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

in Research May 10, 2023 From Malaria Journal


Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparummalaria. 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.


Peripheral 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.


There 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 ofP. 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.


The 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.


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