Defining and Defeating the Defining and Defeating the Intolerable Intolerable Burden of Malaria Burden of Malaria Joel G. Breman, MD, DTPH Joel G. Breman, MD, DTPH Fogarty International Center Fogarty International Center U.S. National Institutes of Health U.S. National Institutes of Health BioVisionAlexandria 2008 BioVisionAlexandria 2008 New Life Sciences: From Promises to New Life Sciences: From Promises to Practice Practice Alexandria, Egypt Alexandria, Egypt April 14, 2008 April 14, 2008
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Defining and Defeating the Intolerable Burden of Malaria Joel G. Breman, MD, DTPH Fogarty International Center U.S. National Institutes of Health BioVisionAlexandria.
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Defining and Defeating the Intolerable Defining and Defeating the Intolerable Burden of MalariaBurden of Malaria
Joel G. Breman, MD, DTPHJoel G. Breman, MD, DTPH
Fogarty International CenterFogarty International Center
U.S. National Institutes of HealthU.S. National Institutes of Health
BioVisionAlexandria 2008BioVisionAlexandria 2008
New Life Sciences: From Promises to PracticeNew Life Sciences: From Promises to Practice
Alexandria, EgyptAlexandria, Egypt
April 14, 2008April 14, 2008
Our Goal Malaria Free Mothers and Malaria Free Mothers and
ChildrenChildren
and all others
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
Interventions
Progress
Research
Transmission of Transmission of PlasmodiumPlasmodium from from Mosquito to Human…to MosquitoMosquito to Human…to Mosquito
White and Breman, 2008 (after Hoffman), Harrison’s Principles of Internal Medicine
P. falciparum
P. vivax
P. ovale
P. malariae
P. knowlsei
Defining Malaria and its ConquestDefining Malaria and its Conquest
ManifestationsBurden
Goals
Interventions
Progress
Research
Manifestations of the Malaria BurdenManifestations of the Malaria Burden
Infected Mosquito
Infected Human
Chronic effects
Anemia
Neurologic
Cognitive
Developmental
Impaired growth and development
Malnutrition
Acute febrile illness
Severe illness
Anemia
Hypoglycemia
Cerebral malaria
DeathRespiratory distress
Pregnancy
Fetus
MaternalAcute illness
Anemia
Low birth weight
Abortion, stillbirth
Infant and fetal mortality
Long-termsequelae
Hypovolemia
Long-termsequelaeBreman, Alilio, Mills, 2004, Am J Trop Med Hyg
Overlap of Cerebral Malaria, Anemia, Respiratory Distress in Children
Marsh et al, 1995, NEJM
Respiratory Distress
Severe Malarial Anemia
Hypoglycemia
Cerebral Malaria
22/177(12%)
3/7(43%)
2/126(2%)
1/14(7%)
1/4(25%)
2/2(100%)
1/1(100%)
3/7(43%)
3/4(75%)
1/2(50%)
2/23(9%)
Ranque et al 2008, Ped Inf Dis J( ) = number of patients
31/58(53%)
KenyaMali
% = CFR
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
BurdenGoals
Interventions
Progress
Research
Global Malaria and Endemicity, Global Malaria and Endemicity, 20032003
Global Distribution of Malaria Global Distribution of Malaria Anopheline VectorsAnopheline Vectors
Parenteral treatment Parenteral treatment with artemisinins, with artemisinins, quinine or quinidinequinine or quinidine
Selected Severe Clinical Malaria Conditions Requiring Diagnosis, Selected Severe Clinical Malaria Conditions Requiring Diagnosis, Assessment and Reporting (2)Assessment and Reporting (2)
a in addition to antimalarial drugs; referral to a secondary or temporary care facility for patients requiring parenteraltherapy and intensive supportive care.b consider exchange transfusion for parasitemia >10%* essential measurement
Breman and Holloway, 2007, Am J Trop Med Hyg
*
*
*
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
InterventionsProgress
Research
Environmental and Behavioral
Modification
Genetic modification
of vectorsFuture Interventions
Vaccines (preerythrocytic,
blood stage, transmission-
blocking)
Protection (insecticide-impregnated
materials)
Control of the Malaria Burden
Current Interventions
Drugs (treatment, prevention)
Insecticides (house
spraying, larvicides)
0 5 10 15 20 25 30
Intermittent preventive treatment
Insecticide-treated bed nets
Insecticide residual spraying
Intermittent preventive treatment/
pregnancy (SP)
Cost-effectiveness ratio ($ per DALY averted)
Cost-Effectiveness of Interventions Cost-Effectiveness of Interventions Against Malaria in Sub-Saharan AfricaAgainst Malaria in Sub-Saharan Africa
Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.
Artemisinin comb.therapy
(resistance)
Malaria: Prevention and Malaria: Prevention and TreatmentTreatment
Treatment with a new group of Treatment with a new group of antimalarials – the artemisinin antimalarials – the artemisinin compounds, in combination with compounds, in combination with lumefantrine, amodiaquine, sulfadoxine–lumefantrine, amodiaquine, sulfadoxine–pyrimethamine, or otherspyrimethamine, or others
O
O
O O
O
Spread of chloroquine resistanceArtemesia annua
The Process for the Microbial Production of The Process for the Microbial Production of Artemisinin Artemisinin
Hale et al, 2007, Am J Trop Med Hyg
WHO/Tropical Diseases Research/Crump
Verband Forschender Arzneimittelhersteller e.V.
Insecticide Treated Materials WorkInsecticide Treated Materials Work
Children < 5 yrs Children < 5 yrs sleeping under sleeping under ITNITN
1616 —— 2727
Pregnant women Pregnant women sleeping under sleeping under ITN ITN
88 1212 2424
Roll Back Malaria
Results from Zanzibar Results from Zanzibar Island, TanzaniaIsland, Tanzania
Population: 1,116,001 (2006)
Outpatient Malaria Cases (Confirmed and non-confirmed)
per 1000 of the population
Results from ZanzibarResults from ZanzibarProportion of malaria Proportion of malaria
confirmed casesconfirmed cases
Ali, et al 2007, EARN Meeting
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
Interventions
Progress
Research
Research Needs: Disease Burden that Can or Cannot be Averted with Existing Interventions
Not Avertable
Disease Burden:
Avertable
Already averted
coverage
Biomedical research to identify new and improved interventions
Increase effectiveness or reduce costs of existing interventions
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 Malaria Research Needs: Major Gaps and Controversies Requiring Gaps and Controversies Requiring