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

Abstract

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. However, here 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.

Zoonotic Malaria: Non-Laverania Plasmodium Biology and Invasion Mechanisms

“…Large deletions within the coding region of reticulocyte-binding protein 2a (RBP2a) were observed in P. simium compared with P. vivax [ 68 ]. This is corroborated by another study conducted recently in which the authors observed host switching from humans to sylvatic monkeys in P. simium , indicating reverse zoonosis [ 77 ]. The study suggested the cause of the adaptation of P. simium to non-human primate hosts could be due to the >40% deletion of the coding sequence of PvRBP2a in the P. simium genome.…”

“…The study suggested the cause of the adaptation of P. simium to non-human primate hosts could be due to the >40% deletion of the coding sequence of PvRBP2a in the P. simium genome. Hence, the lack of PvRBP2a-mediated erythrocyte binding in P. simium may lead to a facilitation of alternative ligands for a more efficient monkey host cell infection [ 77 ]. While information about the genetic basis of P. simium zoonosis is scarce, the deletions suggest the existence of a possible facilitator of zoonotic transfer.…”

Primate malarias as a model for cross-species parasite transmission

“…Historical DNA from pre-eradication Spain suggest a recent introduction and close relationship between historical Southern European P. vivax and modern South American P. vivax ( van Dorp et al, 2020 ). This is consistent with a host switch of historical P. vivax into howler monkeys to become what is today known as P. simium , supported by the low genetic diversity of P. simium and high similarity morphologically and genetically to P. vivax ( Escalante and Ayala, 1995 ; Lim et al, 2005 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ). Since then, P. simium has built up a handful of genetic differences from P. vivax , perhaps through drift or adaptations to a new host ( Brasil et al, 2017 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ).…”

“…This is consistent with a host switch of historical P. vivax into howler monkeys to become what is today known as P. simium , supported by the low genetic diversity of P. simium and high similarity morphologically and genetically to P. vivax ( Escalante and Ayala, 1995 ; Lim et al, 2005 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ). Since then, P. simium has built up a handful of genetic differences from P. vivax , perhaps through drift or adaptations to a new host ( Brasil et al, 2017 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ). Occasional cases of P. falciparum have also been reported in South American monkeys, though these cases are rare and largely unconfirmed ( Duarte et al, 2008 ; Yamasaki et al, 2011 ).…”

“…Genomic data provides some support for differentiation between P. simium and P. vivax ( Mourier et al, 2021 ; de Oliveira et al, 2021 ), but is weaker for P. brasilianum and P. malariae comparisons, which lack whole-genome data. Currently, most South American P. malariae cases are linked to international travel, but NHPs may serve as a reservoir for disease ( Figure 2 ).…”