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Genomic analysis of local variation and recent evolution in Plasmodium vivax.

ABSTRACT: The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.

SUBMITTER: Pearson RD

PROVIDER: S-EPMC4966634 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Genomic analysis of local variation and recent evolution in Plasmodium vivax.

Pearson Richard D RD Amato Roberto R Auburn Sarah S Miotto Olivo O Almagro-Garcia Jacob J Amaratunga Chanaki C Suon Seila S Mao Sivanna S Noviyanti Rintis R Trimarsanto Hidayat H Marfurt Jutta J Anstey Nicholas M NM William Timothy T Boni Maciej F MF Dolecek Christiane C Hien Tinh Tran TT White Nicholas J NJ Michon Pascal P Siba Peter P Tavul Livingstone L Harrison Gabrielle G Barry Alyssa A Mueller Ivo I Ferreira Marcelo U MU Karunaweera Nadira N Randrianarivelojosia Milijaona M Gao Qi Q Hubbart Christina C Hart Lee L Jeffery Ben B Drury Eleanor E Mead Daniel D Kekre Mihir M Campino Susana S Manske Magnus M Cornelius Victoria J VJ MacInnis Bronwyn B Rockett Kirk A KA Miles Alistair A Rayner Julian C JC Fairhurst Rick M RM Nosten Francois F Price Ric N RN Kwiatkowski Dominic P DP

Nature genetics 20160627 8

The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genet ...[more]

PMID: 27348299

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Project description:Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission.A global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse.Differences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas.The results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to exploit seasonal changes in vector survival and therefore optimize transmission. Geographic patterns in P. vivax relapse are important to clinicians treating individual infections, epidemiologists trying to infer P. vivax burden, and public health officials trying to control and eliminate the disease in human populations.

Dataset Information

Genomic analysis of local variation and recent evolution in Plasmodium vivax.

Publications

Genomic analysis of local variation and recent evolution in Plasmodium vivax.

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