Post on 03-Jan-2016
Malaria and its conquering
Joel G. Breman, MD, DTPH
Fogarty International Center
National Institutes of Health
Tropical Infectious Diseases Workshop
Oswaldo Cruz Foundation (FIOCRUZ)
Rio de Janeiro, Brazil
28 April–1 May 2003
Conquering Malaria
• Ecology and burden
• Interventions
• Successes
• Economics
• Research questions
• Controversies
Ecology and Burden
Malaria and Ecology and Burden
Intrinsic and Extrinsic Factors
Controland prevention
measuresHuman
Parasite Mosquito
Social, behavioral, economic and
political factors
Environmental conditions
Malaria Ecology and BurdenClinical Manifestations
Infected Mosquito
Infected Human
Chronic effects
Anemia
Neurologic/ cognitive
Developmental
Impaired growth and development
Malnutrition
Acute febrile illness
Severe illness
Hypoglycemia
Anemia
Cerebral malaria
DeathRespiratory distress
Pregnancy
Fetus
MaternalAcute illness
AnemiaImpaired productivity
Low birth weight Infantmortality
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)
MARA/ARMA Model of Malaria Transmission, 2003
Deaths and Malaria-related Deaths (1000s), 2000
Population All deaths (%)
Malaria Deaths (%)
Malaria/
total (%)
World 6,122,210 56,554 1,124 2.0
Africa 655,476 10,681 (18.9) 963 (85.7) 9.0
Americas 837,967 5,911 (10.5) 1 (-) 0.02
East Med. 493,091 4,156 (7.3) 55 (4.9) 1.3
Europe 874,178 9,703 (17.2) 0 -
SE Asia 1,559,810 14,467 (25.6) 95 (8.5) 0.7
West Pacific
1,701,689 11,636 (20.6) 10 (0.9) 0
Disability–adjusted 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
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
3,000,000
Worldwide Africa Asia
Estimated World and Regional Malaria Deaths, 1952-1999
Disease
Malaria 57.9%
Childhood Diseases 55.0%
Diarrheal Diseases 53.2%
Perinatal Conditions 45.0%
Tuberculosis 44.4%
Maternal Conditions 43.2%
Respiratory Infections 42.6%
HIV/AIDS 41.8%
Weighted Average 48.6%
Percentage of Deaths from Disease OccurringAmong the Poorest 20% of Global Population
% Deaths
Interventions
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
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
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
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
Interventions, Control and Economics
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
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
Research Questions
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
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
Controversies (2)
• Transmission– Cost-effective vector control
approaches in urban and rural areas– Impregnated materials, how to improve
and make the social standard
• Basic research– Immunologic, genetic
Malaria, Annual WHO Estimates, 1997
Region
Population at risk (1000s)
Total Cases
(%) (1000s)
P. Falciparum
(%) (1000s)
P.vivax
(%) (1000s)
SE Asia,
Western Pacific
1,284,000 86,401 44,400 42,006
Eastern Mediterranean
64,600 14,539 2,883 11,656
Central America/ Caribbean
64,200 3,676 580 3,096
South America 23,500 11,325 3,347 7,978
Central Asia/ Cancasus
8,480 167 0 167
World total outside Africa
1,444,780 116,334 51,211 65,124
Africa 550,000 300,000 Most of total 6-15,000
Imported malaria² 1,590,000 33 11 22
Total ³
Malaria in Sri Lanka
0
100000
200000
300000
400000
500000
600000
1963 1968 1973 1978 1983 1988 1993
Year
Nu
mb
er o
f ca
ses
0
10
20
30
40
50
60
P.falcip
arum
as %
of to
tal malaria
DDT spraying
ends
First report of chloroquine
resistant P.falciparum
Plasmodium falciparum
Plasmodium vivax
0.01
0.10
1.00
0.000 0.001 0.010 0.100 1.000 10.000
Annual malaria incidence rate (%)
Pro
po
rtio
n o
f P
.viv
ax
: :
% P
lasm
od
ium
viv
ax100
10
1
Total Annual Malaria Incidence Rate (%)
0.000 0.01 0.001 0.1 1.0 10.0
0.01
0.10
1.00
0.000 0.001 0.010 0.100 1.000 10.000
Annual malaria incidence rate (%)
Pro
po
rtio
n o
f P
.viv
ax
: :
% P
lasm
od
ium
viv
ax100
10
1
0.000 0.01 0.001 0.1 1.0 10.0 More Northerly, more temperate
More Southerly, more tropical