BACKGROUND A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. METHODS We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. RESULTS Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. CONCLUSIONS Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

中文翻译：

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两年的纵向调查显示，在乌干达大规模用药之初，曼氏血吸虫的遗传多样性很高，其成虫在吡喹酮治疗后仍能存活。


背景技术血吸虫病控制的一个关键组成部分是使用吡喹酮进行大规模给药。虽然控制干预措施在一些流行地区取得了成功，但大规模药物管理在其他地区却不太有效。这里我们重点研究吡喹酮重复治疗对曼氏血吸虫种群结构和遗传多样性的影响。方法 我们研究了曼氏沙门氏菌流行病学、群体遗传学以及从乌干达国家控制计划开始时高流行地区三所小学儿童中分离出的寄生虫的吡喹酮敏感性变化。在两年内的 11 个时间点对儿童进行了采样，包括吡喹酮治疗后 1 周和 4 周，以评估对清除率的短期影响以及吡喹酮敏感性自然变化的证据。结果 基线时曼氏沙门氏菌的流行率为 85%。从 203 名儿童中分离出总共 3576 只毛蚴幼虫寄生虫，并在 7 个位点进行了基因分型。总体而言，遗传多样性较高，遗传分化较低，表明寄生虫基因流率较高。在治疗前和治疗后 4 周均发现了血吸虫兄弟姐妹，这表明成虫在治疗中存活下来，并且在大规模给药开始时这些人群中吡喹酮的自然敏感性存在差异。然而，我们没有找到对这些寄生虫进行选择的证据。虽然遗传多样性在短期内（治疗后四个星期）有所下降，但尽管进行了四轮大规模治疗，但在整个时期内，多样性并未下降。此外，宿主内遗传多样性受到宿主年龄、宿主性别、感染强度和最近吡喹酮治疗的影响。 结论 我们的研究结果表明，吡喹酮治疗对这些寄生虫种群有短期影响，但影响是短暂的，并且没有观察到遗传多样性的长期减少。高基因流降低了局部适应的可能性，因此即使观察到寄生虫在治疗中存活下来，这些寄生虫在乌干达国家控制计划开始时很可能被稀释。总之，这些结果表明，单独的 MDA 可能不足以减少遗传多样性和基因流较高地区的血吸虫种群。