Tropical Medicine Research Center for Talaromycosis in Vietnam

越南踝部真菌病热带医学研究中心

基本信息

批准号：
10444448
负责人：
Thuy Le
金额：
$ 52.9万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10444448
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 Gold HIV Hot Spot Human Iatrogenesis Immigration Immune response Immune system Immunoglobulin G Immunoglobulin M Immunosuppression Incidence Individual Infection International Investigation 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 Sensitivity and Specificity Seroprevalences Southeastern Asia Talaromyces Testing Thailand Time Transcript Travel Tropical Medicine Tube Tuberculosis United States National Institutes of Health Urine Vietnam Whole Blood air sampling antigen detection base biobank burden of illness cohort data quality design detection assay diagnostic accuracy differential expression disease transmission disorder control disorder prevention 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

项目摘要

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.

抽象的踝节菌病是一种由二形性真菌马尔尼菲踝节菌引起的侵袭性真菌病，该病在以下地区流行：东南亚。三分之一的免疫系统受损的感染者会因感染而死亡。尽管占世界人口一半的地区发病率和死亡率很高，缺乏疾病负担和储存库。目前的诊断依赖于已有十年历史的培养方法，缺乏敏感性，并且需要 14 天才能识别，导致治疗延误和更高的死亡率。过去的十年来，我们在越南的踝关节菌病研究项目为我们的知识做出了里程碑式的贡献流行病学、诊断和治疗。我们在越南建立了广泛的合作者网络在东南亚，并拥有一系列新型非文化诊断方法，以推进诊断模式和了解疾病储存库和向人类传播的知识。我们相信我们最有能力领导通过综合研究和能力计划建立踝部真菌病热带医学研究中心发展。我们提出以下具体目标：目的 1. 确定实时 PCR 检测和 4 种新抗原检测的诊断准确性开发后期用于快速诊断踝部真菌病的检测。在这里我们将利用整体从正在进行的 NIH 资助的踝部真菌病队列（35HN，N=1,400）收集血液、血清、尿液样本比较 5 种非培养测定的诊断性能以进行快速诊断。目的 2. 确定区分踝部真菌病的差异宿主转录组特征其他机会性感染。在这里，我们将利用 PAXgene 管中收集的全血样本 35HN 踝部真菌病队列，以确定区分踝部真菌病和其他疾病的转录特征机会性感染。我们的目标是确定踝部真菌病独有的基因组，该基因组可以发展为护理点诊断测试。目标 3. 确定人类疾病与空气传播暴露之间的流行病学联系以及 Tm 可能导致人类原发性肺部感染。在这里，我们将进行综合基于社区的血清流行率和空气采样研究并比较从空气中分离出的 Tm 负担居住在高风险高地省份的 300 名成年人和居住在低风险省份的 300 名成年人血液中的 Tm IgG 和 Tm IgG 低地省份。在每个地理组中，我们将招募 150 名患有呼吸道疾病的成年人和 150 名没有呼吸道疾病的成年人通过检测 Tm IgM 和 Tm IgM 来确定 Tm 引起原发性肺部感染的可能性入组时和血清转换时的 IgG 水平。影响声明。这些研究旨在验证踝部真菌病的多种非培养诊断方法并开发其临床和公共卫生应用的途径。基于社区的血清流行率和空气采样研究有可能增进我们对疾病储存库和空气传播的了解人类。这些知识将为个人和群体层面的疾病控制提供信息。