Parasites and Microbes, Wellcome Sanger Institute, Hinxton, United Kingdom.
Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and the London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
PLoS Negl Trop Dis. 2022 Aug 18;16(8):e0010188. doi: 10.1371/journal.pntd.0010188. eCollection 2022 Aug.
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.
在血吸虫病控制地区,特别是在非洲,建议采用定期大规模药物治疗(MDA),使用吡喹酮(PZQ)作为控制疾病的主要策略。PZQ 治疗对血吸虫遗传学的影响知之甚少,并且受到这些控制地区寄生虫种群结构缺乏高分辨率遗传数据的限制。我们从乌干达维多利亚湖岛屿上的渔民社区的儿童和成人中收集的 174 个尾蚴个体中生成了全基因组序列数据,这些个体在四年内接受了每年或每季度一次的 PZQ MDA,包括在治疗前和治疗后四周收集的样本。对样本内和样本间的基因组变异进行了特征描述,并研究了对这些种群起作用的自然选择的基因组特征,这些特征可能是由于 PZQ 治疗引起的。这些岛屿上的寄生虫种群比湖边附近的村庄更加多样化。我们发现村庄之间或不同治疗强度的村庄之间几乎没有或没有遗传分化,但与治疗后寄生虫种群相比,治疗前寄生虫种群的遗传多样性略高。我们确定了在基因组中具有近期正选择证据的区域内显著富集的基因类别,这些区域内存在与 PZQ 治疗相关的寄生虫的敏感性降低。治疗后和治疗前寄生虫种群中观察到的差异选择可能与寄生虫对吡喹酮治疗的敏感性降低有关。