title: Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge.
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.
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.|Division of Infectious Diseases, Department of Pediatrics.|Department of Microbiology, Batson Children's Hospital, University of Mississippi Medical Center, Jackson.|Division of Infectious Disease and Immunology, Department of Pediatrics, New York University School of Medicine.
authors.forename: Charlotte V
authors.initials: CV
authors.lastname: Hobbs
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Charles
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Jillian
authors.initials: J
authors.lastname: Neal
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Tejram
authors.initials: T
authors.lastname: Sahu
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Solomon
authors.initials: S
authors.lastname: Conteh
authors.affiliation: Biological Sciences Department, New York City College of Technology, City University of New York.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Voza
authors.affiliation: Mill Hill Laboratory, Francis Crick Institute, London, United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
authors.affiliation: Division of Infectious Disease and Immunology, Department of Pediatrics, New York University School of Medicine.
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D015658:HIV Infections / Q000469:parasitology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008018:Life Cycle Stages; D008288:Malaria / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009894:Opportunistic Infections / Q000188:drug therapy / Q000517:prevention & control; D010961:Plasmodium / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D007371:Interferon-gamma
keywords: HIV; antiretroviral therapy; children; eradication; immunity; liver stages; malaria; trimethoprim-sulfamethoxazole