All-cause Mortality and Malaria in African children: Trends and Controversies

1. All-cause Mortality and Malaria in African children: Trends and Controversies Joel G. Breman, MD, DTPH Fogarty International Center National Institutes of Health The Epidemiology of Malaria Gordon Research Conference Oxford, England 6 – 11 July 2003

2. Mortality and Malaria • All-cause • Malaria • Controversies • Research

3. All-cause Mortality • Regional, 1990 and 2000 • Trends, 1970 to 2015 • Africa, by area, 1960 to 2000

4. Trends in Under-Five Mortality • In 2002, about 10.5 million child deaths • Down from 12.4 in 1990 • Child deaths (millions): 2000 1990 AFR 4.5 4.0 SAR 3.7 4.0 EAP 1.4 2.2 LAC 0.4 0.6 MNA 0.4 0.6 ECA 0.2 0.3

5. Reducing child deaths

7. Malaria Burden • Percent of deaths, 2002 • Percent of DALYS, 2002 • Estimation of deaths, Africa, 1952 to 1999 • Manifestations • Hospital visits and admissions, 1985 to 2000 • Chloroquine resistance • Epidemics

8. Deaths and Malaria-related Deaths (1000s), 2000

9. Disability–adjusted Life Years (DALYs, 1000s),All Cause and Malaria-related, 2002

10. Estimated World and Regional Malaria Deaths, 1952-1999

11. Hypoglycemia Anemia Acute febrile illness Severe illness Death Respiratory distress Cerebral malaria Infected Mosquito Anemia Chronic effects Impaired growth and development Neurologic/ cognitive Malnutrition Infected Human Developmental Low birth weight Infantmortality Fetus Pregnancy Acute illness Maternal Impaired productivity Anemia Malaria BurdenClinical Manifestations

17. MARA/ARMA Model of Malaria Transmission, 2003

18. Place, year Population exposed Episodes Deaths Causes Historic examples of severe epidemics Madagascar highlands, 1987-1988 (1) 2.5 million Over 200,000 each yr; at peak, 27% of outpatient attendances 15,000-30,000 each year Abandonment of IRS and shortage of antimalarials Ethiopia highlands/ Dumbia plain, 1958(1) 8-10 million 3 million Over 150,000 (case fatality rate >5%) High rainfall and temperature Ethiopia, Dec. 1997 Feb. 1998 (1) 45 million >1 million 3271 officially reported High rainfall and temperature Abandonment of control (in relation to complex emergency), chloroquine resistance and expanded rice cultivation 2 million during 6 months – a 4-fold increase in confirmed cases (10) 1287 reported, true number estimated to be 10-15x higher NE Burundi, Oct-2000 – May 2001 (9) Table 5.1

19. RBM baseline survey Table 5.3 Note: SAMC – reference 7

20. Controversies

21. Controversies • Reliability of WHO and World Bank data • - Demographic Surveillance Systems • - Demographic and Health Surveys • Do we accept • - Overall mortality trends? • - Disease-specific trends?

22. Controversies (2)Whither Malaria • Is malaria withering? • Directly causes acute neurologic disease • Indirectly contributes to conditions and co-morbidity • - Anemia • - Malnutrition • - Low birth weight • - Decreased cognition • - Susceptibility to other infections • - Hypoglycemia • - Respiratory distress

23. Malaria Morbidity and Mortality Estimates for African Children <5 years: Possible Gaps Case fatality rate (%) Morbidity total cases Mortality total cases Manifestations Cerebral malaria 19.2 575,000 110,000 sequelae* < 6 mos. > 6 mos. - - 47,000 - 75,000 9,000 - 19,000 No data No data Severe anemia 13.4 - 17.2 1.42 – 5.66 million 190,000 – 974,000 13.9 792,000 110,000 Respiratory distress Hypoglycemia 20 – 35 764,000 153,000 – 267,000 Low-birth weight 37.5 167,000 – 967,000 62,000 – 363,000 3.718 – 8.758 million 625,000 – 1.824 million

24. Contribution (%) of Specific Gaps to African Childhood Malaria Morbidity (up to 8.76 million children affected) * Cerebral malaria 7% Hypoglycemia 9% Respiratory disease Severe anemia 9% 64% Low birth weight 11% *maximum estimate; all children <5 years of age except cerebral malaria (<10 years)

25. Contribution (%) of Specific Gaps to African Childhood Malaria Mortality (up to 1.82 million children die) Cerebral malaria 6% Respiratory disease 6% Hypoglycemia 15% Severe Anemia 53% Low birth weight 20%

26. Controversies (3) • Measurements • - Hospital-based admissions: total and with malaria and anemia • - Hospital-base deaths: total and with malaria and anemia • - Patient management: clinical and laboratory diagnosis, treatment, education, referral • - Maternal and fetal care: low birth weight babies in hospitals, with and without maternal infection

27. Research

28. Research • Relationship between research training and support • Themes tied to burden • Definition of burden of epidemic and urban malaria

29. Research, Training, and Support Needs According to Understanding of Diseases andEfficacy of Control Methods High High Training Efficacy of Control Methods Research Needs Low Low Some Moderate High Research Support Needs

30. Research, Training, and Support Needs According to Understanding of Diseases andEfficacy of Control Methods High High Training Efficacy of Control Methods Malaria Dengue HIV/AIDSTuberculosisEbola/Marburg InfluenzaCancersAlzheimer’s SmallpoxGuinea wormPoliomyelitisH. influenzae type BMeaslesTetanus Research Needs Low Low Some Moderate High Research Support Needs

31. Research Needs for Determining All-cause and Malaria Mortality • Pathology and pathogenesis (case control) • Population based studies (prospective) • Passive/routine surveillance vs. surveys • Intervention-linked research • Patient management • Chemoprophylaxis • Personal protection • Vector control • Environmental improvement • Vaccination

32. Fevers of the South “Humanity has but three great enemies, Fever, famine and war: of these by far the greatest, by far the most terrible is fever.” William Osler,1896