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

Authors Mandala WL, Gondwe EN, Nyirenda TS, Drayson M, Molyneux ME, MacLennan CA

Received 11 September 2018

Accepted for publication 21 November 2018

Published 19 December 2018 Volume 2019:10 Pages 9—18

DOI https://doi.org/10.2147/JBM.S187081

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


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

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