黑热病对人体危害严重，在全球范围再度回升，经由利什曼原虫引起和白蛉传播。了解这些寄生虫的种群结构与遗传分化有助于解析其流行病学和在人类的传播。中国利什曼原虫异质性高，种群结构和遗传关系仍不清楚。申请者在前期研究中发现中国分布有一独特的谱系，与蜥蜴利什曼原虫形成一支，暗示中国利什曼虫株的异质性和演化历史比先前想象的更复杂。本项目在此基础上，拟广泛采样，整合多位点微卫星分型、临床症状、以及地理特征等数据，联合基于贝叶斯模型的聚类算法和遗传距离等种群遗传学方法重建中国利什曼原虫的演化历史；阐明中国利什曼原虫复合体种群结构和遗传分化；检验其起源和散布方式；探讨遗传型和临床症状及地理起源之间的关系；揭示地理分布、宿主、传播媒介等因素对利什曼原虫的演化和扩布的影响。研究结果将促进利什曼原虫的分类、种群遗传学和流行病学研究，进而为黑热病的正确诊断、预测以及制定治疗和控制措施提供科学依据。

Representatives of the genus Leishmania cause a variety of clinical syndromes ranging from self-healing cutaneous forms (CL) through to mucocutaneous (MCL) and lethal visceral diseases (VL).The leishmaniasis is transmitted via the bite of infected female sandflies. Understanding molecular changes associated with population structure in these parasites can help to understand their epidemiology and spread in humans. In the current context of worldwide (re-)emergence and spreading of leishmaniasis,the relevance of distinction of strains further gains importance.Multilocus microsatellite typing (MLMT) is able to discriminate below the zymodeme level and seems to be the best candidate for becoming the gold standard for distinction of strains. In our previous phylogenetic studies, we provided evidence for the occurrence of a distint lineage in China as yet unclassfied members of Leishmania. That lineage is more closely reated to Sauroleishmania than to L. onovani complex, further indicating that the strains in China may have had a more complex evolutionary history than previously thought. In the present study,we will integrate genotype, clinical manifestations, hosts and vectors, as well as climatic and geographical features into investigating the population genetics and phylogeography of Leishmania strains in China. A more comprehensive sampling is necessary to cover as many as possible endemic foci in China. We will use a panel of standard microsatellite loci to investigate population-level diversity in Leishmania strains isolated from endemic foci in China, and compared their variation to that found in diverse strains of the L. donovani complex isolates from Europe, Africa and Asia. MLMT data will be analysed by using a Bayesian model-based clustering algorithm and reconstructing phylogenetic tree based on genetic distances. Our obejectives are (i) to understand the population structure and genetic differentiation of L. donovani complex strains in China; (ii) to test the hypotheses for the origin of spread of L. donovani complex in China; (iii) to infer the phylogeographic patterns of Leishmania isolates, and reveal the cryptic diversity; and (iv) to test whether specific genetic traits are related to different clinical manifestations of strains infections, such as VL, MCL and CL.The reuslts of this study will facilitate global taxonomic, population genetic and epidemiological studies of the Leishmania parasites. This is crucial for correct diagnosis and prognosis of the diseases as well as for making decisions regarding treatment and control measures.