Tropical Medicine Research Center for Talaromycosis in Vietnam

点击翻译按钮获取中文摘要

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.