Plasmodium simium: Population Genomics Reveals the Origin of a Reverse Zoonosis

Background. The population history of Plasmodium simium, which causes malaria in sylvatic Neotropical monkeys and humans along the Atlantic Coast of Brazil, remains disputed. Genetically diverse P vivax populations from various sources, including the lineages that founded the species P simium, are thought to have arrived in the Americas in separate migratory waves. Methods. We use population genomic approaches to investigate the origin and evolution of P simium. Results. We find a minimal genome-level differentiation between P simium and present-day New World P vivax isolates, consistent with their common geographic origin and subsequent divergence on this continent. The meagre genetic diversity in P simium samples from humans and monkeys implies a recent transfer from humans to non-human primates - a unique example of malaria as a reverse zoonosis of public health significance. Likely genomic signatures of P simium adaptation to new hosts include the deletion of > 40% of a key erythrocyte invasion ligand, PvRBP2a, which may have favored more efficient simian host cell infection. Conclusions. New World P vivax lineages that switched from humans to platyrrhine monkeys founded the P simium population that infects nonhuman primates and feeds sustained human malaria transmission in the outskirts of major cities.