Delayed acquisition of Plasmodium falciparum antigen-specific CD4+ T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis

Malaria Journal

Research

Herbert Longwe¹  Wilson L. Mandala²  Kondwani C. Jambo³  Nyanyiwe M. Mbeye⁴  Thandile Gondwe⁴  Kamija S. Phiri⁴ 

[1] Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi;Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi;Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi;Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi;Liverpool School of Tropical Medicine, Liverpool, UK;Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi;Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi;

关键词: Plasmodium falciparum;    Cotrimoxazole;    HIV-exposed children;    CD4 T cells;   

DOI  :  10.1186/s12936-016-1318-2

 received in 2015-12-04, accepted in 2016-04-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4+ T cells-mediated immunity in HEU children is still not fully understood.MethodsPeripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4+ T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4+ T cells responses were measured by intracellular cytokine staining assay.ResultsThere were no differences in the proportions of naïve, effector and memory CD4+ T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4+ T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4+ T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis.ConclusionThe results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4+ T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4+ T cells leads to higher risk to malaria disease remains unknown and warrants further investigation.

【 授权许可】

CC BY   
© The Author(s) 2016