1. Epidemiology and control of malaria (with a focus on sub-Saharan Africa)
Grant Dorsey, MD, PhD
Division of Infectious Diseases
University of California, San Francisco

2. Burden of Disease
Over 40% of the world’s population live in endemic areas
Estimated 500 million clinical cases and 1-2 million deaths/year
3rd most common cause of death due to a communicable agent

3. Annual malaria mortality rates per 100,000 population since 1900

4. Burden of Malaria in Africa
One African child dies of malaria every 30 seconds
Higher in poor and rural areas
In all malaria-endemic countries in Africa, malaria accounts for 25-40% of outpatient visits and 20-50% of hospital admissions

5. Malaria mortality in African children

6. Unique Epidemiological Aspects of Malaria in Africa
Infection is incredibly common and heterogeneous
High density of mosquitoes
Mosquitoes like to bite humans and live indoors
Very little vector control in Africa
Gold standard for measuring the frequency of infection is termed the entomological inoculation rate (EIR)
EIR = number of bites by anopheles mosquito per night x proportion of mosquitoes carrying malaria parasites in their salivary glands x 365 days per year

9. Unique Epidemiological Aspects of Malaria in Africa cont.
Clinical consequences of infection vary greatly
Disease manifestations range from asymptomatic parasitemia to life-threatening illness
Risk of illness and death strongly influenced by development of “semi-immunity” over one’s lifetime
High risk groups include young children, pregnant women, HIV-infected patients, and non-immune adults (i.e. travelers)

10. Estimating risk of infection, disease, and death
~ 50 billion infections with malaria parasites each year in Africa
~ 1:100 infections leads to clinical illness = 500 million cases of malaria each year
~ 1:50 cases of malaria results in the severe form of disease = 10 million cases of severe malaria each year
~ 1:5 cases of severe malaria leads to death = 1-2 million deaths due to malaria each year

12. Transmission intensity, incidence, and age
Dielmo, Senegal – 200 infections/year
Ndiop, Senegal – 20 infections/year

13. In the 20th century, the boundary of malaria transmission was progressively rolled back from the north
Elimination < 1960
Elimination
Elimination
Elimination program ongoing
Elimination newly targeted

14. Countries targeting elimination do not currently spend more per population at risk than some control programs…
Estimated annual malaria financing per population at risk1
~$22
Funding Source
International2
Domestic
$4.43
$3.17
$2.41
$2.53
$0.91
$0.19
DR Congo
South Africa
Swaziland
Tanzania
(mainland)
Botswana
Zambia
UAE
1 Estimated based on Mapping Malaria Risk in Africa project updated for 2007 population levels
2 Includes funding allocations by the Global Fund, World Bank, and US President’s Malaria Initiative

15. …but do spend significantly more per case, which will continue to increase as incidence declines further
Estimated annual malaria financing per case1
>$10m
$200,000
$40
$800
$10.74
$5.76
$0.36
DR Congo
Tanzania
(mainland)
Zambia
Botswana
South Africa
UAE2
Oman2
1 Includes both reported and unconfirmed cases as estimated by the national program and/or partners
2 Based on 2003 estimates

16. Available tools for the control and elimination of malaria
1. Effective case management
2. Insecticide treated bednets (ITNs)
3. Vector control
4. Chemoprevention
5. Vaccine

17. Effective case management in the era of ACTs
ACT’s have now become the standard of care throughout the world
Artesunate+mefloquine
Artemether-lumefantrine
Artesunate+amodiaquine
Dihydroartemisinin-piperaquine
Excellent efficacy unless resistance to partner drug
Early reports of artemisinin resistance in Thai-Cambodia border
May decrease transmission through anti-gametocyte effects
Concern about drug availability and cost

18. Effective case management Issues in resource poor settings
Government recommends one first-line therapy for the whole country
Policy based on clinical surveillance studies
Drug subsidized for the public sector
ACTs currently too expensive in the private sector
Most fevers are treated empirically as malaria at home
Urgent need to promote rationale use of ACTs

19. Joint malaria training program
Objective: To evaluate the impact of integrated team-based training of health care workers on malaria case management.
Design and Participants: Malaria surveillance data 120 days before and after training were compared for all patients presenting to eight government-run health centers.
Setting: The eight sites represent the diversity of malaria transmission in Uganda. Data were collected one year after artemether-lumefantrine was introduced as the recommended first-line treatment for uncomplicated malaria.
Intervention: Six day integrated team-based training course targeting clinical, laboratory and records staff with site visits approximately 6 and 12 weeks post training.

20. Proportion of patients suspected of having malaria referred for a blood smear

21. Proportion of patients with a positive blood smear treated for malaria

22. Proportion of patients with a negative blood smear treated for malaria

23. Proportion of patient prescribed antimalarial therapy who were given a correct regimen

24. Insecticide treated bednets (ITNs)
Several randomized trials in a range of endemic settings have documented the efficacy of ITNs
Interventions done at the population level
~ 10 fold reduction in transmission
~ 2 fold decrease in incidence of clinical malaria
~ 20% reduction in all cause childhood mortality
One of the most cost effective interventions available
Bednets cost only a few dollars
Long lasting ITNs
Insecticide impregnated into nets
Last 5 years
Remaining issues are coverage and distribution

25. Vector control Primary tool indoor residual spraying (IRS)
Very effective in low transmission areas
Starting to be used in higher transmission settings in Africa
Limited data on what is the best insecticide and how often to spray
Very expensive
Other vector control measures
Larvicide
Genetically modified mosquitoes

26. IRS in moderate endemic setting in Uganda

27. Chemoprevention Two main strategies Target groups Chemoprophylaxis
Intermittent preventative therapy
Target groups
Pregnant women
HIV infected patients
Daily trimethoprim-sulfamethoxazole
Infants and young children
Active area of research

28. Summary of studies evaluating IPTi with SP
given at the time of routine immunizations
Study parameter
Country and year(s) of recruitment
Tanzania
Ghana
Mozambique
2003
2004
Gabon
EIR*/year
Transmission
Age at dosing, months
Incidence in placebo group†
# enrolled, placebo/intervention
Preventive efficacy, % (95% CI)
Clinical malaria
Hospital admission
Anemia 29
Perennial
2, 3, 9
0.36
351/350
at 12 mo.
62 (44-75)
30 (8-47)
50 (8-73)
418
Seasonal
3, 4, 9, 12
1.02
1242/1243
at 15 mo.
25 (14-34)
13 (-5-27)
36 (11-53) 38
3, 4, 9
0.43
755/748
23 (2-39)
19 (4-31)
13 (-17-35)
not reported
3, 9, 15
1.16
600/600
at 18 mo.
23 (12-32)
31 (3-51)
24 (4-39)
400
1.20
535/535
20 (11-29)
9 (-23-34)
7 (-8-20) 50
0.16
595/594
At 18 mo.
17 (-24-44)
22 (-1-40)

29. Control of Malaria in Africa cont.
Vaccines
1973 vaccine made from whole malaria parasites killed by irradiation could protect healthy persons from infection
Not a viable option for large scale production
Decades of research failed to develop an effective vaccine
Limited understanding of immune correlates of protection
Organism extremely diverse and complicated
Recent vaccine trials
RTS,S vaccine
Surface protein found in form of parasite injected by mosquitoes conjugated to Hep B surface Ag
Pilot study in 360 Gambian men: 34% efficacy in protecting against malaria infection but waned to 0% by 15 weeks
1500 children in Mozambique: 30% reduction in clinical malaria and 58% reduction in severe malaria after 6 months
Plans for large phase III trial underway

30. Success Story in South Africa
Area of low seasonal transmission in setting of highly competent national malaria control program
Wide scale implementation of IRS (A+B) and AL (C)