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

Abstract

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 Mâncio 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 (π = 4.7 × 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.

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

“…Not surprisingly, relapses can be caused by siblings that remained undetected during the primary infection (e.g., Bright et al, 2014 ; Cowell et al, 2018 ). However, recurrences caused by meiotic siblings are not synonymous with relapses, as siblings can occasionally be found in new infections, especially in areas with low to moderate malaria transmission where highly inbred parasite lineages co-circulate over extended periods of time ( de Oliveira et al, 2020 ).…”

Genetic Diversity of Plasmodium vivax Cysteine-Rich Protective Antigen (PvCyRPA) in Field Isolates from Five Different Areas of the Brazilian Amazon

“…Some discrete P. vivax lineages can remain stable across time in one of the areas with the highest malaria transmission in the Americas. Relapses can account for some clonal persistence because P. vivax strains are repeatedly reintroduced in the population as hypnozoites reactivate [46]. Maybe this context can be to explain why only Mâncio Lima and Oiapoque showed no significant positive values of Tajima's D. However, genomic epidemiology approaches can help better to reveal the complex distribution of this parasite in the Brazilian Amazon, as well as the relationships with the worldwide genetic diversity.…”

Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain is conserved in field isolates from Brazilian Amazon

“…Since functional disruption of the single metacaspase (MCA1) in Saccharomyces cerevisiae by mutagenesis was already shown to induce in vitro drug-resistance as a result of refractoriness to apoptosis in the yeasts, 18 one possibility is that polymorphism of Pv MCA1 could be related to chemoresistance phenomena reported in vivax malaria, whose occurrence is reported to be infrequent in Juruá Valley 19 and that was not characterised in our cross-sectional study. Indeed, metacaspases have been implicated in apoptosis-like cell-death pathways in different microorganisms 20 and drug-resistant strains of P. falciparum seem to be insensitive to choroquine-induced apoptosis 21 as well as to anti-cell death effect promoted by inhibition of metacaspase activity.…”