Publications & Reports

Effective antimalarial chemoprevention in childhood enhances CD4+ T cell quality and limits CD4 production of immunoregulatory IL-10.

Jagannathan P, Bowen K, Nankya F, McIntyre T, Auma A, Wamala S, Sikyomu E, Naluwu K, Nalubega M, Boyle MJ, Farrington L, Bigira V, Kapisi J, Aweeka F, Greenhouse B, Kamya M, Dorsey G, Feeney ME
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, USA.


BACKGROUND: Experimental inoculation of viableP. falciparumsporozoites administered with blood-stage chemoprevention results in protective immunity. It is unclear if chemoprevention similarly enhances immunity following natural exposure to malaria. METHODS: We assessedPf-specific T cell responses among Ugandan children who were randomized 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, then clinically followed for an additional year. RESULTS: During the intervention, monthly DP reduced malaria episodes by 55% (P<0.001), and by 97% among children who were highly adherent to DP (P<0.001). In the year after the cessation of chemoprevention, children who were highly adherent to DP had a 55% reduction in malaria incidence compared to children given no chemoprevention (P=0.004). Children randomized to DP had higher frequencies of iRBC-specific CD4+T cells co-producing IL-2/TNFalpha (P=0.003), which were associated with protection from subsequent clinical malaria and parasitemia, and fewer CD4+T cells co-producing IL-10/IFNgamma (P=0.001), which were associated with increased risk. CONCLUSION: In this setting, effective antimalarial chemoprevention fostered the development of TNF/IL2-producing CD4+T cells that were associated with prospective protection, while limiting CD4 production of immunoregulatory IL10.

Link to publisher’s web site

Link to fuul text at PubMed Central


  • Journal: The Journal of infectious diseases
  • Published: 10/04/2016
  • Volume: 214
  • Issue: 2
  • Pagination: 329-338

Health Issue