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: 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
• 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

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.

摘要 Talaromycosis是一种侵袭性真菌病，由马尔尼菲Talaromycesmarneffei引起， 东南亚感染导致三分之一的免疫系统受损的感染者死亡。尽管 占世界人口一半的区域发病率和死亡率高， 缺乏疾病负担和储存库。目前的诊断依赖于十年前的培养方法， 这一点非常敏感，需要14天的时间才能确定，导致治疗延误和死亡率上升。在过去 十年来，我们在越南的踝菌病研究计划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伙伴网络 和东南亚，并拥有一系列新型非文化诊断方法来推进诊断模式， 了解疾病储存库和向人类传播。我们相信，我们处于最佳位置， 热带医学研究中心在Talaromycosis通过研究和能力的综合方案 发展我们提出以下具体目标： AIM 1.确定实时PCR检测和4种新抗原检测的诊断准确性 快速诊断踝足真菌病的晚期试验。在这里，我们将利用整个 从正在进行的NIH资助的足癣菌病队列（35HN，N= 1，400）中采集血液、血清、尿液样本， 比较5种快速诊断非培养检测的诊断性能。 AIM 2.为了确定区分踝菌病和 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足癣菌病组群鉴定区分足癣菌病与其它足癣菌病转录特征 机会性感染我们的目标是确定一个基因集独特的足癣，可以发展成为一个 即时诊断测试 AIM 3.确定人类疾病与空气接触之间的流行病学联系， Tm可能导致人类原发性肺部感染。在这里，我们将进行一个综合的 以社区为基础的血清阳性率和空气采样研究，并比较从空气中分离的Tm的负担 300名生活在高风险高原省份的成年人和300名生活在低风险 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。 症状，通过检测Tm IgM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。 影响陈述。这些研究旨在验证踝菌病的多种非培养诊断方法， 临床和公共卫生应用的途径。以社区为基础的血清阳性率和空气采样 研究有可能促进我们对疾病储存库和空气传播的理解， 人类这一知识将为个人和人口层面的疾病控制提供信息。