Nguyen T M Thu1,2, Jasper F W Chan3,4, Vo Trieu Ly5,6, Hoa T Ngo1, Ha T A Hien1, Nguyen P H Lan5, Nguyen V V Chau5, Jian-Piao Cai3, Patrick C Y Woo3, Jeremy N Day1,7, Rogier van Doorn1,7, Guy Thwaites1,7, John Perfect2, K Y Yuen3,4, Thuy Le1,2. 1. Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam. 2. Division of Infectious Diseases and International Health, Duke University School of Medicine, Durham, NC, USA. 3. State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong. 4. Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, China. 5. Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam. 6. University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. 7. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK.
Abstract
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.
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.
Authors: R S Ying; T Le; W P Cai; Y R Li; C B Luo; Y Cao; C Y Wen; S G Wang; X Ou; W S Chen; S Z Chen; P L Guo; M Chen; Y Guo; X P Tang; L H Li Journal: HIV Med Date: 2020-12 Impact factor: 3.180
Authors: George R Thompson; David R Boulware; Nathan C Bahr; Cornelius J Clancy; Thomas S Harrison; Carol A Kauffman; Thuy Le; Marisa H Miceli; Eleftherios Mylonakis; M Hong Nguyen; Luis Ostrosky-Zeichner; Thomas F Patterson; John R Perfect; Andrej Spec; Dimitrios P Kontoyiannis; Peter G Pappas Journal: Open Forum Infect Dis Date: 2022-03-04 Impact factor: 4.423
Authors: Vo Trieu Ly; Nguyen Tat Thanh; Nguyen Thi Mai Thu; Jasper Chan; Jeremy N Day; John Perfect; Cao Ngoc Nga; Nguyen Van Vinh Chau; Thuy Le Journal: Open Forum Infect Dis Date: 2020-10-19 Impact factor: 3.835