HIV coinfection influences the inflammatory response but not the outcome of cerebral malaria in Malawian children. Issue 3 (September 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of infection. Volume 73:Issue 3(2016)
• Page Start: 189
• Page End: 199
• Publication Date: 2016-09
• Subjects: Cerebral malaria -- HIV -- Paediatric -- TNF; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2016.05.012
• Languages: English
• ISSNs: 0163-4453

Abstract

Summary: 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. Highlights: Characteristic malaria retinopathy refined the diagnosis of cerebral malaria. HIV-infected cases had markedly lower TNF, IL10 and ICAM-1 than uninfected cases. HIV-infected children were older and more likely to have comorbidities. Peripheral parasite count, HRP2 and mortality were unaffected by HIV status.