Malaria and HIV coinfection

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Malaria and HIV co-infection

• Jimmy Whitworth
• IAS Conference on HIV Pathogenesis and Treatment
• Rio de Janeiro
• July 2005

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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.

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Geographical Distribution
Malaria distribution
HIV distribution
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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).
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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.

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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.

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Effect of HIV on malaria

• Non-pregnant adults
• Stable malaria situations
• Unstable malaria situations
• Pregnant women
• Children

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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
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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)

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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).

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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.

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Public health implications

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

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Effect of malaria on HIV

• Non-pregnant adults
• Pregnant women
• Children no convincing effects noted

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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.

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Pregnant women

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

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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)

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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)

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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.

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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.

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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.

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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.

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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?