Conquering Malaria Through Actions Linking Control to Research
Joel G. Breman, MD, DTPHMartin Alilio, Ph.D.
Fogarty International CenterNational Institutes of Health
Global Disease Programs and Policy CourseSchool of Public Health
Johns Hopkins University12 May 2003
Research, Training, and Support Needs Research, Training, and Support Needs According to Understanding of Diseases According to Understanding of Diseases andand
Efficacy of Control MethodsEfficacy of Control Methods
Research Needs
Efficacy of
Control Methods
High HighTraining
Some HighModerateResearch Support Needs
Low Low
Research, Training, and Support Needs Research, Training, and Support Needs According to Understanding of Diseases According to Understanding of Diseases andand
Efficacy of Control MethodsEfficacy of Control Methods
Research Needs
Efficacy of
Control Methods
High HighTraining
Some HighModerateResearch Support Needs
Low Low
SmallpoxGuinea wormPoliomyelitisH. influenzae type BMeaslesTetanus
Malaria Dengue
HIV/AIDSTuberculosis
Ebola/Marburg InfluenzaCancers
Alzheimer’s
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
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
Intrinsic and Extrinsic Factors Linked to the Malaria Burden
Human
MosquitoParasite
Social, behavioral, economic
and political factors
Environmental conditions
Controland
prevention measures
Malaria Transmission Cycle
Plasmodia Causing Human Malarias
Plasmodium falciparumP. Vivax (relapsing)P.malariaeP.ovale (relapsing)
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
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 19th century (pink) late 20th century (purple)
Infected Mosquito
Infected Human
Chronic effects
AnemiaNeurologic/ cognitiveDevelopmental
Impaired growth and development
Malnutrition
Manifestations of the Malaria Burden
Acute febrile illness
Severe illness
Hypoglycemia
Anemia
Cerebral malaria
DeathRespiratory distress
Pregnancy
Fetus
MaternalAcute illness
AnemiaImpaired productivity
Low birth weight Infantmortality
% of all deathsRankMalaria 1 20.3
Respiratory inf. 2 17.2Diarrhoea 3 12.3HIV/AIDS 4 9.0Measles 5 8.4
Low birth weight 6 5.8
Leading causes of death for children under 5,
in the WHO African Region, 2000
Num
ber o
f est
imat
ed c
ases
/yea
r
1,000,000,000
100,000,000
10,000,000
1,000,000
100,000
10,000
1,000
Worldwide AfricaAsia
AmericasEast Med
USA2000
cases
WH
O 1
997
Stur
chle
r 198
9
Bau
don
1987
WH
O 1
997
Brin
kman
199
1
Stur
chle
r 198
9
Snow
199
9
Stur
chle
r 198
9
WH
O 1
997
PAH
O 1
991
E M
ed W
HO
199
7
Stur
chle
r 198
9
CD
C 1
994
Estimated World and Regional Malaria Cases1987-1999
Estimated World and Regional Malaria Deaths1952-1999
Num
ber o
f est
imat
ed c
ases
/yea
r 3,000,000
2,500,000
2,000,000
1,500,000
1,000,000
500,000
0
Worldwide
Africa
Americas
USA
Mur
ray
(dev
)19
96
Naj
era
1996
Stur
chle
r 198
9
WH
O 1
997
Bre
man
/Cam
pbel
l(,5
yrs
) 198
8
Naj
era
1996
Bru
ce-C
hwat
t (<
10 y
rs) 1
952
WH
O 1
997
Stur
chle
r 198
9
Snow
199
9
Stur
chle
r 198
9
Stur
chle
r 198
9
MARA/ARMA Model of Malaria Transmission, 2003
Acute Febrile Episodes and Malaria-Associated Febrile Episodes in African Children 0-4 years Living in Endemic
Areas, 1995-20202000
1800
1600
1400
1200
1000
800
600
400
200
0
Mill
ions
846
423
188
1919
960
400
Febrile Illness
Malaria
1995 2020
“The Ears of the Hippopotamus”Where Malaria Patients are Managed ... and Die
Dispensary 15%
Home >80%
Hospital 5%
Contribution (%) of Specific Gaps to African Childhood Malaria Morbidity (up to 8.76 million
children affected) *Cerebral malaria7%
Hypoglycemia9%
Respiratory disease
9%
Low birth weight11%
Severe anemia64%
*maximum estimate; all children <5 years of age except cerebral malaria (<10 years)
Contribution (%) of Specific Gaps to African Childhood Malaria (up to 1.82 million children die)
Severe Anemia53%
Low birth weight20%
Hypoglycemia15%
Respiratory disease
6%
Cerebral malaria6%
Disability–adjusted Life Years (DALYs, 1000s),All Cause and Malaria-related, 2002
PopulationDALYs fromall 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
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
Environmental and Behavioral
ModificationGenetic
modification of vectorsFuture Interventions
Vaccines (preerythrocytic,
blood stage, transmission-
blocking)
Protection (insecticide-impregnated
materials)
Control of the Malaria BurdenCurrent Interventions
Drugs (treatment, prevention)
Insecticides (house
spraying, larvicides)
Estimated Cost of Malaria Control in an Endemic Area: One Million People, One Round
of Residual House Spraying
InsecticideOne application
(tons) Price/ton Total costCost per
capita
DDT 147 $3,950 $580,650 $0.58
Malathion 220 $4,300 $946,000 $0.95Deltamethrin 110 $20,000 $2,200,000 $2.20Pyrimiphos-methyl
220 $16,000 $3,520,000 $3.52
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 $1.30Artesunate (5 d) 13.5 (50 mg) $365.00 $4,927,500 $4.93
Type of ControlVector Control
• Environmental modification (urban)*• Chemical and biological larvicides*• Indoor residual insecticide spraying*• Outdoor residual insecticide spraying
*costly and effective
Type of ControlPersonal protection (2)
• Insecticide–impregnated materials:nets, curtains, clothing*
• House screening• House location• Repellents• Fumigants
* Shown cost effective for low-income countries
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
Antenatal care in AfricaAntenatal care in AfricaProportion of Pregnant Women Seeking Antenatal Clinic CareProportion of Pregnant Women Seeking Antenatal Clinic Care
0
10
20
30
40
50
60
70
80
90
100
Countries
ZambiaRwanda
ZimbabweBotswanaKenyaUgandaMalawiTanzaniaGhanaNamibiaComoros
Cote d'IvoireSenegalLiberiaTogoBeninCameroonMadagascarGuineaSudanMozambiqueCAR
Burkina FasoNigeriaEritreaMali-96NigerChad
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
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
• 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
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
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; 68:1-173, 23 papers.
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 < 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
Eradication ProgramsHuman
Hookworm, 1909
Yellow fever, 1915
Aedes aegypti, 1934-42
Anopheles gambiae, 1939-68
Malaria, 1955-1973Yaws, 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
Malaria in Sri Lanka
0
100000
200000
300000
400000
500000
600000
1963 1968 1973 1978 1983 1988 1993
Year
Num
ber o
f cas
es
0
10
20
30
40
50
60
P.falciparum
as % of total m
alaria
DDT spraying
endsFirst report of chloroquine
resistant P.falciparum
Plasmodium falciparumPlasmodium vivax
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
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
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.
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.
• 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
Promising developments
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• 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
For More InformationFor More InformationJoel Breman [email protected] Alilio [email protected]
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