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



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.



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).



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.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi; Department of Paediatrics, University of Malawi College of Medicine, Malawi.
Emmie W
EW
Mbale
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi; Institute of Infection and Global Health, University of Liverpool, UK. Electronic address: cmoxon@liverpool.ac.uk.
Christopher A
CA
Moxon
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi.
Mavuto
M
Mukaka
Blantyre Malaria Project, University of Malawi College of Medicine, Malawi.
Maganizo
M
Chagomerana
School of Medicine, University of St. Andrews, UK.
Simon
S
Glover
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi.
Ngawina
N
Chisala
Department of Paediatrics, University of Malawi College of Medicine, Malawi.
Sofia
S
Omar
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi; Liverpool School of Tropical Medicine, UK.
Malcolm
M
Molyneux
Blantyre Malaria Project, University of Malawi College of Medicine, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States.
Karl
K
Seydel
Liverpool School of Tropical Medicine, UK.
Alister G
AG
Craig
Blantyre Malaria Project, University of Malawi College of Medicine, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States.
Terrie
T
Taylor
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi; Liverpool School of Tropical Medicine, UK; University College London, UK.
Robert S
RS
Heyderman
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi; Department of Paediatrics, University of Malawi College of Medicine, Malawi.
Macpherson
M
Mallewa
D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D016779:Malaria, Cerebral / Q000150:complications* / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy; D008297:Male; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10
Cerebral malaria; HIV; Paediatric; TNF