mNGS for Talaromyces marneffei pulmonary infection in HIV-negative patients in Sichuan: a case series with narrative literature review

Increasing cases of Talaromyces marneffei (TM) infection have been documented among HIV-negative individuals. Conventional microbiological assays frequently yield false-negative results for TM identification, while metagenomic next-generation sequencing (mNGS) enables rapid pathogen detection. Recent large-scale summaries highlighted that HIV-negative TM infection is easily misdiagnosed owing to non-specific manifestations, and mNGS-positive results should be interpreted cautiously to distinguish true infection from colonization. Nevertheless, systematic real-world data based on bronchoalveolar lavage fluid (BALF)​-mNGS for TM-associated pulmonary infections remain scarce in Sichuan Province, China. Herein, we presented a single-center case series combined with a narrative literature review to characterize HIV-negative TM pulmonary infection. We retrospectively enrolled 10 HIV-negative patients with BALF-mNGS-confirmed TM pulmonary infection. Clinical profiles, conventional laboratory findings and mNGS results were systematically summarized. A narrative literature review was performed with reference to two recently published cohorts: the systematic NGS-based review by Woo et al. (2025) [1] and the non-endemic-area case series reported by Wu et al. [2]. Demographic, clinical, diagnostic and prognostic variables were compared across cohorts. All 10 patients were long-term residents of Sichuan Province; 70% were male with ages ranging from 27 to 79 years. Ninety-percent of patients harbored underlying cellular immunodeficiency. Cough with expectoration (100%) and fever (80%) were predominant symptoms, whereas characteristic cutaneous lesions were absent in all subjects. Chest CT mainly demonstrated patchy infiltrates, consolidation and pleural effusion (70%). BALF-mNGS achieved high diagnostic sensitivity for TM within a mean turnaround time of 24 h, and co-existing pathogens were uncovered in 90% of cases. By contrast, 7-day BALF culture and 24-hour serum BDG testing both yielded only a 20% positivity rate. Compared with published cohorts, our Sichuan cohort exhibited a markedly higher proportion of cellular immunodeficiency, which may partly explain the high co-pathogen rate and 20% poor-outcome proportion. Distinct from the non-endemic cohort reported by Wu et al., all mNGS-positive cases in our series were comprehensively adjudicated as active TM infection rather than colonization. Consistent with Woo et al., our findings reinforced the speed advantage of mNGS relative to time-consuming fungal culture. In Sichuan, HIV-negative patients with TM pulmonary infection predominantly present with respiratory symptoms without typical skin lesions and demonstrate a high rate of mixed co-pathogen infection. BALF-mNGS allows sensitive and rapid identification of TM as well as concurrent pathogens. Clinicians should always integrate mNGS outputs with clinical, radiological and therapeutic responses to differentiate active infection from colonization. For unexplained pulmonary infection in HIV-negative immunocompromised hosts in this region, BALF-mNGS can be recommended as a valuable diagnostic modality to mitigate misdiagnosis and therapeutic delay.