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
 Research, Training, and Support Needs
According to Understanding of Diseases and
Efficacy of Control Methods
High High
Training

Efficacy
of Research
Control Needs
Methods

Low Low
Some Moderate High
Research Support Needs
 Research, Training, and Support Needs
According to Understanding of Diseases and
Efficacy of Control Methods
High High
Training

Efficacy Malaria
of Smallpox Dengue Research
Guinea worm HIV/AIDS Needs
Control Poliomyelitis Tuberculosis
Methods H. influenzae type B Ebola/Marburg
Measles Influenza
Tetanus Cancers
Alzheimer’s

Low Low
Some Moderate High
Research Support Needs
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

Social,
Control behavioral,
and economic
prevention Human and
measures political factors

Parasite Mosquito

Environmental
conditions
Malaria Transmission Cycle
Plasmodia Causing Human
Malarias

Plasmodium falciparum
P. Vivax (relapsing)
P.malariae
P.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
Global distribution of Plasmodium vivax
maximum distribution 19th century (pink)
late 20th century (purple)
 Manifestations of the Malaria Burden
Hypoglycemia
Anemia
Acute Severe illness Respiratory Death
febrile distress
illness
Cerebral malaria
Infected
Mosquito

Anemia
Chronic Neurologic/ Impaired
Malnutrition
effects cognitive growth and
Infected development
Developmental
Human

Fetus Low birth weight Infant

mortality
Pregnancy
Acute illness
Maternal Impaired
Anemia productivity
 Leading causes of death
for children under 5,
in the WHO African Region, 2000

Rank % of all deaths

Malaria 1 20.3
Respiratory inf. 2 17.2
Diarrhoea 3 12.3
HIV/AIDS 4 9.0
Measles 5 8.4
Low birth weight 6 5.8
 Number of estimated cases/year

1,000,000,000

10,000,000

1,000
100,000
100,000,000

10,000
1,000,000
WHO 1997

Sturchler 1989
Worldwide

Baudon 1987

WHO 1997

Brinkman 1991
Africa

Sturchler 1989
1987-1999

Snow 1999

Sturchler 1989
Asia

WHO 1997

Sturchler 1989
Americas

PAHO 1991

E Med WHO 1997

East Med

CDC 1994
Estimated World and Regional Malaria Cases

2000
USA

cases
 Number of estimated cases/year

500,000
1,000,000
1,500,000
2,000,000
2,500,000
3,000,000

0
Murray (dev)
1996

Najera 1996

Sturchler 1989
Worldwide

WHO 1997

Breman/Campbell
(,5 yrs) 1988

Najera 1996
Bruce-Chwatt
1952-1999

(<10 yrs) 1952

Africa

WHO 1997

Sturchler 1989

Snow 1999

Sturchler 1989

Sturchler 1989
Americas

USA
Estimated World and Regional Malaria Deaths
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, 1995-2020
2000
1919
1800

1600

Febrile Illness
1400
Millions

1200 960

1000

Malaria
846
800

600
423 400
400

188
200

0
1995 2020
 “The Ears of the Hippopotamus”
Where Malaria Patients are Managed ... and Die

Hospital 5%

Dispensary 15%

Home >80%
 Contribution (%) of Specific Gaps to African
Childhood Malaria Morbidity (up to 8.76 million
children affected) *
Cerebral malaria
7%
Hypoglycemia
9%

Respiratory
disease
9% Severe anemia
64%

Low birth weight

11%

*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)

Cerebral malaria
Respiratory 6%
disease
6%

Hypoglycemia
15%
Severe Anemia
53%

Low birth weight

20%
 Disability–adjusted Life Years (DALYs, 1000s),
All Cause and Malaria-related, 2002
DALYs from DALYs from
DALYs from malaria malaria
Population all deaths (%) deaths (%) /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
 Control of the Malaria Burden
Current Interventions

Drugs
(treatment,
prevention)
Protection Insecticides
(insecticide- (house
impregnated spraying,
materials) larvicides)
Environmental and
Behavioral
Modification
Vaccines
Genetic
(preerythrocytic,
blood stage, modification
transmission-
Future Interventions of vectors
blocking)
 Estimated Cost of Malaria Control in an
Endemic Area: One Million People, One Round
of Residual House Spraying

One application Cost per

Insecticide (tons) Price/ton Total cost 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- 220 $16,000 $3,520,000 $3.52
methyl
 Estimated Cost of Malaria Control: One Million
People, One Full-dose Treatment, 1999

Tablets in Price/ Cost

millions 1000 per
Drug (dose) tabs Total cost capita
Chloroquine 11.25 (100 $6.05 $68,063 $0.08
(3 days) mg)
Sulfadoxine- 2.5 (500 mgS/ $47.00 $117,500 $0.12
pyrimethamine 25 mgP)
(one dose)
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
 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
 Antenatal care in Africa
Proportion of Pregnant Women Seeking Antenatal Clinic Care
Zambia
100 Rwanda
Zimbabwe
90 Botswana
Kenya
Uganda
80 Malawi
Tanzania
70 Ghana
Namibia
60 Comoros
Cote d'Ivoire
50 Senegal
Liberia
Togo
40 Benin
Cameroon
30 Madagascar
Guinea
20 Sudan
Mozambique
CAR
10 Burkina Faso
Nigeria
0 Eritrea
Mali-96
Countries Niger
Chad
 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
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
 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
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 Programs
Human
Hookworm, 1909 Animal

Yellow fever, 1915 Bovine contagious

pleuropneumonia (cows),
Aedes aegypti, 1934-42 1884
Anopheles gambiae, Glanders (horses, mules)
1939-68 Piroplasmosis (cattle,
“Texas fever”
Malaria, 1955-1973
Dourine (STD of horses)
Yaws, 1950
Rinderpest
Smallpox, 1958, 1966-80
Sheep pox
Poliomyelitis, 1985
Dracunculiasis, 1987
 Malaria in Sri Lanka
DDT Plasmodium vivax
600000 spraying Plasmodium falciparum 60
ends

P.falciparum as % of total malaria

First report of
500000 50
chloroquine
resistant
Number of cases

400000 P.falciparum 40

300000 30

200000 20

100000 10

0 0
1963 1968 1973 1978 1983 1988 1993

Year
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.
 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
 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 Information
Joel Breman jbreman@nih.gov
Martin Alilio aliliom@mail.nih.gov