Infectious Diseases on an Empty Stomach:
Malnutrition as a Neglected Disease
Dr. Frances Davidson
USAID
Burden of disease
Each year…
Malaria:1 million deaths 750,000 children
Malnutrition: 2 to 5 million under five deaths
HIV:
2.9 million deaths 540,000 children infected
TB:
AI:
*since 2003
1.6 million deaths
200 deaths*
Are these conditions related?
Is malnutrition a neglected disease?
WHO definition of Neglected Diseases:
•Afflict the poor and most vulnerable (kids and women) •Affect rural areas of low-income countries •Cause suffering, life-long disabilities •High degree of morbidity •Associated with social stigmatization •Impair childhood growth and development •Do not receive attention and funding of highmortality diseases
Lymphatic Filariasis: 120 million cases, 5 million DALYs Onchocerciasis: 18 million cases, 1 million blind or visually-impaired
Trachoma: 84 million cases, 8 million blind or visuallyimpaired
•No commercial markets for drugs or vaccines
Schistosomiasis and soiltransmitted helminths: 300 million infected, 20,000 annual deaths
9.7 million under five deaths in 2006
The single largest common denominator in global child deaths is malnutrition
Malnutrition…
•Causes lymphoid atrophy, reducing the size of the thymus and spleen •Decreases phagocytic activity by neutrophils and macrophages •Decreases number of circulating T cells
•Impairs lymphokine production
MICRONUTRIENTS
Vitamin A deficiency: reduces leukocyte numbers, lymphoid tissue weights, T cell function, natural killer cell numbers and complement activation
•Depresses integrity of skin and mucosal surfaces of the lung and GI tract
•Impairs complement activation
Vitamin B deficiencies: reduce lymphocyte number, lymphoid tissue weights, antibody responses, and depress phagocyte functions and T cell proliferation Iron deficiency: reduces cytotoxic activity of phagocytes and proliferation of T helper cells
Zinc deficiency: reduces T cell development and function
Under Five Mortality
20-50% of the 9.7 million child deaths each year…
60.7% of diarrhea deaths
57.3% of malaria deaths
52.3% of pneumonia deaths 44.8% of measles deaths …are attributable to undernutrition
Caulfield et al, 2004
And Infection…
•Causes protein catabolism and negative nitrogen balance
•Increases resting energy metabolism •Redistributes trace elements like iron and zinc •Increases vitamin utilization and excretion
MICRONUTRIENTS
Reduces serum Vitamin A concentrations, precipitating xerophthalmia Sequesters serum iron in reticuloendothelial system and phagocytes release lactoferrin—deprives infectious agent of iron for replication by competing with bacteria for iron
Decreases plasma zinc concentrations due to redistribution of metal to the liver (acute infections)
Risk Factors
Lopez, et al. Lancet 2006
Nutrition in the Life Cycle
Keith West
Maternal anemia
Iron deficiency anemia is associated with 22% of maternal deaths worldwide, and about 50% of all anemia
The risk of maternal mortality decreases by 20% for each 1 g/dL increase in hemoglobin.
Measles (4% of child deaths): 200,000 IUs vitamin A decreases
measles-specific mortality by 50%
ARIs (19-25% of child deaths):
Low Birth Weight: Children born below 2,500 g at birth are 2.9 times more likely to die of ALRI and pneumonia Breastfeeding: Children who are not breastfed are two times more likely to die of ALRIs Weight-for-height: Wasted kids are over 4 times as likely to die of ARIs
Diarrhea (17% of child deaths):
Zinc decreases the duration and severity of acute and persistent diarrhea Vitamin A supplementation decreases the severity of diarrheal episodes and diarrhea case-fatality rates (but not incidence) Wasting and stunting both associated with increased incidence, severity, and duration of diarrhea Consumption of specific lactic acid producing organisms reduces incidence of diarrheal infections by as much as 50%
Malaria (8%)
•Stunted children are over 2 times more likely to die from malaria
•Children 1-7 months who were breastfeeding poorly were 5.5 times more likely to die than those feeding normally •Children in the lower quartile of weight-for-age were 2.5 times as likely to die
Undernutrition reduces T lymphocytes, impairs antibody formation, decreases complement formation, and causes atrophy of lymphoid tissues—all necessary in combating the malaria parasite
Neonatal (37%)
The risk of neonatal death for infants weighing 2000-2499g at birth is four times higher than those weighing 2500-2999g.
•Infants born LBW are 2-4 times more likely to develop acute diarrhea or to be hospitalized for diarrhea
•Infants born LBW are twice as likely to contract ALRIs
Bryce, et al. 2005
Maternal undernutrition is a major causal factor, including low gestational weight gain, low pre-pregnancy BMI, short maternal stature, micronutrient deficiencies
Newborn VAS
HIV (3%)
HIV compromises nutritional status and increases susceptibility to secondary infections
Malnutrition exacerbates the effects of HIV by further weakening the immune system
Low serum retinol levels associated with increased risk of vertical transmission of HIV
HIV/AIDS
Increases susceptibility to infections
Malnutrition
Loss of appetite Nausea
Weight loss
Diarrhea
Difficulty swallowing
Medication malabsorption
Loss of livelihoods Loss of economic productivity
Depression
Infant feeding practices
Nutrient malabsorption
Maternal mortality
Increases mortality and morbidity from infectious agents
Undernutrition isn’t just a risk factor for increased mortality and morbidity, but also a barrier for effective treatment of infectious diseases
“Some poor ART clients have benefited clinically from ARVs through improved CD4 counts and reduced viral load but have continued to lose weight. These are normally clients from poor backgrounds and this may point to the unmet need for food support. We are now convinced that food is key to the success of treatment with ARVs”.
Interaction between food and ARVs
FANTA
Is the USG funding the right stuff?
In FY2005, PEPFAR provided $482 million to support ART for 401,000 AIDS patients
PEPFAR Guidance on the use of funds to address food and nutrition needs:
•Food support may be provided only to severely malnourished patients, defined as BMI<16 •“Emergency Plan funds may pay for the procurement of food only as a last resort.”
•Supplemental and replacement feeding to children and pregnant/lactating women
Ethiopia Case Study
Total Population:
Under Fives: HIV Adult Prevalence:
77.4 million
15.8 million 0.9-3.5%
Causes of death in children under five
Children 0-14 infected: 0.1-0.7% Stunting: Underweight: 50.7% 34.6%
Causes of death in children under five (2005)
Other 14% Injuries 2% Neonatal 31%
FY06 PEPFAR funding: $66,526,307 FY06 child survival and nutrition funding: $5,427,000
Pneumonia 22% HIV/AIDS 4% Malaria 6% Measles 4%
Diarrheal Diseases 17%
US Private Foundation Funding
$0
Infectious Diseases Human Rights Education Conflicts Sanitation/Clean Water Economic Development Natural Disasters Reproductive Health The Environment Malnutrition
$50
$100
$150
$200
$250
Cost-effectiveness
VCT Vitamin A Supplements US$0.50 per child (US$182-327 per child death averted) Iron Supplements US$3.17-5.30 per child (In Africa, US$30-66 per DALY averted) Zinc Supplements with ORS US$0.47 per child (US$2,100 per child death averted) US$249-346 per case of HIV averted Obesity in middle school students US$4,300 per DALY averted Expanded Program on Immunization US$14-20 per year of healthy life gained in lowincome countries Treatment for hypertension in the US US$4,430-87,940
The importance of nutrition
So, is nutrition a neglected disease?
Afflict the poor and most vulnerable
Affect rural areas of low-income countries and urban populations Cause suffering, life-long disabilities and death
High degree of morbidity and mortality Associated with social stigmatization Impair childhood growth and development with life-long consequences Do not receive attention and funding of high-mortality diseases No commercial markets for drugs or vaccines
Nutrition is THE neglected disease.
Everyone is scared of avian influenza AI HIV Malaria
Nutrition
And we know what to do