野鼠作为日本血吸虫病传染源并形成与野鼠有关的血吸虫株的研究

Schistosoma japonicum is the schistosome species for which zoonotic transmission is considered important, and the roles, acting as reservoirs for S. japonicum, of humans, bovines, goats and so on in the transmission of the parasite have been recognized. The importance of small rodents in the transmission of the parasite, however, has long been neglected. Reasons for this may partly relate to much lower amount of excreted faeces from rodents, and the reported 'natural resistance' against this parasite in rats (a non-susceptible host for S. japonicum) or in Microtus fortis (a non-permissive host for S. japonicum). However, our previous parasitological surveys demonstrated that in the hill region, rodents (including Rattus norvegicus) had the highest infection prevalence of up to 26.5% and the highest infection intensity (230.7 eggs plus miracidia per gram of faeces on average) with up to 3311.7 eggs plus miracidia /g faeces in one rodent host. The analyses of the cercarial shedding patterns of S. japonicum from captured infected snails in the two regions, marshland and hill regions, demonstrated chronobiological polymorphism of cercarial emergence with a late afternoon shedding pattern (17:00-21:00) observed in the hilly region, compatible with a nocturnal rodent reservoir, and a morning shedding pattern (7:00－11:00) within marshland areas, consistent with a diurnal bovine major reservoir. Characterization of the parasite population genetics demonstrated that there was a population genetic substructure (or potential multiple 'strains') of parasites in relation to geographical locations. Such findings may raise the hypotheses as follows: 1) whether rodents serve as reservoirs in the hilly areas and also a rodent-associated strain of parasites are developed; 2) whether such strain of parasites are more able to infect rats and Microtus fortis than those parasites from lake/marshlands. Therefore, field parasitological surveys, experiment of parasite-host relationships, observation of chronobiology of cercarial emergence and population genetic analyses of parasites will be performed in order to determine whether rodents act as reservoirs for S. japonicum and any final host-associated strain of parasites exist in the hilly region, and to what extent such parasites could be transmitted. Moreover, the evolution of the parasites and their relationship to their hosts will be explored. The results from this would have both practical and theoritical implications.

日本血吸虫病人畜共患,其中人、牛及羊等作为传染源已明确，但野鼠作为传染源却长期被忽略，原因系野鼠排粪少和认为野鼠中大鼠系非易感宿主和东方田鼠系不相容宿主。然而，我们前期发现：在山区流行区，野鼠(含大鼠)血吸虫感染率高达26.5%，平均感染度（毛蚴或虫卵/g粪）230.7,个别鼠达3311.7；山区感染性钉螺中尾蚴逸出高峰在17:00-21:00（野鼠活跃时辰），而湖区为7:00－11:00（耕牛牧草时辰）；山区与湖区尾蚴基因结构不同。故提出假设：1）野鼠可作为山区血吸虫病传染源，并且血吸虫因野鼠长期影响形成与其有关的血吸虫株；2）此虫株较湖区血吸虫易感染大鼠(及东方田鼠)。因此，本项目旨结合现场调查，通过对血吸虫的感染性、逸蚴昼夜节律性及种群遗传学研究，阐明野鼠在山区血吸虫病流行中传染源的地位及与其相关的虫株的存在，探讨此虫株在湖区潜在的传播能力及其进化趋势；研究结果具有实际和理论意义。

本项目旨在阐明野鼠在山区血吸虫病流行中传染源的地位，及与野鼠相关的血吸虫虫株的存在；分析此血吸虫株群体结构和潜在传播能力。通过对现场血吸虫中间宿主钉螺调查、实验室内毛蚴攻击感染钉螺实验、室内尾蚴感染小鼠实验和血吸虫群体遗传学分析，观察山区血吸虫尾蚴逸出的昼夜节律性，山区血吸虫与湖区钉螺相容性，和血吸虫群体遗传结构特征；同时，通过Meta分析，综合评价血吸虫群体化疗、人群流动和宠物饲养在血吸虫和其它人畜共患寄生虫病中作用。.研究发现：1）日本血吸虫性别在钉螺间分布非随机，钉螺感染率（0.67%）很低，但感染性钉螺中单性血吸虫感染比例占95.65%；2）山区血吸虫表现为‘晚逸蚴’，其逸蚴特征不受其所寄生宿主钉螺的影响；3）光照周期变化对血吸虫逸蚴节律性有一定的影响；4）山区血吸虫与湖区钉螺具有高度相容性；5）山区血吸虫群体遗传结构特征与其它地区血吸虫株（包括实验室株）不同；6）日本血吸虫对小鼠的致病性与配对血吸虫雌雄虫间的基因差异性有关，与配对虫体间杂合度无关，并且基因差异越大，其致病性越弱；7）血吸虫STR位点在分型错误率和效率上有差别；8）群体化疗在预防控制血吸虫病中效果明显，而流行区外出人群数量庞大，对其它地区的血吸虫病复燃具有潜在威胁。.通过本研究进一步阐明了在此山区血吸虫病流行区，在其它家畜作为血吸虫病传染源意义下降情况下，野鼠作为其传染源，有极为重要地位；山区血吸虫晚逸蚴特征和异于其它地区血吸虫株的群体遗传特征，明确了与野鼠有关的日本血吸虫(株)的存在；山区血吸虫与湖区钉螺的高度相容性，说明野鼠作为其传染源的‘晚逸蚴’血吸虫易传播扩散到其它地区。此类鼠源性血吸虫病疫区，血吸虫可能因防治策略改变、人畜等流动，而对血吸虫病已传播阻断地区产生威胁。通过此项目实施，已培养硕士研究生4名，公开发表论文（国基项目标注）11篇，其中SCI论文10篇。

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