Key Determinants Of The Natural History Of Leishmania major Infection

人畜共患皮肤利什曼病（ZCL）是一种在北非和中东高度流行的疾病，由利什曼原虫引起。 TMRC计划有三个主要目标：1-描述L的自然历史。在流行地区表现为严重感染，特别是无症状感染。疾病严重程度和疾病复发的风险; 2-分析媒介特有因素的各自作用（沙蝇唾液），或寄生虫（种内多态性）或宿主免疫反应（先天或适应性），在ZCL的临床表现中，特别强调识别保护免受初次感染、疾病发生或复发的免疫相关性; 3.在方案执行的所有各级加强流行病学临床和实验室良好做法的应用。 为了达到这些目标，我们将在ZCL流行的地区进行一项大规模的临床前瞻性调查。所有入组的个体将进行广泛的临床和免疫学研究，以准确确定其关于利什曼原虫感染的临床病史（包括LST反应性）以及它们在基线时对载体唾液组分和寄生虫抗原的体外免疫应答。然后对所有ZCL病例进行主动检测，将在接下来的两年中进行队列成员中出现的利什曼原虫分离株的功能水平的广泛研究，以确定种内多样性是由于毒力因子的差异表达。 该研究将描绘该地区L主要感染的自然历史。此外，该程序生成的临床、免疫学和寄生虫学信息将被整合到多参数分析中。这将允许识别考虑到L主要和水库多样性的种内功能多态性的最终影响的保护的免疫相关性。这些数据对于有效疫苗或抗利什曼病药物的开发和评价至关重要。

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.