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

Malaria in Latin America is largely caused by <i>Plasmodium vivax</i>, but the closely related monkey parasite <i>Plasmodium simium</i> 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 <i>Plasmodium</i>-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 <i>P. simium</i> and 405 <i>P. vivax</i> isolates, we investigated their evolutionary history and population genetics. <i>P. vivax</i>, 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 <i>P. simium</i> originated from a host jump approximately one to two centuries ago. Also other alternatives are possible, this host shift may have followed <i>P. vivax</i> migration from Central/North America to Brazil. Genome-wide scans revealed signals of positive selection in <i>P. simium</i> genes implicated in interactions with primate hosts, including <i>PvRBP2a</i> and <i>PvRBP1b</i>, as well as genes involved in interactions with mosquito vectors, such as <i>PvCMRP1</i>, <i>PvPAT</i>, and <i>Pvs47</i>. These findings shed light on <i>P. simium</i> evolutionary history. They also underscore the zoonotic risks, and the need to include monkeys in malaria prevention measures while ensuring human-wildlife coexistence.