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

Beyene Petros, Sarah Auburn, Lemu Golassa, Ric N Price, Dominic P Kwiatkowski, Julian C Rayner, Rintis Noviyanti, Francois Nosten, Angela Rumaseb, Daniel Yilma, Rezika Mohammed, Eugenia Lo, Alebachew Messele Kebede, Abraham Aseffa, Sisay Getachew, Ashenafi Assefa, Berhanu Erko, Sasha V Siegel, Richard D Pearson, Mariana Barnes, Ernest Diez Benavente, Hidayat Trimarsanto, Edwin Sutanto

Journal: Scientific reports 2023;13(1):20788

PMID: 38012191

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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.

Address: Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.; Exeins Health Initiative, Jakarta, Indonesia.; Menzies School of Health Research and Charles Darwin University, Casuarina, PO Box 41096, Darwin, NT, 0811, Australia.; Eijkman Institute for Molecular Biology, Jakarta, Indonesia.; Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.; Wellcome Sanger Institute, Hinxton, UK.; Ethiopian Public Health Institute, Addis Ababa, Ethiopia.; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia.; Armauer Hansen Research Unit (AHRI), Addis Ababa, Ethiopia.; Addis Ababa University, Addis Ababa, Ethiopia.; Millipore Sigma (Bioreliance), Rockville, USA.; Department of Microbiology and Immunology, College of Medicine, Drexel University, Philadelphia, USA.; University of Gondar, Gondar, Ethiopia.; Jimma University Clinical Trial Unit, Department of Internal Medicine, Jimma University, Jimma, Ethiopia.; Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.; Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.; Menzies School of Health Research and Charles Darwin University, Casuarina, PO Box 41096, Darwin, NT, 0811, Australia. [email protected].; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [email protected].; Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand. [email protected].

DOI: 10.1038/s41598-023-47889-w

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MeSH Terms: Humans, Plasmodium vivax, Malaria, Vivax, Ethiopia, Chloroquine, Malaria, Falciparum, Genomics, Protozoan Proteins, Antimalarials, Drug Resistance, Plasmodium falciparum