Superiority of a novel Mp1p antigen detection enzyme immunoassay compared to standard BACTEC blood culture in the diagnosis of talaromycosis.
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BACKGROUND:Talaromycosis is an invasive mycosis endemic in Southeast Asia and causes substantial morbidity and mortality in individuals with advanced HIV disease. Current diagnosis relies on isolating Talaromyces marneffei in cultures, which takes up to 14 days and is detectable only during late-stage infection, leading to high mortality. METHODS:In this retrospective case-control study, we assessed the accuracy of a novel Mp1p antigen-detecting enzyme immunoassay (EIA) in stored plasma samples of 372 patients who had culture-proven talaromycosis from blood or sterile body fluids(reference standard) and of 517 individuals without talaromycosis (338 healthy volunteers; 179 with other infections). All participants were recruited between 2011-2017 in Vietnam. RESULTS:66.1% and 75.4% of cases and controls were male; the median age was 33 and 37, respectively. All cases were HIV-infected; median CD4 count was 10 cells/mm3. At an optical density cut-off of 0.5, the specificity was 98.1% (95% CI: 96.3%-99.0%); the sensitivity was superior to blood culture, 86.3% (95% CI: 82.3%-89.5%) versus 72.8% (95% CI: 68.0%-77.2%), P<0.001, McNemar test. The time-to-diagnosis was 6 hours versus 6.6 ± 3.0 days for blood culture. Paired plasma and urine testing in the same patients (N=269) significantly increased sensitivity compared to testing plasma alone P<0.001, or testing urine alone P=0.02, McNemar tests. CONCLUSIONS:The Mp1p EIA is highly specific and is superior in sensitivity and time-to-diagnosis compared to blood culture for the diagnosis of talaromycosis. Paired plasma and urine testing further increases sensitivity, introducing a new tool for rapid diagnosis, enabling early treatment and potentially reducing mortality.
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Thu, Nguyen TM, Jasper FW Chan, Vo Trieu Ly, Hoa T Ngo, Ha TA Hien, Nguyen PH Lan, Nguyen VV Chau, Jian-Piao Cai, et al. (2020). Superiority of a novel Mp1p antigen detection enzyme immunoassay compared to standard BACTEC blood culture in the diagnosis of talaromycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 10.1093/cid/ciaa826 Retrieved from https://hdl.handle.net/10161/21279.
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Research in my laboratory focuses around several aspects of medical mycology. We are investigating antifungal agents (new and old) in animal models of candida and cryptococcal infections. We have examined clinical correlation of in vitro antifungal susceptibility testing and with in vivo outcome. Our basic science project examines the molecular pathogenesis of cryptococcal infections. We have developed a molecular foundation for C. neoformans, including transformation systems, gene disruptions, differential gene expression screens, and cloning pathogenesis genes. The goal of this work is to use C. neoformans as a model yeast system to identify molecular targets for antifungal drug development. There are a series of clinical trials in fungal infections which are being coordinated through this laboratory and my work also includes a series of antibiotic trials in various aspects of infections. Finally, we have now been awarded a NIH sponsored Mycology Unit for 5 years with 6 senior investigators which is focused on C. neoformans as a pathogenic model system, but will include multiple areas of medical mycology from diagnosis to treatment.
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