Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge

Charlotte V. Hobbs, Charles Anderson, Jillian Neal, Tejram Sahu, Solomon Conteh, Tatiana Voza, Jean Langhorne, William Borkowsky, Patrick E. Duffy

Research output: Contribution to journalArticle

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8+ T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis.

Original languageEnglish (US)
Pages (from-to)122-130
Number of pages9
JournalThe Journal of infectious diseases
Volume215
Issue number1
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

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Keywords

  • antiretroviral therapy
  • children
  • eradication
  • HIV
  • immunity
  • liver stages
  • malaria
  • trimethoprim-sulfamethoxazole

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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