Malaria and its conquering Joel G Breman MD

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

Conquering Malaria • • • Ecology and burden Interventions Successes Economics Research questions Controversies

Ecology and Burden

Malaria and Ecology and Burden Intrinsic and Extrinsic Factors Control and prevention measures Parasite Human Social, behavioral, economic and political factors Mosquito Environmental conditions

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

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

MARA/ARMA Model of Malaria Transmission, 2003

Deaths and Malaria-related Deaths (1000 s), 2000 Malaria/ All deaths (%) Deaths (%) total (%) 56, 554 1, 124 2. 0 World Population 6, 122, 210 Africa 655, 476 10, 681 (18. 9) 963 (85. 7) 9. 0 Americas 837, 967 East Med. 493, 091 Europe 874, 178 SE Asia 1, 559, 810 West 1, 701, 689 Pacific 5, 911 (10. 5) 4, 156 (7. 3) 9, 703 (17. 2) 14, 467 (25. 6) 11, 636 (20. 6) 1 (-) 55 (4. 9) 0 95 (8. 5) 10 (0. 9) 0. 02 1. 3 0. 7 0

Disability–adjusted Life Years (DALYs, 1000 s), All Cause and Malaria-related, 2002 Population DALYs from all deaths (%) DALYs from malaria deaths (%) World 6, 122, 210 1, 467, 257 42, 280 Africa 655, 476 357, 884 (24. 4) Americas 837, 967 145, 217 (9. 9) 108 (0. 2) East Med. 493, 091 136, 221 (9. 3) 2, 050 (4. 8) Europe 874, 178 151, 223 (10. 3) SE Asia 1, 559, 810 418, 844 (28. 5) 3, 680 (8. 7) 0. 9 West Pacific 1, 701, 689 257, 868 (17. 6) 409 (1. 0) 0. 2 36, 012 (85. 2) 20 (0. 04) DALYs from malaria /total (%) 2. 9 10. 1 0. 07 1. 5 0. 01

Estimated World and Regional Malaria Deaths, 1952 -1999

Percentage of Deaths from Disease Occurring Among the Poorest 20% of Global Population Disease % Deaths Malaria 57. 9% Childhood Diseases 55. 0% Diarrheal Diseases 53. 2% Perinatal Conditions 45. 0% Tuberculosis 44. 4% Maternal Conditions 43. 2% Respiratory Infections 42. 6% HIV/AIDS 41. 8% Weighted Average 48. 6%

Interventions

Estimated Cost of Malaria Control in an Endemic Area: One Million People, One Round of Residual House Spraying Insecticide DDT One application Cost per (tons) capita Price/ton Total cost 147 $3, 950 $580, 650 $0. 58 Malathion Deltamethrin 220 110 $4, 300 $20, 000 $946, 000 $2, 200, 000 $0. 95 $2. 20 Pyrimiphosmethyl 220 $16, 000 $3, 520, 000 $3. 52

Estimated Cost of Malaria Control: One Million People, One Full-dose Treatment, 1999 Tablets in millions (dose) Drug Chloroquine (3 11. 25 (100 days) mg) Sulfadoxine 2. 5 (500 mg. S/ pyrimethamine 25 mg. P) (one dose) Quinine (7 d) 31. 5 (300 mg) Artesunate (5 d) 13. 5 (50 mg) Price/ 1000 tabs Cost per capita $6. 05 Total cost $68, 063 $47. 00 $117, 500 $0. 12 $41. 25 $1, 299, 375 $1. 30 $365. 00 $4, 927, 500 $4. 93 $0. 08

Successes

Successes • 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 (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 antimosquito measures in Cyprus, Sandinia, Guyana, Venezuela and Greece; indoor residual spraying with DDT, a major strategy

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

Interventions, Control and Economics

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

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

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

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

Research Questions

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

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

Controversies

Controversies • 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

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

Malaria, Annual WHO Estimates, 1997 Region SE Asia, Western Pacific Population at risk (1000 s) Total Cases (%) (1000 s) P. Falciparum (%) (1000 s) P. vivax (%) (1000 s) 1, 284, 000 86, 401 44, 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 8, 480 167 1, 444, 780 116, 334 51, 211 65, 124 550, 000 300, 000 Most of total 1, 590, 000 33 Central Asia/ Cancasus World total outside Africa Imported malaria² Total ³ 11 6 -15, 000 22

Malaria in Sri Lanka Plasmodium vivax Plasmodium falciparum

: % Plasmodium vivax 100 10 1 0. 000 0. 001 0. 1 1. 0 Total Annual Malaria Incidence Rate (%) 10. 0

: % Plasmodium vivax 100 10 1 More 0. 001 0. 000 Northerly, 0. 01 more temperate 0. 1 More Southerly, 1. 0 10. 0 more tropical