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HIV coinfection influences the inflammatory response but not the outcome of cerebral malaria in Malawian children.

HIV coinfection influences the inflammatory response but not the outcome of cerebral malaria in Malawian children.
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Mbale EW, Moxon CA, Mukaka M, Chagomerana M, Glover S, Chisala N, Omar S, Molyneux M, Seydel K, Craig AG, Taylor T, Heyderman RS, Mallewa M,


Mbale EW, Moxon CA, Mukaka M, Chagomerana M, Glover S, Chisala N, Omar S, Molyneux M, Seydel K, Craig AG, Taylor T, Heyderman RS, Mallewa M, (click to view)

Mbale EW, Moxon CA, Mukaka M, Chagomerana M, Glover S, Chisala N, Omar S, Molyneux M, Seydel K, Craig AG, Taylor T, Heyderman RS, Mallewa M,

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The Journal of infection 2016 06 1473(3) 189-99 doi 10.1016/j.jinf.2016.05.012

Abstract
OBJECTIVES
Study of the effect of HIV on disease progression in heterogeneous severe malaria syndromes with imprecise diagnostic criteria has led to varying results. Characteristic retinopathy refines cerebral malaria (CM) diagnosis, enabling more precise exploration of the hypothesis that HIV decreases the cytokine response in CM, leading to higher parasite density and a poor outcome.

METHODS
We retrospectively reviewed data on clinical progression and laboratory parameters in 877 retinopathy-positive CM cases admitted 1996-2011 (14.4% HIV-infected) to a large hospital in Malawi. Admission plasma levels of TNF, interleukin-10, and soluble intercellular adhesion molecule (sICAM-1) were measured by ELISA in 135 retinopathy-positive CM cases.

RESULTS
HIV-infected CM cases had lower median plasma levels of TNF (p = 0.008), interleukin-10 (p = 0.045) and sICAM-1 (p = 0.04) than HIV-uninfected cases. Although HIV-infected children were older and more likely to have co-morbidities, HIV-status did not significantly affect parasite density (p = 0.90) or outcome (24.8% infected, vs. 18.5% uninfected; p = 0.13).

CONCLUSION
In this well-characterised CM cohort, HIV-coinfection was associated with marked blunting of the inflammatory response but did not affect parasite density or outcome. These data highlight the complex influence of HIV on severe malaria and bring into question systemic inflammation as a primary driver of pathogenesis in human CM.

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