Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

Genomic analyses of Ethiopian P. vivax to inform for Epidemiology, Population structure and selection (#405)

Alebachew Messele Kebede 1 , Hidayat Trimarsanto 2 , Ernest Diez Diez Benavente 3 , Sasha V Siegel 4 , Roberto Amato 4 , Richard Pearson 4 , Ashenafi Assefa 5 , Sisay Getachew 6 , Berhanu Erko 1 , Abraham Aseffa 7 , Beyene Petros 6 , Eugenia Lo 8 , Dominic Kwiatkowski 4 , Ric N Price 9 10 11 , Sarah Auburn 9 10 11 , Lemu Golassa 1
  1. Department of Medical Parasitology, Aklilu Lemma Institute of Pathobiology, Addis Ababa, Ethiopia
  2. Eijkman Institute for Molecular Biology, Jakarta, Indonesia
  3. University Medical Center Utrecht, Utrecht, Netherlands
  4. Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom
  5. Ethiopian Public Health Institute,, Addis Ababa, Ethiopia
  6. College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia
  7. Armauer Hansen Research Institute, Addis Ababa, Ethiopia
  8. Departments of Bioinformatics and Genomics,, University of North Carolina at Charlotte, Charlotte, USA
  9. Mahidol‐Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
  10. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  11. The Global and Tropic Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia

Ethiopia has the greatest burden of P. vivax in Africa, accounting for almost 40% of malaria cases. Efforts to eliminate P. vivax are constrained by limited knowledge of the major adaptations and epidemiological drivers sustaining local endemicity. In a previous genomic study, we have identified candidate markers of drug resistance and other adaptations but were constrained by small sample size. In this study, we conducted a more in-depth genomic analysis on 155 Ethiopian P. vivax genomes.  

High-quality genomic data was generated the Illumina platform for an additional 124 isolates collected from cross-sectional surveys undertaken between 2013,2014 and 2015. When combined with published genomes, data were available from 155 Ethiopian isolates in 9 districts. Population genomic analyses were conducted using scikit-allel, ADMIXTURE, isoRelate, and custom scripts.  

Approximately 40% of infections were polyclonal (FWS<0.95), indicative of frequent co-transmission and superinfection. ADMIXTURE analysis revealed limited evidence of population structure , but isoRelate demonstrated several clusters of infections sharing recent identity by descent suggesting epidemiologically relevant gene flow between districts. Amplification of the Duffy binding protein (DBP1) was present at high frequency in 8 districts (16%-75%), with up to 5 copies, suggestive of a local adaptative function in red blood cell invasion or immune evasion. Evidence of selection using Tajima’s D was also observed in the chloroquine resistance transporter (pvcrt-o) and several genes putatively involved in red blood cell invasion. Further investigation is underway using haplotype-based methods to detect and confirm signals of selection. 

The genomic patterns highlight adaptations of potential public health concern in a setting with moderately high and stable transmission within and between districts. Enhanced P. vivax interventions and surveillance are needed to identify and contain new adaptative variants that threaten control and elimination efforts.