4.5 Article

Genome-wide analysis of Schistosoma mansoni reveals limited population structure and possible praziquantel drug selection pressure within Ugandan hot-spot communities

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PLOS NEGLECTED TROPICAL DISEASES
卷 16, 期 8, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pntd.0010188

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  1. Wellcome Trust [206194, 095778]

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This study aims to understand the impact of praziquantel (PZQ) treatment on the genetics of schistosomes. The authors obtained whole-genome sequence data from 174 individual miracidia collected from fishing communities in Uganda and investigated the genetic variation and genomic signatures of natural selection in pre- and post-treatment parasite populations. The study found higher genetic diversity in pre-treatment parasite populations and identified genes with evidence of recent positive selection in post-treatment and intensively treated parasites that could be related to reduced susceptibility to PZQ treatment.
Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.

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