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Malaria and HIV coinfection

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HIV and malaria are two of the greatest global public health challenges today. ... Are effects due to re-infection or recrudescence? ... – PowerPoint PPT presentation

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Title: Malaria and HIV coinfection


1
Malaria and HIV co-infection
  • Jimmy Whitworth
  • IAS Conference on HIV Pathogenesis and Treatment
  • Rio de Janeiro
  • July 2005

2
Introduction
  • HIV and malaria are two of the greatest global
    public health challenges today.
  • There is considerable geographical overlap eg
    SubSaharan Africa
  • 25 million HIV infections in subSaharan Africa
    (gt60 global total)
  • 300 million acute episodes and 1 million deaths
    from malaria in subSaharan Africa annually.
  • Even a small interaction between HIV and malaria
    has very important public health consequences.

3
Geographical Distribution
Malaria distribution
HIV distribution
4
Sub-Saharan Africa
HIV distribution
Malaria distribution
Dual burden seen especially in Southern Africa
(Zimbabwe, Zambia, Malawi, Mozambique, Tanzania),
West central Africa (Nigeria, Cameroon, Central
African Republic).
5
Basic scienceHIV? malaria
  • HIV impairs T-cell mediated immunity.
  • T-cells are essential mediators of antimalarial
    immunity.
  • HIV immunosuppression increases susceptibility to
    malaria infection and severity of clinical
    consequences.

6
Basic sciencemalaria?HIV
  • Malaria activates T-cells.
  • T-cell activation promotes HIV infection and
    replication.
  • HIV viral loads are transiently increased during
    acute episodes of malaria.

7
Effect of HIV on malaria
  • Non-pregnant adults
  • Stable malaria situations
  • Unstable malaria situations
  • Pregnant women
  • Children

8
Malaria immunity
Exposure to malaria
Exposure to malaria
  • Death
  • Control of severe/complicated disease
  • Control of febrile illness
  • Control of parasite density
  • Parasitological infection

HIV immunosuppression
9
Non-pregnant adults
  • HIV erodes whatever malaria immunity has been
    acquired through exposure.
  • Increases with degree of immunosuppression.
  • In stable malaria situation (substantial
    immunity)
  • ? rates of parasitaemia and clinical malaria
    (fever) (x2)
  • No effect on severe malaria or death
  • In unstable malaria situation (little immunity)
  • No effect on parasitaemia and fever (all
    vulnerable)
  • ? risks of severe and complicated malaria (x2)
    and death (x7)

10
Pregnant women
  • HIV infection reduces pregnant womans ability to
    control malaria infection (in stable malaria
    situation)
  • ? prevalence and density of peripheral and
    placental
  • parasitaemia (x1.7)
  • ? clinical malaria (x3)
  • ? antimalarial use and hospitalisation
  • ? adverse birth outcomes
  • infant low birth weight (x2.2)
  • infant severe anaemia ( 1g/dl)
  • infant mortality (x3.5)
  • Effect is mainly in multigravidae (unlike
    malaria).

11
Children
  • Information is limited.
  • No effect on number of episodes of parasitaemia
    (expected as little immunity).
  • If infected with malaria, HIV infected children
    have difficulty clearing parasitaemia ?risk of
    severe anaemia.
  • Unstable malaria situation more likely to get
    severe disease, coma and die.

12
Public health implications
  • HIV estimated to increase clinical malaria in
    population by
  • 6, if HIV prevalence 10,
  • 15, if HIV prevalence 30.

13
Effect of malaria on HIV
  • Non-pregnant adults
  • Pregnant women
  • Children no convincing effects noted

14
Non-pregnant adults
  • HIV viral loads significantly higher (half a log)
    in those with acute malaria episodes.
  • Reversible with treatment. Lasts up to 10 weeks.
  • Increases greatest in those with clinical malaria
    (fever), high-density parasitaemia and well
    preserved immune function (high CD4 counts). ?
    because T-cells to activate?
  • Uncertain whether transiently increased viral
    loads lead to faster CD4 decline and clinical
    progression.

15
Pregnant women
  • increase in maternal viral load (x2).
  • Effect on maternal to child transmission?
  • 3 studies 1 no effect, 1 increased, 1 decreased.

16
Maternal to child transmission
  • Why the discrepancy in studies?
  • Study differences or due to maternal
    immunocompetence?
  • Hypothesis (Ned et al.Trends Parasitol 2005 in
    press)

17
Treatment issues1 antimalarials
  • HIV pregnant women need more frequent
    intermittent presumptive treatment with SP for
    same benefit on placental malaria and LBW as HIV-
    women.
  • If HIV infected and immunosuppressed ?treatment
    response to
  • Chloroquine
  • Sulphadoxine- pyrimethamine (Fansidar SP)
  • Artemether- lumefantrine (Co-artem)
  • Are effects due to re-infection or recrudescence?
    (Antimalarials more effective if patient has some
    pre-existing immunity)

18
Treatment issues2 cotrimoxazole
  • Cotrimoxazole (CTX) is a wide spectrum antibiotic
    recommended as prophylaxis for people with
    symptomatic HIV disease.
  • CTX has antimalarial activity (similar antifolate
    to SP).
  • In non-pregnant adults and children with HIV
    daily CTX reduces malaria 80 and may reduce
    transmission.
  • Is this protection adequate in pregnancy? Any
    need for IPT?
  • How to treat malaria in HIVves on CTX?
    Especially if SP is first-line treatment.
  • Try to avoid giving both SP and CTX? ? adverse
    reactions.

19
Treatment issues3 antiretrovirals
  • Protease inhibitors suppress P falciparum
    development in vitro at relevant concentrations.
    Especially ritonavir saquinavir/lopinavir.
    Cost? Toxicity?
  • Protease inhibitors and delaviridine
    (non-nucleoside reverse transcriptase inhibitor)
    ? toxicity with halofantrine, artemether,
    lumefantrine.
  • NNRTI (nevirapine, efavirenz) ? reduced levels of
    lumefantrine artemether ? malaria treatment
    failure.
  • ? Quinine may interact with PIs and NNRTIs.

20
What can be done? Encourage HIV infected
patients to avoid malaria infections
  • avoid mosquito bites,
  • insecticide impregnated bednets,
  • regular use of prophylactic CTX,
  • chemoprophylaxis or IPT repeated single doses of
    SP at antenatal clinics for pregnant women,
  • consider IPT for all HIV people,
  • early clinical diagnosis and treatment.

21
What can be done? Encourage more links between
control programmes
  • HIV and malaria have overlapping risk population
    groups,
  • same health personnel and service delivery sites,
  • VCT sites could be used for malaria intervention
    delivery,
  • ensure clean needles and syringes, screen blood
    for HIV,
  • common intervention tools eg diagnostics, fever
    investigation and treatment, CTX
  • Shared programme and resource mechanisms, eg
    global fund, country coordinating mechanisms,
    PPPs.

22
Conclusions
  • Malaria is not a florid opportunistic infection,
    but subtle interactions do certainly exist.
  • Most evidence of effect is in direction of HIV on
    malaria.
  • Many questions remain
  • What is effect of HIV on malaria in children?
  • What is effect of HIV on malaria transmission?
  • What is clinical effect of malaria on HIV?
  • What is effect of malaria on transmission of HIV
    from mother to child?
  • Are interactions similar for non-falciparum
    malaria?
  • Does improved avoidance and clinical management
    of malaria slow progression of HIV?
  • What are the effects of ARVs and CTX on the
    association between HIV and malaria, at the
    individual and population levels?
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