Genomic Insights Into Host Shifts Between <i>Plasmodium vivax</i> and <i>Plasmodium simium</i> in Latin America

ABSTRACT Malaria in Latin America is largely caused by Plasmodium vivax , but the closely related monkey parasite Plasmodium simium has recently been observed in humans, thus raising new public health concerns. By screening 719 monkey samples from five Latin America countries, we identified 23 Plasmodium ‐positives. However, only four samples yielded sufficient mitochondrial DNA sequencing data to allow reliable species identification, and their inclusion in genome‐wide population analyses. Using whole‐genome variation data from these samples together with whole genome variations of 19 P. simium and 405 P. vivax isolates, we investigated their evolutionary history and population genetics. P. vivax , typically restricted to humans, was identified in three Colombian and one Brazilian monkeys, suggesting possible host niche expansion. Genetic analyses reveal recent genetic exchanges between both species and indicate that P. simium originated from a host jump approximately one to two centuries ago. Also other alternatives are possible, this host shift may have followed P. vivax migration from Central/North America to Brazil. Genome‐wide scans revealed signals of positive selection in P. simium genes implicated in interactions with primate hosts, including PvRBP2a and PvRBP1b , as well as genes involved in interactions with mosquito vectors, such as PvCMRP1 , PvPAT , and Pvs47 . These findings shed light on P. simium evolutionary history. They also underscore the zoonotic risks, and the need to include monkeys in malaria prevention measures while ensuring human‐wildlife coexistence.