Clinical Spectrum of Talaromyces marneffei Infections in HIV-Negative Patients: An 18-Case Series Including a Rare Presentation with Gastrointestinal Onset, Adrenal Mass, and Hemophagocytic Lymphohistiocytosis

Background : The diverse manifestations of Talaromyces marneffei (TM) infection in HIV-negative patients complicate and often delay diagnosis. This study reviews 18 cases to better characterize the clinical spectrum of this disease, with the goal of improving recognition of its varied presentations. Methods : Retrospective analysis of 18 patients assessing underlying diseases, manifestations, co-infections, diagnostics, treatment, and outcomes. Diagnosis required TM positivity via culture, histopathology, or metagenomic next-generation sequencing(mNGS). Results : This cohort (14 males and 4 females; mean age 57.94±11.12years) exhibited diverse comorbidities, including renal transplantation (27.8%), tuberculosis (22.2%), cancer (16.7%), bronchiectasis (16.7%), and anti-interferon-γ autoantibody (AIGA) syndrome (11.1%). Common manifestations included respiratory symptoms (72.2%), fever (55.6%), and anemia (50.0%). Immunodeficiency was frequent, with an abnormal CD4/CD8 ratio in in 10/15 patients (66.7%). Notably, 94.4% of cases were initially misdiagnosed—often as tuberculosis (35.3%) or bacterial pneumonia (23.5%)—leading to a mean diagnostic delay of 8.97±7.02 weeks. mNGS provided diagnosis in 77.8% of cases. Overall mortality was 22.2%, with two relapses linked to AIGA syndrome. We report the first documented TM triad in a patient with systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) coinfection: concurrent gastrointestinal onset (manifesting as ileocolonic ulcers), adrenal mass, and hemophagocytic lymphohistiocytosis (HLH). Conclusions : TM infection in HIV-negative hosts demonstrates broad clinical heterogeneity, often masked by comorbidities and leading to delayed diagnosis. mNGS is critical for early identification. The unprecedented triad of gastrointestinal onset, adrenal mass, and HLH underscores TM’s capacity for atypical dissemination. AIGA may predict relapse.