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

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

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / administration & dosage*
  • Artemisinins / administration & dosage
  • CD4-Positive T-Lymphocytes / immunology*
  • Chemoprevention / methods*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Interleukin-10 / metabolism*
  • Malaria, Falciparum / pathology*
  • Malaria, Falciparum / prevention & control*
  • Male
  • Quinolines / administration & dosage
  • Uganda
  • Young Adult

Substances

  • Antimalarials
  • Artemisinins
  • IL10 protein, human
  • Quinolines
  • Interleukin-10
  • dihydroartemisinin
  • piperaquine