Trimethoprim-sulfamethoxazole prophylaxis during live malaria sporozoite immunization induces long-lived, homologous, and heterologous protective immunity against sporozoite challenge
More about Open Access at the CrickAuthors list
Charlotte V Hobbs Charles Anderson Jillian Neal Tejram Sahu Solomon Conteh Tatiana Voza Jean Langhorne William Borkowsky Patrick E DuffyAbstract
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.
Journal details
Journal Journal of Infectious Diseases
Volume 215
Issue number 1
Pages 122-130
Available online
Publication date
Full text links
Publisher website (DOI) 10.1093/infdis/jiw482
Europe PubMed Central 28077589
Pubmed 28077589
Keywords
Related topics
Type of publication