Abstract
Plasmodium vivax causes >70% of malaria cases in Latin America. The emergence of Plasmodium simium , transmitted from humans to monkeys, increased the malaria burden, notably after an outbreak in 2015 in Brazil. To investigate P. simium evolutionary history, we screened 646 monkey samples and analyzed whole genome variations for 19 P. simium and 408 P. vivax isolates. P. vivax strains were identified in Colombian (n=3) and Brazilian monkeys (n=1), suggesting host reinvasion in Colombia and genetic exchange between P. vivax and P. simium in Brazil. Genetic analysis indicates that P. simium originated from a host jump approximately a century ago, possibly linked to P. vivax migration from Mexico to Brazil. Genome-wide scans identified selection in genes interacting with primate hosts and vectors. These findings highlight P. simium evolutionary history and zoonotic malaria risks, and underscore the need to include monkeys in malaria prevention measures while ensuring human-wildlife coexistence.