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

Abstract

BACKGROUND:

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 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.

METHODS:

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.

RESULTS:

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 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.

CONCLUSION:

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.

• Authors: Herbert Longwe, Kamija S Phiri, Nyanyiwe M Mbeye, Thandile Gondwe, Wilson L Mandala, Kondwani C Jambo
• Journal: Malaria journal (Malar J) Vol. 15 Issue 1 Pg. 264 (05 10 2016) ISSN: 1475-2875 [Electronic] England
• PMID: 27165269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Cytokines
• Trimethoprim, Sulfamethoxazole Drug Combination

Topics

• Antimalarials (administration & dosage)
• CD4-Positive T-Lymphocytes (immunology)
• Chemoprevention (methods)
• Cytokines (analysis)
• Female
• HIV Infections (immunology)
• Humans
• Immunophenotyping
• Infant
• Malaria, Falciparum (immunology)
• Malawi
• Male
• Maternal Exposure
• Plasmodium falciparum (immunology)
• Pregnancy
• Trimethoprim, Sulfamethoxazole Drug Combination (administration & dosage)