Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms

Author:

Auburn Sarah12,Getachew Sisay34,Pearson Richard D56,Amato Roberto56,Miotto Olivo567,Trimarsanto Hidayat89,Zhu Sha Joe6,Rumaseb Angela1,Marfurt Jutta1,Noviyanti Rintis8,Grigg Matthew J110,Barber Bridget110,William Timothy101112,Goncalves Sonia Morgado5,Drury Eleanor5,Sriprawat Kanlaya13,Anstey Nicholas M1,Nosten Francois213,Petros Beyene3,Aseffa Abraham4,McVean Gil6,Kwiatkowski Dominic P56,Price Ric N12

Affiliation:

1. Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia

2. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

3. College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia

4. Armauer Hansen Research Institute, Addis Ababa, Ethiopia

5. Wellcome Sanger Institute, Hinxton, Cambridge

6. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, United Kingdom

7. Mahidol–Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand

8. Eijkman Institute for Molecular Biology, Jakarta, Indonesia

9. Agency for Assessment and Application of Technology, Jakarta, Indonesia

10. Infectious Diseases Society, Sabah-Menzies School of Health Research Clinical Research Unit, Sabah, Malaysia

11. Clinical Research Centre, Queen Elizabeth Hospital, Sabah, Malaysia

12. Jesselton Medical Centre, Sabah, Malaysia

13. Shoklo Malaria Research Unit, Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand

Abstract

Abstract The Horn of Africa harbors the largest reservoir of Plasmodium vivax in the continent. Most of sub-Saharan Africa has remained relatively vivax-free due to a high prevalence of the human Duffy-negative trait, but the emergence of strains able to invade Duffy-negative reticulocytes poses a major public health threat. We undertook the first population genomic investigation of P. vivax from the region, comparing the genomes of 24 Ethiopian isolates against data from Southeast Asia to identify important local adaptions. The prevalence of the Duffy binding protein amplification in Ethiopia was 79%, potentially reflecting adaptation to Duffy negativity. There was also evidence of selection in a region upstream of the chloroquine resistance transporter, a putative chloroquine-resistance determinant. Strong signals of selection were observed in genes involved in immune evasion and regulation of gene expression, highlighting the need for a multifaceted intervention approach to combat P. vivax in the region.

Funder

Wellcome Trust Senior Research Fellowship in Clinical Science

Australian National Health and Medical Research Council

Bill and Melinda Gates Foundation

Asia-Pacific Malaria Elimination Network

Malaysian Ministry of Health

Hot North” Earth Career Fellowship

Medical Research Council and UK Department for International Development

Wellcome Trust

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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