses, its
ment long enough to benefit from it (Gerstein and Harwood                       effects can last for up to three days, while its antagonist effects
1990).                                                                          substantially reduce overdose and abuse (Oliveto and Kosten
    Recovering drug users run Narcotics Anonymous groups                        1997; Ward, Hall, and Mattick 1998). Meta-analyses have found
using an adaptation of the 12-step philosophy of Alcoholics                     that buprenorphine is effective in the treatment of heroin
Anonymous. Some individuals use these groups as their sole                      dependence (Mattick and others 2003) and is of equivalent effi-
form of support for abstinence, whereas for others these groups                 cacy to MMT when delivered in primary health care and spe-
complement therapeutic communities that are based on the                        cialist treatment settings in Australia (Gibson and others 2003).
same principles. Such groups are usually not open to people                         Bammer and others (2003) have proposed injectable heroin
who are in opioid substitution treatment programs.                              maintenance as a way of attracting into treatment those heroin
    The most extensive research on self-help has been in the                    users who are not interested in or have failed to respond to
treatment of alcohol dependence. Treated alcoholics who par-                    MMT. This method has recently been evaluated in the
ticipate in Alcoholics Anonymous groups have higher rates of                    Netherlands (Central Committee on the Treatment of Heroin
abstinence than those who do not (see, for example, Tonigan,                    Addicts 2002) and Switzerland (Perneger and others 1998;
Connors, and Miller 2003; Tonigan, Toscova, and Miller 1996).                   Uchtenhagen, Gutzwiller, and Dobler-Mikola 1998). Perneger
The good outcome in those who attend Alcoholics Anonymous                       and others (1998) report a randomized controlled trial of
meetings may reflect the self-selection of motivated partici-                   injectable heroin maintenance in people who had failed at
pants into self-help groups. Recent studies that have attempted                 MMT. Stabilizing and safely maintaining heroin addicts on
to control for this possibility using sophisticated statistical                 injectable heroin (self-administered on-site in a comprehensive
methods have produced mixed results, with some showing the                      health and social service) proved feasible for six months and
persistence of an effect of self-help after correction (Tonigan,                substantially improved their health and social well-being. The
Connors, and Miller 2003) while others do not (Fortney and                      Swiss trials showed that it was possible to maintain opioid
others 1998).                                                                   addicts on injectable heroin for up to two years (Rehm and
    Shepard and others (forthcoming) evaluate the effect of self-               others 2001; Uchtenhagen, Gutzwiller, and Dobler-Mikola
help participation on substance abuse 24 months after treat-                    1998). A recent randomized controlled trial in the Netherlands
ment for members of a mixed population of substance abusers                     (Central Committee on the Treatment of Heroin Addicts 2002)
treated at two treatment facilities in the United States, some of               confirms the findings of Perneger and others (1998).
whom had problems with heroin. They find that participation
in self-help groups was associated with longer abstinence from                  Criminal Justice Interventions for Dependent Illicit Opioid
all drugs. Correction for self-selection did not eliminate the                  Users. The most common intervention for illicit opioid
association in one treatment setting, but it made the results                   dependence in most developed societies is imprisonment
much more equivocal in the other.                                               (EMCDDA 2003; Gerstein and Harwood 1990). Imprisonment
                                                                                is not intended to be a health intervention. Nonetheless, it is an
Oral Methadone Maintenance Treatment. This treatment                            ineffective way of reducing opioid dependence, when judged
substitutes a long-acting, orally administered opioid for the                   by the high recidivism in longitudinal studies of dependent
shorter-acting heroin, with the aim of stabilizing dependent                    heroin users (see, for example, Hser, Anglin, and Powers 1993;
heroin users so that they are amenable to rehabilitation (Marsh                 Manski, Pepper, and Petrie 2001).
and others 1990; Ward, Hall, and Mattick 1998). When given in                       Legally coerced treatment is treatment that is legally forced
high or blockade doses, methadone blocks the euphoric effects                   on those who have been charged with or convicted of an

                                                                                                                              Illicit Opiate Abuse | 911

                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
offense to which their drug dependence has contributed                                   Detoxification. The National Evaluation of Pharma-
(W. Hall 1997). It is most often provided as an alternative to                           cotherapies for Opioid Dependence Project in Australia con-
imprisonment, under the threat of imprisonment if the person                             ducted a cost-effectiveness analysis of five interventions:
fails to comply with the treatment (W. Hall 1997; Manski,
Pepper, and Petrie 2001; Spooner, Hall, and Mattick 2001). Its                           • naltrexone-induced rapid opioid detoxification under
major justification is that it is an effective way of treating                             anesthesia
offenders’ drug dependence that reduces the likelihood of their                          • naltrexone-induced rapid opioid detoxification under
offending again (Gerstein and Harwood 1990). A consensus                                   sedation
view prepared for the World Health Organization (WHO)                                    • conventional inpatient detoxification
(Porter, Arif, and Curran 1986) was that compulsory treatment                            • conventional outpatient detoxification
was legally and ethically justified only if the rights of the                            • buprenorphine outpatient detoxification.
individuals were protected by due process and if the treatment
provided was effective and humane.                                                          A successful outcome was defined as achieving abstinence
    Research into the effectiveness of legally coerced treatment                         from heroin for one week (Mattick and others 2001).
for opioid dependence has been limited to observational studies                             Rapid detoxification under sedation was the most cost-
(W. Hall 1997; Manski, Pepper, and Petrie 2001; Wild, Roberts,                           effective method of detoxification (US$2,355 for one week of
and Cooper 2002). Anglin’s (1988) quasi-experimental studies                             abstinence) and conventional outpatient detoxification the least
of the California Civil Addict Program provide the strongest                             cost-effective (US$12,031). Rapid detoxification under anesthe-
evidence of efficacy. These studies compared heroin-dependent                            sia achieved high rates of abstinence in the first week, but its
offenders who entered the program between 1962 and 1964                                  expense reduced its cost-effectiveness (Mattick and others
with a group of similar offenders who went through the crimi-                            2001).
nal justice system during the same period. They found that com-                             Doran and others (2003) compared the cost-effectiveness of
pulsory hospital treatment followed by close supervision in the                          detoxification from heroin using buprenorphine in a specialist
community substantially reduced heroin use and crime.                                    Australian clinic and in a shared care setting. They conducted
    The effectiveness of less coercive forms of treatment has                            a randomized controlled trial with 115 heroin-dependent
been supported by analyses of the effectiveness of community-                            patients receiving a five-day treatment regime of buprenor-
based treatment provided while on probation or parole                                    phine. The specialist clinic was a community-based treatment
(Hubbard and others 1989; Simpson and others 1986). These                                agency in Sydney. Shared care involved treatment by a general
studies showed that individuals who entered community-based                              practitioner, supplemented by weekend dispensing and some
therapeutic communities and drug-free outpatient counseling                              counseling at the specialist clinic. They estimate that buprenor-
under legal pressure did as well as those who did so voluntarily                         phine detoxification in the shared care setting was US$17 more
(Hubbard and others 1988; Simpson and Friend 1988). The                                  expensive per patient than the costs of treatment at the clinic
recent creation of specialized drug courts in the United States to                       (US$236 per patient).
process those arrested for drug-related offenses awaits rigorous
evaluation (Belenko 2002; Manski, Pepper, and Petrie 2001).                              Drug-Free Treatment. The limited economic evaluations of
    Legally coerced MMT is also effective. The strongest                                 drug-free treatment have used data from observational studies
evidence comes from a study in which drug offenders were ran-                            of treatment outcomes in samples of patients who have mixed
domly assigned to parole with and without community-based                                substance abuse problems that include opioids. For example,
MMT (Dole and others 1969). This study showed a greater                                  Shepard, Larson, and Hoffmann (1999) calculate a range of
reduction in heroin use and lower rates of incarceration among                           estimated costs for achieving an abstinent year in 408 patients
those enrolled in MMT in the year following their release from                           at two different treatment facilities in the United States. The
prison. These findings are supported by observational studies                            cost-effectiveness depended on the severity of the problem and
that found no major differences in response to MMT between                               the intensiveness and cost of the intervention. For outpatients
those who enrolled under legal coercion and those who did not                            with the least severe drug problems, the cost of an abstinent
(Anglin, Brecht, and Maddahain 1989; Brecht, Anglin, and                                 year was US$7,000, whereas the same outcome in patients with
Wang 1993; Hubbard and others 1988).                                                     more severe problems who received long-term residential treat-
                                                                                         ment cost US$20,000.
Economic Evaluations of Interventions for Illicit                                           Shepard and others (forthcoming) use these data to esti-
Opioid Dependence                                                                        mate the cost-effectiveness of involvement in mutual self-
The few published economic evaluations of treatment inter-                               help groups, such as Alcoholics Anonymous and Narcotics
ventions for illicit opioid dependence indicate varying levels of                        Anonymous, in sustaining abstinence for up to 24 months after
cost-effectiveness.                                                                      treatment. They find a positive association between self-help

912 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
involvement and abstinence 12 and 24 months after treat-                             The costs of injectable heroin maintenance in the Dutch
ment. Applying statistical methods to correct for the effects of                  study was between US$18,015 and US$23,243 per patient per
self-selection into self-help, they find that in a Veterans                       year (Bammer and others 2003). Most of the costs arose from
Administration hospital, the effects of self-help on abstinence                   the supervision of heroin use and the security required to pre-
persisted after the statistical correction, but at the other site, the            vent the diversion of heroin to the black market. Injectable
results depended on the method of analysis that was used. They                    heroin maintenance needs to produce substantially greater
estimate the cost of achieving an abstinent year by means of                      benefits for each participant than MMT to make it as cost-
self-help in the year following treatment at US$13,000, all of                    effective as MMT.
that due to the costs that participants incurred in attending
a group.                                                                          Economic Modeling of the Cost-Effectiveness of Opioid
                                                                                  Maintenance Treatment. Barnett (1999), using data on the
Oral Opioid Maintenance Treatment. Goldschmidt’s (1976)                           efficacy of MMT in reducing mortality derived from
economic evaluation of MMT found that it was as effective                         Gronbladh, Ohlund, and Gunne’s (1990) Swedish study and
as a therapeutic community intervention and twice as cost-                        U.S. cost data, estimated that MMT saved an additional year of
effective. Cartwright’s (2000) review of the literature since 1976                life at a cost of US$5,900. Barnett, Zaric, and Brandeau (2001),
identified a number of studies, all of which reported positive                    using a similar approach, estimated that the use of buprenor-
benefit-cost ratios for MMT.                                                      phine by patients who would not use methadone would cost
   Gerstein, Harwood, and Suter’s (1994) California Drug and                      less than US$45,000 per quality-adjusted life year. Overall,
Alcohol Treatment Assessment study is the most comprehen-                         however, they found that BMT was much less effective and
sive cost-benefit analysis carried out to date. The authors exam-                 more costly than MMT. Zaric, Barnett, and Brandeau (2000)
ine the effects of treatment—residential programs, outpatient                     assessed the economic benefits of using MMT to reduce HIV
programs, and methadone programs—on alcohol and drug                              transmission in heroin users. They found that for heroin users
use, criminal activity, health and health care utilization, and                   living in a community with a high prevalence of HIV infection,
source of income. For each treatment modality, they found that                    expanding MMT use produced an additional year of quality-
the benefits during the first year of treatment significantly                     adjusted life at a cost of US$8,200.
exceeded the cost of delivering the care. The benefit-cost ratio
was 4.8 for residential treatment and 11.0 and 12.6 for outpa-                    Comparing the Cost-Effectiveness of Different Interventions
tients and discharged methadone participants, respectively.                       Comparative cost-effectiveness analyses of these interventions
   Doran and others (2003) compared the cost-effectiveness                        face major obstacles because the small number of published
of buprenorphine and methadone treatment for opioid                               studies used different methods to cost interventions and differ-
dependence. In a randomized controlled trial, 405 subjects                        ent endpoints to assess the outcome of treatment. The follow-
were randomly assigned to each treatment at one of three                          ing list, therefore, only ranks treatment interventions in the
specialist outpatient drug treatment centers. The study found                     approximate order of their cost-effectiveness. We believe that
that treatment with methadone was less expensive and more                         estimates of their likely contribution to DALYs worldwide
effective than treatment with buprenorphine, but the differ-                      would be too speculative.
ence in cost (US$143 per additional heroin-free day gained)
had a wide range of uncertainty around it ( US$1,469 to                           • Detoxification. Buprenorphine and supervised naltrexone-
US$1,284).                                                                          accelerated withdrawal delivered on an outpatient basis are
   The National Evaluation of Pharmacotherapies for Opioid                          the most efficient and effective ways to achieve withdrawal
Dependence Project also provided a cost-effectiveness analysis                      from opioids.
of methadone, buprenorphine, LAAM (levo-alpha-acetyl-                             • Self-help groups. These groups provide the simplest form of
methadol), and naltrexone maintenance treatments (Mattick                           postwithdrawal support for enduring abstinence and are
and others 2001). The daily costs of these maintenance treat-                       also a low-cost intervention, because patients bear most of
ments were similar for methadone and LAAM, but naltrexone                           the costs; however, they have a low rate of uptake, and their
was slightly more expensive. Buprenorphine maintenance                              effectiveness is only modest.
treatment (BMT) was more expensive, but its cost-efficiency                       • Oral opioid agonist maintenance treatment. This form of
could have been improved to make its cost similar to that for                       treatment is the most widely used intervention for illicit
the other treatments. MMT was the most cost-effective treat-                        opioid dependence in developed societies. It has a better
ment for opioid dependence because it achieved one of the                           uptake than other interventions, and it is moderately effec-
highest rates of retention in treatment among the four phar-                        tive under the usual delivery conditions.
macotherapies examined. Naltrexone treatment was the least                        • Drug-free residential treatment. This form of treatment has a
cost-effective.                                                                     relatively low rate of treatment uptake and is costly because

                                                                                                                              Illicit Opiate Abuse | 913

                                   ©2006 The International Bank for Reconstruction and Development / The World Bank
  of its residential character and the need for intensive staff-                         mortality by 25 percent. In the sensitivity analysis, we varied
  patient interaction. It is effective for the minority of people                        the reduction from 15 to 35 percent (using the confidence
  who are retained in treatment long enough to benefit from                              intervals around the estimated reduction). We assumed that
  it (usually three months). Retention in treatment may be                               the reduction in mortality associated with BMT was 20 per-
  improved if patients enter treatment under some form of                                cent, which we varied in the sensitivity analysis from 10 to
  legal coercion.                                                                        30 percent. Finally, we assumed that those who were alive and
• Naltrexone maintenance treatment. This form of treatment                               in treatment experienced a 25 percent reduction in disability,
  has not been rigorously evaluated.                                                     consistent with the Dutch disability weights.
• Injectable opioid maintenance. This intervention is a more                                 The third step was to estimate the burden for those not
  expensive variant of agonist maintenance treatment that has                            treated. For those users not in treatment, we calculated DALYs
  been used for patients with more severe cases of dependency                            using the original mortality rates.
  but for whom retention and treatment outcomes have been                                    The fourth step was to estimate the total avertable burden
  good.                                                                                  from treatment with methadone or buprenorphine by (a) adding
                                                                                         the results of the second and third steps, the revised DALYs for
Calculation of the Averted, Avertable,                                                   those in treatment, and the residual for those not in treatment
and Unavertable Burden                                                                   and (b) subtracting those figures from the base case estimates.
Assuming that the disease burden from opioid dependence is                                   The fifth step was to cost the interventions using data on
potentially avertable, we used the following approach to esti-                           MMT and BMT from Doran and others (2003). They estimated
mate the avoidable burden of opioid dependence. We initially                             the cost of MMT at $A 1,415 and of BMT at $A 1,729 for six
modeled the avertable burden using MMT and used this model                               months of treatment.We converted these estimates into U.S. dol-
for BMT. The first step was to establish the base case for opioid                        lars and multiplied them by two to provide yearly estimates
dependence using 2002 as the baseline year. We established the                           of treatment costs of US$1,732 for MMT and US$2,117 for BMT.
model of the base case for opioid dependence for regions and                                 We applied relative price weights for each region using the
subregions according to WHO country classifications. We used                             Western Pacific as the reference case (1.00). We calculated the
population estimates for each region for those age 15 to 59, the                         relative price weights for each cost type using data provided by
age range in which heroin dependence is most prevalent. We                               the World Bank. The prices are a reflection of the public health
incorporated Degenhardt, Hall, and others’ (2004, table 13.1)                            systems in each region, and as far as possible they reflect the
figures for the prevalence of opioid use by region, assuming                             opportunity cost of health care resources in these regions.
that the prevalence was 30 percent higher among male users
than female users.                                                                       Results. Our results are presented in table 48.1. We explored
    We obtained population-attributable fractions related to                             various combinations of coverage and reductions in mortality
opioid dependence from the editors of this volume. We used                               for MMT and BMT. For each intervention, as coverage and
nine relevant WHO categories to estimate the burden of dis-                              reductions in mortality increased, the number of DALYs averted
ease attributable to opioid dependence—namely HIV/AIDS,                                  increased. The wide discrepancies in DALYs averted within
drug-use disorders, road traffic accidents, poisonings, falls,                           regions primarily reflect differences in population-attributable
fires, drownings, other unintentional injuries, and self-inflicted                       fractions for HIV/AIDS. Costs increased as a consequence of
injuries.                                                                                increased coverage for both interventions, whereas results for
    We calculated the mortality rate for opioid deaths by divid-                         cost-effectiveness differ by both intervention and mortality.
ing the number of deaths by the estimated number of users. We                                The cost-effectiveness analysis suggests that for MMT (with
took estimates of years of life lost (YLLs) and years lived with                         a coverage of 25, 50, or 75 percent and reductions in mortality of
disability (YLDs), by gender, for each region from data                                  35 percent) the cost in international dollars per DALY averted
obtained from the editors of this volume. We then used those                             ranges from a low of $128 in Africa, with high child and adult
estimates to calculate the DALYs for male users, female users,                           mortality where the prevalence of illicit opioid dependence is
and all users (YLL YLD DALY). We discounted the YLLs,                                    low (0.01 percent), to a high of $3,726 in Eastern Europe, with
YLDs, and DALYs using a 3 percent discount rate.                                         low child and adult mortality where the prevalence of illicit
    The second step was to estimate the avertable burden by                              opioid dependence is high (0.55 percent). Across all the
treatment with methadone or buprenorphine. Using the popu-                               regions, the average cost-effectiveness ratio for MMT (with 25,
lation and prevalence data, we assumed, in the first instance,                           50, and 75 percent coverage and 35 percent reduction in mor-
that 50 percent of those dependent on opioids entered treat-                             tality) is estimated at $2,236 per DALY averted.
ment. In the sensitivity analysis, we varied this proportion from
25 to 75 percent coverage. On the basis of Caplehorn and                                 Assessment. The results shown in table 48.1 provide a first
others’ (1994) meta-analysis, we assumed that MMT reduced                                approximation of the potential avertable burden in DALYs if

914 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 48.1 Cost-Effectiveness Results

                                                         Total effect (DALYs averted per 1 million population)

                                                                     The                   Mediter-                                   Southeast           Western
                                                Africa               Americas              ranean                    Europe           Asia                Pacific
              Coverage       Mortality
 Treatment       (%)           (%)        AFR-D AFR-E AMR-A AMR-B AMR-D EMR-A EMR-D EUR-A EUR-B EUR-C SEAR-B SEAR-D WPR-A WPR-B

 MMT              25             15           125        79   153       107       158       179       105      117       48    198      63        48       39         26
 MMT              50             15           251     158     306       214       316       358       210      234       96    397     126        97       77         53
 MMT              75             15           376     237     459       321       474       538       315      352      144    595     190     145        116         79
 MMT              25             25           150        81   184       121       173       217       151      141       59    264      93        70       51         35
 MMT              50             25           300     163     369       243       347       435       303      283      117    527     185     140        102         70
 MMT              75             25           450     244     553       364       520       652       454      424      176    791     278     211        152       105
 MMT              25             35           174        84   216       136       189       256       198      165       69    329     122        92       63         43
 MMT              50             35           349     167     432       272       378       511       396      331      139    657     244     184        126         87
 MMT              75             35           523     251     648       408       566       767       594      496      208    986     367     276        189       130
 BMT              25             10           113        78   137       100       150       160        82      105       43    166      48        38       32         22
 BMT              50             10           226     156     274       199       301       320       163      210       85    331      97        75       65         44
 BMT              75             10           339     234     412       299       451       480       245      315      128    497     145     113         97         67
 BMT              25             20           138        80   169       114       166       198       128      129       53    231      78        59       45         31
 BMT              50             20           275     160     337       228       332       397       256      258      107    462     156     119         89         61
 BMT              75             20           413     240     506       342       497       595       384      388      160    693     234     178        134         92
 BMT              25             30           162        82   200       129       181       237       175      153       64    296     107        81       57         39
 BMT              50             30           324     165     400       258       362       473       350      307      128    592     215     162        114         78
 BMT              75             30           487     247     601       386       543       710       524      460      192    888     322     243        171       117

 Total costs (US$ per 1 million population)

 MMT              25         15, 25, 35       0.10    0.01    0.25      0.06      0.12     0.95      0.65     0.20     0.16    0.35    0.06    0.19      0.07       0.03
 MMT              50         15, 25, 35       0.19    0.02    0.50      0.11      0.24     1.90      1.30     0.40     0.32    0.71    0.11    0.39      0.13       0.07
 MMT              75         15, 25, 35       0.29    0.03    0.74      0.17      0.36     2.86      1.95     0.60     0.49    1.06    0.17    0.58      0.20       0.10
 BMT              25         10, 20, 30       0.12    0.01    0.30      0.07      0.15     1.16      0.80     0.24     0.20    0.43    0.07    0.24      0.08       0.04
 BMT              50         10, 20, 30       0.24    0.03    0.60      0.14      0.29     2.33      1.59     0.49     0.40    0.86    0.14    0.47      0.16       0.08
 BMT              75         10, 20, 30       0.35    0.04    0.91      0.20      0.44     3.49      2.39     0.73     0.59    1.29    0.20    0.71      0.24       0.12

 Cost-effectiveness (US$ per DALY averted)

 MMT          25, 50, 75         15           768     136 1,618         520       755     5,315     6,213    1,711    3,379   1,782    875    3,984     1,716     1,284
 MMT          25, 50, 75         25           643     132 1,342         458       688     4,381     4,300    1,419    2,764   1,341    597    2,749     1,301       974
 MMT          25, 50, 75         35           552     128 1,146         408       632     3,726     3,288    1,212    2,339   1,074    453    2,099     1,048       784
 BMT          25, 50, 75         10       1,041       168 2,204         682       969     7,269     9,764    2,329    4,646   2,606   1,396   6,277     2,493     1,867
 BMT          25, 50, 75         20           855     164 1,793         595       880     5,869     6,210    1,895    3,716   1,869    867    3,975     1,809     1,354
 BMT          25, 50, 75         30           726     159 1,510         527       805     4,921     4,553    1,598    3,096   1,458    629    2,909     1,419     1,062

 DALYs averted per US$1 million spent

 MMT          25, 50, 75         15       1,302      7,363    618      1,922    1,325       188       161      585      296    561    1,142    251        583       779
 MMT          25, 50, 75         25       1,556      7,575    745      2,185    1,453       228       233      705      362    746    1,676    364        768     1,027
 MMT          25, 50, 75         35       1,811      7,787    873      2,448    1,582       268       304      825      428    931    2,210    476        954     1,275
 BMT          25, 50, 75         10           961    5,939    454      1,465    1,032       138       102      429      215    384     717     159        401       536
 BMT          25, 50, 75         15       1,170      6,112    558      1,681    1,137       170       161      528      269    535    1,153    252        553       739
 BMT          25, 50, 75         20       1,378      6,286    662      1,896    1,242       203       220      626      323    686    1,590    344        705       942

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                                          ©2006 The International Bank for Reconstruction and Development / The World Bank
MMT and BMT were applied to 50 percent of the opioid-                                        Third, in societies with a sizable illicit opioid dependence
dependent population in each region. Because the methods and                             problem, cultural attitudes and beliefs will affect societal
data used to estimate avertable DALYs are subject to certain                             responses, especially attitudes toward illicit opioid use and
limitations, those results should be considered preliminary.                             dependence (Gerstein and Harwood 1990). A critical determi-
                                                                                         nant of the social response will be the relative dominance of
                                                                                         moral and medical understandings of drug dependence in gen-
                                                                                         eral and opioid dependence in particular. A moral model of
                                                                                         addiction sees addiction as largely a voluntary behavior, in
Much of the epidemiological research on illicit opioid depend-                           which case it is seen as an excuse for bad behavior that allows
ence, its disease burden, and its societal harm comes from                               drug users to continue to take drugs without assuming respon-
Australasia, Europe, and the United States. The major excep-                             sibility for their conduct (Szasz 1985). In this view, drug users
tion is research on the role of injecting drug use in HIV trans-                         who offend against the criminal code should be imprisoned
mission in developing countries (see, for example, Beyrer and                            (Szasz 1985). This model is the dominant one in many devel-
others 2000; Yu and others 1998). In addition, research on the                           oped societies, which imprison drug users at high rates without
effectiveness and cost-effectiveness of interventions for illicit                        any effect on the prevalence of drug abuse. Countries that
opioid dependence has been conducted primarily in developed                              adopt punitive policies toward drug users are reluctant to
countries (Ward, Hall, and Mattick 1998), with the exception of                          embrace harm reduction measures, such as needle and syringe
studies of the effectiveness of methadone treatment in Hong                              programs and opioid maintenance treatment (Ainsworth,
Kong, China (see, for instance, Newman and Whitehill 1979),                              Beyrer, and Soucat 2003). A medical model of addiction, by
and in Thailand (Vanichseni and others 1991), both of which                              contrast, recognizes that dependent opioid users require spe-
showed comparable effectiveness to that found in developed                               cific treatment if the sufferer is to become and remain abstinent
countries (W. Hall, Ward, and Mattick 1998).                                             (see, for example, Leshner 1997).
    Translating findings on interventions for opioid depend-                                 These competing views will affect the societal acceptability
ence in developed countries into disease control priorities for                          of opioid maintenance and abstinence-oriented approaches to
opioid dependence in developing countries presents three                                 the treatment of opioid dependence (Cohen 2003). Those who
major challenges. First, countries differ in the scale of illicit                        have a moral view of addiction will tend to prefer drug-free and
opioid use and in the resulting disease burden. This variation                           self-help approaches toward treatment. Supporters of medical
reflects the effects of differences in the prevalence of injecting                       models of addiction will favor some form of opioid substitu-
and noninjecting opioid users; the dependent opioid users’                               tion treatment and the provision of clean needles and syringes
access to treatment and health services for overdoses, blood-                            to reduce the transmission of bloodborne viruses by injecting
borne viruses, and other complications of drug use; the access                           opioid and other drug users. Stronger advocacy by interna-
to needle and syringe programs; the extent to which illicit                              tional organizations and agencies is needed for the adoption of
opioid use is concentrated in socially disadvantaged minority                            such harm reduction measures as needle and syringe programs
groups; and the capacity of public health services to monitor                            and agonist substitution programs.
and respond to emerging infectious disease and drug-use epi-
demics. The burden is likely to be greatest in settings where the                        RESEARCH AND DEVELOPMENT
primary route of administration is injecting and where public
and personal health services are poorly developed, as appears to                         Two main areas are important for research and development.
be the case in Asia and in Eastern Europe.                                               First, better estimates are needed of the prevalence of illicit opi-
    Second, societal wealth and health care infrastructure                               oid dependence and prospective studies of the morbidity and
affect the capacity of developing societies to treat illicit opioid                      mortality that it causes in both developed and developing
dependence. A country’s capacity to provide opioid substitution                          countries. These estimates are especially needed in countries
treatment will be affected by the cost of oral opioid drugs, such                        where illicit opioid use is high because of their proximity to
as methadone, LAAM, and buprenorphine, and the existence of                              source countries. Second, we need evaluations of the effective-
specialist drug treatment centers; trained medical, nursing, and                         ness and cost-effectiveness of self-help, drug-free, and oral opi-
pharmacy staff; and a drug regulatory system, which are                                  oid substitution treatment in developing countries. A priority
required so as to deliver opioid substitution treatment safely                           should be the identification of safe, innovative, and less expen-
and effectively. Few developing countries possess this infra-                            sive ways of effectively delivering culturally acceptable forms of
structure. However, examples exist of apparently successful drug                         opioid maintenance treatments in developing countries. This
substitution programs, using such tools as sublingual buprenor-                          effort may require experimentation with a range of substitute
phine, that have been conducted with minimal resources in                                opioids, such as buprenorphine, and cheaper options, such as
extremely poor settings (Crofts and others 1998).                                        codeine and opium tincture.

916 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
CONCLUSIONS: PROMISES AND PITFALLS                                               and the United States, with the highest rates in Denmark,
                                                                                 France and the United Kingdom (EMCDDA 2002; W. Hall and
Illicit opioid use, especially injecting use, contributes to prema-              Pacula 2003). The limited data from developing countries
ture mortality and morbidity in many developed and develop-                      suggest that, with some exceptions (for example, Jamaica and
ing societies. Fatal overdoses and HIV/AIDS resulting from the                   South Africa), rates of cannabis use are lower in Africa, Asia,
sharing of dirty injecting equipment are major contributors                      the Caribbean, and South America than they are in Europe
to mortality and morbidity, and the economic costs of illicit                    and in English-speaking countries (W. Hall, Johnston, and
opioid dependence are substantial. Illicit opioid dependence                     Donnelly 1999).
generates substantial externalities that are not included in                        Surveys in the United States have found long waves of
burden-of-disease estimates, principally law enforcement costs                   cannabis use among young people since 1975. Cannabis use
incurred in handling drug dealing and property crime.                            increased during the 1970s to peak in 1979, before declining
    The most popular interventions for illicit opioid depend-                    steadily between 1980 and 1991. Use rose sharply in 1992 and
ence in many developed societies have been law enforcement                       increased throughout the 1990s, before leveling off in the late
efforts to interdict the drug supply and enforce legal sanctions                 1990s (Johnston, O’Malley, and Bachman 1994a, 1994b). There
against the use of opioid drugs. One consequence of this strat-                  was also a rise in cannabis use during the early 1990s in
egy has been that most illicit opioid users have been exposed                    Australia, Canada, and some European countries (W. Hall and
to the least effective intervention: imprisonment for drug or                    Pacula 2003).
property offenses. Prisons rarely take the opportunity to treat                     The natural history of cannabis use in the United States
dependence using opioid maintenance or to reduce the harm                        typically begins in the mid to late teens and reaches its maxi-
caused by illicit opioid use by providing access to clean inject-                mum in the early 20s before declining in the mid to late 20s.
ing equipment.                                                                   Only a minority of young adults continue to use cannabis into
    In treatment settings, the most popular interventions have                   their 30s (Bachman and others 1997; Chen and Kandel 1995).
been detoxification (which is not a treatment but a prelude to                   Getting married and having children substantially reduces rates
treatment) and drug-free treatment (which is the least attrac-                   of cannabis use (Bachman and others 1997).
tive and the least effective in retaining opioid-dependent peo-                     Cannibis use can have several adverse health effects, as dis-
ple in treatment). Opioid agonist maintenance treatment has                      cussed below.
been ambivalently supported in many developed societies
despite its being the treatment for which there is the best evi-                 Acute Effects of Cannabis Use. The most frequent unpleasant
dence of effectiveness, safety, and cost-effectiveness. The range                effects of cannabis use are anxiety and panic reactions, which
of opioid agonists available for maintenance treatment is                        most often occur in users who are unfamiliar with the drug’s
increasing. A number of developed countries have approved                        effects. Psychotic symptoms such as delusions and hallucina-
the use of BMT, which the limited data suggest may be approx-                    tions may be experienced following very high doses. There are
imately equivalent to MMT in efficacy and cost-effectiveness.                    no cases of fatal cannabis poisoning in the medical literature,
Opioid antagonists have a niche role in the treatment of opioid                  and the fatal dose in humans is likely to exceed what recre-
dependence because of poor compliance and an increased                           ational users are able to ingest (W. Hall and Pacula 2003).
risk of overdose on return to heroin use. Their efficacy may                         Cannabis intoxication impairs a wide range of cognitive and
improve with the development of long-acting injectable forms                     behavioral functions that are involved in driving an automobile
of the drug.                                                                     or operating machinery (Beardsley and Kelly 1999; Jaffe 1985).
                                                                                 It has been difficult to determine whether these impairments
                                                                                 increase the risk of being involved in motor vehicle accidents
ANNEX 48.A: PREVALENCE OF USE, ADVERSE                                           (Smiley 1999). Studies of the effect of cannabis on driving per-
HEALTH EFFECTS OF AND INTERVENTIONS                                              formance on the road have found only modest impairments,
FOR CANNABIS, COCAINE, AMPHETAMINES,                                             because cannabis-intoxicated drivers drive more slowly and
AND MDMA USE AND DEPENDENCE                                                      take fewer risks than drivers intoxicated by alcohol (Smiley
Cannabis                                                                             Cannabinoids are found in the blood of substantial propor-
Cannabis is the most widely used illicit drug globally, with                     tions of persons killed in motor vehicle accidents (Bates and
about 150 million users, or 3.7 percent of the world’s popula-                   Blakely 1999; Chesher 1995; Walsh and Mann 1999), but these
tion age 15 and older (UNODCCP 2003). Patterns of cannabis                       findings have been difficult to evaluate because they have not
use have been most extensively studied in Australia, Canada,                     distinguished between past and recent cannabis use
the United States, and Europe (W. Hall and Pacula 2003).                         (Ramaekers and others 2004). More recent research using bet-
Europe generally has lower rates of use than Australia, Canada,                  ter indicators of recent cannabis use has found a dose-response

                                                                                                                             Illicit Opiate Abuse | 917

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
relationship between cannabis and risk of motor vehicle                                  disease, and coronary atherosclerosis (Chesher and Hall 1999;
crashes (Ramaekers and others 2004). Cannabis used in com-                               Sidney 2002). One controlled study suggests that cannabis use
bination with alcohol substantially increases risk of accidents                          can precipitate heart attacks in middle-aged cannabis users
(Bates and Blakely 1999; Ramaekers and others 2004).                                     who have atherosclerosis in the heart, brain, and peripheral
                                                                                         blood vessels (Mittleman and others 2001).
Health Effects of Chronic Cannabis Use. Cannabis smoke is                                   Regular cannabis smoking impairs the functioning of the
a potential cause of cancer because it contains many of the                              large airways and causes chronic bronchitis (Tashkin 1999;
same carcinogenic substances as cigarette smoke (Marselos and                            Taylor and others 2002). Given that tobacco and cannabis
Karamanakos 1999). Cancers have been reported in the aerodi-                             smoke contain similar carcinogenic substances, it is likely that
gestive tracts of young adults who were daily cannabis smokers                           chronic cannabis smoking increases the risks of respiratory
(W. Hall and MacPhee 2002), and a case-control study has                                 cancer (Tashkin 1999).
found an association between cannabis smoking and head and
neck cancer (Zhang and others 1999). A prospective cohort                                Psychological Effects of Chronic Cannabis Use. Psychological
study of 64,000 adults did not find any increase in rates of head                        effects of chronic cannabis use can include a dependence
and neck or respiratory cancers (Sidney and others 1997).                                syndrome, cognitive effects, and psychotic disorders.
Further studies are needed to clarify the issue.
    Three studies of different types of cancer have reported                             Dependence Syndrome A cannabis dependence syndrome
an association with maternal cannabis use during pregnancy                               occurs in heavy chronic users of cannabis (American
(W. Hall and MacPhee 2002). There have not been any increases                            Psychiatric Association 1994). Regular cannabis users develop
in the rates of these cancers that parallel increases in rates of                        tolerance to THC. Some experience withdrawal symptoms on
cannabis use (W. Hall and MacPhee 2002).                                                 cessation of use (Kouri and Pope 2000), and some report prob-
    High doses of cannabinoids impair cell-mediated and                                  lems controlling their cannabis use (W. Hall and Pacula 2003).
humoral immunity and reduce resistance to infection by                                   The risk of dependence is about 1 in 10 among those who ever
bacteria and viruses in rodents (Klein 1999). Cannabis smoke                             use the drug, between 1 in 5 and 1 in 3 among those who use
impairs the functioning of alveolar macrophages, the first line                          cannabis more than a few times, and about 1 in 2 among daily
of the body’s immune defense system in the lungs. The doses                              users (W. Hall and Pacula 2003).
that produce these effects have been very high, and extrapola-
tion to the doses used by humans is complicated by the fact that                         Cognitive Effects Long-term daily cannabis use does not
tolerance to these effects develops (Hollister 1992). There is as                        severely impair cognitive function, but it may more subtly
yet no epidemiological evidence that rates of infectious disease                         impair memory, attention, and the ability to integrate complex
are higher among chronic heavy cannabis users. Several large                             information (Solowij 1998; Solowij and others 2002). It remains
prospective studies of HIV-positive homosexual men have not                              uncertain whether these effects are due to the cumulative effect
found that cannabis use makes it more likely that HIV-positive                           of regular cannabis use on cannabinoid receptors in the brain or
men develop AIDS (W. Hall and Pacula 2003).                                              whether they are residual effects of THC that will disappear after
    Chronic administration of tetrahydrocannabinol (THC)                                 an extended period of abstinence (W. Hall and Pacula 2003).
disrupts male and female reproductive systems in animals,
reducing testosterone secretion and sperm production, motil-                             Psychotic Disorders There is now good evidence that chronic
ity, and viability in males and disrupting ovulation in females                          cannabis use may precipitate psychosis in vulnerable individu-
(Brown and Dobs 2002). It is uncertain whether cannabis use                              als (see, for example, Arseneault and others 2002; van Os and
has these effects in humans because of the limited research on                           others 2002; Zammit and others 2002). It is less likely that
human males and females (Murphy 1999).                                                   cannabis use can cause psychosis de novo, because the inci-
    The use of cannabis during pregnancy is associated with                              dence of schizophrenia has either remained stable or declined
smaller birthweight (English and others 1997; Fergusson,                                 while cannabis use has increased among young adults
Horwood, and Northstone 2002), but it does not appear to                                 (Degenhardt, Hall, and Lynskey 2003).
increase the risk of birth defects (W. Hall and Pacula 2003). In
                                                                                         Effects of Cannabis Use on Adolescents. Cannabis use has a
some studies, infants exposed to cannabis during pregnancy
                                                                                         number of effects on adolescents.
show behavioral and developmental effects during the first few
months after birth; these effects are smaller than those seen                            Gateway Hypothesis Adolescents in developed societies typi-
after tobacco use during pregnancy (Fried and Smith 2001).                               cally use alcohol and tobacco before using cannabis, which in
    The changes that cannabis smoking causes in heart rate                               turn, they use before using hallucinogens, amphetamines,
and blood pressure are unlikely to harm healthy young adults,                            heroin, and cocaine (Kandel 2002). Generally, the earlier the
but they may harm patients with hypertension, cerebrovascular                            age of first use and the greater the involvement with any drug

918 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
in the sequence, the more likely a young person is to use the                    Cocaine
next drug in the sequence (Kandel 2002). The role played by                      After cannabis, cocaine is one of the most widely used illicit
cannabis in this sequence remains controversial (W. Hall and                     drugs in developed and developing societies. Some 14 million
Lynskey forthcoming; W. Hall and Pacula 2003).                                   people were estimated to have used cocaine globally in 2003,
    The simplest hypothesis is that cannabis use has a pharma-                   with demand for treatment second only to heroin (UNODCCP
cological effect that increases the risk of using drugs later in the             2003). The highest rates of reported cocaine use—and the best
sequence. Equally plausible hypotheses are that it is due to a                   data on trends in cocaine use—come from the United States,
combination of (a) early recruitment into cannabis use of                        the world’s largest cocaine market. Rates of cocaine use in the
nonconforming and deviant adolescents who are likely to use                      United States increased from the mid 1970s until 1985, when
alcohol, tobacco, and illicit drugs; (b) a shared genetic vulnera-               5.7 million Americans age 12 and older reported using cocaine
bility to dependence on alcohol, tobacco, and cannabis; and                      in the preceding month. Rates of cocaine use in the preceding
(c) socialization of cannabis users within an illicit drug–using                 month have declined steadily since 1985. In 2000, 11.2 percent
subculture, which increases the opportunity, and encourage-                      of Americans over age 12 reported that they had used cocaine
ment to use other illicit drugs (W. Hall and Pacula 2003).                       at some time in their lives, and 0.4 percent (800,000 people)
                                                                                 reported weekly cocaine use (SAMHSA 2001). Among young
Adolescent Psychosocial Outcomes Cannabis use is associated                      U.S. adults age 18 to 25, lifetime prevalence was 14.9 percent in
with early withdrawal from high school, early family formation,                  2001, rising slightly to 15.4 percent in 2002 (SAMHSA 2003).
poor mental health, and involvement in drug-related crime. In                    In 2002, annual prevalence figures from student surveys were
the case of each of these outcomes, the strong associations in                   15 percent lower than 1998 figures and 60 percent lower than
cross-sectional data are more modest when account is taken of                    1985 figures (UNODCCP 2003). A more recent study of U.S.
the fact that cannabis users show characteristics before they use                adults age 35 years found that 6 percent of men and 3 percent
cannabis that predict these outcomes. For example, they have                     of women had used cocaine within the preceding 12 months
lower academic aspirations and poorer school performance than                    (Merline and others 2004).
peers who do not use cannabis (Lynskey and Hall 2000; Macleod                        The reported prevalence of cocaine use in other developed
and others 2004). Nonetheless, the evidence increasingly sug-                    societies is much lower than that in the United States. In
gests that regular cannabis use adds to the risk of these outcomes               Europe, for example, rates of lifetime cocaine use range from
in adolescents already at risk (W. Hall and Pacula 2003).                        0.5 percent to 5 percent (EMCDDA 2003), compared with
                                                                                 12.3 percent among American adults in 2001 (SAMHSA 2001).
Interventions for Cannabis Dependence. Although many                             Rates of cocaine use in Australia resemble those in Europe, with
dependent cannabis users may succeed in quitting without                         4.3 percent of adults reporting lifetime use (Darke and others
professional help, some are unable to stop on their own and                      2000).
will need assistance to do so. There has not been a great deal of                    The prevalence of cocaine use is likely to be lower in devel-
research on pharmacological treatments for cannabis depend-                      oping societies, but the poor quality of the available data makes
ence, although a recent study trialed divalproex sodium with                     it difficult to be sure (UNDCP 1997). There probably has been
promising results (Levin and others 2004). Limited research                      an increase in cocaine use in some developing countries in
exists on the effectiveness of different types of psychosocial                   recent years, but it is difficult to estimate the size of the increase
treatments for dependent cannabis use (Budney and others                         (United Nations Commission on Narcotic Drugs 2000). The
2000; Copeland and others 2001; Stephens, Roffman, and                           region with the highest rates of cocaine use among developing
Simpson 1994). These approaches have involved short-term                         societies is likely to be Central and South America. The botan-
cognitive behavioral treatments modeled on similar treatments                    ical source is indigenous to the region and has traditionally
for alcohol dependence, usually given in three to six sessions on                been used by local populations. Moreover, several nations in
an outpatient basis.                                                             Central and South America have a history of production and
   In all of these studies, rates of abstinence at the end of                    export to global markets. Recent reports indicate that cocaine
treatment have been modest (20 to 40 percent), and subse-                        abuse is increasing in South America (UNODCCP 2003), and
quent high rates of relapse mean that rates of abstinence after                  a recent household survey on drug abuse in São Paulo, Brazil,
12 months have been very modest (Budney and Moore 2002).                         estimated cocaine prevalence at 2.1 percent (Galduroz and
Nonetheless, treatment does substantially reduce cannabis use                    others 2003).
and problems. These outcomes are not very different from
those observed in the treatment for alcohol and other forms
of drug dependence (Budney and Moore 2002). Much more                            Adverse Health Effects of Cocaine. Most cocaine use is infre-
research is needed before sensible advice can be given about the                 quent; regular cocaine use (monthly or more frequently) can
best ways to achieve abstinence from cannabis.                                   be a major public health problem. Regular cocaine users who

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                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
inject cocaine or smoke crack cocaine are especially likely to                           Previous studies have documented a variety of neuropsycho-
develop dependence and to experience problems related to                                 logical effects of cocaine use, including deficits in memory and
their cocaine use (Platt 1997). In the United States, it has been                        problem solving (Beatty and others 1995; Hoff and others
estimated that one in six of those who ever use cocaine become                           1996; O’Malley and others 1992). More recently, a twin study
dependent on the drug (Anthony, Warner, and Kessler 1994).                               indicated that cocaine may lead to impaired attention and
High rates of cocaine dependence are found among people                                  motor skills up to one year after the conclusion of heavy use
treated for alcohol and drug problems and among arrestees in                             (Toomey and others 2003).
the United States (Anglin and Perrochet 1998).                                              The method by which cocaine is administered can result in
    In large doses, cocaine may be harmful in both cocaine-                              adverse health effects (Platt 1997). Snorting cocaine through
naive and cocaine-tolerant individuals (Platt 1997; Vasica and                           the nose can lead to rhinitis, damage to the nasal septum, and
Tennant 2002). The vasoconstrictor effects of cocaine in large                           loss of the sense of smell. Smoking cocaine can lead to respira-
doses place great strains on a number of the body’s physiolog-                           tory problems, and injecting cocaine leads to the risks of infec-
ical systems (McCann and Ricaurte 2000). Effects on the car-                             tions and bloodborne viruses associated with all injecting drug
diovascular system can result in a range of difficulties, from                           use.
chest pain to fatal cardiac arrests (Lange and Hillis 2001).                                Users who inject cocaine, either on its own or in combina-
Neurological problems include cerebral vascular accidents such                           tion with heroin (“speedballs”), inject much more frequently
as strokes or seizures. Other effects of cocaine can include gas-                        than other injecting drug users and, as a consequence, engage
trointestinal problems such as vomiting, colitis, and bowel                              in more needle sharing, take more sexual risks, and have
infarction and respiratory problems such as asthma, respiratory                          higher rates of HIV infection (Chaisson and others 1989;
collapse, pulmonary edema, and bronchitis. Hyperthermia                                  Schoenbaum and others 1989; van Beek, Dwyer, and Malcolm
may occur because of the increased metabolism, peripheral                                2001). Associations between cocaine use and HIV risk-taking
vasoconstriction, and inability of the thalamus to control                               have been reported in Europe (Torrens and others 1991),
body temperature (Crandall, Vongpatanasin, and Victor 2002).                             Australia (Darke and others 1992), and the United States
Obstetric complications can include irregularities in placental                          (Chaisson and others 1989). Recent Australian research
blood flow, premature labor, and low neonate birthweight                                 has indicated that injecting cocaine users report more prob-
(Majewska 1996; Platt 1997; Vasica and Tennant 2002).                                    lems related to injecting drug use—such as vascular problems,
    Adverse health effects from cocaine are potentially fatal and                        abscesses, and infections—than other injecting drug users
can occur among healthy users irrespective of cocaine dose and                           (Darke, Kaye, and Topp 2002).
frequency of use (Lange and Hillis 2001; Vasica and Tennant                                 The link between cocaine use and HIV risk is not restricted
2002). Although the likelihood of health problems may                                    to those who inject cocaine. Crack smoking has been linked to
increase with dosage and frequency of use, there is wide indi-                           higher levels of needle risk, sexual risk taking, and HIV infec-
vidual variation in reactions to cocaine and, therefore, no spe-                         tion (Chaisson and others 1989; Chirgwin and others 1991;
cific combination of conditions under which adverse health                               Desjalais and others 1992; Grella, Anglin, and Wugalter 1995).
effects can be predicted. There is no antidote to cocaine over-                          Two mechanisms probably underlie the relationship between
dose as there is for an overdose of heroin (Platt 1997).                                 cocaine use and HIV infection. First, the short half-life of
    The impact of cocaine on mental health is also complex.                              cocaine promotes a much higher frequency of injecting by
Although cocaine can produce feelings of pleasure, it may also                           users than that seen in heroin injectors. Second, cocaine itself
result in negative psychological symptoms such as anxiety,                               disinhibits and stimulates users, encouraging them to take
depression, paranoia, hallucinations, and agitation (American                            greater risks with sexual activity and needle use (Darke and
Psychiatric Association 1994). Regular cocaine users experience                          others 2000).
high rates of psychiatric disorders. In the United States, regular                          Cocaine is associated with a risk of intentional injuries and
cocaine users report high rates of anxiety and affective disor-                          injuries in general. A recent review reported that 28.7 percent of
ders (Gawin and Ellinwood 1988; Platt 1997). The repeated use                            people with intentional injuries and 4.5 percent of injured driv-
of large doses of cocaine can also produce a paranoid psychosis                          ers tested positive for cocaine (Macdonald and others 2003).
(Majewska 1996; Manschreck and others 1988; Platt 1997; Satel                            Users are also at risk of death from an accidental overdose of
and Edell 1991). People who are acutely intoxicated by cocaine                           cocaine. A recent study of accidental deaths from drug overdose
can become violent, especially those who develop a paranoid                              in New York between 1990 and 1998 found that 70 percent of
psychosis (Platt 1997).                                                                  deaths were caused by cocaine, often in combination with opi-
    Animal studies suggest that cocaine use may be neurotoxic                            ates (Coffin and others 2003). The causes of cocaine-related
in large doses—that is, it can produce permanent changes in                              deaths are usually related to cardiovascular complications
the brain and neurotransmitter systems (Majewska 1996; Platt                             (Vasica and Tennant 2002), but death may also be due to brain
1997). It is unclear whether use is also neurotoxic in humans.                           hemorrhage, stroke, and kidney failure (Brands, Sproule, and

920 | Disease Control Priorities in Developing Countries | Wayne Hall, Chris Doran, Louisa Degenhardt, and others

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Marshman 1998). Injection of cocaine is most likely to cause an                there is evidence of previous or consequent symptoms of
overdose, followed by smoking it, with intranasal use involving                depression. Other antidepressants have been used with mixed
the least risk (Pottieger and others 1992).                                    results: imipramine and trazodone have been found to have
    Much less is known about nonfatal cocaine overdose. A                      more adverse effects than desipramine, and fluoxetine has not
study in Miami, Florida, found that 40 percent of users had                    been found to be effective (Mendelson and Mellon 1996). A
overdosed on cocaine at least once (Pottieger and others 1992).                recent systematic review found no current evidence to support
More recently, a study in Brazil found that 20 percent of users                the use of antidepressants in the treatment of cocaine depend-
had experienced an overdose, with 50 percent knowing some-                     ence (Lima and others 2003).
one who had died from an overdose (Mesquita and others                             Dopamimetic drugs have also been used to treat cocaine
2001). A study in Sydney, Australia, found that 17 percent of                  dependence; such treatments are based on the action of cocaine
injecting cocaine users and 6 percent of noninjecting cocaine                  to block reuptake of dopamine. Unfortunately, although some of
users had ever overdosed, with 9 percent and 3 percent, respec-                these drugs are relatively effective, they also result in quite
tively, overdosing in the preceding 12 months (Kaye and Darke                  severe adverse effects (Mendelson and Mellon 1996). Current
2003). Frequency of cocaine use, severity of dependence, and                   evidence does not support the clinical use of dopamine ago-
route of administration did not predict an overdose, support-                  nists for cocaine dependence (Soares and others 2003). Opioid
ing the view that cocaine overdose is an unpredictable event.                  antagonists (for example, naltrexone) or opioid mixed agonist-
                                                                               antagonists (such as buprenorphine) have been explored, on
Interventions for Cocaine Dependence. Efforts at interven-                     the basis that cocaine dependence may be accompanied by
tion have included pharmacological treatments as well as psy-                  dependence on opiates. Although there have been problems
chotherapy and cognitive behavioral therapy.                                   with compliance with naltrexone therapy (National Research
                                                                               Council Committee on Clinical Evaluation of Narcotic
Pharmacological Interventions Despite much research effort                     Antagonists 1978), buprenorphine has shown promising pre-
there are no effective pharmacological treatments for cocaine                  clinical and clinical trial results (Kosten, Kleber, and Morgan
dependence (Kreek 1997; McCance 1997; Mendelson and                            1989). Other promising directions include cannabinoid recep-
Mellon 1996; Nunes 1997; Silva de Lima and others 2002; van                    tor antagonists and cortisol synthesis inhibitors (van den Brink
den Brink and van Ree 2003). Attempts have been made to                        and van Ree 2003) and vaccination against the effects of
develop longer-acting agonist drugs that act on the same                       cocaine (Kantak 2003), but there is as yet no evidence on the
molecular targets as cocaine without producing its euphoric                    effectiveness of any of these interventions.
effects (for example, methylphenidate) (Kreek 1997) or that                        Acupuncture has also been used to treat cocaine depend-
block its rewarding and euphoric effects (McCance 1997).                       ence. Auricular acupuncture is frequently used, but the small
There has also been a search for drugs that indirectly change                  number of trials that have been conducted have not provided
the effects that cocaine has on the brain by acting on other                   sufficient evidence of effectiveness (van den Brink and van Ree
neurotransmitter systems, such as the serotonergic system                      2003).
(for example, fluoxetine) (McCance 1997). None of these
approaches has produced an effective pharmacotherapy for                       Psychotherapy and Cognitive Behavioral Therapy The lack of
cocaine dependence (Lima and others 2003; Platt 1997; Soares                   evidence for pharmacological therapy means that treatment
and others 2003).                                                              for cocaine dependence currently relies on cognitive behavior
   Development of pharmacological therapies for cocaine                        therapies combined with contingency management strategies.
dependence and their evaluation is complicated by the multiple                 Unfortunately, psychosocial treatments for cocaine dependence
interactive processes that may have contributed—for example,                   are also of limited effectiveness. Treatments such as therapeutic
coexisting substance abuse or mental health issues (Mendelson                  communities, cognitive behavioral treatments, contingency
and Mellon 1996). Many of the approaches to the treatment of                   management, and 12 step–based self-help approaches benefit
cocaine dependence have also been used in treating patients                    cocaine-dependent people by reducing their rates of cocaine
with alcoholism and other substance abuse disorders.                           use and improving their health and well-being, but rates of
   A number of drugs have been used to treat cocaine based on                  relapse to cocaine use after treatment remain high (Platt 1997).
their relevance to the symptoms of cocaine dependence (Silva de                   Mendelson and Mellon (1996) conclude that there are no
Lima and others 2002; van den Brink and van Ree 2003). The                     specific cognitive or behavioral interventions that are uniquely
frequency of depressive symptoms has led to the exploration of                 effective in treating cocaine dependence. However, some success
the effectiveness of antidepressant drugs. Desipramine has been                has been demonstrated with incentive-based programs in which
used with mixed effectiveness for cocaine detoxification and the               rewards are provided for urine samples that are free of cocaine,
maintenance of abstinence (Covi and others 1994; Gawin,                        although there is doubt about whether results are sustained
Kleber, and Byck 1989), but it appears to be most effective when               (Roozen and others 2004). Such programs are generally more

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                                ©2006 The International Bank for Reconstruction and Development / The World Bank
effective when the patient’s family and friends are involved                             for stimulant drugs such as hallucinogens and cocaine (Darke
(Higgins and others 1994). Petry and others (2004) suggested                             and Hall 1995; Hando and Hall 1994; Vincent and others 1998).
that contingency management was effective in reducing                                       Globally, Europe is the main center of amphetamine produc-
cocaine use in a community-based treatment setting. They                                 tion, particularly Belgium, the Netherlands, and Poland, with
found that the benefits of treatment depended on the magni-                              production increasing in Eastern Europe (UNODCCP 2003).
tude of reward, with those earning up to US$240 obtaining bet-                           Half of all Western European countries reported an increase in
ter results than those earning up to US$80. They suggested that                          amphetamine abuse in 2000, but in 2001 the figure fell to 33 per-
this form of intervention may work best for people with more                             cent (UNODCCP 2003). Lifetime use of amphetamines is
severe dependence on cocaine.                                                            reported to be between 0.5 percent and 6 percent among
    A multicenter investigation examining the efficacy of four                           European Union countries, with the exception of the United
psychosocial treatments for cocaine-dependent patients con-                              Kingdom, where the figure is 11 percent. Denmark and Norway
cluded that individual drug counseling in combination with                               also have relatively higher rates of use (EMCDDA 2003).
group drug counseling showed the most promise for effective
treatment of cocaine dependence over two forms of traditional                            Adverse Health Effects of Amphetamine Use. Amphetamine
psychotherapy (Crits-Christoph and others 1999). Community                               users who inject the drug are at high risk of bloodborne infec-
reinforcement involving an intensive, biopsychosocial, multi-                            tions through needle sharing. Amphetamine users are as likely
faceted approach to lifestyle change has shown positive effects                          as opioid users to share injection equipment (Darke, Ross,
over four to six weeks and has the advantage of being tailored                           Cohen, and others 1995; Darke, Ross, and Hall 1995; W. Hall,
to individual goals (Roozen and others 2004).                                            Bell, and Carless 1993; Hando and Hall 1994; Kaye and Darke
    The few studies of the long-term effects of treatment have not                       2000; Loxley and Marsh 1991). In addition, the youth of
shown particularly encouraging results. A one-year follow-up of                          amphetamine users places them at risk of sexual transmission
the U.S. Drug Abuse Treatment Outcome Studies reported that                              of diseases such as HIV and hepatitis B virus (although not
reductions in the use of cocaine in the year following treatment                         hepatitis C). Primary amphetamine users have been demon-
were associated with longer duration of treatment, particularly                          strated to be a sexually active group, and small proportions
six months or more in long-term residential or outpatient treat-                         engage in paid sex to support their drug use (Darke, Ross,
ments (Hubbard, Craddock, and Anderson 2003). A five-year                                Cohen, and others 1995; Hando and Hall 1994). Among gay
national follow-up study of 45 U.S. treatment programs found                             and bisexual men, amphetamines may be used to enhance sex-
that only 33 percent of the sample had highly favorable out-                             ual encounters, which may lead to unprotected anal intercourse
comes (Flynn and others 2003).                                                           and increased risk of HIV infection (Urbina and Jones 2004).
                                                                                            High-dose amphetamine use, especially by injection, can
                                                                                         result in a schizophreniform paranoid psychosis, associated
Amphetamines                                                                             with loosening of associations, delusions, and hallucinations
According to WHO, amphetamines and methamphetamines                                      (Gawin and Ellinwood 1988; Jaffe 1985). The psychosis could
are the most widely abused illicit drugs after cannabis, with an                         be reproduced by the injection of large doses in addicts (Bell
estimated 35 million users worldwide (Rawson, Anglin, and                                1973) and by the repeated administration of large doses to nor-
Ling 2002).                                                                              mal volunteers (Angrist and others 1974).
    In Australia, the lifetime prevalence of amphetamine use is                             High proportions of regular amphetamine injectors describe
between 6 and 8 percent in the general population, making                                symptoms of anxiety, panic attacks, paranoia, and depression.
amphetamines the most commonly used illicit drug after                                   The emergence of such symptoms is associated with injecting
cannabis during that period (Makkai and McAllister 1998). In                             the drugs, greater frequency of use, and dependence on amphet-
1998, the lifetime prevalence of amphetamine use was highest                             amines (W. Hall and others 1996; McKetin and Mattick 1997,
(25 percent) among male users age 20 to 29.                                              1998). Recent evidence also suggests that women may experi-
    The use of amphetamines is generally less frequent than that                         ence more emotional effects of amphetamine intoxication than
of opioids (Darke and Hall 1995; Darke, Kaye, and Ross 1999; W.                          men and higher rates of anorexia nervosa than women without
Hall, Bell, and Carless 1993; Hando, Topp, and Hall 1997;                                amphetamine disorders (Holdcraft and Iacono 2004).
Vincent and others 1998). This pattern is no doubt due to the                               In sufficiently high doses, amphetamines can be lethal
physical and psychological toll taken by regular amphetamine                             (Derlet and others 1989). However, the risk is low compared
use. Although such use is less frequent overall, however, there is                       with the high risks of overdose associated with central nervous
widespread bingeing on amphetamines, with frequent use over                              system depressants such as heroin. Typically, amphetamine-
several consecutive days, which may be followed by benzodi-                              related deaths are associated with the effects of amphetamines
azepine use to “come down.” Polydrug use is particularly com-                            on the cardiovascular system—for example, cardiac failure and
mon among amphetamine users, who show a marked preference                                cerebral vascular accidents (Mattick and Darke 1995).

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                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
   There is evidence that amphetamines are neurotoxic                          that those who received more Matrix treatment had better
(Robinson and Becker 1986). Evidence from animal studies                       abstinence rates than those who had less treatment but that
indicates that heavy amphetamine use results in dopaminergic                   desipramine had no effect on treatment outcome.
depletion (Ellison 1992; Fields and others 1991). The few stud-                   J. Hall and others (1999) conducted an evaluation of the
ies of the neuropsychological effects of amphetamine abuse                     effectiveness of the Iowa Case Management Project. The proj-
report findings similar to those found with cocaine abuse.                     ect was designed to supplement interventions provided by a
Deficits in memory and attention have been attributed to                       drug abuse treatment agency and is a comprehensive social
amphetamine use (McKetin and Mattick 1997, 1998). More                         work intervention, including outreach activities and provision
recently, a twin study indicated that amphetamine abuse might                  of limited emergency funds. The results of the evaluation
lead to impaired attention and motor skills up to one year after               showed that comprehensive case management was effective in
the conclusion of heavy use (Toomey and others 2003).                          improving employment status among amphetamine users sub-
                                                                               sequent to treatment. There was an almost significant lower
Interventions for Amphetamine Dependence. Treatment for                        incidence of depression among those who received the pro-
methamphetamine abuse has been a relatively recent develop-                    gram compared with controls. Drug use decreased significantly
ment and has generally been based on previous treatments for                   for clients in both control and program conditions.
cocaine abuse (Huber and others 1997). Cretzmeyer and oth-                        More recently, an Australian study evaluated the effective-
ers (2003) reviewed treatments for methamphetamine abuse,                      ness of brief cognitive-behavioral interventions among regular
noting that there has been little research on the effectiveness                users of amphetamines (Baker, Boggs, and Lewin 2001). The
of drug treatment, probably because many amphetamine                           researchers found a clinically significant reduction in daily
users use multiple drugs. The combination of methampheta-                      amphetamine use among the intervention groups compared
mine use with use of marijuana or other sedating drugs indi-                   with controls and concluded that further studies of brief
cates that effective treatments need to address the use of mul-                cognitive-behavioral interventions are feasible and warranted.
tiple drugs. A Cochrane Review concluded that evidence for                     Although some promising interventions have been identified
success in treatment of amphetamine dependence is very lim-                    to assist methamphetamine abusers, no single treatment
ited, with no pharmacological treatment demonstrated to be                     option has yet been established as better than any other in a
effective (Srisurapanont, Jarusuraisin, and Kittirattanapaiboon                randomized controlled trial (Cretzmeyer and others 2003).
    An early study explored the use of aversion therapy in a                   Methylenedioxymethamphetamine
multimodal treatment program using educational groups,                         Methylenedioxymethamphetamine is more widely known
individual counseling, occasional family counseling, and after-                as ecstasy or MDMA. In Australia, the lifetime prevalence of
care planning. The intervention paired an aversive stimulus                    MDMA use increased from 1 percent of the population in 1988
(either chemical or electrical) with the act of using metham-                  to 4.6 percent (about one in 20 persons ) in 1998, with 2.3 per-
phetamines. Cocaine use was also treated in this way. After                    cent reporting MDMA use in the preceding 12 months (Topp
12 months, 53 percent of patients were abstinent and the                       and others 1998). In 2001, 6.1 percent of Australians age 14
researchers noted that their results were promising, despite a                 years or older reported lifetime use of MDMA, with 2.9 percent
number of limitations to the study (Frawley and Smith 1992).                   reporting use within the preceding year (Degenhardt, Barker,
    An intervention combining imipramine, a tricyclic antide-                  and Topp 2004). Rates of use are generally higher among males
pressant, with intensive group counseling has been evaluated                   than females (3.1 percent versus 1.5 percent). MDMA use in
with cocaine and methamphetamine abusers. Patients received                    the preceding 12 months is most common among those age
either a low or higher dose (as needed) of imipramine, as well                 20 to 29 (5 percent of females and 12 percent of males) (Topp
as intensive group counseling and access to medical and psy-                   and others 1998).
chiatric care. Those who received the higher dose stayed in                       The availability of MDMA has also increased, as indicated by
treatment longer, but the results did not support the use of                   the proportion of the population who have been offered MDMA
imipramine for methamphetamine abuse (Galloway and                             (from 4 percent in 1988 to 7 percent in 1991) (Makkai and
others 1994).                                                                  McAllister 1998), with 14 percent of those age 14 to 29 reporting
    The Matrix Program for methamphetamine and cocaine                         that they had been offered MDMA in the preceding year.
abusers has also been evaluated. The Matrix Program uses a                        Research suggests that the pattern of MDMA use changed
cognitive behavioral approach with an emphasis on relapse                      during the 1990s (Topp and others 1998). Users of MDMA are
prevention (Huber and others 1997). The study evaluated the                    commencing use at a younger age, and they appear to be using
effectiveness of three conditions: Matrix treatment alone,                     larger doses more frequently. The incidence of bingeing on
Matrix treatment plus desipramine, and Matrix treatment plus                   MDMA appears to have increased, as does the prevalence of the
placebo (Shoptaw and others 1994). The researchers concluded                   parenteral use of this drug. The increase in the use of MDMA

                                                                                                                            Illicit Opiate Abuse | 923

                                ©2006 The International Bank for Reconstruction and Development / The World Bank
by injection has been noted among surveys of MDMA users                                  A recent U.K. study of 430 regular users of MDMA reported
and of injecting drug users generally.                                                   that 83 percent of participants reported low mood and 80 per-
    An examination of trends in the United States suggested                              cent experienced impaired concentration. Long-term effects
that, although the use of MDMA has increased over time, its                              of MDMA included the development of tolerance to MDMA
prevalence is significantly less than that of other drugs of abuse                       (59 percent), impaired ability to concentrate (38 percent), and
(Yacoubian 2003b). A study of 14,520 U.S. college students                               depression (37 percent) (Verheyden and others 2003).
indicated 6 percent lifetime use of MDMA, 3 percent within the                               Physical symptoms that were perceived as being due to
preceding 12 months, and 1 percent within the preceding                                  MDMA use alone (Topp and others 1998) included an inability
30 days. Those who had used MDMA in the preceding                                        to urinate, blurred vision, vomiting, numbness or tingling, loss
12 months were more likely to be white and a member of a fra-                            of sexual urge, and hot and cold flushes. As with amphetamines,
ternity or sorority and to have used a range of other drugs                              the use of MDMA to facilitate sexual encounters may lead to
(Yacoubian 2003a). Rates of use are much higher in surveys of                            risky sexual behavior and risk of sexually transmitted infections
club attendees. A recent U.S. survey found 86 percent reporting                          such as HIV. Studies of gay and bisexual men have found an
lifetime use, 51 percent 30-day use, and 30 percent use within                           association between MDMA use and high-risk sexual behavior
the preceding 2 days (Yacoubian and others 2003).                                        (Urbina and Jones 2004).
    Abuse of MDMA had showed signs of decreasing in Western                                  MDMA has been implicated in a growing number of deaths,
Europe but has recently shown signs of increase (UNODCCP                                 both in Australia and in other countries (Henry, Jeffreys, and
2003). Although MDMA use appears to be still diffusing, in                               Dawling 1992; Solowij 1993; White, Bochner, and Irvine 1997).
2003 only four countries (Ireland, the Netherlands, Spain, and                           Although the reasons for extreme reactions have yet to be
the United Kingdom) reported a rate of more than 3 percent                               clearly determined, deaths have most often been attributed to
use among young adults in the preceding 12 months                                        hyperthermia when MDMA was used at dance venues. A com-
(EMCDDA 2003). In the United States, use declined in 2002 for                            bination of sustained exertion, high ambient temperatures, and
the first time, but it increased in other regions, particularly the                      inadequate fluid replacement appears to compound the effect
Caribbean, parts of South America, Oceania, Southeast Asia,                              of MDMA on thermoregulatory mechanisms, causing a rapid
the Near East, and southern Africa (UNODCCP 2003).                                       and fatal rise in body temperature (Topp and others 1998).
Lifetime experience of MDMA is reported to range from                                    Some deaths have been attributed to excessive water consump-
0.5 percent to 5 percent in European Union countries, with use                           tion, which causes cerebral edema (Cook 1996; Matthai and
more common in the Netherlands (EMCDDA 2003).                                            others 1996).
    Population survey findings from New Zealand reported an
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©2006 The International Bank for Reconstruction and Development / The World Bank
                                                                                     Chapter 60

                                                   Occupational Health
                                                                                Linda Rosenstock, Mark Cullen, and Marilyn Fingerhut

Workers around the world—despite vast differences in their                      health in the workplace is integrated into all aspects of daily life
physical, social, economic, and political environments—face                     for these often subsistence agricultural workers. For example,
virtually the same kinds of workplace hazards. These hazards                    pesticide poisoning is a hazard faced by workers and their fam-
are traditionally categorized into four broad types: chemical,                  ilies and communities.
biological, physical, and psychosocial. What emerges from our                       The informal workforce, which in industrial countries is
incomplete knowledge of their risk, however, is that the more                   rarely larger than 10 percent of total employment, looms large
than 80 percent of the world’s workforce that resides in the                    in developing countries. This workforce includes self-
developing world disproportionately shares in the global bur-                   employed, household-based unpaid labor (family members,
den of occupational disease and injury. Several classic occupa-                 for example) and independent service workers such as street
tional diseases, such as silicosis and lead poisoning, that have                vendors. In the developing world, employment in the informal
been substantially eliminated in industrial countries remain                    sector may reach 70 percent, with the contribution to the gross
endemic elsewhere in the world. Whether this high and pre-                      domestic product (GDP) ranging from 10 to 60 percent
ventable burden of ill health faced by workers in the develop-                  (ILO 2002).
ing world is the result of ignorance, inattention, or intent, com-                  Informal economy workers are often unprotected in the reg-
pelling evidence indicates that work-related health conditions                  ulatory arena even in the industrial world. This circumstance
could be substantially reduced, often at modest cost.                           is exacerbated when the vulnerable employment status in the
                                                                                developing world is coupled with problems of poverty and ill
                                                                                health. Cottage-industry workers abound in the informal sec-
NATURE AND CAUSES OF OCCUPATIONAL                                               tor, and home-based work can fully blur distinctions between
HEALTH CONDITIONS IN THE DEVELOPING                                             occupational and other environmental hazards. Not uncom-
                                                                                mon across the developing world are lead-poisoned adults who
                                                                                manufacture batteries in crude facilities at home and their
Despite country-to-country differences, some commonalities                      lead-poisoned children, exposed to the lead while sleeping and
exist within the workforce of the developing world that are                     playing in the next room.
worth noting. Workforce distribution by economic sector is                          The migrant workforce, which is increasing worldwide, is
different from that in the industrial world. Compared with                      estimated to be 120 million (ILO 2000). In the industrial world,
industrial countries, where single-digit percentages prevail—                   immigrant workers often perform work deemed unattractive
for example, approximately 2 percent in the United                              (seasonal agricultural work in the United States, service sector
Kingdom—developing countries employ about 70 percent of                         work in the United Kingdom), but the issues of a migrant
their economically active population in the agricultural sector                 workforce in some parts of the developing world take on even
(World Bank 2003). For many of these workers, the distinction                   greater import. In southern Africa, for example, migrant min-
between health at work and health at home is blurred, because                   ing workers face the extraordinary burden of risk for the triad


                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
of silicosis, tuberculosis, and HIV/AIDS—diseases that are                                         would be reduced by 90 percent; even if the smoking exposure
inextricably linked to interactive determinants of workplace,                                      continued, elimination of the asbestos exposure would reduce
housing, and social and economic factors (Trapido and others                                       the overall risk by 80 percent. Those considerations are not the-
1996).                                                                                             oretical but well supported by empirical data. In parts of China
    Workers in the developing world face different risks in the                                    and elsewhere in the developing world, asbestos exposure
health transition than do their counterparts in the industrial                                     abounds as cigarette smoking is rising. Effective intervention
world. They may be exposed to the combined and often syner-                                        strategies will be those based on a comprehensive approach to
gistic risks of both traditional and emerging hazards. Workers                                     the overall burden rather than those addressing the individual
may also face unregulated and unprotected exposures to                                             burdens of specific exposures, recognizing that organizational
known hazards just as those same hazards—silica and asbestos,                                      or institutional interventions (such as eliminating asbestos
for example—were faced decades ago by millions of workers in                                       from the workplace) are far more effective than those targeting
the industrial world. A significant difference, though, is that                                    individual behaviors (such as smoking cessation).
workers in the developing world are being exposed when wide-
spread knowledge is available about the risks and effective pre-
ventive measures (Kjellstrom and Rosenstock 1990). Even as                                         GLOBAL BURDEN OF DISEASE FROM
these workers are forced to replay history, despite the availabil-
                                                                                                   OCCUPATIONAL HEALTH RISKS
ity of information and knowledge transfer unthinkable just a
generation ago, they face other hazards, including the produc-                                     The overall picture that emerges from all parts of the develop-
tion, marketing, and importation of environmental hazards                                          ing world is one of increased health and safety risks in all
such as cigarettes. In the instance of asbestos and tobacco, both                                  occupations for which data are available.
products are being aggressively marketed and exported by the                                           Dramatic changes in the global labor force will occur as
industrial world (especially asbestos from Canada and tobacco                                      globalization and population growth continue to affect the
from the United States) to the developing world.                                                   global economy. For example, the labor force in Latin America
    A real example of hazards faced by developing workers in                                       and the Caribbean is one of the fastest growing in the world,
what might be called the risk transition is that posed by dual                                     with 217 million workers in 2000; the number of workers is
exposure to asbestos and cigarette smoke and risk for lung can-                                    expected to reach 270 million in 2010 (PAHO 2002). The bur-
cer. This example is especially troubling not only because the                                     den of disease and injury attributable to workplace risks in the
risk is dauntingly high but also because exposures to both are                                     formal and informal sectors is grave and will continue to rise.
occurring with full knowledge of their individual and cumula-                                      Inadequate data and reporting systems make capturing the
tive effects. As shown in table 60.1, against a background of rel-                                 effect of workplace risks problematic. Nonetheless, several
ative risk for lung cancer of 1 for a nonsmoking, nonasbestos-                                     recent efforts by international bodies have shed some light on
exposed population, a working population with significant                                          the staggering burden, although in general attempts to derive
asbestos exposure but no tobacco exposure may face a relative                                      evidence-based estimates are likely to systematically and signif-
risk of lung cancer of 5; a smoking population not exposed to                                      icantly underrepresent the extent of the problem.
asbestos faces a relative risk of 10; and rather than these risks                                      The gravity of workplace risks is seen in the recent
being additive (that is, 15) the smoking, asbestos-exposed pop-                                    International Labour Organization (ILO) estimate that among
ulation has the extraordinary relative risk of lung cancer of 50.                                  the world’s 2.7 billion workers, at least 2 million deaths per year
Most important, in this well-recognized multiplicative-effect                                      are attributable to occupational diseases and injuries. The ILO
scenario, if the smoking exposure alone were eliminated among                                      estimates for fatalities are the tip of the iceberg because data for
the asbestos-exposed workers, the overall risk of lung cancer                                      estimating nonfatal illness and injury are not available for most
                                                                                                   of the globe. The ILO also notes that about 4 percent of the
                                                                                                   GDP is lost because of work-related diseases and injuries
Table 60.1 Relationship between Asbestos, Smoking, and                                             (Takala 2002).
Risk for Lung Cancer                                                                                   A recent effort of the World Health Organization (WHO)
                                                                                                   has provided insight into the global dimensions of several
                                                             Asbestos exposurea
                                                                                                   selected occupational health risks. WHO included five occupa-
  Smokingb                                        No                                         Yes   tional risk factors in its comparative risk assessment in a uni-
  No                                                 1                                        5    fied framework of 26 major health risk factors contributing to
  Yes                                              10                                        50    the overall global burden of disease and injury (Ezzati and
                                                                                                   others 2004; WHO 2002). The WHO comparative approach
Source: Kjellstrom and Rosenstock 1990.
a. If asbestos exposure eliminated, eliminate 80 percent lung cancers in asbestos workers.
                                                                                                   used a common statistical model that allows a reader to com-
b. If smoking eliminated, eliminate 90 percent lung cancers in asbestos workers.                   pare the contribution (attributable fraction) of several risk

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                                                         ©2006 The International Bank for Reconstruction and Development / The World Bank
factors to a single outcome—lung cancer, for example.                                The absence of data in much of the developing world
Stringent requirements for consistency in describing risk fac-                   limited the range of occupational risk factors that WHO could
tors limited the number of occupational risk factors that could                  measure, and the available data excluded children under age
be included in the study. For all risk factors, it was necessary to              15 who work. The WHO comparative risk assessment also
estimate an exposed population and exposure levels for 224                       excluded important occupational risks for reproductive disor-
age, sex, and country groups in the 14 WHO geographic                            ders, dermatitis, infectious disease, coronary heart disease,
regions of the world. Where possible, data could be extrapo-                     intentional injuries, musculoskeletal disorders of the upper
lated to age, sex, and country groups for which data were not                    extremities, and most cancers. Psychosocial risk factors such as
available, based on similarities in demographic, socioeco-                       workplace stress could not be studied, nor could pesticide,
nomic, or other relevant indicators. Because knowing the exist-                  heavy metal, or solvent exposures. The potential consequences
ing burden of disease and injury globally was necessary, the                     of omitting just pesticides from the global burden analysis can
only outcomes included were those for which WHO had rates                        be illustrated by the situation in Central America (PAHO
of disease or injury for all regions calculated by International                 2002). The isthmus is primarily an agricultural and forested
Classification of Disease (ICD) codes. Finally, estimates of the                 area of .5 million square kilometers, of which 40 percent is
risk factor–burden relationships by age, sex, and WHO subre-                     arable. Pesticide imports almost tripled from 15,000 metric
gion were generated. Risk measures (relative risks or mortality                  tons in 1992 to 41,000 in 1998, and 35 percent of the pesticides
rates) for the health outcomes resulting from exposure to the                    were restricted in the exporting countries. In 2000, the subre-
risk factors were determined primarily from studies published                    gion imported some 1.5 kilograms of pesticides per inhabitant
in peer-reviewed journals. Adjustments were made to account                      per year, a quantity 2.5 times greater than the world average
for differences in levels of exposure; exposure duration; and                    estimated by WHO. Exposures in the formal and informal sec-
age, sex, and subregion, as appropriate. The information about                   tors extend to the homes and families of the pesticide workers.
each risk factor was entered into the WHO common model for                       Although this situation is common in developing nations, the
comparative analysis. The resulting burden was described as                      WHO comparative risk assessment captured none of these
the attributable fraction of disease or injury, using mortality                  exposures.
and disability-adjusted life years (DALYs) lost, with one DALY                       The ILO and WHO data provide the most current, yet still
being equal to the loss of one healthy life year—the common                      incomplete, picture of the overall problem of occupational
currency measure that includes mortality and morbidity.                          health risks. Nonetheless, with just the few occupational risk
    Because of the requirements for global data, only five occu-                 factors studied in depth by WHO a picture emerges of the sig-
pational risk factors could be described: risks for injuries, car-               nificant effect of largely preventable conditions (Ezzati and
cinogens, airborne particulates, ergonomic risks for back pain,                  others 2004). WHO found that occupational injuries result in
and noise. The exposed worker populations were estimated                         about 312,000 deaths per year for the world’s 2.7 billion work-
using an approach based on the International Standard                            ers; this figure contrasts to the approximately 6,000 deaths per
Industrial Classification of All Economic Activities (ISIC), an                  year caused by occupational injuries for the 150 million work-
economic classification system of the United Nations that                        ers in the United States. As in the industrial world, high injury
organizes all economic activities by economic sectors and rele-                  fatality rates in the developing world are clustered in certain
vant subgroupings (UN 2000). The ISIC system is used almost                      sectors, including agriculture, construction, and mining.
universally by national and international statistical services to                Using this metric, occupational injuries account for more than
categorize economic activity; therefore, it allows global com-                   10 million DALYs and 8 percent of unintentional injuries
parisons. The ILO has developed economically active popula-                      worldwide.
tion (EAP) estimates by applying economic activity rates, by                         The second occupational factor WHO analyzed was the
sex and by age group (older than age 15), to the population                      effect of exposure to workplace lung carcinogens (such as
estimates and projections of the United Nations (ILO 1996).                      asbestos, diesel exhaust, and silica) and leukemogens (such as
The EAP provides the most comprehensive global accounting                        benzene, ionizing radiation, and ethylene oxide). WHO con-
of people who may be exposed to occupational risks because it                    cluded that occupational exposures account for about 9 per-
includes people in paid employment, the self-employed, and                       cent of all cancers of the lung, trachea, and bronchus and about
people who work to produce goods and services for their own                      2 percent of all leukemias. Overall, about 102,000 deaths were
household consumption, both in the formal and in the infor-                      attributable to these two occupational cancers and about 1 mil-
mal sectors (ILO 2002). For the WHO comparative risk assess-                     lion DALYs.
ment, the EAP was further divided into nine economic subsec-                         Estimates of the global burden of chronic lung disease
tors (where people work) and seven occupational categories                       demonstrate the significant contribution of occupational expo-
(what type of work people do), on the basis of country-level                     sures, which account for about 13 percent of all chronic
data for 31 countries (ILO 1995).                                                obstructive pulmonary disease (COPD) and about 11 percent

                                                                                                                            Occupational Health | 1129

                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
of asthma. In total, WHO found the annual worldwide burden                                 countries that have engaged in serious prevention efforts.
of work-related COPD to be about 318,000 deaths per year and                               Proper needle handling and waste management, substitutions
about 3.7 million DALYs. The occupational risk contribution                                for sharps, hepatitis B virus (HBV) immunization, postexpo-
to the worldwide asthma burden was about 38,000 deaths and                                 sure prophylaxis, training, and legislative measures have been
about 1.6 million DALYs, reflecting the fact that a great deal of                          successful. Beyond the personal and workplace consequences,
asthma occurs at younger ages and is not fatal. WHO found                                  the potentially devastating societal impact of loss of this criti-
that 37 percent of all back pain worldwide is attributable to                              cal worker group can be anticipated if prevention measures are
work, resulting in an estimated 800,000 DALYs, a significant                               not ensured in developing countries, where the proportion of
loss of time from work, and a high economic loss. Worldwide,                               health care workers in the population is already small.
16 percent of all hearing loss is attributable to workplace expo-                              In total, the few occupational risk factors considered here
sures, resulting in 4.2 million DALYs.                                                     were responsible for about 800,000 deaths worldwide in 2000.
    WHO made a special risk analysis of hepatitis B, hepatitis C,                          Not considered by WHO because of lack of global data are the
and HIV infections among health care workers caused by con-                                additional 1.2 million deaths that ILO estimated are attributa-
taminated sharps, such as syringe needles, scalpels, and broken                            ble to work-related risks (Takala 2002). The leading occupa-
glass (WHO 2002). This analysis illustrates the general prob-                              tional cause of death was unintentional injuries, followed by
lem of high risks existing in the small worker population hav-                             COPD and lung cancer. Workers who developed outcomes
ing exposure. WHO found that, among the 35 million health                                  related to these occupational risk factors lost about 25 million
workers worldwide, there were 3 million percutaneous expo-                                 years of healthy life. Among the occupational factors analyzed
sures to bloodborne pathogens in 2000. This finding is equiva-                             in this study, injuries, hearing loss, and COPD accounted for
lent to between 0.1 and 4.7 sharps injuries per year per health                            about 80 percent of years of healthy life lost. Low back pain
worker. WHO concluded that of all the hepatitis B and hepati-                              and hearing do not directly produce premature mortality, but
tis C present in health care workers, about 40 percent was                                 they do result in substantial disability. This feature differenti-
caused by sharps injuries, with wide regional variation. WHO                               ates these conditions from the others analyzed in the study.
also found that between 1 and 12 percent of HIV infections in                              Figure 60.2 provides summary results for the occupational risk
health care workers was caused by sharps injuries. The com-                                factors.
parative risk assessment by region and type of infection indi-                                 The WHO comparative risk assessment has accounted for
cates where special emphasis is needed (see figure 60.1).                                  only about 800,000 (40 percent) of the 2 million deaths
Clearly, solutions exist to these problems, as shown by the                                estimated by ILO to occur each year because of occupational
                                                                                           illness and injury. Deaths attributable to a wide range of
                                                                                           occupational exposures could not be included because of the
 90                                                     HCV        HBV         HIV
 80                                                                                         Low back pain (37)                                                               41
 70                                                                                                                                     11
                                                                                              Hearing loss (16)
 60                                                                                                                                                    22
 50                                                                                                                         6
                                                                                                      COPD (13)
 40                                                                                                                                               18

 30                                                                                                                            7
                                                                                                    Asthma (11)                              14
 10                                                                                               Unintentional        2
                                                                                                    injuries (8)                        12
                                                                                           Trachea, bronchus,              5






           Se C









                                                                                             or lung cancer (9)










                                         Regions                                                                       2
                                                                                                   Leukemia (2)                                                  Male        Female
  Source: WHO 2002, 130.
  HCV = hepatitis C virus; HBV = hepatitis B virus; HIV = human immunodeficiency virus;                            0               10             20        30          40            50
  Afr = Africa; Amr = America; Emr = Eastern Mediterranean; Eur = Europe;
  Sear = Southeast Asia; Wpr = Western Pacific.                                             Source: Adapted from Nelson and others 2005.

Figure 60.1 Fraction of Hepatitis C Virus, Hepatitis B Virus, and HIV                      Figure 60.2 Fraction of Global Disease and Injury Attributable to
Infections in Health Care Workers Attributable to Injuries with                            Occupational Risk Factors
Contaminated Sharps, Ages 20 to 65                                                         (percent)

1130 | Disease Control Priorities in Developing Countries | Linda Rosenstock, Mark Cullen, and Marilyn Fingerhut

                                                  ©2006 The International Bank for Reconstruction and Development / The World Bank
strict requirements for global data. Missing are deaths                         • Regional conflict, economic pressures, climatologic factors,
attributable to asbestosis, silicosis, and other dust diseases;                   and lack of foreign exchange may make otherwise straight-
infectious diseases; cardiovascular diseases; and violence.                       forward choices impractical.
Deaths attributable to workplace exposures to pesticides, heavy                 • Supply of labor is often high, as is turnover, so economic
metals, solvents, and other chemicals are not included.                           incentives for investment in health capital are lower than in
Outcomes such as dermatitis, psychological disorders, and                         industrial countries.
upper-extremity musculoskeletal disorders that cause little
mortality but substantial disability are also not captured by the               Strategies for Improving Working Conditions
WHO comparative risk analysis. Additionally, the consequences                   With these differences in context in mind, we now consider the
of underreporting in existing systems and the dearth of record-                 major types of intervention: international, national, workplace,
keeping systems in the developing nations lead to substantial                   and individual.
undercounting by both the ILO and WHO. Nonetheless, the
analyses provide important insights into the immense global                     International Interventions. The ILO–WHO Joint Com-
burden of disease and injury attributable to occupational risk                  mittee on Occupational Health was formed in 1950 to provide
factors.                                                                        guidance to the ILO and WHO regarding international occu-
                                                                                pational health issues. The committee meets periodically. At its
                                                                                13th session, held in December 2003, the committee recom-
INTERVENTIONS                                                                   mended that WHO and ILO pursue the following priorities
                                                                                (ILO and WHO 2003):
Strategies for controlling injury and occupational disease,
developed by industrial hygienists and others over many                         • Guide and support national occupational safety and health
decades in industrial countries, are as fully applicable in devel-                programs. Such guidance and support includes providing
oping countries. The strategies include a hierarchy of controls                   models for organizing at national or subnational levels;
in the following decreasing order of preference: substituting                     providing basic occupational health services; promoting
major hazards for less hazardous materials or processes; apply-                   management systems and tools, including control banding;
ing engineering controls to separate workers from hazards that                    developing national profiles and indicators; assessing the
remain; using administrative controls to minimize contact                         cost-effectiveness of interventions; and establishing effective
uncontrollable by engineering; and, as the last line of defense,                  enforcement agencies.
using personal protective equipment such as respirators and                     • Enhance regional collaboration and coordination, including
protective garments. What differs in developing countries is the                  the development and dissemination of models for coopera-
context in which the paradigm must be applied. Options are                        tion, such as the African Joint Effort.
often sharply limited, and knowledge of them even more so;                      • Coordinate and enhance information and educational pro-
economic and political factors may impede otherwise obvious                       grams and materials (for example, by developing a joint
or desirable solutions; and the differing workplace context                       Internet-based global portal) and statistics.
may demand that attention be paid to certain problems and                       • Provide awareness-raising activities and instruments
concerns that would not be relevant in industrial countries in                    through campaigns, events, and special days.
temperate climates.
   The following generic factors associated with work in devel-                 State or Government Interventions. The major role the gov-
oping countries may alter industrial hygiene practice and must                  ernment can play is to establish workplace rules and provide
be considered in every effort to intervene to improve working                   a system of dissemination and enforcement. Evidence from
conditions and occupational health:                                             industrial countries is overwhelming that conditions are sub-
                                                                                stantially improved when both a strong regulatory framework
• Access to industrial hygiene consultation is limited; pro-                    and enforcement are achieved. An added benefit of govern-
  fessionals, sampling equipment, and laboratories are all in                   ment, rather than private sector, control is to “level the playing
  short supply.                                                                 field”: all employers in an economic sector carry the same bur-
• Knowledge level about occupational health among man-                          den. Conversely, improved health of the workforce, achieved by
  agers and workers is often limited.                                           developing strategies beyond the minimum required, could be
• Markets for production materials as well as safety equip-                     used to confer competitive advantages, a message to reluctant
  ment may be limited and may include more hazardous                            employers that has been used in different parts of the world
  materials or less effective protective equipment “dumped”                     with some success.
  from industrial countries where they are no longer mar-                           Regulatory decisions, such as the choice of exposure limits
  ketable (Hecker 1991; Ives 1985; Jeyaratnam 1990).                            or allowable practices, often stimulate the biggest discussion—

                                                                                                                            Occupational Health | 1131

                                 ©2006 The International Bank for Reconstruction and Development / The World Bank
for example, the debate about dust levels to be allowed in South                         have markets in industrial countries that have banned or
African mines—but the larger issue for most countries is gar-                            restricted their use—for example, solvent mixtures containing
nering resources to ensure compliance, to attract adequately                             benzene and construction materials containing asbestos.
trained personnel to conduct inspections, and to establish and                           Similarly, equipment such as machines that are well guarded to
monitor laboratories to support regulatory efforts. The most                             prevent injury or well baffled to limit noise may be prohibi-
stringent exposure levels (often referred to as threshold limit                          tively expensive in a marketplace geared to “hand-me-downs”
values, or TLVs) are useless if the offending hazard cannot be                           compared with respirators or gloves. Unfortunately, even these
routinely and accurately measured. Indeed, the South African                             last lines of defense may be difficult to obtain or relatively
experience, despite the presence of excellent regulations, is not                        expensive unless local suppliers are available.
encouraging in this regard (Joubert 2002).                                                   The single strategy for which no compelling economic dis-
    Other forms of government intervention may indirectly                                incentive exists—training—may also be difficult. Through the
improve working conditions. Among these are workers’ com-                                efforts of the ILO and numerous nongovernmental organiza-
pensation regulations and stipulations that employers of cer-                            tions and with widening access to the Internet, vast resources
tain sizes must engage professionals in health and safety (most                          have become available. Ample documentation from the indus-
often nurses). Each of these interventions has the advantage of                          trial and developing world indicates that even rudimentary
stimulating certain behaviors and practices without requiring                            knowledge by supervisors and workers about risks and risk-
the government to maintain the elaborate and technically com-                            prevention measures is beneficial. Major impediments remain,
plex machinery required for direct monitoring of workplace                               however, such as educational proficiency, language barriers,
conditions.                                                                              and the applicability of training materials—often developed in
    Constraints on governmental regulatory and other inter-                              other contexts—to local situations. Thus, for example,
ventions are many. Occupational and environmental regula-                                although the ILO has recently reported success with informa-
tions are often perceived as burdensome costs that impede                                tion programs in rural Thailand (Kawakami and Kogi 2001),
investment and growth, perhaps creating what has been                                    a report from Ghana (Smith-Jackson and Essuman-Johnson
referred to as “the race to the bottom,” in which threat of out-                         2002) suggests that workers and supervisors were unable to
migration of industry from one jurisdiction enhances reluc-                              correctly interpret four of the most common warning signs
tance to regulate or enforce control strategies (Frumkin 1999).                          used for hazard identification, despite having been trained in
Moreover, the costs to the government itself, notwithstanding                            their use. Worker training appears, on the whole, widely
technical support from such agencies as the ILO, may be con-                             underused.
siderable in terms of personnel and equipment, and occupa-                                   Problems of infections in patients and health care workers
tional health has to compete with other public health priorities                         from reused needles and needlestick injuries have prompted
for scarce resources. The result may be the promulgation of                              the international organizations to develop model interventions
minimal standards or emasculated enforcement of those that                               that can be transferred elsewhere. WHO initiated Project
already exist. The general impression of those working                                   Focus: Ensuring Immunization Safety in Burkina Faso in July
throughout the developing world is that the level of regulation                          2002 as a pilot project to use WHO materials in a focused effort
and enforcement is woefully inadequate compared with that                                to address all issues related to injection and immunization
in industrial countries. Detailed case examples from Brazil                              safety: availability of equipment and supplies (auto-disposable
(Bedrikow and others 1997); Kenya (Mbakaya and others                                    syringes, safety boxes, incinerators); safe injection practices;
1999); Nigeria (Asuzu 1996); and Taiwan, China (Chen and                                 safe vaccine delivery; and safe waste management (WHO
Huang 1997), underscore the ubiquity of this problem.                                    2002). In 2000, WHO conducted a survey to assess the safety of
                                                                                         injections in a study group of a random sample of 80 health
Workplace-Based Interventions. Issues beyond the economic                                centers. The situation was reassessed in June 2003 to evaluate
and legal ones impede application of the principles of indus-                            the use of safety boxes (which had been provided in a WHO
trial hygiene. A primary factor is ignorance; many employers                             immunization campaign in Burkina Faso in 2001) and the
may be uninformed about available controls and their value.                              impact of Project Focus. Table 60.2 shows results of the
Insurance agencies, local safety groups, and—in some regions                             reassessment. Dramatic reductions were found in needle recap-
of the world—trade unions may serve as facilitators of positive                          ping, needlestick injuries, and misuse of safety boxes.
influence. In general, however, such resources fall short of the                         Additionally, the number of clinics using safety boxes increased
benefit of on-site industrial hygiene expertise that is lacking in                       from fewer than half to 86 percent.
many regions of the world.                                                                   Small enterprises present special challenges because they
    Economic factors often impede efforts to institute voluntary                         lack resources and expertise to address health and safety prob-
controls. Materials used are frequently far cheaper than safer                           lems. Thailand’s National Institute for the Improvement of
substitutes, often precisely because these materials no longer                           Working Conditions and Environment has used the ILO

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                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
Table 60.2 Prevalence of Risk Factors and Injuries at                                        Control of Nonoccupational Exposures
80 Observed Health Centers
                                                                                             In industrial countries, a sharp demarcation exists between
                                                                                             environmental risks associated with work and those associated
             Needle            Needlestick         Lack of              Misuse of            with home life. This differentiation is not the case in many
  Year       recapping         injuries            safety boxes         safety boxes         developing countries, especially at large, remote industrial
  2000            55                 71                   51                  83             complexes and farms. Workers—with or without their
  2003            17                 32                   14                  18             families—often cohabit with the workplace—and often with
                                                                                             many or all of its risks, including noise, chemicals, and biohaz-
Source: S. Khamassi, WHO Mediterranean Centre, personal communication 2003.
                                                                                             ards. The most dramatic examples of this situation were the
                                                                                             industrial disasters at Chernobyl and Bhopal. It is not just in
                                                                                             disaster, however, that risk occurs. Pesticides, for example,
training approach called WISE (Work Improvement in Small                                     result in hundreds of thousands of cases of poisoning a year, a
Enterprises) with some success. In one example, six enterprises                              high fraction from the misuse of farm chemicals for nonwork
in the metal industry in Bangkok with between 15 and 115                                     applications, such as the appropriation of empty (but not
workers participated in the WISE program, in which practical                                 clean) drums for transporting water or other household goods,
workshops involved workers and management in deciding on                                     a disturbingly common practice. In the industrial setting, car-
changes to be made in the workplaces. A wide range of inex-                                  cinogens, neurotoxins, and other hazardous chemicals often
pensive changes were put in place, and a booklet to illustrate                               pollute homes, drinking supplies, and common areas for recre-
good practices for others was prepared (Krungkraiwong 2000).                                 ation on a daily basis, adding to the exposure of workers and
                                                                                             placing nonworking family members at risk from what would
Individual Interventions. The general principle that, for most                               normally be seen as workplace hazards.
public health intervention, organization-level change is more                                    The remedy is often complex and beyond traditional indus-
effective than strategies targeting the individual is even more                              trial hygiene practice. Housing, which in any event may be
true when it comes to the workplace. With the exception of                                   substandard, needs to be modified to exclude the possibility
self-employed workers, such as those in the informal sector and                              of contamination by effluent from farm or factory under any
subsistence farmers, occupational health and safety does not                                 foreseeable circumstances. Children and family members need
lend itself readily to individual solutions, with the same factors                           to be apprised of the hazards of all materials used for work and
limiting employees more likely to limit individuals.                                         prevented from even accidental access, a situation complicated
                                                                                             by the fact that children are themselves often inappropriately
Improvement of Access to Health Care                                                         engaged in the workplace. Food and water supplies need to be
                                                                                             secure and protected from cross-contamination, a particular
In a few developing countries, workers enjoy broad access to                                 problem in the farm setting.
high-quality health care. Chile, for example, has a system of
nonprofit employer mutual associations that provide advice on
reducing risks in workplaces and medical treatment and sick
pay for work-related illness and injury (Contreras and                                       Surveillance and Reporting
Dummer 1997). In most countries, the role of on-site services                                Even in industrial countries, the strategies for recording any
is generally limited to emergency services for an injury or acci-                            aspect of workplace harm beyond acute injury has been an
dental overexposure and the conduct of medical surveillance                                  issue; in most developing countries, even injury reports are
examinations for workers at risk for chronic conditions such as                              largely nonexistent. Still, broad agreement exists on the value of
noise-induced hearing loss, pneumoconiosis, or cancer.                                       statistical summaries of occurrences.
    In the developing world, access to health care is critical both                             Unfortunately, a strong disincentive exists for such report-
for work-related and other health issues. In many areas, espe-                               ing unless it is required by law or by a parent company (as in
cially remote or rural areas, on-site service may be the only                                the case of some multinationals). If reporting is required, as in
health care services available to workers and their families.                                the formal laws of many countries, successful implementation
Moreover, the blurred distinction between “general health” and                               calls for resources for systematic review, verification, and main-
“occupational health” in societies where people live and work                                tenance of the information. Even records whose limitations are
in the same community and environment, and where children                                    otherwise legion, such as workers’ compensation records or
and spouses of workers may share common exposures and                                        regional reporting schemes, have proven highly advantageous
adverse conditions with workers, serves to confer some advan-                                to control efforts in industrial countries. These, too, have a role
tage to a more holistic approach to health services often best                               in developing countries, helping target even rudimentary and
provided at or near the workplace itself.                                                    limited control efforts.

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                                              ©2006 The International Bank for Reconstruction and Development / The World Bank
Capacity Building                                                                        occupational health that work together with WHO and ILO
Human capital in the form of professional capacity is critical to                        headquarters and regional offices and three international non-
improving working conditions. Professional capacity varies                               governmental organizations: the International Commission on
greatly in developing nations but is higher where recognition of                         Occupational Health, the International Occupational Hygiene
the field is high and the need for professionals and for workplace                       Association, and the International Ergonomics Association
expertise is driven by occupational safety and health legislation                        (Fingerhut and Kortum-Margot 2002). These partners, located
and enforcement. In Malaysia, for example, four decades of                               in approximately 40 countries, work together in 15 priority
rapid industrialization have included a series of legislative acts;                      areas within a 2001–2005 Work Plan. More than 300 projects
development of federal agencies; and inclusion of training at                            are under way, independently or jointly, to benefit workers in
various levels in occupational health in universities, the public                        developing and industrializing nations in about 15 priority
sector, and the private sector (Rampal, Aw, and Jefferelli 2002).                        areas (WHO 2003).
Key international events, such as joining the World Trade                                    Another strong regional coalition, coordinated with and
Organization, encourage the development of an economic cul-                              benefiting from the Global Network of Collaborating Centers,
ture that better recognizes the value of safe workplaces.                                is the WHO–ILO Joint Effort on Occupational Health and
Enforcement of national regulations, adoption of International                           Safety in Africa (WHO and ILO 2002b). This partnering
Standards Organization standards, and establishment of man-                              coalition—where centers outside Africa assist African
agement systems lead to broadening of training for workers and                           partners—includes individual occupational safety and health
managers, although the scarcity of trained professionals is a                            professionals, employers, labor unions, and governmental and
major obstacle to adequately implementing regulations and                                academic institutions in all countries in Africa.
policies and providing occupational health services (Christiani,                             Enlarging small but successful existing programs is one
Tan, and Wang 2002; Wang, Cheng, and Guo 2002).                                          approach to capacity building. The U.S. National Institutes of
    In countries with some capacity, the expertise tends to be                           Health Fogarty International Center, NIOSH, and the National
medical, rather than in other areas, such as industrial hygiene,                         Institute of Environmental Health Sciences sponsor a suc-
engineering, or ergonomics. In most countries, ministries of                             cessful program, International Training and Research in
health and of labor have jurisdiction over working conditions                            Occupational and Environmental Health, which has developed
but often have too few experts and inadequate coordination.                              small but strong programs between U.S. universities and insti-
Moreover, the large percentage of work conducted in the infor-                           tutions in more than 30 developing nations (NIH 2003).
mal sector presents a special challenge to these ministries.                                 Capacity building requires high-quality educational op-
Because globalization has brought the need for professionals in                          portunities. Advances in information technology over the past
occupational health to a crisis level, it is appropriate for inter-                      decade are revolutionizing methods of education, and univer-
national trade and development bodies to support national                                sities worldwide are developing large numbers of Internet-
and international capacity-building programs.                                            based courses. Fostering access of students from developing
    In 1970, when the United States enacted the Occupational                             nations to these courses in leading universities is now feasible,
Safety and Health Act that established the National Institute for                        but a national or international program is needed to address
Occupational Safety and Health (NIOSH), the country had                                  issues such as tuition, competition, intellectual property, and
little professional capacity in that field. The new law charged                          degree requirements. This effort might be called Access to
NIOSH with ensuring an adequate number of trained profes-                                Universities, following the model WHO program Access to
sionals and accomplished this task successfully by funding                               Biomedical Journals, through which WHO and the world’s
graduate programs in U.S. universities. A follow-up 25 years                             largest medical journal publishers have provided about 100
later found that 90 percent of NIOSH-supported trainees pur-                             developing countries with Internet access to journals at no cost
sued careers in the field, with more than 50 percent working in                          or at deeply reduced rates (WHO 2001).
private organizations and the balance in government and aca-                                 Professional associations have a long history of assisting in
demia (U.S. DHHS 1996). Similar results could be achieved by                             capacity building through training, research, and conferences.
a determined, large-scale effort focused on assisting developing                         Recently, when the University of Witwatersrand in
countries in achieving adequate professional capacity.                                   Johannesburg developed the first Diploma Occupational
    Both infrastructure and programs are necessary to build                              Hygiene program in South Africa, the country had too few
adequate capacity. In the international arena, a number of suc-                          industrial hygienists to provide mentors for the field research
cessful coalitions exist that provide experienced institutions                           of the graduate students. The American Conference of
and individuals. The WHO Global Network of Collaborating                                 Governmental Industrial Hygienists responded to a request
Centers in Occupational Health is a strong international coali-                          of the International Occupational Hygiene Association, and
tion of 70 national, governmental, and academic centers of                               11 U.S. industrial hygienists volunteered to be occupational
                                                                                         hygiene field practitioner long-distance mentors for the

1134 | Disease Control Priorities in Developing Countries | Linda Rosenstock, Mark Cullen, and Marilyn Fingerhut

                                                ©2006 The International Bank for Reconstruction and Development / The World Bank
incoming students during the 2003 course year. This approach                    country in terms of legal liability and adverse publicity, a lesson
will continue until there are adequate industrial hygienists in                 well taught by Union Carbide’s experience in the aftermath of
country to serve as mentors to future classes (WHO and ILO                      the Bhopal disaster in 1984.
2002a).                                                                            One approach to align economic incentives is to use regula-
   The U.K. Health and Safety Executive developed a model                       tory and legal reform to shift the existing cost burden to those
program that provides clear solutions to chemical control                       in a position to remedy the situation—that is, to employers.
problems in workplaces. This Web-based, user-friendly prod-                     Increasing workers’ compensation benefits, especially those for
uct was launched to enable small business owners in the United                  long-term effects and disabilities, is an example of such an
Kingdom to use information from the suppliers of chemicals to                   approach. Some evidence exists that, at least in southern Africa,
proceed through a series of simple steps to identify practical                  this approach does stimulate preventive behavior by employers.
control solutions that reduce worker exposures to levels that                   An alternative is to critically reexamine the assumption that
present no danger to health (U.K. HSE 2002). This approach,                     employers do not harbor substantial underrecognized costs of
which eliminates the need to measure exposures and meets the                    injury and illness even under the current situation, especially
regulatory requirements of the United Kingdom, has immense                      in terms of indirect costs such as lowered productivity and
potential value for employers in developing nations, who could                  morale. Harari and his colleagues in Ecuador (Cullen and
devote scarce resources to controlling exposures rather than to                 Harari 1995) have been studying the effect of such exposures as
measuring exposures. The approach has gained momentum                           solvents and organophosphate pesticides on production levels.
through adoption by the International Program on Chemical                       They are attempting to make the case that relatively inexpen-
Safety and through formation of an international workgroup                      sive strategies for exposure control are economically advanta-
to advance the approach in developing nations. To enable                        geous to employers.
global use of this approach, the ILO has translated the U.K.-
specific system into a product called the ILO Chemical Control
Banding Toolkit (ILO 2003).                                                     Intervention Costs and Cost-Effectiveness
                                                                                Workplace illness and injury produce personal suffering and
                                                                                high economic costs. The ILO estimates that about 4 percent of
ECONOMIC ASPECTS OF INTERVENTION                                                GDP worldwide is lost because of work-related diseases and
                                                                                injuries (Takala 2002). The European Agency for Occupational
Measures to prevent occupational risks are not cost-free, and                   Safety and Health at Work (1998) indicates that the costs to
where those costs ultimately come to rest affects the willingness               society in European countries ranged from 0.4 percent to
of employers to implement the preventive measures.                              4 percent of gross national product.

                                                                                Examining Industrial Countries. Identifying interventions
Who Bears the Costs of Preventive Measures?                                     to successfully reduce or prevent workplace injuries and ill-
In industrial countries, compelling economic incentives exist                   nesses will benefit society, employers, and workers. In 1996,
for employers to control risks for injury and illness on the job,               stakeholders in the United States identified intervention effec-
especially those that result in demonstrable near-term lost                     tiveness research as one of 21 priority areas in occupational
work or function. These include the high cost of medical care                   health research for the next decade (U.S. DHHS 1996). From
(especially in the United States), the burden of workers’ com-                  1996 to 2002, research conducted or funded by NIOSH to
pensation payments, high replacement costs for the labor, risk                  develop and evaluate the effectiveness of solutions to prevent
of litigation and liability, and negative business consequences                 work-related injury and illness has increased nearly sixfold,
of adverse publicity. Although these factors may differ by coun-                from about US$5.5 million to US$33 million (U.S. DHHS
try and sector, they are less likely in the developing world to                 2003).
confer on employers a strong economic imperative for                                Research studies of workplace interventions often use sur-
prevention—labor is plentiful, its replacement cost is low,                     rogate or implied measures for economic evaluation. For
and—most important—a high portion of the real cost of                           example, economic benefit is assumed to occur following an
injury and illness will not be borne by the employer. The statis-               intervention if symptoms of illness or injury in a workforce
tics in Latin America are staggering: although an estimated 2 to                decrease while productivity remains constant. Intensive data-
4 percent of the GDP of the region is lost because of occupa-                   entry workplaces are increasing rapidly in both industrial and
tional fatalities alone, no evidence exists of private sector                   developing nations. Three studies of U.S. Internal Revenue
investment to reduce the risk (Giuffrida, Iunes, and Savedoff                   Service data-entry clerks by NIOSH found that short, strategi-
2002). Multinational companies appear to be an exception. For                   cally placed rest breaks of 5 to 15 minutes during the regular
many, the costs of injury and illness may accrue to the parent                  daily schedule reliably reduced eyestrain, fatigue, and

                                                                                                                            Occupational He