Visceral Leishmaniasis in Bihar State, India

描述（由申请人提供）：内脏利什曼病（VL）仍然是印度的主要健康问题。为了了解VL的复杂发病机制，TMRC研究了流行病学，免疫学和疾病遗传学中的关键问题。我们开发了长期研究活动所需的资源、基础设施和人力。我们实现了所有3个项目的主要目标，获得了有趣的成果，这些成果大多已被带到相关领域的科学界。在TRMC II中，我们希望以TMRC I的结果为基础，更好地了解人类宿主/病原体关系的演变。因此，屯门公路资源中心第二期分为四个主要项目和四个核心设施。项目1将研究疾病进展的决定因素和潜伏感染在传播中的作用，并将研究无症状感染者在临床和公共卫生层面的作用。通过产生这些证据，我们希望能够为控制计划以及临床决策提供信息，以减少流行地区的疾病传播。我们还将研究其他NTD在VL合并感染中的作用。项目2是对白蛉病媒的研究，以改进目前病媒控制工作的不足。该项目将测试一些假设，挑战与比哈尔邦的VL白蛉媒介P. argentipes相关的现行惯例。VL免疫调节项目3将继续开展工作，旨在了解导致未经治疗的VL严重进展和致命结局的免疫抑制途径。在TMRC I中，我们证明了活性VL的全血具有产生抗原特异性IFNg和IL-10的能力，其在防止寄生虫杀死中具有生物活性。我们想知道如何破坏IL-10的活性。项目4将携带TMRC I进行的GWAS的主要发现，以确定HLA II类分子的分子和细胞作用，这将对治疗干预和疫苗设计产生重大影响。除了这些项目外，还将有一个科学和行政核心A;一个数据管理和生物统计核心B;一个人口监测系统（DSS）核心C，分两个阶段覆盖Muzaffarpur的125 000多人;以及一个分子分型和诊断核心D。

DESCRIPTION (provided by applicant): Visceral leishmaniasis (VL) remains a major health problem in India. To understand the complex pathogenesis of VL, TMRC examined key questions in epidemiology, immunology and genetics of disease. We developed the resources, infrastructure and manpower necessary for long term research activities. We achieved the major objectives of all 3 projects, obtaining interesting results that have mostly been brought to the scientific community working in related fields. In TRMC II we want to build on the results of TMRC I, to gain greater understanding of the evolution of the human host/pathogen relationship. TMRC II has therefore been divided into 4 major projects with 4 core facilities. Project 1 will be on the determinants of disease progression and role of latent infection in transmission and will study the role of asymptomatic infection in VL at clinical and public health levels. By generating this evidence we expect to be able to inform control programs, as well as clinical decision-making, to decrease spread of disease in the endemic region. We will also be investigating the role of other NTDs in coinfection with VL. Project 2 constitutes studies of the sand fly vector to improve currently inadequate vector control efforts. This project will test a number of hypotheses, challenging current conventions related to the sand fly vector of VL in Bihar, P. argentipes. Project 3 on immune regulation in VL will continue work aimed at understanding the ever evading immunosuppressive pathways that account for severe progression and fatal outcome of untreated VL. In TMRC I, we demonstrated that whole blood of active VL has the capacity to produce antigen specific IFNg and IL-10, which is biologically active in preventing parasite killing. We want to learn how to subvert the activity of IL-10. Project 4 will carry forwad major findings from a GWAS undertaken in TMRC I to determine the molecular and cellular action of HLA class II molecules, which will have major implications for therapeutic intervention and vaccine design. In addition to these projects, there will be a Scientific and Administrative Core A; a Data Management and Biostatistics Core B; a Demographic Surveillance System (DSS) Core C covering over 125,000 people in Muzaffarpur in 2 phases; and a Molecular Typing and Diagnostics Core D.