32191 - Defining and Defeating the Intolerable Burden of...

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Unformatted text preview: Defining and Defeating the Intolerable Burden of Malaria Burden Joel G. Breman, MD, DTPH Fogarty International Center U.S. National Institutes of Health BioVisionAlexandria 2008 New Life Sciences: From Promises to Practice Alexandria, Egypt April 14, 2008 Our Goal Malaria Free Mothers and Children and all others Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Transmission of Plasmodium from Transmission of Mosquito to Human…to Mosquito P. falciparum P. vivax P. ovale P. malariae P. knowlsei White and Breman, 2008 (after Hoffman), Harrison’s Principles of Internal Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Manifestations of the Malaria Burden Manifestations Anemia Hypoglycemia Acute febrile illness Severe illness Infected Mosquito Long-term sequelae Respiratory distress Hypovolemia Death Cerebral malaria Anemia Infected Human Chronic effects Neurologic Cognitive Developmental Fetus Low birth weight Abortion, stillbirth Pregnancy Maternal Breman, Alilio, Mills, 2004, Am J Trop Med Hyg Impaired growth and development Acute illness Anemia Malnutrition Infant and fetal mortality Long-term sequelae Overlap of Cerebral Malaria, Anemia, Respiratory Distress in Children Mali Kenya Respiratory Distress Cerebral Malaria 22/177 (12%) 31/58 (53%) 3/7 (43%) 1/14 (7%) 1/1 2/2 1/4 (100%) (25%) (100%) 3/7 3/4 (43%) (75%) 2/126 (2%) 1/2 (50%) 2/23 (9%) Severe Malarial Anemia Hypoglycemia Ranque et al 2008, Ped Inf Dis J ( ) = number of patients % = CFR Marsh et al, 1995, NEJM Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Global Malaria and Endemicity, 2003 Global Malaria and Endemicity, 2003 Global Distribution of Malaria Anopheline Vectors Global Distribution of Malaria Anopheline Vectors Kizewski et al., 2004, Am J Trop Med Hyg Plasmodium falciparum in 2005 Clinical Cases Region Population at risk (million) Cases (%) Africa 521 365 (215 ­ 374) (57%) South East Asia 1,314 119 (66 ­ 224) (34%) Western Pacific 142 15 (9 ­ 26) (4%) Eastern Med. 176 12 (5 ­ 25) (4%) Americas 55 4 (2 ­ 8) (1%) Europe 4 1 (0 ­ 1) (<1%) Total 2,211 515 (298 – 659) (100%) Snow et al, 2005, Nature (million) Leading Causes of Disability­Adjusted Burden of Malaria on Health Systems in Leading Causes of Disability­Adjusted Life Years (DALYs) in Sub­Saharan Sub­Saharan Africa, 1999­2004 African Region, 2001 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Total DALYs HIV/AIDS % 17.8 Lower respiratory infections Perinatal conditions Diarrheal diseases Measles Tuberculosis Whooping cough Road traffic accidents Protein­energy malnutrition 8.4 6.3 6.1 4.6 2.4 1.9 1.8 1.6 Malaria Total Source: Mathers, et al., 2006, Global Burden of Disease and Risk Factors 10.3 61.2 O U T P A T I E N T S H FE I V S E T R O R Y A D M I S S I O N S H O S P I T A L Source: WHO 2005 D E A T H S Deaths from Malaria: Children Under Five and Total, Africa 2001 Cause of malaria-related death ● Number of malaria deaths Under fives Severe anemia Hypoglycemia 153,000-267,000 Low birth weight 62,000-363,000 Cerebral malaria 110,000 Respiratory distress 110,000 Total deaths from malaria ● 190,000-974,000 625,000-1,824,000 Total, all ages 962,000-2,806,000 Sources Breman, Alilio and Mills, 2004, Am J Trop Med Hyg; Murphy and Breman, 2001, Am J Trop Med Hyg Population at Risk of P. vivax and Population at Risk of Clinical Cases Per Year (in millions) South East Asia Population at risk Infections/year (millions) (millions) 1,347 90­248 Western Pacific 89 20­77 East Mediterranean 211 11­34 Americas 78 10­28 Europe 20 1­4 Africa 50 — Central Asia Total — 2,596 — 132­391 Price et al, 2007, Am J Trop Med Hyg Surveys of P. falciparum, Eastern Mediterranean Regional Office (EMRO), 1985­2007 Countries With Widespread Transmission, 2006 Afghanistan Djibouti Pakistan Somalia Sudan Yemen Total Breman and Holloway, 2007, Am J Trop Med Hyg Population Cases (millions) Confirmed 31.6 83,000 0.6 2,000 164.7 24,000 8.8 16,000 40.2 589,000 19.8 55,000 265.2 569,000 Cases Estimated 1,500,000 60,000 1,600,000 1,300,000 5,000,000 900,000 10,360,000 Malaria in Eastern Mediterranean Region, WHO: Countries Having Interrupted or Limited Transmission Country Bahrain Cases 70 Country Morocco Cases 83 Egypt 29 Iran Iraq 15,909 (13,127) 24 Oman Palestine 443 2 Qator 198 Jordan 116 (2) 1,278 (26) Kuwait Lebanon 235 42 Saudi Arabia Syria Tunisia Libya 10 ( ) local transmission Breman and Holloway, 2007, Am J Trop Med Hyg 34 36 United Arab 1,663 Republic Total 20,142 (13,432) Community Surveys of P. falciparum Prevalence Community Surveys of Conducted between 1985 and 2007 in AFRO Guerra et al, 2008, PLoS Med MARA/ARMA (http://www.mara.org.za) Community Surveys of P. falciparum Prevalence Community Surveys of Conducted between 1985 and 2007 in AMRO and SEARO­WPRO Guerra et al, 2008, PLoS Med Malaria Cases and Death in South East Asia Region of WHO, 2004 Malaria Cases and Death in South East Asia Region of WHO, 2004 DEMOCRATIC PEOPLE’S REPUBLIC OF KOREA 0.5% Malaria Cases = 2,525,715 Cases of Malaria in the European Region , 2005 Malaria Deaths = 3,768 Malaria Danger in Central Asia and Kazakhstan Breman and Holloway, 2007 Am J Trop Med Hyg Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Roll Back Malaria’s Goals, Strategies, and Targets To Halve the Burden of Malaria by 2010 Abuja Malaria Summit, April 2000, revised 2007 RBM strategy Abuja target (by 2005), RBM (2007) Prompt access to effective treatment 80% patients using correct/affordable treatment w/in 24 hrs Insecticide­treated nets (ITNs) 80% of children <5 years and pregnant women having ITNs Prevention and control in 80% of pregnant women using intermittent preventive treatment pregnant women Epidemics 60% detected w/in 2 weeks of onset 60% responded to w/in 2 weeks RBM, WHO, 2008 Major Manifestations of Malaria Major Manifestations of Malaria Anemia Lennart Nielson (Karolinska Instituteg), Hedvig Perlmann (Stockholm University) Martin Weber George Grau Roll Back Malaria Info Sheet Cerebral malaria Low birthweight Rick Steketee National Human Genome Research Institute Selected Severe Patient Management Clinical Malaria Conditions Selected Requiring Diagnosis and Reporting Requiring Condition Condition Manifestations Required Equipment Managementa Coma * Unable to respond to stimuli Unable Blantyre coma scale Parenteral therapy Convulsions Convulsions (grand and Convulsions petit mal) petit Observation Anticonvulsants, Anticonvulsants, protection from injury protection Renal failure Renal Urine output in 24h Urine Biochemical analysis Rehydration (no Rehydration overhydration) overhydration) Serum creatinine Serum Urine collections Urine Hemofiltration if Hemofiltration needed needed Other Sepsis Sepsis* Low birth weight* Low Febrile, hypotensive, shock (after malaria treatment) (after Blood culture, complete Blood blood count blood Antibiotics, supportive Antibiotics, care care Rehydration, Rehydration, <2500 gm Scale (calibrated) Resuscitation, breast, Resuscitation, warmth warmth Breman and Holloway, 2007, Am J Trop Med Hyg Selected Severe Clinical Malaria Conditions Requiring Diagnosis, Selected Assessment and Reporting (2) Assessment Condition Condition Hematologic Hematologic Anemia * Manifestations Required Equipment Managementa Hematocrit<15% Hematocrit<15% Hemoglobin <50 g/dL Hemoglobin Hematocrit equipment Hematocrit Hemoglobinometer Blood transfusion Hypoglycemia* Hypoglycemia Plasma glucose Plasma Analytic equipment Glucosometer Glucose infusion Acidosis Acidosis Arterial pH Arterial Plasma bicarbonate Plasma Blood gas analysis Correct hypovolemia Hemofiltration >100,000 parasites/ml >100,000 Microscopy (or Rapid Microscopy Diagnostic Test) Diagnostic Parenteral treatment with artemisinins, quinine or quinidine quinine Biochemical Biochemical Parasitologic: Parasitologic: Hyperparasitemia * Hyperparasitemia Microscope, slides, Microscope, reagents in addition to antimalarial drugs; referral to a secondary or temporary care facility for patients requiring parenteral therapy and intensive supportive care. b consider exchange transfusion for parasitemia >10% * essential measurement a Breman and Holloway, 2007, Am J Trop Med Hyg Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Control of the Malaria Burden Current Interventions Drugs (treatment, prevention) Protection (insecticideimpregnated materials) Insecticides (house spraying, larvicides) Environmental and Behavioral Modification Vaccines (preerythrocytic, blood stage, transmissionblocking) Future Interventions Genetic modification of vectors Cost­Effectiveness of Interventions Against Malaria in Sub­Saharan Africa Intermittent preventive treatment/ pregnancy (SP) Insecticide residual spraying Artemisinin comb. therapy (resistance) Insecticide-treated bed nets Intermittent preventive treatment 0 5 10 15 20 25 30 Cost-effectiveness ratio ($ per DALY Laxminarayan et al (DCPP authors), 2006, averted) et al, Disease Control Priorities in Developing Countries, in Jamison nd 2 ed. Malaria: Prevention and Treatment Malaria: Prevention and Treatment Treatment with a new group of antimalarials – the artemisinin compounds, in combination with lumefantrine, amodiaquine, sulfadoxine– pyrimethamine, or others OO O O O Artemesia annua Spread of chloroquine resistance The Process for the Microbial Production of Artemisinin The Process for the Microbial Production of Artemisinin WHO/Tropical Diseases Research/Crump Verband Forschender Arzneimittelhersteller e.V. Hale et al, 2007, Am J Trop Med Hyg Insecticide Treated Materials Work Insecticide Treated Materials Work Sleep Inside the Net Anopheles Mosquito, Larva Breeding Sites Anopheles Insecticides recommended by the World Health Organization Insecticides recommended by the World Health Organization for Indoor Residual Spraying Insecticide DDT Fenitrothion Malathion Pirimiphos-methyl Propoxur Bendiocarb Alpha-cypermethrin Cyfluthrin Deltamethrin Etofenprox Lambda-cyhalothrin Bifenthrin Class Organochlorine Organophosphate Organophosphate Organophosphate Carbamate Carbamate Pyrethroid Pyrethroid Pyrethroid Pyrethroid Pyrethroid Pyrethroid Sadasivaiah et al, 2007, Am J Trop Med Hyg 1-2 2 2 1-2 1-2 0.1-0.4 0.02-0.03 0.02-0.05 0.02-0.025 0.1-0.3 0.02-0.03 0.025-0.05 Duration of effective action (months) >6 3-6 2-3 2-3 3-6 2-6 4-6 3-6 3-6 3-6 3-6 3-6 Photo: W orld Health Organization *DDT, dichlorodiphenyltrichloroethane Cost/house/6 months Cost/ratio DDT $1.6/1.0 Deltamethrin 1.6/1.0 Malathion 8.2/5.1 Lambda-cyhalothrin 8.6/5.4 Bendiocarb 13.8/8.6 Fenitrothion 14.8/9.3 Propoxur 18.8/11.8 Recommended dosage of active ingredient (g/m2) Insecticides Used for Malaria Vector Control, 1995­2006 Vector Surveillance Capacity in Sub­Saharan Africa, 2006 9000 8000 7000 DDT thousands of kg 6000 5000 OP 4000 C 3000 PY 2000 1000 19 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 30 20 0 20 4 05 0 thousands of kg Entomological Capacity, 2006 no capacity basic for control or research basic/advanced for control, advanced in research WHO, 2004, Sadasavaiah, Tozan, Breman, 2007 Flamboyant Trees on the Grounds of the Lamumba Flamboyant Trees on the Grounds of the Lamumba Health Clinic in Kisumu, Kenya Omlin et al, 2007, Am J Trop Med Malaria Diagnostics: Microscopy and Rapid Malaria Diagnostics: Microscopy and Rapid Diagnostic Testing Blood Smears RDT Global Fund: HIV/AIDS, Global Tuberculosis, and Malaria per-capita funding levels per-capita Source: UNICEF, 2007 Countries with Countries President’s Malaria Initiative and World Bank Booster Funding World Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Rwanda: Malaria Progress Rwanda: Malaria Progress Vital Statistics Malaria Population: 9.3 million Risk: 4.8 million Women 15-45 yrs: 2.7 million Cases: 1.4 million (2005) Children <5 yrs: 4.0 million Deaths <5yrs: 510 (2006) Infant mortality: 152 (2005) Indicator 2000(%) 2005 (%) 2007 (%) — 17 60 — 0 65 Children with fever (%) receiving anti-malaria drugs receiving 13 12 — receiving drugs <24 hours receiving — 3 — sleeping under ITN sleeping 5 13 60 Pregnant women sleeping under ITN sleeping received IPT (≥2 doses) received Roll Back Malaria Ethiopia: Malaria Progress Ethiopia: Malaria Progress Vital Statistics Malaria Population: 77.3 million Risk: 52.5 million < 5 mortality: 123 Cases (est): 12 million (2006) (reported): 3.7 million Child Deaths : 94,400 Indicator 2005 (%) 2006 (%) % Households with ≥1 ITN Households ≥1 3 91 Children < 5 yrs sleeping under ITN previous night 2 87 Pregnant women sleeping under ITN Pregnant previous night previous 1 — Roll Back Malaria Vital Statistics Zambia: Malaria Progress Zambia: Malaria Progress Malaria Cases: 2.1 million (2005) Population: 11.7 million Indicator Indicator 2002 2002 (%) (%) 2004 2004 (%) (%) 2006 2006 (%) (%) % Households Households with ≥1 ITN ≥1 14 27 44 Children < 5 yrs Children sleeping under ITN ITN 16 — 27 Pregnant women Pregnant sleeping under ITN 8 12 24 Roll Back Malaria Results from Zanzibar Island, Results from Zanzibar Island, Tanzania Population: 1,116,001 (2006) Results from Zanzibar Outpatient Malaria Cases (Confirmed and non-confirmed) per 1000 of the population Ali, et al 2007, EARN Meeting Proportion of malaria Proportion confirmed cases confirmed Defining Malaria and its Conquest Defining Manifestations Burden Goals Interventions Progress Research Research Needs: Disease Burden that Can or Cannot be Averted with Existing Interventions Disease Burden: Not Avertable Already averted Avertable Biomedical research to identify new and improved interventions Increase effectiveness or reduce costs of existing interventions coverage Broader implementation of cost-effective interventions; identify obstacles to expansion of coverage Research and Development Categories and Results for Implementation New basic understanding • Fundamental research • Basic epidemiology, risk factors, modeling New and improved tools • Drugs • Vaccines • Diagnostics • Devices • Vector control • Environmental modification • Behavioral, social, and economic change Research and Development Categories and Results for Implementation New and improved intervention methods • • • • • Treatment algorithms and guidelines Intervention packaging Priority setting via costing and cost-effectiveness studies Delivery: health systems and health services New and improved policy instruments Malaria Research Needs: Major Gaps and Malaria Research Needs: Major Gaps and Controversies Requiring Attention Multiple pathologies – Anemia – Low birthweight – Malnutrition – HIV – Enteritis – Sepsis – Neurocognitive – Neglected diseases Host factors – Immunity and vaccines – Genetic susceptibility Plasmodium – falciparum – vivax – Antigenic diversity – Drug resistance Anopheles – Transmission dynamics – Human Correlation of Entomologic Inoculation Rate with clinical manifestations Special conditions – Epidemics – Urbanization – Migration Fetal Growth Velocity and Impact of Intermittent Fetal Growth Velocity and Impact of Intermittent Preventive Treatment for Malaria of Mothers Rogerson et al, 2007 Overlapping Burden of Neglected Diseases and Malaria Overlapping Burden of Neglected Diseases and Malaria (leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, soil­transmitted helminths and trachoma) Neglected Tropical Diseases, 2007 Malaria Transmission to Human and Mosquito Malaria Transmission to Human and Mosquito Vaccine Targets White and Breman, 2007 (adapted from Hoffman), Harrison’s Principles of Internal Medicine October 17, 2007 Thank you Thank you jbreman@nih.gov ...
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