HIV infection compounds the lymphopenia associated with cerebral malaria in Malawian children

Abstract

Wilson L Mandala,1–3 Esther N Gondwe,1,† Tonney S Nyirenda,1,4 Mark Drayson,5 Malcolm E Molyneux,1,6 Calman A MacLennan1,7 1Malawi Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; 2Biomedical Sciences Department, College of Medicine, Blantyre, Malawi; 3Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi; 4Pathology Department, College of Medicine, Blantyre, Malawi; 5Institute of Immunology and Immunotherapy, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK; 6Liverpool School of Tropical Medicine, Liverpool, UK; 7Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK †Esther N Gondwe passed away on April 5, 2018 Aim: Cerebral malaria (CM), unlike severe malarial anemia (SMA), has previously been characterized by pan-lymphopenia that normalizes in convalescence, while HIV infection is associated with depletion of CD4+ T cells. In this study, we investigate whether HIV infection in Malawian children exacerbates the pan-lymphopenia associated with CM. Methods: We investigated the absolute and percentage lymphocyte-subset counts and their activation and memory status in Malawian children presenting with either CM who were HIV-uninfected (n=29), HIV-infected (n=9), or SMA who were HIV-uninfected (n=30) and HIV-infected (n=5) in comparison with HIV-uninfected children without malaria (n=42) and HIV-infected children without malaria (n=4). Results: HIV-infected CM cases had significantly lower absolute counts of T cells (P=0.006), CD4+ T cells (P=0.0008), and B cells (P=0.0014) than HIV-uninfected CM cases, and significantly lower percentages of CD4+ T cells than HIV-uninfected CM cases (P=0.005). HIV-infected SMA cases had significantly lower percentages of CD4+ T cells (P=0.001) and higher CD8+ T cells (P=0.003) in comparison with HIV-uninfected SMA cases. HIV-infected SMA cases had higher proportions of activated T cells (P=0.003) expressing CD69 than HIV-uninfected SMA cases. Conclusion: HIV infection compounds the perturbation of acute CM and SMA on lymphocytes, exacerbating subset-specific lymphopenia in CM and increasing activation status in SMA, potentially exacerbating host immunocompromise. Keywords: HIV, cerebral malaria, severe malarial anemia, Malawian children

Keywords

• HIV
• Cerebral Malaria
• Severe Malarial Anaemia
• Malawian Children