Visceral Leishmanasis in Bihar State, Indian

印度比哈尔邦的内脏利什曼病

• 批准号: 7673885
• 负责人: SHYAM SUNDAR
• 金额: $ 71.86万
• 依托单位: BANARAS HINDU UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673885
• 关键词: Visceral; Leishmanasis; Bihar; State; Indian

DESCRIPTION (provided by applicant): There has been a recent expansion in the distribution and the incidence of leishmaniasis. Visceral leishmaniasis is particularly troublesome as it causes most fatalities. India, Nepal, Bangladesh, Sudan and Brazil harbor 90% of the worldwide reported VL cases. Amongst the millions at risk in India, the state of Bihar accounts for nearly 90% of cases, followed by the states of West Bengal, Jharkhand and Eastern Uttar Pradesh. This proposed Tropical Medicine Research Center is divided into 3 projects that will address epidemiological, clinical, immunological and genetic factors that influence the prevalence, distribution and pathogenesis of visceral leishmaniasis in individuals and communities in Bihar State in India. The individual projects that make up this TMRC are also designed to provide new data that will be more broadly applicable to the continuing development of control programs in the other major global foci of disease, including development of novel vaccines and diagnostic aids. Themes of the three major projects are: Project 1: Clinical and epidemiological studies of Visceral Leishmaniasis in Bihar, India: Goals of this project are to provide the epidemiological and clinical evidence that is required to guide efforts to eliminate or control visceral leishmaniasis in the state of Bihar, India, and to provide epidemiological data that will more broadly inform future control programs including development of novel vaccines and diagnostic aids. Project 2: The role of regulatory T cell subsets and cytokines in the pathogenesis of human VL in Bihar, India. This project is a focused study that will investigate the role of regulatory T cells and suppressive cytokines in the pathogenesis of human visceral leishmaniasis, with a view toward the development of immune-based therapies that will reverse the immunosuppression associated with active disease. Project 3: Genetic risk factors for Visceral Leishmaniasis in Bihar, India. This project will address genetic factors that underly genetic susceptibility to visceral leishmaniasis, with the purpose of identifying genes/ mechanisms/ pathways that contribute to the pathogenesis of disease. The TMRC will bring together a unique combination of epidemiologists, clinicians, immunologists and molecular geneticists to tackle the problem of visceral leishmaniasis in one of the major global foci of this fatal disease. PROJECT 1: Clinical and epidemiological studies of Visceral Leishmaniasis in Bihar, India (Singh, S. P.) PROJECT 1 DESCRIPTION (provided by applicant): Lay statement: Visceral leishmaniasis (VL) is a parasitic disease that is fatal if untreated. Several hundred thousand people are affected in the Indian subcontinent. Most are poor and depend on public funds or charity for treatment. Disease control is based on early diagnosis and treatment, and control of sandflies that transmit disease. Control efforts to date have given only temporary reprieve, with periodic rebound of major epidemics. This is because there are gaps in our understanding of the dynamics of disease transmission. This study is designed to identify these factors, and to evaluate novel diagnostics and vaccine candidates that have arisen through genomic sequencing of the parasite. The study will provide new knowledge and tools to allow regional governments to achieve their aim of disease control by 2015. Project description: VL in India is patchy in distribution. The determinants of disease transmission at a village and household level are not well understood. Subclinical infection is thought to play a significant role in disease transmission, but markers of subclinical infection have yet to be validated. We don't fully understand why only a small proportion of infected subjects develop clinical disease. To gain a better understanding of disease dynamics and transmission, this study will undertake (1) an exhaustive population survey of 50,000 persons for two consecutive years using household interviews, CIS technology, remote sensing data and multi-level modelling, to identify the ecological risk markers that will permit better targeting of control interventions; (2) a nested case control study to document the modifiable risk factors (e.g. nutritional) and risk markers (clinical, genetic, immunological) for VL at household and individual level, with two annual rounds of sero-survey allowing us to document incident leishmanial infections, and a 3-year longitudinal follow-up to document development of full blown VL; (3) evaluation of existing (rK39 ELISA, Direct Agglutination Test, LST) markers of infection against standard Western blot and qualitative kDNA PCR and new Quantiferon assays for T cell responses; (4) evaluation of novel (Leishmania donovanicomplex specific genes) markers using qualitative and quantitative PCR, ELISA and T-cell assays; and (5) immune profiling of novel vaccine candidate in patients and endemic controls. The results will inform policy and practice for disease control in the Indian sub-continent, and add to global understanding of VL disease.

描述（由申请人提供）：最近利什曼病的分布和发病率有所扩大。内脏利什曼病是特别麻烦，因为它导致大多数死亡。印度、尼泊尔、孟加拉国、苏丹和巴西的VL病例占全球报告病例的90%。在印度数百万处于危险之中的人中，比哈尔邦占近90%的病例，其次是西孟加拉、贾坎德和东部北方邦。这个拟议的热带医学研究中心分为3个项目，将解决影响内脏利什曼病在印度比哈尔邦的个人和社区的流行病学，临床，免疫学和遗传因素。构成该TMRC的各个项目还旨在提供新的数据，这些数据将更广泛地适用于全球其他主要疾病疫源地控制计划的持续发展，包括开发新型疫苗和诊断辅助工具。三个主要项目的主题是：项目1：印度比哈尔邦内脏利什曼病的临床和流行病学研究：该项目的目标是提供流行病学和临床证据，以指导在印度比哈尔邦消除或控制内脏利什曼病的努力，并提供流行病学数据，为未来的控制计划提供更广泛的信息，包括开发新疫苗和诊断辅助工具。项目2：调节性T细胞亚群和细胞因子在印度比哈尔邦人VL发病机制中的作用。该项目是一项重点研究，将调查调节性T细胞和抑制性细胞因子在人类内脏利什曼病发病机制中的作用，以期开发基于免疫的疗法，逆转与活动性疾病相关的免疫抑制。项目3：印度比哈尔邦内脏利什曼病的遗传危险因素。本项目将探讨内脏利什曼病遗传易感性的遗传因素，目的是确定基因/机制/途径 导致疾病的发病机制。TMRC将汇集一个独特的组合， 流行病学家，临床医生，免疫学家和分子遗传学家，以解决内脏的问题， 利什曼病是这一致命疾病的主要全球疫源地之一。 项目1：印度比哈尔邦内脏利什曼病的临床和流行病学研究（Singh，S.第页） 项目1描述（由申请人提供）：非专业人士声明：内脏利什曼病（VL）是一种寄生虫病，如果不治疗会致命。印度次大陆有数十万人受到影响。大多数人很穷，依靠公共基金或慈善机构治疗。疾病控制的基础是早期诊断和治疗，以及控制传播疾病的白蛉。迄今为止的控制努力只是暂时缓解，主要流行病周期性反弹。这是因为我们对疾病传播动力学的理解存在差距。这项研究旨在确定这些因素，并评估通过寄生虫基因组测序产生的新诊断和候选疫苗。这项研究将提供新的知识和工具，使区域政府能够在2015年前实现疾病控制的目标。 项目简介：VL在印度的分布不均匀。在村庄和家庭一级，疾病传播的决定因素还没有得到很好的理解。亚临床感染被认为在疾病传播中起重要作用，但亚临床感染的标志物尚未得到验证。我们不完全理解为什么只有一小部分受感染的受试者发展为临床疾病。为了更好地了解疾病的动态和传播情况，这项研究将：（1）利用家庭访谈、CIS技术、遥感数据和多层次模型，连续两年对50，000人进行详尽的人口调查，以确定生态风险标志，从而能够更好地确定控制干预措施的目标;（2）巢式病例对照研究，以记录可改变的风险因素（如营养）和风险标志（临床，遗传，免疫学）在家庭和个人水平的VL，每年两轮血清调查，使我们能够记录事件利什曼原虫感染，和3年纵向随访，以记录完全成熟的VL的发展;（3）评估现有的（rK 39 ELISA，直接凝集试验，LST）针对标准蛋白质印迹和定性kDNA PCR的感染标志物和用于T细胞应答的新Quantiferon测定;（4）使用定性和定量PCR、ELISA和T细胞测定法评价新的（杜氏利什曼原虫复合体特异性基因）标记物;和（5）患者和地方病控制中新疫苗候选物的免疫谱。研究结果将为印度次大陆的疾病控制政策和实践提供信息，并增加全球对VL疾病的了解。