Early, AngelaLievens, MarcMacInnis, Bronwyn L.Ockenhouse, Christian F.Volkman, Sarah K.Adjei, SamuelAgbenyega, TsiriAnsong, DanielGondi, StaceyGreenwood, BrianHamel, MaryOdero, ChrisOtieno, KephasOtieno, WalterOwusu-Agyei, SethAsante, Kwaku PokuSorgho, HermannTina, LucasTinto, HalidouValea, InnocentWirth, DyannNeafsey, Daniel2018-05-302018Early, A. M., M. Lievens, B. L. MacInnis, C. F. Ockenhouse, S. K. Volkman, S. Adjei, T. Agbenyega, et al. 2018. “Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections.” Nature Communications 9 (1): 1381. doi:10.1038/s41467-018-03807-7. http://dx.doi.org/10.1038/s41467-018-03807-7.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37068208Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasite Plasmodium falciparum using haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses to P. falciparum act in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.en-USJournal Article2018-05-3010.1038/s41467-018-03807-7