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Proc Natl Acad Sci U S A DOI:10.1073/pnas.2122165119

Declines in prevalence alter the optimal level of sexual investment for the malaria parasite Plasmodium falciparum.

Publication TypeJournal Article
Year of Publication2022
AuthorsEarly, AM, Camponovo, F, Pelleau, S, Cerqueira, GC, Lazrek, Y, Volney, B, Carrasquilla, M, de Thoisy, B, Buckee, CO, Childs, LM, Musset, L, Neafsey, DE
JournalProc Natl Acad Sci U S A
Date Published2022 Jul 26
KeywordsAnimals, Humans, Malaria, Malaria, Falciparum, Parasites, Plasmodium falciparum, Prevalence

Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite's optimal life history strategy. Here, we explore whether declining infection rates can alter 's investment in sexual versus asexual growth. Using a multiscale mathematical model, we demonstrate how the proportion of polyclonal infections, which decreases as parasite prevalence declines, affects the optimal sexual development strategy: Within-host competition in multiclone infections favors a greater investment in asexual growth whereas single-clone infections benefit from higher conversion to sexual forms. At the same time, drug treatment also imposes selection pressure on sexual development by shortening infection length and reducing within-host competition. We assess these models using 148 parasite genomes sampled in French Guiana over an 18-y period of intensive intervention (1998 to 2015). During this time frame, multiple public health measures, including the introduction of new drugs and expanded rapid diagnostic testing, were implemented, reducing malaria cases by an order of magnitude. Consistent with this prevalence decline, we see an increase in the relatedness among parasites, but no single clonal background grew to dominate the population. Analyzing individual allele frequency trajectories, we identify genes that likely experienced selective sweeps. Supporting our model predictions, genes showing the strongest signatures of selection include transcription factors involved in the development of 's sexual gametocyte form. These results highlight how public health interventions impose wide-ranging selection pressures that affect basic parasite life history traits.


Alternate JournalProc Natl Acad Sci U S A
PubMed ID35867831
Grant ListU19AI110818 / / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
ANR-10-LABX-25-01 / / Agence Nationale de la Recherche (ANR) /
R35GM-124715 / / HHS | NIH | National Institute of General Medical Sciences (NIGMS) /
1902214 / / National Science Foundation (NSF) /
REGPOT-CT-2011-285837-430 STRonGer / / European Commission (EC) /