Tropical Medicine Research Center for Talaromycosis in Vietnam

摘要 马尔尼菲霉菌病是一种侵袭性真菌病，由马尔尼菲塔拉霉菌引起。 东南亚。感染会导致免疫系统受损的感染者中有三分之一死亡。尽管 在一个占世界人口一半的地区，高发病率和高死亡率，基础知识 缺乏疾病负担和蓄水池。目前的诊断依赖于十年前的文化方法，而这种方法缺乏 这种病毒很敏感，需要14天才能确诊，导致治疗延误和更高的死亡率。在过去的几年里 十年来，我们在越南的距菌病研究项目为我们了解 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 和东南亚，并拥有一系列新的非文化诊断方法，以改进诊断模式和 关于疾病传播和人类传播的知识。我们相信我们处于最有利的位置来领导 塔拉霉病热带医学研究中心通过研究和能力的综合计划 发展。我们提出了以下具体目标： 目的1.确定实时定量聚合酶链式反应和4种新的抗原检测方法的诊断准确性 发育后期的快速诊断距菌病的检测方法。在这里，我们将利用 血液、血清、尿液样本采集自美国国立卫生研究院资助的距菌病队列(35HN，N=1,400)至 比较5种非培养快速诊断方法的诊断性能。 目的2.确定区别于距菌病的不同宿主转录特征。 其他机会性感染。在这里，我们将利用在PAX基因管中收集的全血样本 35HN距菌病队列以确定将距菌病与其他疾病区分开来的转录特征 孔虫性感染。我们的目标是确定一组独有的距菌病基因，这种基因可以发展成一种 护理点诊断测试。 目的3.确定人类疾病和空气传播暴露之间的流行病学联系 TM可能导致人类的原发肺部感染。在这里，我们将进行一次综合的 基于社区的血清阳性率和空气采样研究和比较从空气中分离的TM的负担 300名高危高原省份成年人和300名低危省份成年人血液中TM-Ig G 低地省份。在每个地理小组中，我们将招募150名患有呼吸系统疾病的成年人和150名没有呼吸道疾病的成年人 通过检测TM IgM和Tm来确定TM是否有可能导致原发肺部感染 登记时和血清转换时的免疫球蛋白水平。 影响声明。这些研究的目的是验证多种非培养诊断距菌病，并开发 它们的临床和公共卫生应用途径。基于社区的血清阳性率与空气采样 研究有可能促进我们对疾病宿主和空气传播的了解 人类。这些知识将为个人和人口层面的疾病控制提供信息。

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.