Superiority of a novel Mp1p antigen detection enzyme immunoassay compared to standard BACTEC blood culture in the diagnosis of talaromycosis

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.