Population genomics reveals the expansion of highly inbred Plasmodium vivax lineages in the main malaria hotspot of Brazil

Autor(es)

de Oliveira, Thais Crippa ^[1] ; Corder, Rodrigo M. ^[1] ; Early, Angela ^{[2, 3]} ; Rodrigues, Priscila T. ^[1] ; Ladeia-Andrade, Simone ^[4] ; Alves, Joao Marcelo P. ^[1] ; Neafsey, Daniel E. ^{[2, 3]} ; Ferreira, Marcelo U. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA - USA

^[3] Broad Inst MIT & Harvard, Infect Dis & Microbiome Program, Cambridge, MA - USA

^[4] Fiocruz MS, Inst Oswaldo Cruz, Lab Parasit Dis, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 14, n. 10 OCT 2020.
• Citações Web of Science: 1

Resumo

Background Plasmodium vivax is a neglected human malaria parasite that causes significant morbidity in the Americas, the Middle East, Asia, and the Western Pacific. Population genomic approaches remain little explored to map local and regional transmission pathways of P. vivax across the main endemic sites in the Americas, where great progress has been made towards malaria elimination over the past decades. Methodology/Principal findings We analyze 38 patient-derived P. vivax genome sequences from Mancio Lima (ML)-the Amazonian malaria hotspot next to the Brazil-Peru border-and 24 sequences from two other sites in Acre State, Brazil, a country that contributes 23% of malaria cases in the Americas. We show that the P. vivax population of ML is genetically diverse (pi = 4.7 x 10(-4)), with a high polymorphism particularly in genes encoding proteins putatively involved in red blood cell invasion. Paradoxically, however, parasites display strong genome-wide linkage disequilibrium, being fragmented into discrete lineages that are remarkably stable across time and space, with only occasional recombination between them. Using identity-by-descent approaches, we identified a large cluster of closely related sequences that comprises 16 of 38 genomes sampled in ML over 26 months. Importantly, we found significant ancestry sharing between parasites at a large geographic distance, consistent with substantial gene flow between regional P. vivax populations. Conclusions/Significance We have characterized the sustained expansion of highly inbred P. vivax lineages in a malaria hotspot that can seed regional transmission. Potential source populations in hotspots represent a priority target for malaria elimination in the Amazon. Authors' summary Plasmodium vivax is the geographically most widespread human malaria parasite and causes 80% of the malaria burden in the Americas. Here we use whole-genome sequencing to explore levels of parasite relatedness and infer P. vivax transmission networks in the upper Jurua Valley, the main transmission hotspot in Amazonian Brazil. We characterize a genetically diverse population that displays significant linkage disequilibrium, consistent with the local circulation of highly inbred but genetically distant parasite lineages. Noteworthy, these discrete lineages remain stable over time and share recent ancestry with parasites at a large geographic distance. These results illustrate the power of genomic epidemiology approaches to map potential source parasite populations and prioritize areas for targeted control interventions to eliminate residual P. vivax transmission in the Amazon and similar endemic settings worldwide. (AU)

• Processo FAPESP: 16/18740-9 - Bases científicas para a eliminação da malária residual na Amazônia Brasileira
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático