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Epidemiology of TB
and its control
Dr. V. K. Chadha
Sr. Epidemiologist
National TB Institute
Bangalore
I. General concepts in TB Epidemiology
II. Epidemiological indicators of TB and their estimation
III. Global epidemiological trends of TB
IV. TB situation in South East Asia
- presentations by Country participants
V. Prospects of TB control
Why do we need to study
Epidemiology of TB?
Aims of Epidemiology ?
• To describe natural history of disease
• Describe Distribution and relative importance
• Measure frequency
• To define risk groups
• To evaluate interventions
• To describe trends
• To predict future trends and changes in disease
presentation.
What is Epidemiology ?
Epi - among ; Demos - People ; Logos - Study
DEFINITION
Epidemiology is the study of the -
• Frequency
• Distribution - time, place & person
• Determinants - physical, biological, social,
behavioural & cultural
of health problems & health related events and
application of this study to control health
problems.
A Model for the Epidemiology of Tuberculosis
Risk Risk Risk Risk
factors factors factors factors
Infectious
tuberculosis
Subclinical
Exposure infection Death
Non-infectious
tuberculosis
Rieder HL. Infection 1995;23:1-4
Risk of exposure ?
* Incidence / prevalence of infectious TB in
the community
* Duration of infectiousness
* opportunities for case - contact interactions
-Urban/Rural
-No. of individuals in the house holds
Risk of Infection ?
* No. of infectious droplets produced
* Volume of shared air space
* Length of exposure
* Ventilation
* Climatic conditions
Tuberculous Infection Among Children by Type of
Contact and Bacteriologic Status of Index Case,
British Columbia and Saskatchewan, 1966 - 1971
40
Close
35
30
Per cent infected
25
20
15
Casual Close
10
5 Casual
0
Smear + Smear -
Grzybowski S, et al. Bull Int Union Tuberc 1975;50:90-106
Household transmission of TB
- important epidemiological factor
• Case control study in Malawi
TB among contacts
Cases 770 56/2766
P<0.001
Controls 918 11/3203
Each case leads to two cases
-_-_-
1 Infectious case
20 contacts
2 cases
of TB
1 Non-infectious
Risk of Infection Among Contacts as a Function of the Proximity of Contact
What is the most important risk
factor for TB?
Example of Risk Differences in Individuals
Following Infection with M. tuberculosis
Cases per 1,000 person-years 1000 ??
100
(log scale)
10
1
Long-standing Recent Super- Underlying
infection infection imposed HIV infection
HIV infection
Risk factors for disease given that infection has
occurred ?
Risk factor Relative Risk
AIDS 200
HIV Infection 30-40
[Relative Risk of
Silicosis 30 remotely acquired
infection = 1]
Recent Infection 20 (0.2% per year)
Under-nutrition 2-5
Diabetes mellitus 2-5
Incidence of TB in South Africa per 1000 population
30
25
20
General population
15
Gold miners
10
5
0
IJTLD,3(9),1999,791-798
Other High Risk Groups
Populations in war / civil unrest
Refugees and migrants
Slum dwellers
Homeless people/Foot path dwellers
Smoking
Prisoners
TB in prisons
Studies in Thailand
* TB incidence 90 times higher in prisons
* High HIV sero-positivity in TB cases
* High levels of drug resistance
• RFLP studies signify role of recent transmission
Determinants of death?
* Severity of illness
* Smear positivity
* delay in diagnosis
* quality of treatment
* drug susceptibility pattern
Epidemiological indicators of TB and
their estimation
Enumerate epidemiological
indicators of TB you know of?
Epidemiological indicators of tuberculosis ?
* Prevalence of infection
* Incidence (average annual risk) of infection
(ARI)
* Prevalence of disease
* Incidence of disease
* Tuberculosis mortality rates
How to estimate prevalence of
infection?
Estimating prevalence of infection
* Study population-sampling
* Registration of eligible age group
- house-to-house / school based.
* Informed consent.
* Examination for BCG scar.
* Tuberculin testing with 1TU/2TU PPD RT23 with tween 80.
* Reading of reaction sizes appx. 72 hours later.
What is the rationale behind tuberculin
surveys in children ?
• Extent or recent transmission
• Study trends in TB epidemiology
(Ultimate aim of control programme is to
replace older more infected cohorts with
younger less infected cohorts)
Analysis of tuberculin survey
ction size % of Reaction size % of
children children
1 mm 16 mm
2 mm 17 mm
3 mm 18 mm
4 mm 19 mm
5 mm 20 mm
6 mm 21 mm
7 mm 22 mm
8 mm 23 mm
9 mm 24 mm
10 mm 25 mm
11 mm 26 mm
12 mm 27 mm
13 mm 28 mm
14 mm 29 mm
15 mm 30 mm
Frequency Distribution of Tuberculin Skin
Test Reaction Sizes, Korea 1975
0.15
Fraction reacting
0.10
0.05
0.00
0 5 10 15 20 25 30
Induration (mm)
Korean Institute of Tuberculosis 1976:1-116
Frequency distribution of tuberculin reaction
sizes among children aged 1-9 years - Kota
40
35
N = 3870
30
25
Percentage
20
15
10
5
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
Reaction in mm
Estimation of incidence of
infection?
Dual skin testing at two different periods
-Conversion
-Boosting
Compute average annual risk of infection
(ARTI) = 1-(1-P)1/A
A RT I
• Key epidemiological indicator in developing
countries.
• It is the probability of acquiring new
tuberculosis infection or re-infection over the
course of one year.
A R I expresses the overall impact of various
factors influencing the transmission of tubercle
bacilli !
- Load of infectious cases
- Efficiency of case finding
- Efficiency of treatment programme
ARI identifies the regions of high transmission
It provides an indirect estimate of size of sources
of infection
Any change in disease burden and programme
implementation is first reflected in the change in
ARI
It holds the key to the study of epidemiological
trends which are more important than exact
estimates of disease prevalence
How to estimate prevalence of
disease?
DISEASE SURVEY METHODOLOGY
Sampling of representative population
House to house registration
Screening:
- MMR X-ray of all above five years of age
- Symptomatic screening
X-ray pictures read by two independent readers and by an
umpire reader
Sputum specimens (2/3) collected from persons with abnormal
X-ray shadows & / or chest symptomatics
Sputum examination by direct microscopy (and culture).
How to estimate disease incidence?
Relationship between ARTI and
incidence of disease
Styblo derived the following relationship
from data of pre- chemotherapy
• Every one percent of ARTI corresponds to
50 new smear positive cases per 100,000
population per year
Relationship between ARI & Incidence of smear
positive cases of Pulmonary Tuberculosis
(Indian studies)
Incidence / 100,000
pop for every one
percent of ARI
NTI Longitudinal
53
study (1961 – 1968)
BCG Prevention Trial 42-74 (57)
Relation between ARI and Incidence !
* Situation : Disease incidence remains same
but the risk of infection declines
Q 1. When is this situation likely?
Q 2. What is the impact on equation
(relationship) ?
What happens to the equation in
high HIV settings?
The equation is dependent more on
number of infections generated per
case and not merely on incidence
Disease mortality rates !
* Community based prospective studies
* Death certification
ESTIMATION OF ANNUAL RISK OF
TUBERCULOUS INFECTION IN
DIFFERENT ZONES OF INDIA
-A CROSS SECTIONAL STUDY
2000-2003
Districts selected for National Sample Survey -ARI
The proportion of children with BCG scar by zone
North Zone 45.3%
South Zone 64.3%
West Zone 52.0%
East Zone 51.5%
The estimated prevalence of infection and ARTI by zone
Prevalence
Zone ARTI
of infection
10.3% 1.9%
North
(8.4-12.2) (1.5-2.2)
9.3% 1.8%
West
(6.8-11.8) (1.3-2.3)
6.1% 1.1%
South
(4.9-7.2) (0.9-1.3)
6.9% 1.3%
East
(5.5-8.2) (1.0-1.6)
( ) : 95% C.I.
Prevalence of infecton by zone and stratum (1-9 years)
16
14.1
14 Rural Urban Zone
12.6
12
10.3
9.8
10 9.1 9.3 9.0
7.8
%
8 6.9
6.5
6.1
6
4.5
4
2
0
North South West East
Does higher ARTI in urban areas
indicate higher incidence of
smear positive cases
Programme inputs
The survey findings provide baseline estimates of ARI for
- evaluation of TB Control Measures.
- Study of epidemiological trends in years to
come
High rate of ARI indicates high load of infectious cases of TB in
most parts of India. Prolonged and sustained efforts required to
control TB.
There are significant inter-regional differences in tuberculosis
situation.
Intensification of TB control services in urban areas with
higher ARI rates to be taken up on priority basis.
Case finding expectations cannot be applied uniformly all over
the country
Other Epidemiological indicators of
Tuberculosis
* Ratio of prevalence and incidence
* Age distribution of cases
* Case fatality rates
* Force of MDR cases
* TBM notification rates
* Disability adjusted life years (DALY)
Epidemiological trends of TB
Tuberculosis Mortality in Three European Cities,
Modeled From Available Data, 1750 - 1950
1000
London Stockholm
Deaths per 100,000
800 Hamburg
600
400
200
0
1750 1800 1850 1900 1950
Year
Grigg ERN. Am Rev Tuberc Pulm Dis 1958;78:151-72
Tuberculosis Mortality Rates in Germany, 1892 - 1940
250
Deaths per 100,000
200
150
100
50
0
1890 1900 1910 1920 1930 1940
Year
Redeker F. In: Handbuch der Tuberkulose (Hein J, et al, eds) 1958;1:473
Secular Trend in Annual Risk of Infection,
Selected European Countries
Engl
and
and
W ales Serbia
10 Poland
Slo
ven
ia
Per cent risk (log scale)
Slope reference: No
% decline / year rw
ay
1 0%
5% Fr
an
ce
10% Ne
th
0.1 erla
15% nd
s
0.01
1900 1920 1940 1960 1980
Calendar year
Waaler H, et al. Bull Int Union Tuberc 1975;50:5-61 Sutherland I, et al. Tubercle 1983;64:241-253
Sutherland I, et al. Bull Int Union Tuberc 1971;45:75-114 Styblo K, et al. Bull Int Union Tuberc 1969;42:5-104
Lotte A, et al. Int J Epidemiol 1973;2:265-82 Vynnycky E, et al. Int J Tuber Lung Dis 1997;1:389-96
TB trends in Europe
Median age in Finland
70 65.1
60 55.7
50
39.4
40 1954
31.1
30 1986
20
10
0
Males Females
TB trends in Europe
Netherlands
Year ARI Median Age
1950 0.53% 28.9 year
1980 0.21% 43.7 year
Global drug resistance surveillance
D.R. among new D.R. among
cases previously treated
cases
1994-96 1.4% 13%
1996-99 1.0% 9.3%
Reported Tuberculosis Cases in the United States, 1953 - 1997
80000
Number of cases (log scale)
40000
20000
1950 1960 1970 1980 1990 2000
Year of notification
Centers for Disease Control and Prevention. Reported Tuberculosis in the United States 1996:1997:5
Centers for Disease Control and Prevention. MMWR 1998;47:253-7
Annual Risk of Tuberculous Infection
WHO South-East Asia Region
5
2
Risk of infection (%)
(log scale)
1
Slope reference:
% decline / year
0.5 1%
5% India
0.2 Indonesia
10%
Thailand
0.1
50 60 70 80
Year
Cauthen GM. WHO Document 1988;WHO/TB/88.154:1-34
Trends in ARI-
Chingleput
At intake in 1969 : 1.8%
After 4 years in 1973 : 1.8%
After 10 years : 1.9%
After 15 years : 1.7%
How does HIV pandemic
influence TB epidemic
• Higher rate of progression from latent infection
to disease (5-10% per year compared to 10% per
year among HIV negative)
• Previously HIV infected persons when exposed
to TB rapidly develop the disease.
• Excess cases due to the above lead to increased
transmission of infection
• Higher case fatality due to HIV infection
Evidence of association between
HIV and TB
* Increase in TB in areas worst affected by HIV
* Higher increase in age group affected by HIV.
* 50 to 70% AIDS cases develop TB in SEAR.
* HIV positivity higher among TB cases than
general population.
-Northern Thailand: HIV positivity in TB cases :
40%
: Malawi : 75%
Determinants for the Frequency of HIV-Associated Tuberculosis in a Community
Total population
Prevalence of infection with
Infected with M. tuberculosis
M. tuberculosis
Prevalence and incidence
of HIV infection
Overlap of the two respective
population segments
Infected with HIV
Impact of HIV Infection on Tuberculosis Notifications
in Chiang Rai, Thailand, 1985 - 1994
500
No. of cases (log scale)
All cases
400
300
HIV-neg cases
200
85 90 95
Year of notification
Yanai H, et al. AIDS 1996;10:527-31
TB trends in Africa
(countries with high HIV rates)
350
Standardized notification rate
300
250
200
150
100
50
0
1980 1985 1990 1995 2000
Estimated TB incidence vs
HIV prevalence
800
Estim ated TB incidence
600
(per 100K, 1999)
400
200
0
0.0 0.1 0.2 0.3 0.4
HIV prevalence, adults 15-49 years
Notification Rates of Sputum Smear-Positive Tuberculosis,
by Age, Tanzania Mainland, 1984 and 1995
Notifications per 100,000 200 1995
150
100
1984
50
0
0 15 25 35 45 55 65
Age group (years)
Tanzania NTLP / IUATLD. Progress Report 1996;No. 36
TB morbidity rates in Russia
90
80
70
per lakh pop.
60
50
40
30
20
10
0
1970 1980 1990 1997 1998 1999
20% of all patients in Russia have MBR TB
Case fatality rates in Russia
35
30
25
20
% 15
10
5
0
1987 1997
Increase in CFR attributable to increase in drug resistance cases
Culture Positive cases, Prevalence:Incidence
- Chingleput
4.5
3
Average - 3.4
(3.6 for smear pos)
1.5
0
1968-70 1971-73 1973-75 1976-78 1979-81 1981-83
In your opinion, what should be the
practical methods of monitoring
epidemiological trends in any given
community
Global picture
• 3rd largest cause of death (2.8%) and loss of DALYs in
15-59 year age group
• Incidence all cases - 8.8 million (2002)-141/100000
• in 22 HBCs - 7.0 million (80%)
• Smear + - 3.9 (63/100000) million
• Case notifications of smear positive cases increasing @
4% per year- 5% in eastern Europe and 7% in high HIV
African countries.
Epidemiological situation of TB
in South East Asian countries
Format for Country presentations
Estimated incidence of New smear
positive cases
Latest estimates of ARTI
Population mortality rates
Any information on disease trends
HIV sero-prevalence among TB
cases
MDR in new cases
MDR in previosly treated cases
Any other epidemiological
information eg, age sex distribution
of cases, TB in prisoners etc.
TB in South-East Asia
EUR AMR
EMR 6% 5%
8%
SEAR
AFR 38%
18%
Incidence: 3 mill
Deaths : 1 mill (1500/day)
WPR
25%
India, Bangladesh, Indonesia, Myanmar & Thailand
contribute 95% of regional burden
HIV-TB in SEAR
* Second largest number of HIV positives after SSA
SSA:60% SEAR:30%
* 6 million HIV positives in SEAR
India :4 mill
Thailand :1 mill
Myanmar :0.5 mill
* Low sero-positivity in Bangladesh, Maldives, Bhutan,
Indonesia and Sri lanka
* Nepal : Low in antenatal women, high among IDUs.
TB situation in India
Prevalence of sputum positive pulmonary TB
Area Year Preval. Rate
per 1000 pop.
National Sample Survey 1955-58 4
Tumkur 1960-61 4.1
1979 4.4
Rural Bangalore 1960-61 4.1
1967-68 3.9
1974-75 3.2
1984-86 4.4
Chingleput 1968-71 10.7
1973-75 8.9
1979-81 7.7
1984-86 6.9
1999-2001 6.9
Raichur 1988-89 10.7
Morena, M.P. 1991-94 12.7
Annual Risk of Infection (%)
0
0.5
1
1.5
2
2.5
3
3.5
4
TumkurDistt,1960-61
TumkurDistt,1972-73
Rural Bangalore, 1961
Rural Bangalore, 1970
Bangalore(Rural), 1977-78
Bangalore Rural, 1984
Peri urban Bangalore, 1992
Bangalore City, 1997
Chingleput, TN1969
Chingleput, TN1979
Chingleput, TN1984
Car Nicobar Island, 1986
A RT I i n I ndi a
Trivandrum, 1991-92
Bikaner Raj, 1992
M P,
orena,M 1989
Tiruvallur, 1999-2001
orth
N Zone-India 2000-02
West Zone-India2000-02
South Zone-India 2000-02
East zone India 2001-03
INCIDENCE OF PULMONARY
TUBERCULOSIS IN INDIA
Study Period Method Incidence
1961-62 1.36
Bangalore Rural
1962-64 Repeated Surveys 0.80
Age 5years
1964-68 1.04
Def : Culture +ve
1968-71 Repeated Surveys, 3.83
BCG.TRIAL,
passive case
Chingleput 1976-78 2.30
finding , selective
Age > 15 years
1981-83 case finding 3.00
Def: Culture positive &/or Microsopy +ve
CMC – Vellore 1981-83 Active case finding 1.10
Age> 10 yrs
Def:Smear +ve
HIV Sero-prevalence among TB Cases
Year of study % HIV +ve
Govt Hospital Tanjavur, TN 1999 8.9
General Hospital, Pune, MH 2000 28.8
TB & Chest Hospital,Goa 2000 10.9
AIIMS, Delhi 2000-02 9.4
Medical College, Lucknow 2000-01 4.3
Medical College, Aligarh 2000-01 2.8
Multi Drug Resistance in new TB cases
Year of study % MDR
23 districts of Tamilnadu 1997 3.4
DOT centres, Bangalore 1999 2.2
DTP centres, Raichur, Karnataka 1999-2000 2.5
Wardha, Maharashtra 2000-01 0.5
Jabhalpur, Madhya Pradesh 2001-02 1.0
Hoogli, West Bengal 2000-01 3.0
Mayurbhanj, Orissa 2000-02 0.7
Multi Drug Resistance in previously treated
TB cases
Year of study % MDR
TB Sanatorium, Chennai, TN 1997-2000 54.8
DOT centres, Tiruvallur, TN 1999-2000 18.3
State TB Centre, Ahmedabad, GJ 2000-01 33.0
ARI in other countries
Country wise Epidemiology situation
Country Pop. in Global % Incidence of all
million rank contribution cases
Total Rate
(000) /100000
India 1045 1 20 1761 168
Indonesia 217 3 6 557 256
Bangladesh 144 5 4 318 221
Thailand 62 19 1 80 128
Myanmar 49 22 1 75 154
Country wise Epidemiology situation - Continued
Country Incidence of ss + Prevalence TB HIV + %
Total Rate (ss +) Mortality/ TB cases
(000) /100000 /100000 100000 cases MDR
India 787 75 156 37 4.6 3.4
(0.4-28)
Indonesia 250 115 272 59 0.6 0.7
Bangladesh 143 99 188 520 0.1 1.4
Thailand 35 57 254 86 24 0.5
Myanmar 33 68 83 26 11 1.5
Country DOTS Treatment DOTS detection
population success (%) rate
coverage – 2001 (ss +) - 2002 (%)
(%) - 2002 cohort
India 52 85 31
Indonesia 98 86 30
Bangladesh 95 84 34
Thailand 100 56 47
Myanmar 88 81 73
Progress of DOTS in high burdened
countries
High treatment success (>70%)
Low treatment
Case detection under
success >50%
DOTS 10-49%
Brazil, Russia, Afghanisthan, Cambodia, Cango,
South Africa, Bangladesh, China, Myanmar, Philipines,
Uganda Euthopia, India, Thailand, Vietnam
Indonesia, Kenya,
Mozambique, Nigeria,
Pakistan, Tanzania,
Zimbabwe
What is meant by control ?
• To move from high to low endemicity or
elimination
Objectives of TB control
programmes
• Decrease transmission of infection by:-
- Rapidly identifying cases
- Adequate treatment
• Decrease deaths due to TB.
• Cure of maximum number of cases.
• To prevent relapse.
• To prevent emergence of drug resistance.
• To reduce TB in children by preventive treatment.
• IEC - Purpose ?
Each case leads to two cases
-_-_-
1 Infectious case
20 contacts
2 cases
of TB
1 Non-infectious
How does DOTS strategy help
control TB?
DOTS
• Decreases deaths
• Decreases duration of infectiousness
• Increased case detection plus high cure rate
decreases transmission of infection that
will ultimately lead to decline in incidence.
• Prevents emergence of MDR
A good programme like DOTS
reduces disease burden
• Case fatility rate reduced to <5% compared to
60%-70% in a few years among untreated cases.
• Cure of every case under DOTS with about 4
months diagnostic delay prevents 0.7 new smear
positive cases.(further prevention possible by
reducing diagnostic delay)
• Preventive treatment to each child prevents 0.03
new case and 0.007 deaths.
How does a poor programme
worsen the TB situation
• Poor programme with low cure rate (<50%)
and low detection rate worsen TB situation
by decreasing case fatility rates leading to
increased prevalence and transmission of
infection.
HIV prevention and control is of
major importance towards TB
control
Priority to smear positive cases
• To reduce transmission of infection. A good
DOTS programme would reduce
transmission of infections by about 73%
• Cost per DALY highest for treating smear
positive cases.
The Cuba example
• Very low levels of MDR in Cuba
• Cuba is a low HIV country
HIV-TB Vs. DOTS - TB trends in Tanzania
100 1.2
90
1
80
70 smear positive
0.8 notification
rate/ 100,000
60 pop
Treatment
completion
50 0.6 rates
ARI
40
0.4
30
20
0.2
10
0 0
1978-82 1983-87 1988-92 1993-97
• Increased case detection will decrease transmission
rapidly provided cure rates are high.
• It has been estimated that achievement of 70% case
detection and 85% cure rate by 2010 will result in
greatest benefits in cases and deaths averted in regions
with highest burden - South East Asia, Africa and
Western Pacific.
• Longer the time taken to reach targets, incidence will
decrease more slowly.
• The proportion of deaths averted by DOTS would be
greater than the proportion of cases
– Non curative treatment can prevent death without
eliminating infectiousness.
– Programme will treat non-infectious cases also
Control TB since every breadth
counts (World TB day 2004 theme)
Business as usual will not eliminate TB
It is time for business unusual
