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): 20001990 AFR 4.54.0 SAR 3.74.0 EAP1.42.2 LAC 0.40.6 MNA 0.40.6 ECA0.20.3

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 PopulationAll deaths (%) Malaria Deaths (%) Malaria/ total (%) World6,122,210 56,5541,124 2.0 Africa 655,476 10,681 (18.9)963 (85.7) 9.0 Americas 837,967 5,911 (10.5)1 (-) 0.02 East Med. 493,091 4,156 (7.3)55 (4.9) 1.3 Europe 874,178 9,703 (17.2) 0 - SE Asia1,559,810 14,467 (25.6) 95 (8.5) 0.7 West Pacific 1,701,689 11,636 (20.6) 10 (0.9) 0

9. Disability–adjusted Life Years (DALYs, 1000s), All Cause and Malaria-related, 2002 Population DALYs from all deaths (%) DALYs from malaria deaths (%) DALYs from malaria /total (%) World6,122,2101,467,25742,280 2.9 Africa 655,476 357,884 (24.4)36,012 (85.2) 10.1 Americas 837,967 145,217 (9.9) 108 (0.2) 0.07 East Med. 493,091 136,221 (9.3) 2,050 (4.8) 1.5 Europe 874,178 151,223 (10.3) 20 (0.04) 0.01 SE Asia1,559,810 418,844 (28.5) 3,680 (8.7) 0.9 West Pacific1,701,689 257,868 (17.6) 409 (1.0) 0.2

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

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

17. MARA/ARMA Model of Malaria Transmission, 2003

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

19. Epidemics identified 1998-2000 Percentage detected within 2 weeks Percentage responded to within 2 weeks of detection Source Angola 300 SAMC Botswana 2100 SAMC Malawi --- SAMC Mozambique 367 SAMC Namibia 3033 SAMC South Africa 4100 SAMC Swaziland 2100 SAMC Tanzania --- SAMC Zambia --- SAMC Zimbabwe 33367 SAMC Eritrea 4 (districts) 75100 RBM baseline survey Ethiopia 10255100 RBM baseline survey Uganda ? 0100 Note: SAMC – reference 7 Table 5.3 RBM baseline survey

20. Controversies

21. 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 625,000 – 1.824 million 3.718 – 8.758 million 62,000 – 363,000167,000 – 967,00037.5Low-birth weight 153,000 – 267,000764,00020 – 35Hypoglycemia 110,000792,00013.9 Respiratory distress 190,000 – 974,0001.42 – 5.66 million13.4 - 17.2Severe anemia No data 47,000 - 75,000 9,000 - 19,000 ---- sequelae* < 6 mos. > 6 mos. 110,000575,00019.2Cerebral malaria Mortality total cases Morbidity total cases Case fatality rate (%) Manifestations

24. Contribution (%) of Specific Gaps to African Childhood Malaria Morbidity (up to 8.76 million children affected) * Cerebral malaria 7% Hypoglycemia 9% Respiratory disease 9% Low birth weight 11% Severe anemia 64% *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) Severe Anemia 53% Low birth weight 20% Hypoglycemia 15% Respiratory disease 6% Cerebral malaria 6%

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. 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 and Efficacy of Control Methods Research Needs Efficacy of Control Methods High Training SomeHighModerate Research Support Needs Low

30. Research, Training, and Support Needs According to Understanding of Diseases and Efficacy of Control Methods Research Needs Efficacy of Control Methods High Training SomeHighModerate Research Support Needs Low Smallpox Guinea worm Poliomyelitis H. influenzae type B Measles Tetanus Malaria Dengue HIV/AIDS Tuberculosis Ebola/Marburg Influenza Cancers Alzheimer’s

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. F evers of the S outh “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