Tropical Medicine Research Center for Talaromycosis in Vietnam

越南踝部真菌病热带医学研究中心

• 批准号: 10598580
• 负责人: Thuy Le
• 金额: $ 49.9万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598580
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Adult; Air; Amphotericin B; Antigens; Asia; Biological Assay; Blood; Blood specimen; Cause of Death; Cessation of life; China; Clinical; Communities; Country; Cryptococcosis; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Management; Disease Reservoirs; Early Diagnosis; Epidemiology; Exposure to; Foundations; Funding; Gene Expression Profile; Genes; Genetic Transcription; Geography; Goals; HIV; Hot Spot; Human; Iatrogenesis; Immigration; Immune response; Immune system; Immunoglobulin G; Immunoglobulin M; Immunosuppression; Incidence; Individual; Infection; International; Itraconazole; Knowledge; Lead; Link; Lung infections; Methods; Modality; Morbidity - disease rate; Neoadjuvant Therapy; Opportunistic Infections; Pathway interactions; Patient-Focused Outcomes; Patients; Performance; Persons; Population; Positioning Attribute; Predictive Value; Prevalence; Province; Public Health Applications Research; Research; Residencies; Respiratory Signs and Symptoms; Respiratory Tract Infections; Risk; Sampling; Sampling Studies; Seroprevalences; Southeastern Asia; Specificity; Talaromyces; Testing; Thailand; Time; Transcript; Travel; Tropical Medicine; Tube; Tuberculosis; United States National Institutes of Health; Urine; Vietnam; Whole Blood; air sampling; antigen detection; biobank; burden of illness; cohort; data quality; design; detection assay; diagnostic accuracy; differential expression; disease transmission; disorder control; disorder prevention; epidemiology study; feature selection; fungus; high risk; human disease; improved; innovation; mortality; novel; point-of-care diagnostics; programs; prospective; randomized trial; rapid diagnosis; rapid test; recruit; screening; seroconversion; transcriptome sequencing; transcriptomics; transmission process; treatment guidelines

ABSTRACT Talaromycosis is an invasive mycosis caused by a dimorphic fungus Talaromyces marneffei that is endemic in Southeast Asia. Infection kills one in three infected people with a compromised immune system. Despite the high morbidity and mortality in a region encompassing half of the world population, fundamental knowledge of disease burden and reservoir are lacking. Current diagnosis relies on decade-old culture methods which lacks sensitivity and takes 14 days for identification, leading to treatment delays and higher mortality. Over the last decade our talaromycosis research program in Vietnam has made landmark contributions to our knowledge of epidemiology, diagnosis, and treatment. We have established an extensive network of collaborators in Vietnam and in Southeast Asia and have a pipeline of novel non-culture diagnostics to advance diagnostic modalities and knowledge of disease reservoir and transmission to humans. We believe we are in the best position to lead a Tropical Medicine Research Center in Talaromycosis through an integrated program of research and capacity development. We propose the following specific aims: AIM 1. To determine the diagnostic accuracy of a real-time PCR assay and 4 novel antigen detection assays in late stage of development for rapid diagnosis of talaromycosis. Here we will leverage whole blood, sera, urine samples collected from an ongoing NIH-funded talaromycosis cohort (35HN, N=1,400) to compare diagnostic performance of 5 non-culture assays for rapid diagnosis. AIM 2. To determine the differential host transcriptomic signatures that differentiate talaromycosis from other opportunistic infections. Here we will leverage whole blood samples collected in PAXgene tubes from the 35HN talaromycosis cohort to identify transcriptional signatures that differentiate talaromycosis from other oportunistic infections. Our goal is to identify a gene set unique to talaromycosis that can be developed into a point-of-care diagnostic test. AIM 3. To determine the epidemiological link between human disease and airborne exposure and the potential for Tm to cause a primary pulmonary infection in humans. Here, we will conduct an integrated community-based seroprevalence and air sampling study and compare the burden of Tm isolated from the air and Tm IgG in the blood of 300 adults living in high-risk highland provinces and 300 adults living in low-risk lowland provinces. In each geographic group, we will recruit 150 adults with and 150 without respiratory symptoms to determine the potential for Tm to cause a primary pulmonary infection by testing for Tm IgM and IgG levels at enrolment and at time of seroconversion. Impact statement. These studies aim to validate multiple non-culture diagnostics for talaromycosis and develop pathways for their clinical and public health applications. The community-based seroprevalence and air sampling studies have the potential to advance our understanding of disease reservoir and airborne transmission to humans. This knowledge will inform disease control at the individual and the population levels.

抽象的 tal骨菌病是由二态真菌Marneffei引起的一种侵入性真菌病，它是特有的 东南亚。感染杀死了三分之一的感染免疫系统的感染者。尽管有 在一个涵盖世界一半人口的地区的高发病和死亡率，对 缺乏疾病负担和水库。当前的诊断依赖于缺乏十年历史的培养方法 敏感性，需要14天才能识别，导致治疗延迟和更高的死亡率。最后 十年我们在越南的talomomycosis研究计划为我们的知识做出了里程碑意义的贡献 流行病学，诊断和治疗。我们已经在越南建立了广泛的合作者网络 在东南亚，并有一条新型的非文化诊断渠道，以提高诊断方式和 了解疾病储藏和向人类传播的知识。我们相信我们处于领导A的最佳位置 通过研究和能力的综合计划 发展。我们提出以下具体目标： 目标1。确定实时PCR测定和4个新型抗原检测的诊断精度 在开发后期的测定中，用于快速诊断tal骨菌病。在这里，我们将利用整个 血液，血清，尿液样品从正在进行的NIH资金资助的塔拉米病毒队列（35HN，n = 1,400）中收集到 比较5种非文化测定法以快速诊断的诊断性能。 目的2。确定区分塔骨霉素与 其他机会性感染。在这里，我们将利用从Paxgene管中收集的全血样品 35HN的talomomycosis队列，以识别将塔骨霉素与其他区分开的转录特征 oportunistic感染。我们的目标是确定可以发展为塔菌病独有的基因集，该基因可以发展为 护理点诊断测试。 目的3。确定人类疾病与空中暴露与空中疾病之间的流行病学联系 TM在人类中引起原发肺部感染的潜力。在这里，我们将进行集成 基于社区的血清阳性和空气采样研究，并比较了从空中隔离的TM负担 和居住在高风险高地省的300名成年人的血液中的TM IgG和300名居住在低风险中的成年人 低地省。在每个地理组中，我们将招募150名没有呼吸道的成年人和150名成年人 通过测试TM IgM和 注册时和血清转化时的IgG水平。 影响声明。这些研究旨在验证多种非文化诊断症的talomycomisosis并发展 其临床和公共卫生应用的途径。基于社区的血清阳性和空气采样 研究有可能提高我们对疾病储层和空中传播的理解 人类。这些知识将为个体和人口水平的疾病控制提供信息。