1. Malaria and its conquering Joel G. Breman, MD, DTPH Fogarty International Center National Institutes of Health Tropical Infectious Diseases Workshop Oswaldo Cruz Foundation (FIOCRUZ ) Rio de Janeiro, Brazil 28 April–1 May 2003

2. Conquering Malaria Ecology and burden Interventions Successes Economics Research questions Controversies

3. Ecology and Burden

4. Malaria and Ecology and Burden Intrinsic and Extrinsic Factors Control and prevention measures Human ParasiteMosquito Social, behavioral, economic and political factors Environmental conditions

5. Malaria Ecology and 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

7. Mendis K, Sina B J, Marchesini P, Carter R (2001) The neglected burden of P.vivax malaria. American Journal of Tropical Medicine and Hygiene 64; Supplement titled "The Intolerable Burden of Malaria: A New Look at the Numbers" 1-106. Global distribution of Plasmodium vivax maximum distribution 19 th century (pink) late 20 th century (purple)

8. MARA/ARMA Model of Malaria Transmission, 2003

9. 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

10. 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

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

12. Disease Malaria57.9% Childhood Diseases55.0% Diarrheal Diseases53.2% Perinatal Conditions45.0% Tuberculosis44.4% Maternal Conditions43.2% Respiratory Infections42.6% HIV/AIDS41.8% Weighted Average48.6% Percentage of Deaths from Disease Occurring Among the Poorest 20% of Global Population % Deaths

13. Interventions

14. Estimated Cost of Malaria Control in an Endemic Area: One Million People, One Round of Residual House Spraying Insecticide One application (tons) Price/tonTotal cost Cost per capita DDT147 $3,950 $580,650$0.58 Malathion220 $4,300 $946,000$0.95 Deltamethrin110$20,000$2,200,000$2.20 Pyrimiphos- methyl 220$16,000$3,520,000$3.52

15. Estimated Cost of Malaria Control: One Million People, One Full-dose Treatment, 1999 Drug Tablets in millions (dose) Price/ 1000 tabs Total cost Cost per capita Chloroquine (3 days) 11.25 (100 mg) $6.05 $68,063$0.08 Sulfadoxine- pyrimethamine (one dose) 2.5 (500 mgS/ 25 mgP) $47.00 $117,500$0.12 Quinine (7 d)31.5 (300 mg) $41.25$1,299,375$1.30 Artesunate (5 d)13.5 (50 mg)$365.00$4,927,500$4.93

16. Successes

17. 1899, (large scale) demonstration of successful Anopheline control in Cuba: antilarval and adult measures (large-scale) 1899–1914, multiple demonstrations of control by reduction of Anopheline larvae and adults –1899, Sierra Leone (antilarval); Cuba (large-scale); Malaysia (antilarval) –1904–1914, Panama Canal Zone; control by larviciding, large-scale environmental modification 1927, elimination of A. albimanus in Barbados (first area-wide success with invading species) Successes

18. Successes (2) 1935-1939, large-scale control by pyrethrum spraying in South Africa, Netherlands and India 1939-1957 –1939-1940, Elimination of invading A.gambiae from Brazil –1942-1945, A.gambiae eliminated from northern Egypt –1946-1957, Interruption of transmission by anti-mosquito measures in Cyprus, Sandinia, Guyana, Venezuela and Greece; indoor residual spraying with DDT, a major strategy

19. Successes (3) 1987-2003 –Multiple projects and programs using insecticide-impregnated bed nets demonstrate overall mortality reduction and decrease in several malaria indices

20. Interventions, Control and Economics

21. Type of Control Vector Control Environmental modification (urban)* Chemical and biological larvicides* Indoor residual insecticide spraying* Outdoor residual insecticide spraying *costly and effective

22. Type of Control Personal protection (2) Insecticide–impregnated materials: nets, curtains, clothing* House screening House location Repellents Fumigants * Shown cost effective for low-income countries

23. Type of Control Antiplasmodial (3) Patient management: early diagnosis, treatment, referral, education Chemoprophylaxis Intermittent treatment (pregnancy)* Radical therapy for relapses (P.vivax, P.ovale) * cost effective

24. Type of Control Social Action Mobilization of individual, family, community Health education Management Effectiveness Health systems effectiveness (quality), efficiency Leadership, planning, policies, strategies, tactics Surveillance Monitoring and evaluation

25. Research Questions

26. Research Agenda Pathogenesis Drug development Vaccine development Diagnostics Clinical and community-based trials Entomology

27. Research Agenda (2) Clinical issues –anemia –neurologic and cognition –pregnancy-related Health services delivery Social, legal, ethical

28. Controversies

29. Drugs –Combination artemisinin-based compounds for treatment –Chemoprophylaxis for high risk persons Burden –Malaria as a cause or risk-factor (co-morbidity) –Cognition and developmental issues

30. Controversies (2) Transmission –Cost-effective vector control approaches in urban and rural areas –Impregnated materials, how to improve and make the social standard Basic research –Immunologic, genetic

31. Malaria, Annual WHO Estimates, 1997 Region Population at risk (1000s) Total Cases (%) (1000s) P. Falciparum (%) (1000s) P.vivax (%) (1000s) SE Asia, Western Pacific 1,284,000 86,40144,400 42,006 Eastern Mediterranean 64,600 14,539 2,883 11,656 Central America/ Caribbean 64,200 3,676 580 3,096 South America 23,500 11,325 3,347 7,978 Central Asia/ Cancasus 8,480 167 0 World total outside Africa 1,444,780116,33451,211 65,124 Africa 550,000300,000Most of total6-15,000 Imported malaria²1,590,000 33 11 22 Total ³

32. Malaria in Sri Lanka Plasmodium falciparum Plasmodium vivax

33. :: % Plasmodium vivax 100 10 1 Total Annual Malaria Incidence Rate (%) 0.000 0.01 0.001 0.11.010.0

34. :: % Plasmodium vivax 100 10 1 0.000 0.01 0.001 0.11.010.0 More Northerly, more temperate More Southerly, more tropical