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Mbale, Emmie W; Moxon, Christopher A; Mukaka, Mavuto; Chagomerana, Maganizo; Glover, Simon; Chisala, Ngawina; Omar, Sofia; Molyneux, Malcolm; Seydel, Karl; Craig, Alister G; Taylor, Terrie; Heyderman, Robert S; Mallewa, Macpherson (2016)
Publisher: Elsevier BV
Journal: Journal of Infection
Languages: English
Types: Article
Subjects: ws_20, RA0421, Infectious Diseases, wc_503_5, wc_503, TNF, RJ101, Article, Paediatric, wc_750, HIV, wa_20_5, RA0421 Public health. Hygiene. Preventive Medicine, NDAS, Cerebral Malaria, Microbiology (medical), RJ101 Child Health. Child health services
This work was supported by grants from the NIH (T.E.T., 5R01AI034969-14) and a Clinical Fellowship from The Wellcome Trust, United Kingdom (C.A.M, 88758). The Malawi-Liverpool-Wellcome Clinical Research Programme is supported by core funding from The Wellcome Trust, UK. 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). Conclusions. 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. Publisher PDF Peer reviewed

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