Cutaneous Leishmaniasis in West Africa: the Parasite, Vector and Disease

西非皮肤利什曼病：寄生虫、媒介和疾病

• 批准号: 8896293
• 负责人: SEYDOU DOUMBIA
• 金额: $ 37万
• 依托单位: UNIV OF SCIENCES, TECH & TECH OF BAMAKO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8896293
• 关键词: Affect; Africa; African; Antibodies; Antigen-Presenting Cells; Area; Biological Markers; Bite; Cells; Cellular Immunity; Country; Cutaneous; Cutaneous Leishmaniasis; Data; Dendritic Cells; Development; Disease; Disease Vectors; Doctor of Philosophy; Drug Formulations; Environment; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Exposure to; Future; Ghana; Goals; Human; Immune; Immune response; Immunity; In Vitro; Incidence; Individual; Infection; Integration Host Factors; Knowledge; Laboratories; Leishmania; Leishmaniasis; Life; Mali; Microfilaria; Molecular Profiling; Outcome; Parasites; Parasitic infection; Pathogenesis; Phlebotominae; Phlebotomus; Population; Population Dynamics; Predisposition; Prevalence; Proteins; Public Health; Recording of previous events; Research; Resistance; Rodent Model; Role; Saliva; Salivary; Salivary Proteins; Sampling; Sand Flies; Scientist; Seasonal Variations; Site; Structure; T cell response; Testing; Time; Training; Vaccines; Vector-transmitted infectious disease; Visceral Leishmaniasis; Work; adaptive immunity; base; co-infection; combat; control trial; design; exposed human population; field study; fly; immunogenic; in vivo; macrophage; monocyte; neglect; novel; pathogen; prevent; resistance mechanism; success; tool; transmission process; vaccine candidate; vaccine development; vaccine trial; vector

DESCRIPTION (provided by applicant): Cutaneous leishmaniasis (CL) has a long history in West Africa, but one of the less recognized parasitic infections in the region. The disease is endemic Saharan desert countries in the North, in Sahelian band from west to East Africa. Currently, there is no vaccine against the diseases. However, studies have consistently shown that sand fly saliva generally enhances infectivity of Leishmania parasites in a naive host while an adaptive immune response to whole saliva or a distinct salivary protein generally protects against both cutaneous and visceral leishmaniasis in rodent models of infection. In the proposed work, 3 sites in West Africa each with distinct epidemiological and ecological environment will be compared with regard to intensity and prevalence of cutaneous leishmania infection, sand fly vector population dynamics, and disease pathogenesis with a focus on parasite and host factors and the immune response to candidate vaccines (sand fly proteins in particular). The hypothesis underlying this proposal is that a combination of parasite, vector, and human exposure to other parasitic infection such as infection with microfilariae determine the immunomodulatory effects of candidate vaccines, specifically sand fly proteins. The proposal seeks to 1] understand the basic epidemiology of cutaneous leishmaniasis and its vector in different foci of West Africa; 2] understand mechanism of resistance/susceptibility to the disease; 3] assess how an active infection with microfilariae alters the human immune response to sand fly salivary proteins and 4] reinforce local research capacity for future vaccine trials. RELEVANCE: This proposal is directly relevant to public health because Leishmaniasis take an enormous toll across the globe. Its goals are to examine the epidemiology, transmission of cutaneous leishmaniasis and a component that has been largely overlooked: the immuno-modulation of sandfly proteins. Project 1: Epidemiology of Cutaneous Leishmaniasis Project Leader: Ousmane Faye, MD, PhD (Description as provided by applicant): Leishmaniasis is a vector-borne disease transmitted to the host via the bite of a Leishmania infected phlebotomine sand fly. Cutaneous leishmaniasis (CL) has a long history in West Africa, but is one of the less recognized parasitic infections in the region. Studies have consistently shown that sand fly saliva generally enhances infectivity of Leishmania parasites in a naive host while an adaptive immune response to whole saliva or a distinct salivary protein generally protects against both cutaneous and visceral leishmaniasis in rodent models of infection. In the proposed work, three sites in West Africa each with distinct epidemiological and ecological environment will be compared with regard to intensity and prevalence of cutaneous leishmania infection, sand fly vector population dynamics, and disease pathogenesis with a focus on parasite and host factors and the immune response to candidate vaccines (sand fly proteins in particular). This project seeks to 1] Determine the prevalence/incidence (of infection and disease) of CL and characterize the Leishmania parasites circulating in Malian and Ghanaian classical and cryptic foci of CL; 2] Correlate specific human immune responses to sand fly salivary proteins with CL outcome. In the Aim 1 we will possibly characterize new species of Leishmania parasites from a site where the infected individuals presented with asymptomatic CL and compare it to a classical CL focus. We will also in Aim 2, for the first time, establish if sand fly salivary cellular immunity can influece the CL outcome in endemic populations. RELEVANCE: This project is at the center of the entire proposal because it will assess the relationship between human exposure to sand fly vector bite (Project 2), the parasite and immune response to sand fly salivary proteins (Project 3) and the disease. Understanding of these relationship is important for vaccine development and field trials of control strategies.

描述（由申请人提供）：皮肤利什曼病（CL）在西非有很长的历史，但是该地区知名度不佳的寄生虫感染之一。该疾病是北部地区的地方性撒哈拉沙漠国家，从西到东非。目前，没有针对疾病的疫苗。然而，研究一直表明，沙蝇唾液通常会增强幼稚宿主中利什曼原虫的感染性，而对整个唾液或独特的唾液蛋白的适应性免疫反应通常可以预防啮齿动物感染模型中皮肤和内脏利什曼病。在拟议的工作中，在西非的3个地点将与皮肤利什曼原虫感染的强度和患病率，沙蝇载体种群动态和疾病发病机理相比，将进行不同的流行病学和生态环境，并将重点放在寄生虫和宿主因素和宿主因素以及对候选疫苗的免疫反应（尤其是沙蝇蛋白）上。该提案的基本假设是，寄生虫，载体和人类暴露于其他寄生虫感染（例如用微丝菌感染）确定候选疫苗的免疫调节作用，特别是沙蝇蛋白。该提案寻求1]了解皮肤利什曼病及其在西非不同焦点的载体的基本流行病学； 2]了解抗疾病的抗药性/敏感性的机制； 3]评估微丝菌的主动感染如何改变人类对沙蝇唾液蛋白的免疫反应，4]增强了未来疫苗试验的局部研究能力。 相关性：该提案与公共卫生直接相关，因为利什曼病在全球范围内造成巨大损失。它的目标是检查流行病学，皮肤利什曼病的传播以及在很大程度上被忽略的成分：沙蝇蛋白的免疫调节。 项目1：皮肤利什曼病的流行病学 项目负责人：医学博士Ousmane Faye （申请人提供的描述）：利什曼病是一种媒介传播的疾病，该疾病是通过感染的利什曼原虫感染的静脉鼻蝇传播给宿主的。皮肤利什曼病（CL）在西非有悠久的历史，但是该地区知名的寄生虫感染之一。研究一直表明，沙蝇在天真的宿主中通常会增强利什曼原虫的感染性，而对整个唾液的适应性免疫反应或不同唾液蛋白通常可以预防啮齿动物感染模型中的皮肤和内脏利什曼病。在拟议的工作中，将在西非的三个地点与皮肤利什曼原虫感染的强度和患病率，沙蝇载体种群动力学以及疾病发病机理的强度和患病率进行比较，并侧重于寄生虫和宿主因素，以及对候选疫苗的免疫反应（尤其是沙蝇蛋白）。该项目寻求1]确定CL的患病率/发病率（感染和疾病的发生率/发病率），并表征了CL的马利亚和加纳古典和隐性灶中循环的利什曼原虫寄生虫； 2]将特定的人类免疫反应与CL结果相关联。在目标1中，我们可能会从一个寄生虫中表征新的利什曼原虫寄生虫，在该地点被感染的个体出现了无症状的CL并将其与经典的CL焦点进行比较。我们还将在AIM 2中首次确定Sand Fly唾液细胞免疫是否可以影响流行种群的CL结果。 相关性：该项目是整个提案的核心，因为它将评估人类接触沙蝇矢量咬合（项目2），寄生虫和对沙蝇唾液唾液蛋白（项目3）的免疫反应与疾病之间的关系。了解这些关系对于控制策略的疫苗开发和现场试验很重要。