Epidemiology and control of malaria (with a focus on sub-Saharan Africa)

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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

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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

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Annual malaria mortality rates per 100,000
population since 1900
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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

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Malaria mortality in African children
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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

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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)

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Estimating risk of infection, disease, and death

• 50 billion infections with malaria parasites
  each year in Africa
• 1100 infections leads to clinical illness
  500 million cases of malaria each year
• 150 cases of malaria results in the severe
  form of disease 10 million cases of severe
  malaria each year
• 15 cases of severe malaria leads to death
  1-2 million deaths due to malaria each year

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Transmission intensity, incidence, and age
Dielmo, Senegal 200 infections/year
Ndiop, Senegal 20 infections/year
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In the 20th century, the boundary of malaria
transmission was progressively rolled back from
the north
Elimination lt 1960
Elimination 1960 - 1975
Elimination 1975 - 2007
Elimination program ongoing
Elimination newly targeted
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Countries targeting elimination do not currently
spend more per population at risk than some
control programs
Estimated annual malaria financing per population
at risk1
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Funding Source
International2
Domestic
4.43
3.17
2.53
2.41
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 Presidents
Malaria Initiative
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but do spend significantly more per case, which
will continue to increase as incidence declines
further
Estimated annual malaria financing per case1
gt10m
200,000
40
800
10.74
5.76
0.36
DR Congo
South Africa
UAE2
Tanzania (mainland)
Botswana
Zambia
Oman2
1 Includes both reported and unconfirmed cases as
estimated by the national program and/or
partners 2 Based on 2003 estimates
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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

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Effective case management in the era of ACTs

• ACTs have now become the standard of care
  throughout the world
• Artesunatemefloquine
• Artemether-lumefantrine
• Artesunateamodiaquine
• 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

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Effective case managementIssues 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

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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.

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Proportion of patients suspected of having
malaria referred for a blood smear
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Proportion of patients with a positive blood
smear treated for malaria
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Proportion of patients with a negative blood
smear treated for malaria
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Proportion of patient prescribed antimalarial
therapy who were given a correct regimen
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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

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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

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IRS in moderate endemic setting in Uganda
IRS
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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

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Summary of studies evaluating IPTi with SP given
at the time of routine immunizations
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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

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Success Story in South Africa

• Area of low seasonal transmission in setting of
  highly competent national malaria control program
• Wide scale implementation of IRS (AB) and AL (C)