Sie sind auf Seite 1von 30

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
Burden of Disease

Over 40% of the worlds 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
Annual malaria mortality rates per 100,000
population since 1900
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
Malaria mortality in African children
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
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 ones lifetime
High risk groups include young children, pregnant
women, HIV-infected patients, and non-immune
adults (i.e. travelers)
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
Transmission intensity, incidence, and age
Dielmo, Senegal 200 infections/year

Ndiop, Senegal 20 infections/year


In the 20th century, the boundary of malaria transmission was
progressively rolled back from the north

Elimination < 1960


Elimination 1960 - 1975
Elimination 1975 - 2007
Elimination program ongoing
Elimination newly targeted
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 Botswana Zambia UAE


(mainland)

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 Presidents Malaria Initiative
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 Zambia Botswana South Africa UAE2 Oman2
(mainland)

1 Includes
both reported and unconfirmed cases as estimated by the national program and/or partners
2 Based on 2003 estimates
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
Effective case management in the
era of ACTs
ACTs 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
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
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.
Proportion of patients suspected of having
malaria referred for a blood smear
Proportion of patients with a positive blood
smear treated for malaria
Proportion of patients with a negative blood
smear treated for malaria
Proportion of patient prescribed antimalarial
therapy who were given a correct regimen
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
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
IRS in moderate endemic setting in Uganda

IRS
Chemoprevention
Two main strategies
Chemoprophylaxis
Intermittent preventative therapy
Target groups
Pregnant women
HIV infected patients
Daily trimethoprim-sulfamethoxazole
Infants and young children
Active area of research
Summary of studies evaluating IPTi with SP
given at the time of routine immunizations
Country and year(s) of recruitment
Study parameter

Tanzania Ghana Mozambique Ghana Ghana Gabon


1999-00 2000-02 2002-04 2003 2004 2002-05

EIR*/year 29 418 38 not reported 400 50

Transmission Perennial Seasonal Perennial Perennial Perennial Perennial

Age at dosing, months 2, 3, 9 3, 4, 9, 12 3, 4, 9 3, 9, 15 3, 9, 15 3, 9, 15

Incidence in placebo group 0.36 1.02 0.43 1.16 1.20 0.16

# enrolled, placebo/intervention 351/350 1242/1243 755/748 600/600 535/535 595/594

Preventive efficacy, % (95% CI) at 12 mo. at 15 mo. at 12 mo. at 18 mo. at 18 mo. At 18 mo.
Clinical malaria 62 (44-75) 25 (14-34) 23 (2-39) 23 (12-32) 20 (11-29) 17 (-24-44)
Hospital admission 30 (8-47) 13 (-5-27) 19 (4-31) 31 (3-51) 9 (-23-34) not reported
Anemia 50 (8-73) 36 (11-53) 13 (-17-35) 24 (4-39) 7 (-8-20) 22 (-1-40)
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
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)