Augusto Ronaldo de Carvalho, Tetreau Guillaume, Chan Philippe, Walet-Balieu Marie-Laure, Mello-Silva Clélia Christina, Santos Claudia Portes, Grunau Christoph
Laboratório de Avaliação e Promoção da Saúde Ambiental, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brasil.
Univ. Perpignan Via Domitia, IHPE UMR 5244, CNRS, IFREMER, Univ. Montpellier, Perpignan, France.
PLoS Negl Trop Dis. 2017 Jul 28;11(7):e0005789. doi: 10.1371/journal.pntd.0005789. eCollection 2017 Jul.
Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite's biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite's life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts.
METHODOLOGY/PRINCIPAL FINDINGS: We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics.
CONCLUSIONS/SIGNIFICANCE: We describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).
血吸虫病已在78个流行国家被报道，全球有2.4亿人受其影响。双殖吸虫曼氏血吸虫需要淡水来完成其生命周期。在淡水中，它易受可直接和/或间接影响寄生虫生物学特性的可溶性化合物的影响。尾蚴阶段是寄生虫易受不同可溶性化合物影响的关键点之一，这些化合物可显著改变寄生虫的生命周期。世界卫生组织推荐使用杀螺剂来控制血吸虫病传播，而麒麟血藤乳胶对中间宿主螺类有效。
方法/主要发现：我们使用寄生虫学工具和电子显微镜来验证尾蚴暴露于天然杀螺剂（麒麟血藤乳胶）对成虫形态、生理和适应性的影响。为了深入了解导致观察到的表型的关键代谢途径，我们使用了比较转录组学和蛋白质组学。
结论/意义：我们在此描述，乳胶对成虫的影响并非由于直接毒性，而是它引发了发育轨迹的早期变化，并扰乱了细胞记忆、移动性、能量代谢和其他关键途径。我们得出结论，乳胶不仅对媒介有影响，还具有持久的血吸虫生长抑制作用。我们认为，这些结果不仅对寄生虫学家有意义，因为它表明天然化合物可能无副作用，却能对发育过程产生意想不到的影响。在这种情况下，这种附带损害是积极的，因为它影响了治疗行动的真正目标。这种类型的治疗也可为控制其他害虫提供依据。我们的结果将有助于在巴西和其他流行国家推广使用麒麟血藤乳胶，作为吡喹酮大规模药物治疗的廉价替代方案或补充，吡喹酮是目前唯一可用于治疗患者（但不能预防再次感染）的药物。
