The source-sink dynamics of Plasmodium vivax may undermine malaria elimination efforts in the Amazon: an epidemiological and population genomic study.

BACKGROUND Brazil's progress toward malaria elimination has stalled and 163,000 new cases (more than 80% caused by Plasmodium vivax) were recorded in the Brazilian Amazon in 2023. We hypothesize that human mobility continues to disperse parasites from hotspots to areas with decreasing endemicity. METHODS We analyzed 5.5 million malaria case notifications between 2003 and 2023 to describe malaria case mobility and identify sources and sinks of P. vivax in the Brazilian Amazon. We leveraged whole-genome sequence data from 408 P. vivax isolates sampled from across South America to characterize parasite gene flow and infer likely regional routes of parasite dispersal. RESULTS We found that nearly one-third of the P. vivax infections diagnosed in residents in the Brazilian Amazon over 21 years were acquired outside the locality or municipality of residence, but only 1.7% were imported from other countries in South America, mostly from the Guiana Shield. We show that large cities with residual malaria transmission - such as Manaus and Porto Velho - are receptive parasite sinks surrounded by high-risk source rural localities. Although the genetic relatedness of parasites tended to decrease with geographic distance, parasites from sites more than 1,000 km apart often remained genetically connected. CONCLUSIONS Understanding parasite source-sink dynamics on different geographic scales is crucial to target high-risk mobile populations and source localities along with receptive sinks within low-transmission municipalities, with the goal of eliminating malaria transmission and preventing its reintroduction into malaria-free areas across the Amazon.