Objective Metagenomic next‐generation sequencing (mNGS) has emerged as a promising tool for identifying rare fungal pathogens. This study evaluates the clinical utility of mNGS for the timely diagnosis of Talaromyces marneffei (TM) infection in patients with diverse immune statuses, particularly focusing on its diagnostic performance in culture‐negative patients. Methods We retrospectively reviewed 14 patients diagnosed with TM infection at Taizhou Hospital between 2013 and 2024. A synchronous control group of 30 patients with non‐TM respiratory infections was included (1:2 ratio) to establish a background threshold and evaluate specificity. Pathogen detection rates and clinical profiles were compared between mNGS and conventional culture methods. Results Among the 14 infected patients (50% HIV‐positive), mNGS achieved a 100% detection rate (14/14) across blood, sputum, and bronchoalveolar lavage fluid (BALF) specimens. Notably, in a sensitivity analysis of the 11 culture‐confirmed cases, mNGS also demonstrated 100% sensitivity. In contrast, conventional culture positivity was significantly lower, ranging from 7.14% in sputum to 37.50% in BALF. Zero TM‐specific reads were detected in the 30‐patient control group, suggesting high diagnostic specificity within this study cohort and establishing a zero‐background baseline. Subgroup analysis revealed that culture‐negative but mNGS‐positive patients ( n = 3) had significantly higher CD4 + T‐cell counts than culture‐positive patients (450.50 ± 195.87 µL vs. 51.38 ± 122.38 µL, p < 0.05), suggesting that mNGS is especially valuable in patients with preserved immune function. Conclusion In this exploratory cohort, our findings suggest that mNGS is a powerful diagnostic tool for TM infection, particularly in hosts where low fungal burden or relatively preserved immunity limits the yield of traditional cultures. Incorporating mNGS into the diagnostic armamentarium can facilitate early intervention and improve outcomes for this life‐threatening infection.
Chen et al. (Thu,) studied this question.