Key Determinants Of The Natural History Of Leishmania major Infection

人畜共患皮肤利什曼病(ZCL)是由大利什曼原虫引起的一种在北非和中东地区高度流行的疾病。 TMRC计划有三个主要目标：1-描述流行地区主要乳杆菌感染的自然历史，特别是关于无症状感染，疾病的严重性和疾病复发的风险；2-分析媒介(沙蝇唾液)、寄生虫(种内多态)或宿主免疫反应(先天或适应性)的特定因素在ZCL临床表现中的各自作用，特别强调识别免疫相关因素，以防止初级感染、疾病发生或复发；3-加强良好的流行病学临床和实验室实践在计划实施的所有级别的应用。为了达到这些目标，我们将在ZCL流行的地区进行一次大规模的临床前瞻性调查。将对所有登记的个体进行广泛的临床和免疫学调查，以准确定义他们的利什曼病感染的临床病史(包括LST反应性)以及他们对媒介唾液成分和寄生虫抗原的体外免疫反应，然后在接下来的两年里对队列成员中出现的所有ZCL病例进行积极检测。可以从活跃的皮损生长的利什曼原虫分离株将在功能水平上进行广泛调查，以确定由于毒力因子的差异表达而导致的种内多样性。 这项研究将绘制L在该地区重大感染的自然历史图景。此外，该计划产生的临床、免疫学和寄生虫学信息将被整合到多参数分析中。这将允许识别保护的免疫相关因素，考虑到主要L的种内功能多态和储藏者多样性的最终影响。这些数据对于开发和评估有效的疫苗或抗利什曼药物至关重要。

Zoonotic Cutaneous Leishmaniasis (ZCL) is a disease highly prevalent in North Africa and Middle East that is caused by Leishmania major. The TMRC program has three main goals :1-Describe the natural history of L. major infection as expressed in an endemic area especially with regard to asymptomatic infection .disease severity and risk of disease recurrence; 2-Analyse the respective roles of factors specific of the vector(sand fly saliva ),or the parasite(intraspecies polymorphism) or the host immune response(innate or adaptative), in the clinical expression of ZCL with special emphasis on the identification of immune correlates of protection against primoinfection, disease occurrence or recurrence; 3-Reinforce the application of Good Epidemiological Clinical and Laboratory Practices at all levels of programme implementation. In order to reach these goals, we shall conduct a large clinical prospective survey in a region endemic for ZCL. All enrolled individuals will be extensively investigated, clinically and immunologically, in order to accurately define their clinical history with regard to leishmania infection (including LST reactivity) as well as their in vitro immune responses to vector saliva components and parasite antigens at baseline Then an active detection of all ZCL cases, that will emerge among the cohort members will be conducted during the two following years .Leishmania isolates that could be grown from active lesions will be extensively investigated at the functional level in order to identify intraspecies diversity due to differential expression of virulence factors. The study will draw a picture of the natural history of L major infection in the region. In addition the clinical, immunological and parasitological informations generated by the program will be integrated into a multiparametric analysis. This will permit to identify immune correlates of protection that take into consideration the eventual effects of intraspecies functional polymorphism of L major and reservoir diversity. These data are of crucial importance for the development and evaluation of effective vaccines or antileishmanial drugs.