Conquering Malaria Through Actions Linking Control to Research

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Conquering Malaria Through Actions Linking
Control to Research

• Joel G. Breman, MD, DTPH
• Martin Alilio, Ph.D.
• Fogarty International Center
• National Institutes of Health
• Global Disease Programs and Policy Course
• School of Public Health
• Johns Hopkins University
• 12 May 2003

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Research, Training, and Support Needs According
to Understanding of Diseases and Efficacy of
Control Methods
High
High
Training
Efficacy of Control Methods
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
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Research, Training, and Support Needs According
to Understanding of Diseases and Efficacy of
Control Methods
High
High
Training
Efficacy of Control Methods
Malaria Dengue HIV/AIDSTuberculosisEbola/Marbur
g InfluenzaCancersAlzheimers
SmallpoxGuinea wormPoliomyelitisH. influenzae
type BMeaslesTetanus
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Intrinsic and Extrinsic Factors Linked to the
Malaria Burden
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Malaria Transmission Cycle
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Plasmodia Causing Human Malarias

• Plasmodium falciparum
• P. Vivax (relapsing)
• P.malariae
• P.ovale (relapsing)

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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Global distribution of Plasmodium vivax
maximum distribution 19th century (pink)
late 20th century (purple)
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.
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Manifestations of the Malaria Burden
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Leading causes of death for children under 5,in
the WHO African Region, 2000
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MARA/ARMA Model of Malaria Transmission, 2003
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Acute Febrile Episodes and Malaria-Associated
Febrile Episodes in African Children 0-4 years
Living in Endemic Areas, 1995-2020
2000 1800 1600 1400 1200 1000 800 600 400
200 0
1919
960
Febrile Illness
Millions
846
Malaria
400
423
188
2020
1995
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The Ears of the HippopotamusWhere Malaria
Patients are Managed ... and Die
Hospital 5


Dispensary 15

Home gt80
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maximum estimate all children lt5 years of age
except cerebral malaria (lt10 years)
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Disabilityadjusted Life Years (DALYs,
1000s),All Cause and Malaria-related, 2002
Population DALYs from all deaths () DALYs from malaria deaths () DALYs from malaria /total ()
World 6,122,210 1,467,257 42,280 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 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
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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Estimated Cost of Malaria Control in an Endemic
Area One Million People, One Round of Residual
House Spraying
Insecticide One application (tons) Price/ton Total cost Cost per capita
DDT 147 3,950 580,650 0.58
Malathion 220 4,300 946,000 0.95
Deltamethrin 110 20,000 2,200,000 2.20
Pyrimiphos-methyl 220 16,000 3,520,000 3.52
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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
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Type of ControlVector Control

• Environmental modification (urban)
• Chemical and biological larvicides
• Indoor residual insecticide spraying
• Outdoor residual insecticide spraying
• costly and effective

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Type of ControlPersonal protection (2)

• Insecticideimpregnated materials
• nets, curtains, clothing
• House screening
• House location
• Repellents
• Fumigants
• Shown cost effective for low-income countries

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Type of ControlAntiplasmodial (3)

• Patient management early diagnosis, treatment,
  referral, education
• Chemoprophylaxis
• Intermittent treatment (pregnancy)
• Radical therapy for relapses (P.vivax, P.ovale)
• cost effective

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Antenatal care in AfricaProportion of Pregnant
Women Seeking Antenatal Clinic Care
Zambia
100
Rwanda
Zimbabwe
Botswana
90
Kenya
Uganda
80
Malawi
Tanzania
70
Ghana
Namibia
60
Comoros
Cote d'Ivoire
Senegal
50
Liberia
Togo
40
Benin
Cameroon
30
Madagascar
Guinea
Sudan
20
Mozambique
CAR
10
Burkina Faso
Nigeria
0
Eritrea
Mali-96
Countries
Niger
Chad
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Type of ControlSocial Action

• Mobilization of individual, family, community
• Health education
• Management Effectiveness
• Health systems effectiveness (quality),
  efficiency
• Leadership, planning, policies, strategies,
  tactics
• Surveillance
• Monitoring and evaluation

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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Successes

• 1899, (large scale) demonstration of successful
  Anopheline control in Cuba antilarval and adult
  measures (large-scale)
• 18991914, multiple demonstrations of control by
  reduction of Anopheline larvae and adults
• 1899, Sierra Leone (antilarval) Cuba
  (large-scale) Malaysia (antilarval)
• 19041914, Panama Canal Zone control by
  larviciding, large-scale environmental
  modification
• 1927, elimination of A. albimanus in Barbados
  (first area-wide success with invading species)

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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

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Successes (3)

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

See the Western Kenya insecticide-treated bed net
trial, AJTMH, 2003 681-173, 23 papers.
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Insecticide-treated bednets in pregnancy, western
Kenya, 1997-1999

• Among Gravidae 1-4, ITNs were associated with
• During pregnancy
• 38 reduction in peripheral parasitemia
• 21 reduction in all cause anemia (Hb lt 11 g/dl)
• 47 reduction in severe malarial anemia
• At delivery
• 23 reduction in placental malaria
• 28 reduction in LBW
• 25 reduction in any adverse birth outcome

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Eradication Programs
Human Hookworm, 1909 Yellow fever, 1915 Aedes
aegypti, 1934-42 Anopheles gambiae,
1939-68 Malaria, 1955-1973 Yaws, 1950 Smallpox,
1958, 1966-80 Poliomyelitis, 1985 Dracunculiasis,
1987
Animal Bovine contagious pleuropneumonia (cows),
1884 Glanders (horses, mules) Piroplasmosis
(cattle, Texas fever Dourine (STD of
horses) Rinderpest Sheep pox
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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Conquering Malaria Through Actions Linking
Control to Research

• Background ecology and natural history
• Burden manifestations and toll
• Interventions strategies and effectiveness
• Successes and challenges historical and current
• Multilateral initiatives
• Roll Back Malaria
• Multilateral Initiative on Malaria
• The way forward

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Essential Strategies for Dealing with Malaria

• Use simple, cost-effective tools.
• Abolish malaria taxes and distribute
  insecticide-treated bednets.
• Promote and fund research in all its dimensions.
• Fund demonstration projects on and use of
  integrated vector management strategies.
• Scale-up operations.

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Essential Strategies for Dealing with Malaria (2)

• Provide financial assistance to poorer countries.
• Engage public-private partnerships.
• Insure targeted diagnosis and treatment.
• Slow drug resistance.
• Integrate malaria treatment into existing
  programs.
• Invest in malaria drug and combination therapy
  development and distribution.

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Promising developments

• Prompt and effective treatment reduces mortality
  by at least 50
• Mortality further reduced if treatment is
  available in home
• Drug resistance can be delayed through
  combination therapy including artesunates
• Insecticide-treated nets can reduce all cause
  mortality by 20
• New rapid diagnostic techniques becoming
  available at lower cost
• Application of epidemiological and geographical
  information can help predict epidemics

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Research Agenda

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

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Research Agenda (2)

• Clinical issues
• anemia
• neurologic and cognition
• pregnancy-related
• Health services delivery
• Social, legal, ethical

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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

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For More Information
Joel Breman jbreman_at_nih.gov Martin Alilio
aliliom_at_mail.nih.gov