Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia.

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Authors
Kebede, Alebachew Messele 
Sutanto, Edwin 
Trimarsanto, Hidayat 
Benavente, Ernest Diez 
Barnes, Mariana 
Abstract

Ethiopia has the greatest burden of Plasmodium vivax in Africa, but little is known about the epidemiological landscape of parasites across the country. We analysed the genomic diversity of 137 P. vivax isolates collected nine Ethiopian districts from 2012 to 2016. Signatures of selection were detected by cross-country comparisons with isolates from Thailand (n = 104) and Indonesia (n = 111), representing regions with low and high chloroquine resistance respectively. 26% (35/137) of Ethiopian infections were polyclonal, and 48.5% (17/35) of these comprised highly related clones (within-host identity-by-descent > 25%), indicating frequent co-transmission and superinfection. Parasite gene flow between districts could not be explained entirely by geographic distance, with economic and cultural factors hypothesised to have an impact on connectivity. Amplification of the duffy binding protein gene (pvdbp1) was prevalent across all districts (16-75%). Cross-population haplotype homozygosity revealed positive selection in a region proximal to the putative chloroquine resistance transporter gene (pvcrt-o). An S25P variant in amino acid transporter 1 (pvaat1), whose homologue has recently been implicated in P. falciparum chloroquine resistance evolution, was prevalent in Ethiopia (96%) but not Thailand or Indonesia (35-53%). The genomic architecture in Ethiopia highlights circulating variants of potential public health concern in an endemic setting with evidence of stable transmission.

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Acknowledgements: We thank the patients who contributed their samples to the study, the health workers and field teams who assisted with the sample collections, and the staff of the Wellcome Sanger Institute Sample Logistics, Sequencing, and Informatics facilities for their contributions.

Keywords
Humans, Plasmodium vivax, Malaria, Vivax, Ethiopia, Chloroquine, Malaria, Falciparum, Genomics, Protozoan Proteins, Antimalarials, Drug Resistance, Plasmodium falciparum
Journal Title
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Journal ISSN
2045-2322
2045-2322
Volume Title
13
Publisher
Springer Science and Business Media LLC
Sponsorship
World Health Organization Program for Research and Training in Tropical Diseases (WHO/TDR) (P20-0004)
Wellcome Trust (206194, 200909)
Medical Research Council (M006212)
The DELTAS Africa Initiative (107740/Z/15/Z)
Bill and Melinda Gates Foundation (INV-043618)
National Health and Medical Research Council (GNT2001083)