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J Infect Dis. 2016 Jul 15;214(2):329-38. doi: 10.1093/infdis/jiw147. Epub 2016 Apr 10.

Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10.

Author information

1
Department of Medicine, San Francisco General Hospital.
2
Infectious Diseases Research Collaboration.
3
Department of Medicine, San Francisco General Hospital Center for Biomedical Research, The Burnet Institute, Melbourne, Australia.
4
Department of Clinical Pharmacy.
5
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
6
Department of Medicine, San Francisco General Hospital Department of Pediatrics, University of California-San Francisco.

Abstract

BACKGROUND:

Experimental inoculation of viable Plasmodium falciparum sporozoites administered with chemoprevention targeting blood-stage parasites results in protective immunity. It is unclear whether chemoprevention similarly enhances immunity following natural exposure to malaria.

METHODS:

We assessed P. falciparum-specific T-cell responses among Ugandan children who were randomly assigned to receive monthly dihydroartemisinin-piperaquine (DP; n = 87) or no chemoprevention (n = 90) from 6 to 24 months of age, with pharmacologic assessments for adherence, and then clinically followed for an additional year.

RESULTS:

During the intervention, monthly DP reduced malaria episodes by 55% overall (P < .001) and by 97% among children who were highly adherent to DP (P < .001). In the year after the cessation of chemoprevention, children who were highly adherent to DP had a 55% reduction in malaria incidence as compared to children given no chemoprevention (P = .004). Children randomly assigned to receive DP had higher frequencies of blood-stage specific CD4(+) T cells coproducing interleukin-2 and tumor necrosis factor α (P = .003), which were associated with protection from subsequent clinical malaria and parasitemia, and fewer blood-stage specific CD4(+) T cells coproducing interleukin-10 and interferon γ (P = .001), which were associated with increased risk of malaria.

CONCLUSIONS:

In this setting, effective antimalarial chemoprevention fostered the development of CD4(+) T cells that coproduced interleukin 2 and tumor necrosis factor α and were associated with prospective protection, while limiting CD4(+) T-cell production of the immunoregulatory cytokine IL-10.

KEYWORDS:

IL-10; IL-2; T cell; antimalarial chemoprevention; falciparum; immunity; malaria

PMID:
27067196
PMCID:
PMC4918829
DOI:
10.1093/infdis/jiw147
[Indexed for MEDLINE]
Free PMC Article

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