Mp1p antigen as a sensitive diagnostic marker for early detection and treatment monitoring of Talaromyces Marneffei infection

Talaromyces marneffei (TM) is a life-threatening opportunistic fungal pathogen, particularly in individuals with advanced HIV/AIDS. Early and accurate diagnosis remains challenging due to the limited sensitivity and specificity of conventional microbiological and antigen-based tests. Mp1p, a secreted TM-specific virulence protein, has emerged as a promising target for serological diagnosis. This study aimed to evaluate the diagnostic performance of Mp1p antigen and antibody detection using ELISA in sera from HIV infected patients with confirmed TM infection. A total of 36 confirmed TM-infected patients (including fungemia and non-fungemia cases), 269 HIV/AIDS patients with fever but without TM infection, 37 cryptococcosis patients, and 218 healthy blood donors were enrolled from two tertiary hospitals in China (2020–2024). Recombinant Mp1p protein was expressed and purified to develop Mp1p antigen and antibody ELISAs. Diagnostic sensitivity and specificity were calculated. Serial samples before and after antifungal therapy were evaluated to determine the utility of Mp1p antigen and antibody levels in treatment monitoring and recurrence detection. Results were compared with established diagnostic tools, including galactomannan (GM) and cryptococcal antigen (CrAg) assays. Mp1p antigen ELISA demonstrated high sensitivity (94.4%) and specificity (98.5%) for TM infection. In contrast, Mp1p antibody ELISA had lower sensitivity (25.0%) but equally high specificity (98.5%). Mp1p antigen levels significantly declined after amphotericin B (AMB) treatment (mean OD₄₅₀: 1.654 ± 0.723 pre-treatment vs. 0.355 ± 0.488 post-treatment; p < 0.0001), supporting its role in treatment monitoring. Antigen levels were significantly higher in fungemic versus non-fungemic patients (p = 0.001). Among initially antibody-negative patients, 56.3% seroconverted within one year, suggesting delayed antibody response. Mp1p antigen levels rebounded in one relapsed patients before clinical deterioration, while antibody levels did not change, highlighting the antigen's potential for early relapse detection. Mp1p antigen ELISA is a highly sensitive and specific tool for early diagnosis and therapeutic monitoring ofTM infection in HIV-infected patients. Its performance exceeds current serological assays and is especially valuable in identifying fungemia and potential relapse. In contrast, Mp1p antibody detection is limited in early-stage diagnosis due to delayed seroconversion. Incorporating Mp1p antigen testing into clinical workflows may significantly improve patient outcomes through earlier intervention. 1.Mp1p antigen ELISA shows 94.4% sensitivity and 98.5% specificity for TM infection. 2.Antigen levels decline after treatment, supporting use in therapeutic monitoring. 3.Higher Mp1p antigen levels are associated with fungemia in TM infection patients. 4.Antibody response is delayed, limiting its early diagnostic utility. 5.Mp1p antigen rebound may indicate relapse before clinical symptoms appear.