Visceral Leishmaniasis in Bihar State, India

印度比哈尔邦的内脏利什曼病

• 批准号: 8711197
• 负责人: SHYAM SUNDAR
• 金额: $ 63.16万
• 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 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8711197
• 关键词: Accounting; Affect; Alleles; Antigen-Presenting Cells; Antigens; Area; Aspirate substance; Behavior; Biological; Biostatistics Core; Bite; Blood Cells; Breeding; CD8B1 gene; Case-Control Studies; Cell Culture Techniques; Cell physiology; Cells; Clinical; Communities; Complex; Core Facility; Defect; Developing Countries; Development; Diagnostic; Disease; Disease Progression; Environmental Risk Factor; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epitopes; Evolution; Fatal Outcome; General Population; Genetic; Genetic Determinism; Genetic Polymorphism; Goals; Health; Helminths; Hereditary Disease; Household; Human; Human Resources; Immune; Immune response; Immunity; Immunologics; Immunology; Immunosuppression; Immunosuppressive Agents; Immunotherapeutic agent; India; Individual; Infection; Interleukin-10; International; Intervention; Laboratories; Learning; Leishmania; Leishmania donovani; Leishmaniasis; Mass Spectrum Analysis; Matched Case-Control Study; Measures; Messenger RNA; Methods; Molecular; Parasites; Pathogenesis; Pathway interactions; Patients; Peptides; Peripheral; Peripheral Blood Mononuclear Cell; Persons; Phase; Process; Production; Progressive Disease; Proteins; Public Health; Regulation; Regulatory T-Lymphocyte; Research; Research Activity; Research Infrastructure; Resources; Risk; Risk Factors; Role; Saliva; Sampling; Sand Flies; Series; Serological; Silicon Dioxide; Site; Spleen; Surveys; System; T-Lymphocyte; Technology; Testing; Therapeutic Intervention; Tissues; Tropical Disease; Vaccine Design; Vaccines; Visceral Leishmaniasis; Whole Blood; Work; Xenodiagnosis; base; case control; clinical decision-making; clinical research site; cytokine; data management; filaria; genetic risk factor; genome wide association study; improved; interest; killings; latent infection; neglect; pathogen; prevent; programs; research study; spatial temporal variation; therapeutic vaccine; transmission process; vector; vector control

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.

描述(由申请人提供)：内脏利什曼病(VL)在印度仍然是一个主要的健康问题。为了了解VL的复杂发病机制，TMRC研究了疾病的流行病学、免疫学和遗传学方面的关键问题。我们开发了长期研究活动所需的资源、基础设施和人力资源。我们实现了所有3个项目的主要目标，取得了令人感兴趣的成果，这些成果大多带给了从事相关领域工作的科学界。在TRMC II中，我们希望建立在TMRC I结果的基础上，以更好地了解人类宿主/病原体关系的进化。因此，屯门公路管理资源中心第二期工程分为4个主要项目和4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，并将在临床和公共卫生层面研究VL中无症状感染的作用。通过产生这些证据，我们期望能够为控制程序和临床决策提供信息，以减少疾病在流行地区的传播。我们还将调查其他NTD在VL合并感染中的作用。项目2包括对沙蝇媒介的研究，以改进目前不充分的媒介控制工作。该项目将测试一些假设，挑战目前与比哈尔邦银杏沙蝇媒介相关的惯例。关于VL免疫调节的项目3将继续开展工作，旨在了解导致未经治疗的VL严重进展和致命后果的免疫抑制途径。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，这在生物活性上具有防止寄生虫死亡的活性。我们想学习如何颠覆IL-10的活性。项目4将继承在TMRC I进行的GWA的主要发现，以确定人类白细胞抗原II类分子的分子和细胞作用，这将对治疗干预和疫苗设计具有重要意义。除这些项目外，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；一个人口监测系统核心C，分两个阶段覆盖穆扎法尔布尔超过125,000人；以及一个分子分类和诊断核心D。