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J Infect Dis. 2017 Jan 1;215(1):122-130. doi: 10.1093/infdis/jiw482. Epub 2016 Oct 17.

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

Author information

  • 1Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
  • 2Division of Infectious Diseases, Department of Pediatrics.
  • 3Department of Microbiology, Batson Children's Hospital, University of Mississippi Medical Center, Jackson.
  • 4Division of Infectious Disease and Immunology, Department of Pediatrics, New York University School of Medicine.
  • 5Biological Sciences Department, New York City College of Technology, City University of New York.
  • 6Mill Hill Laboratory, Francis Crick Institute, London, United Kingdom.

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.

KEYWORDS:

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

PMID:
28077589
PMCID:
PMC5225250
[Available on 2018-01-01]
DOI:
10.1093/infdis/jiw482
[PubMed - in process]
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