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

Abstract

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

Supplementary materials

Table S1 Monoclonal antibodies used and corresponding cell populations

Table S2 Monoclonal antibodies and names of suppliers

Acknowledgments

We thank the parents, guardians, and children who participated in this study, and the staff at Queen Elizabeth Central Hospital and Beit Cure International Hospital for their assistance. Specifically, we would like to thank Grace Mwimaniwa, Meraby Banda, and Paul Pensulo for collecting blood samples from the participants, and Steve Graham, Elizabeth Molyneux, and Terrie Taylor for clinical assistance in recruitment of the study participants. Dr Esther N Gondwe, who had been involved in the analyses of samples for the study participants, died on April 5, 2018. This work was supported by a PhD studentship from the Gates Malaria Partnership (to WLM), which received support from the Bill and Melinda Gates Foundation, a Wellcome Trust Research Fellowship (grant 067902/Z/02/Z to CAM), a Wellcome Trust Programme Grant (grant 074124/Z/04/Z to MEM), and a Clinical Research Fellowship from GlaxoSmithKline to CAM.

Author contributions

WLM, MEM, and CAM conceived the study. CAM and MEM oversaw clinical aspects of the study. WLM, CLM, and ENG performed the investigations. WLM and TSN analyzed the data. WLM, CAM, MD, TSN, and MEM wrote the report. CAM oversaw the research. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.