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

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

doi:10.1038/s41598-023-47889-w

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

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

Research output: Contribution to journal › Article › peer-review

48 Downloads (Pure)

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.

Original language	English
Article number	20788
Pages (from-to)	1-16
Number of pages	16
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-47889-w
Publication status	Published - Dec 2023

Bibliographical note

Funding Information:
A.M.K. was supported by the Tropical Disease Research Clinical Research and Development Fellowship (award number P20-0004) grant issued by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO/TDR). The patient sampling and metadata collection for new samples from Ethiopia were supported by The DELTAS Africa Initiative [DELGEME grant 107740/Z/15/Z] awarded to L.G. The study was also supported by the Bill and Melinda Gates Foundation (INV-043618 awarded to S.A.), the National Health and Medical Research Council of Australia (GNT2001083 awarded to S.A.), and the Wellcome Trust (200909 and ICRG GR071614MA Senior Fellowships in Clinical Science to R.N.P.). The whole genome sequencing component of the study was supported by the Medical Research Council and UK Department for International Development (award number M006212) and the Wellcome Trust (award numbers 206194 and 204911).

Publisher Copyright:
© 2023, The Author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41598-023-47889-w

91280233-oaFinal published version, 2.68 MBLicence: CC BY

Cite this

Kebede, A. M., Sutanto, E., Trimarsanto, H., Benavente, E. D., Barnes, M., Pearson, R. D., Siegel, S. V., Erko, B., Assefa, A., Getachew, S., Aseffa, A., Petros, B., Lo, E., Mohammed, R., Yilma, D., Rumaseb, A., Nosten, F., Noviyanti, R., Rayner, J. C., ... Auburn, S. (2023). Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia. Scientific Reports, 13(1), 1-16. Article 20788. https://doi.org/10.1038/s41598-023-47889-w

@article{a20c1f428b1c4aed90c152a192f24e93,

title = "Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia",

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.",

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

note = "Funding Information: A.M.K. was supported by the Tropical Disease Research Clinical Research and Development Fellowship (award number P20-0004) grant issued by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO/TDR). The patient sampling and metadata collection for new samples from Ethiopia were supported by The DELTAS Africa Initiative [DELGEME grant 107740/Z/15/Z] awarded to L.G. The study was also supported by the Bill and Melinda Gates Foundation (INV-043618 awarded to S.A.), the National Health and Medical Research Council of Australia (GNT2001083 awarded to S.A.), and the Wellcome Trust (200909 and ICRG GR071614MA Senior Fellowships in Clinical Science to R.N.P.). The whole genome sequencing component of the study was supported by the Medical Research Council and UK Department for International Development (award number M006212) and the Wellcome Trust (award numbers 206194 and 204911). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41598-023-47889-w",

language = "English",

volume = "13",

pages = "1--16",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Kebede, AM, Sutanto, E, Trimarsanto, H, Benavente, ED, Barnes, M, Pearson, RD, Siegel, SV, Erko, B, Assefa, A, Getachew, S, Aseffa, A, Petros, B, Lo, E, Mohammed, R, Yilma, D, Rumaseb, A, Nosten, F, Noviyanti, R, Rayner, JC, Kwiatkowski, DP, Price, RN, Golassa, L & Auburn, S 2023, 'Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia', Scientific Reports, vol. 13, no. 1, 20788, pp. 1-16. https://doi.org/10.1038/s41598-023-47889-w

TY - JOUR

T1 - Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia

AU - Kebede, Alebachew Messele

AU - Sutanto, Edwin

AU - Trimarsanto, Hidayat

AU - Benavente, Ernest Diez

AU - Barnes, Mariana

AU - Pearson, Richard D.

AU - Siegel, Sasha V.

AU - Erko, Berhanu

AU - Assefa, Ashenafi

AU - Getachew, Sisay

AU - Aseffa, Abraham

AU - Petros, Beyene

AU - Lo, Eugenia

AU - Mohammed, Rezika

AU - Yilma, Daniel

AU - Rumaseb, Angela

AU - Nosten, Francois

AU - Noviyanti, Rintis

AU - Rayner, Julian C.

AU - Kwiatkowski, Dominic P.

AU - Price, Ric N.

AU - Golassa, Lemu

AU - Auburn, Sarah

N1 - Funding Information: A.M.K. was supported by the Tropical Disease Research Clinical Research and Development Fellowship (award number P20-0004) grant issued by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO/TDR). The patient sampling and metadata collection for new samples from Ethiopia were supported by The DELTAS Africa Initiative [DELGEME grant 107740/Z/15/Z] awarded to L.G. The study was also supported by the Bill and Melinda Gates Foundation (INV-043618 awarded to S.A.), the National Health and Medical Research Council of Australia (GNT2001083 awarded to S.A.), and the Wellcome Trust (200909 and ICRG GR071614MA Senior Fellowships in Clinical Science to R.N.P.). The whole genome sequencing component of the study was supported by the Medical Research Council and UK Department for International Development (award number M006212) and the Wellcome Trust (award numbers 206194 and 204911). Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85177857710&partnerID=8YFLogxK

U2 - 10.1038/s41598-023-47889-w

DO - 10.1038/s41598-023-47889-w

M3 - Article

SN - 2045-2322

VL - 13

SP - 1

EP - 16

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 20788

ER -

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

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this