We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Symptomatic malaria enhances protection from reinfection with homologous Plasmodium falciparum parasites.
- Authors
Markwalter, Christine F.; Petersen, Jens E. V.; Zeno, Erica E.; Sumner, Kelsey M.; Freedman, Elizabeth; Mangeni, Judith N.; Abel, Lucy; Obala, Andrew A.; Prudhomme-O'Meara, Wendy; Taylor, Steve M.
- Abstract
A signature remains elusive of naturally-acquired immunity against Plasmodium falciparum. We identified P. falciparum in a 14-month cohort of 239 people in Kenya, genotyped at immunogenic parasite targets expressed in the pre-erythrocytic (circumsporozoite protein, CSP) and blood (apical membrane antigen 1, AMA-1) stages, and classified into epitope type based on variants in the DV10, Th2R, and Th3R epitopes in CSP and the c1L region of AMA-1. Compared to asymptomatic index infections, symptomatic malaria was associated with reduced reinfection by parasites bearing homologous CSP-Th2R (adjusted hazard ratio [aHR]:0.63; 95% CI:0.45–0.89; p = 0.008) CSP-Th3R (aHR:0.71; 95% CI:0.52–0.97; p = 0.033), and AMA-1 c1L (aHR:0.63; 95% CI:0.43–0.94; p = 0.022) epitope types. The association of symptomatic malaria with reduced hazard of homologous reinfection was strongest for rare epitope types. Symptomatic malaria provides more durable protection against reinfection with parasites bearing homologous epitope types. The phenotype represents a legible molecular epidemiologic signature of naturally-acquired immunity by which to identify new antigen targets. Author summary: The targets and mechanisms of naturally-acquired immune responses to P. falciparum parasites remain obscured, owing in part to the absence of a legible signature of immunity in humans exposed to repeated natural infections. A hallmark of functional protection for malaria and other pathogens is a reduced risk of re-infection with homologous strains. In a community-based, longitudinal cohort in a high transmission setting in Western Kenya, we analyzed by deep sequencing immunogenic segments of parasite antigens and the time to reinfection following parasite clearance. When classifying parasites at described epitopes within targets of antiparasite immunity, we observed that, compared to parasites cleared following an asymptomatic infection, the hazard of reinfection following a symptomatic infection was reduced by 30–40%. The association of symptomatic infection with delayed homologous reinfection offers a signature of protection by which to identify novel targets of antiparasite immunity.
- Subjects
KENYA; PLASMODIUM; PLASMODIUM falciparum; REINFECTION; MALARIA; PARASITE antigens; CIRCUMSPOROZOITE protein; PARASITES
- Publication
PLoS Pathogens, 2023, Vol 18, Issue 6, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1011442