Santamaria, A. M. | Search bioRxiv

bioRxiv2020

Population Genomics of Plasmodium vivax in Panama to Assess the Risk of Case Importation on Malaria Elimination

Malaria incidence in Panama has plateaued in recent years in spite of elimination efforts, with almost all cases caused by Plasmodium vivax. Notwithstanding, overall malaria prevalence remains low (fewer than 1 case per 1000 persons). We used selective whole genome amplification to sequence 96 P. vivax samples from Panama collected between 2007 and 2019 to study the population structure and transmission dynamics of the parasite. Imported cases resulting from increased levels of human migration could threaten malaria elimination prospects, and four of the samples evaluated came from individuals with travel history. We explored patterns of recent common ancestry among the samples and observed that a single highly genetically related lineage was dominant among the samples (47 out of 59 samples with good sequencing coverage), spanning the entire period of the collection (2007-2019) and all regions of the country. We also found a second, smaller clonal lineage of four parasites collected between 2017 and 2019. To explore the regional context of Panamanian P. vivax we conducted principal components analysis and constructed a neighbor-joining tree using these samples and samples collected worldwide from a previous study. Three of the four samples with travel history clustered with samples collected from their suspected country of origin (consistent with importation), while one appears to have been a result of local transmission. The small number of genetically unique Panamanian P. vivax samples clustered with samples collected from Colombia, suggesting they represent the genetically similar ancestral P. vivax population in Panama or were recently imported from Colombia. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination. Additionally, while we confirmed that P. vivax is imported to Panama from diverse geographic locations, the lack of impact from imported cases on the overall parasite population genomic profile suggests that onward transmission from such cases is limited and that imported cases may not presently pose a major barrier to elimination. Author SummaryPanama has greatly reduced P. vivax incidence, however, this progress has plateaued. Understanding parasite transmission patterns and identifying imported cases is critical to help Panama and other countries succeed in their elimination efforts. Genomic epidemiology and population genomics can help provide information needed to inform malaria control policy. In this study, we collected 100 Panamanian P. vivax samples from two collection periods (2007-2009 and 2017-2019), of which 59 yielded usable sequencing data. 4 samples had patient travel history data associated with them. We found that the majority of samples belong to a single highly related lineage, termed CL1. This lineage has persisted since at least 2007. We also highlight how genomic epidemiology can be used to spotlight parasites that may be imported as a result of human migration, as well as corroborate or refute the country of origin as suggested by patient travel history. We observe no evidence of outcrossing between these potentially imported parasites and the local Panamanian parasite population, suggesting that imported parasites are not driving ongoing malaria transmission in Panama. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination.

microbiology↗

bioRxiv2017

Human Migration And The Spread Of Malaria Parasites To The New World

BackgroundThe Americas were the last continent to be settled by modern humans, but how and when human malaria parasites arrived in the New World is uncertain. Here, we apply phylogenetic analysis and coalescent-based gene flow modeling to a global collection of Plasmodium falciparum and P. vivax mitogenomes to infer the demographic history and geographic origins of malaria parasites circulating in the Americas. Importantly, we examine P. vivax mitogenomes from previously unsampled forest-covered sites along the Atlantic Coast of Brazil, including the vivax-like species P. simium that locally infects platyrrhini monkeys.\n\nResultsThe best-supported gene flow models are consistent with migration of both malaria parasites from Africa and South Asia to the New World, with no genetic signature of a population bottleneck upon parasite's arrival in the Americas. We found evidence of additional gene flow from Melanesia in P. vivax (but not P. falciparum) mitogenomes from the Americas and speculate that some P. vivax lineages might have arrived with the Australasian peoples who contributed genes to Native Americans in pre-Columbian times. Mitochondrial haplotypes characterized in P. simium from monkeys from the Atlantic Forest are shared by local humans. These vivax-like lineages have not spread to the Amazon Basin, are much less diverse than P. vivax circulating elsewhere in Brazil, and show no close genetic relatedness with P. vivax populations from other continents.\n\nConclusionsEnslaved peoples brought from a wide variety of African locations were major carriers of P. falciparum mitochondrial lineages into the Americas, but additional human migration waves are likely to have contributed to the extensive genetic diversity of present-day New World populations of P. vivax. The reduced genetic diversity of vivax-like monkey parasites, compared with human P. vivax from across this country, argues for a recent human-to-monkey transfer of these lineages in the Atlantic Forest of Brazil.\n\nAuthor summaryMalaria is currently endemic to the Americas, with over 400,000 laboratory-confirmed infections reported annually, but how and when human malaria parasites entered this continent remains largely unknown. To determine the geographic origins of malaria parasites currently circulating in the Americas, we examined a global collection of Plasmodium falciparum and P. vivax mitochondrial genomes, including those from understudied isolates of P. vivax and P. simium, a vivax-like species that infect platyrrhini monkeys, from the Atlantic Forest of Brazil. We found evidence of significant historical migration to the New World of malaria parasites from Africa and, to a lesser extent, South Asia, with further genetic contribution of Melanesian lineages to South American P. vivax populations. Importantly, mitochondrial haplotypes of P. simium are shared by monkeys and humans from the Atlantic Forest, most likely as a result of a recent human-to-monkey transfer. Interestingly, these potentially zoonotic lineages are not found in the Amazon Basin, the main malaria-endemic area in the Americas. We conclude that enslaved Africans were the main carriers of P. falciparum mitochondrial lineages into the Americas, whereas additional migration waves of Australasian peoples and parasites may have contributed to the genetic makeup of present-day New World populations of P. vivax.

microbiology↗