Characterizing the genomic variation and population dynamics of Plasmodium falciparum malaria parasites in and around Lake Victoria, Kenya

Ashley Osborne,Akira Kaneko,Emilia Manko,James Kongere,Mtakai Ngara,Wataru Kagaya,Chim Chan,Kiyoshi Kita,Jesse Gitaka,Susana Campino,Mika Takeda,Taane G Clark,Osamu Kaneko

doi:10.1038/s41598-021-99192-1

Abstract

Characterising the genomic variation and population dynamics of Plasmodium falciparum parasites in high transmission regions of Sub-Saharan Africa is crucial to the long-term efficacy of regional malaria elimination campaigns and eradication. Whole-genome sequencing (WGS) technologies can contribute towards understanding the epidemiology and structural variation landscape of P. falciparum populations, including those within the Lake Victoria basin, a region of intense transmission. Here we provide a baseline assessment of the genomic diversity of P. falciparum isolates in the Lake region of Kenya, which has sparse genetic data. Lake region isolates are placed within the context of African-wide populations using Illumina WGS data and population genomic analyses. Our analysis revealed that P. falciparum isolates from Lake Victoria form a cluster within the East African parasite population. These isolates also appear to have distinct ancestral origins, containing genome-wide signatures from both Central and East African lineages. Known drug resistance biomarkers were observed at similar frequencies to those of East African parasite populations, including the S160N/T mutation in the pfap2mu gene, which has been associated with delayed clearance by artemisinin-based combination therapy. Overall, our work provides a first assessment of P. falciparum genetic diversity within the Lake Victoria basin, a region targeting malaria elimination.

Highlights

Studies in low transmission settings have provided valuable insight into malaria elimination strategies that may be viable for islands, as well as an increased understanding of the role human movement plays in malaria transmission in these e nvironments[5]
The development of methodologies that allow for the amplification of parasite DNA from infections with low parasite density, alongside the reduction in costs associated with next-generation whole genome sequencing (WGS), has made investigating parasite genomic diversity in malaria endemic settings a ttainable[8,9]
Our analysis revealed that P. falciparum isolates from the Lake Victoria region of Kenya have distinct ancestral origins, with a high proportion tied to Central and East African lineages, and form a distinct sub-group within East Africa in population structure analyses

Summary

Introduction

Studies in low transmission settings have provided valuable insight into malaria elimination strategies that may be viable for islands, as well as an increased understanding of the role human movement plays in malaria transmission in these e nvironments[5]. Previous research has assessed the genetic diversity through targeted genotyping of drug resistance genes or using microsatellite markers to gain insight into population d ynamics[4]. Such approaches underestimate the overall genetic variation of a population as only a small proportion of the genome is r epresented[13]. To provide a baseline level of genomic diversity within the Lake region, we generated WGS data for two islands, as well as the mainland sub-county Suba District (population size: North 124,938; South 122,383) and compared the resulting variation to publicly available whole genome sequences, from Kenya and the wider African continent through the Pf3K project (https://www.malariagen.net/parasite/pf3k). Known drug resistance biomarkers were observed in the Lake Victoria isolates at similar frequencies to those of East African parasite populations

Methods

Results

Conclusion