Superiority of a Novel Mp1p Antigen Detection Enzyme Immunoassay Compared to Standard BACTEC Blood Culture in the Diagnosis of Talaromycosis

Abstract

Background: Talaromycosis is an invasive mycosis endemic in Southeast Asia and causes substantial morbidity and mortality in individuals with advanced human immunodeficiency virus (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 517 individuals without talaromycosis (338 healthy volunteers; 179 with other infections). All participants were recruited between 2011 and 2017 in Vietnam.

Results: Of cases and controls, 66.1% and 75.4%, respectively, were male; the median age was 33 and 37, respectively. All cases were HIV infected; median CD4 count was 10 cells/μL. At an optical density cutoff 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%] vs 72.8% [95% CI, 68.0%-77.2%]) (P < .001, McNemar test). The time to diagnosis was 6 hours vs 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 or testing urine alone (P < .001 and P = .02, respectively, McNemar test).

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.

Trial registration: ClinicalTrials.gov NCT04033120.

Keywords: Penicillium marneffei; Talaromyces marneffei; Mp1p enzyme immunoassay; penicilliosis; talaromycosis.

Figure 1.

The flowchart describes the selection of the study population. Cases included 372 patients from the Itraconazole Versus Amphotericin for Penicilliosis trial who had culture-proven talaromycosis and who had plasma samples drawn at the same time of the first blood culture collection. Controls included 517 participants: 338 healthy volunteers and 179 human immunodeficiency virus–uninfected patients hospitalized with a range of common infections at the Hospital for Tropical Diseases in Ho Chi Minh City. Abbreviations: FN, false negative; FP, false positive; HIV, human immunodeficiency virus; IVAP, Itraconazole Versus Amphotericin for Penicilliosis; TmAg, Talaromyces marneffei antigen; TN, true negative; TP, true positive.

Figure 2.

A, Optical density (OD) distribution of talaromycosis cases and non-talaromycosis controls; the difference in OD distribution was statistically significant. B, Receiver operating characteristic (ROC) curve demonstrated excellent discrimination (94.9% accuracy) between talaromycosis cases and non-talaromycosis controls. The OD cutoff of 0.5 was the Youden index calculated from the ROC curve, which maximizes true positives, minimizes false positives, and assumes equal importance of sensitivity and specificity. Abbreviations: AUC, area under the receiver operating characteristic curve; CI, confidence interval; OD, optical density.