Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment: evidence from a laboratory life-history trade-offs selection study
Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment: evidence from a laboratory life-history trade-offs selection study
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DOI：
10.1186/s40249-017-0324-0
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发表时间：
2017-06-16
影响因子：
8.1
通讯作者：
Webster, Joanne P.
中科院分区：
文献类型：
--
作者：
Lamberton, Poppy H. L.;Faust, Christina L.;Webster, Joanne P.
背景：吡喹酮的大规模给药是世界卫生组织认可的血吸虫病控制策略。尽管“热点”仍然存在，但撒哈拉以南非洲地区十年来的年度治疗已导致感染流行率和强度水平显着降低。重复的药物治疗会对寄生虫产生强大的选择压力，这可能会影响影响传播动态的生活史特征。了解药物治疗反应和此类性状的演变有助于了解如何最大限度地降低耐药性发展的风险，最大限度地提高可持续控制计划的成功，并改进诊断方案。 方法：我们在小鼠和蜗牛中进行了四代曼氏血吸虫吡喹酮选择实验。我们使用了三种曼氏链球菌品系：吡喹酮耐药分离株（R）、吡喹酮敏感分离株（S）和共感染株系（RS），采用三种治疗方案：未处理、25 mg/kg 吡喹酮或 50 mg/kg 吡喹酮。记录了所有四代小鼠的生活史特征，包括寄生虫成虫的建立、存活、繁殖（繁殖力）和相关的发病率。在一系列广义线性混合效应模型中测试了预测变量，以确定哪些因素对不同选择方案下的最终宿主中的寄生虫生活史性状具有显着影响。结果：吡喹酮压力显着降低了所有世代和分离株（包括 R 系内）的成虫负担。然而，之前的药物治疗导致成虫数量增加，从 P1 到 F3 的世代不断增加。最高的蠕虫数量出现在共同感染的 RS 系中。吡喹酮治疗减少了成虫负担，但对所有三种寄生虫菌株的平均每日毛蚴数量（繁殖力的代表）产生了较大的负面影响。结论：我们在鼠宿主体内测量的性状并不支持我们预测的抗药性成本。我们没有发现成虫密度依赖性对繁殖力产生负面影响的证据。相比之下，在治疗后存活的成虫中，即使是低剂量的吡喹酮也会显着降低成虫的繁殖力。治疗后蠕虫繁殖力的降低表明，基于鸡蛋的药物功效测量（例如 Kato-Katz）可能高估了吡喹酮对成虫负担的短期影响。这些发现对于曼氏沙门氏菌传播控制、诊断方案以及未检测到的耐药性选择的潜力具有重要意义。
Background: Mass drug administration of praziquantel is the World Health Organization's endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although 'hotspots' remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols.Methods: We performed a four-generation Schistosoma mansoni praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a praziquantel-resistant isolate (R), a praziquantel-susceptible isolate (S), and a coinfected line (RS), under three treatment regimens: untreated, 25 mg/kg praziquantel, or 50 mg/kg praziquantel. Lifehistory traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes.Results: Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates.Conclusions: Our predicted cost of resistance was not supported by the traits we measured within the murine host. We did not find evidence for negative adult worm density-dependent effects on fecundity. In contrast, of the adult worms that survived treatment, even low doses of praziquantel significantly reduced adult-worm fecundity. Such reductions in worm fecundity post treatment suggest that egg - based measures of drug efficacy, such as Kato-Katz, may overestimate the short-term effect of praziquantel on adult - worm burdens. These findings have important implications for S. mansoni transmission control, diagnostic protocols, and the potential for undetected selection toward drug resistance.