Transcript Epidemiology and control of malaria (with a focus on sub

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 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
Annual malaria mortality rates per 100,000
population since 1900
World excluding sub-Saharan Africa
sub-Saharan Africa
250
200
150
100
50
0
1900
1930
1950
1970
1990
1997
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 2050% 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 one’s
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
6
Dielmo, Senegal – 200 infections/year
5
4
3
2
1
0
<1
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 -20 -25 -30 -40 -50>=60
Age (years)
6
Ndiop, Senegal – 20 infections/year
5
4
3
2
1
0
<1
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 -20 -25 -30 -40 -50>=60
Age (years)
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
1 Estimated
South Africa Swaziland
Tanzania
(mainland)
Botswana
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
Zambia
UAE
…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
1 Includes
Tanzania
(mainland)
Zambia
Botswana
South Africa
both reported and unconfirmed cases as estimated by the national program and/or partners
2 Based on 2003 estimates
UAE2
Oman2
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
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 antigametocyte 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 teambased 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
Age less than 5 years
Pre-training Post-training
100%
80%
60%
40%
20%
0%
Kabale
p=0.06
Kamw ezi
p=0.29
Kihihi
p=0.11
Walukuba Kyenjojo
p<0.0001 p<0.0001
Omugu
p=0.46
Nagongera Aduku
p=0.26
p=0.0008
Proportion of patients with a positive blood
smear treated for malaria
Age less than 5 years
Pre-training Post-training
100%
80%
60%
40%
20%
0%
Kabale
p=0.85
Kamw ezi
p=0.68
Kihihi
p=0.64
Walukuba Kyenjojo
p=0.21
p=0.33
Omugu
p=0.12
Nagongera
p=0.64
Aduku
p=0.41
Proportion of patients with a negative blood
smear treated for malaria
Age less than 5 years
Pre-training Post-training
100%
80%
60%
40%
20%
0%
Kabale
p=0.006
Kamw ezi
p=0.11
Kihihi
p=0.0002
Walukuba Kyenjojo
p<0.0001 p=0.0001
Omugu
p=0.07
Nagongera
p=0.0005
Aduku
p=0.02
Proportion of patient prescribed antimalarial
therapy who were given a correct regimen
Age less than 5 years
Pre-training Post-training
100%
80%
60%
40%
20%
0%
Kabale
p=0.41
Kamw ezi
p=0.002
Kihihi
p=0.13
Walukuba Kyenjojo
p=0.97
p=0.09
Omugu
p=0.20
Nagongera
p=0.0003
Aduku
p=0.05
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
Age less than 5 years
Age 5 years or older
60%
IRS
Smear positivity
50%
40%
30%
20%
10%
0%
Aug- Sep- Oct- Nov- Dec- Jan- Feb- Mar- Apr- May- Jun- Jul- Aug- Sep- Oct- Nov- Dec06 06 06 06 06 07 07 07 07 07 07 07 07 07 07 07 07
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
1999-00
Ghana
2000-02
Mozambique
2002-04
Ghana
2003
Ghana
2004
Gabon
2002-05
29
418
38
not reported
400
50
Perennial
Seasonal
Perennial
Perennial
Perennial
Perennial
2, 3, 9
3, 4, 9, 12
3, 4, 9
3, 9, 15
3, 9, 15
3, 9, 15
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)
Clinical malaria
Hospital admission
Anemia
at 12 mo.
62 (44-75)
30 (8-47)
50 (8-73)
at 15 mo.
25 (14-34)
13 (-5-27)
36 (11-53)
at 12 mo.
23 (2-39)
19 (4-31)
13 (-17-35)
at 18 mo.
23 (12-32)
31 (3-51)
24 (4-39)
at 18 mo.
20 (11-29)
9 (-23-34)
7 (-8-20)
At 18 mo.
17 (-24-44)
not reported
22 (-1-40)
EIR*/year
Transmission
Age at dosing, months
Incidence in placebo group†
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)