In this study, we found that Mp1p antigen detection possesses a superior advantage in assisting in talaromycosis diagnosis in patients with AIDS within 3 days of admission, especially those with low CD4 + T cell counts (< 50 Nr/µL).
Culture and histopathology are recognised as the gold standard methods for talaromycosis diagnosis but are time-consuming and have insufficient sensitivity. The median time for identifying T. marneffei from blood cultures was 7 (5–9) days in our study, which is similar to the study finding by Le et al. . The time delay of culture and the difficulty of pathological detection make its rapid clinical diagnosis particularly difficult. PCR testing can help in the early diagnosis of talaromycosis, with a high specificity of 100%; however, it is expensive, with a low sensitivity of 70.4% before treatment . T. marneffei specific antibody detection showed a sensitivity of 25–95% and was strongly cross-reactive to other pathogens, which limited its clinical application . In recent years, an increasing number of studies have focused on the detection of T. marneffei specific antigens, including CYA, GM, and Mp1p. The sensitivity of these methods was 75–95%, and the specificity was 90–100%, indicating their potential for clinical application [9, 14, 16–18]. Mp1p is a type of mannoprotein on the T. marneffei cell wall and can be secreted into the blood after T. marneffei infection . It is a key virulence factor in T. marneffei and has been shown to be highly immunogenic [22, 23].
As shown in our study, the incidence of talaromycosis was higher in the young adult patients with AIDS (65.6% vs 45.8%, P = 0.002), and the incidence of symptoms, such as fever, cough, sputum, and rash, and abnormal laboratory test results was higher in the patients with talaromycosis than in those without. However, these markers do not have sufficient specificity for identifying talaromycosis in clinical practice. In our study, the positivity rate for rash, a specific indicator of talaromycosis, was < 40% in the patients with talaromycosis, which was insufficient to be used as a diagnostic indicator.
The positivity rate in the Mp1p assay in the patients with talaromycosis was similar to that in the blood culture (72% vs 81.7%, P = 0.122) in our study. It had a substantial agreement with the gold standard (kappa: 0.729), and the sensitivity, specificity, PPV, and NPV of Mp1p antigen detection were 72.0%, 96.8%, 91.8%, and 87.6%, respectively, which were generally superior to those of the GM assay. Several studies have been conducted to validate the efficiency of different serum diagnostic methods [9, 12, 14–17, 19]. Wang et al.  detected the Mp1p antigen and antibody in 20 serum specimens of patients with talaromycosis and 525 negative control specimens. They found that the sensitivity of Mp1p antigen ELISA was 75%, which was superior to that of the Mp1p antibody test (30%). Another similar study conducted in Vietnam reported that the Mp1p antigen test had an excellent sensitivity of 86.3% and a specificity of 98.1% for talaromycosis diagnosis in patients with HIV infection . These previous study findings, together with our findings, indicate that Mp1p antigen detection is a good tool for the early diagnosis of talaromycosis. Moreover, this technique is simple to perform and is commercially available; therefore, it is potentially generalizable to routine clinical practice. The sensitivity of the Mp1p assay in our study was lower than that in the study conducted in Vietnam (72.0% vs 86.3%) possibly because of the difference in the control group. Our control group was limited to patients with AIDS without talaromycosis, while the control group in the study conducted in Vietnam included healthy volunteers and patients with non-HIV-related infections. In addition, some of our patients had received antifungal treatment before admission, which could also affect the results. The GM assay is also an available diagnostic tool in talaromycosis diagnosis but was found to be inferior to Mp1p antigen detection. It had a substantial agreement with the gold standard (kappa: 0.603) in our study; however, the sensitivity was only 64.5%, indicating a greater risk of misdiagnosis. A study conducted in Wuhan found that the GM assay had a sensitivity of 95.8% (23/24) and a specificity of 90.9% (30/33) in talaromycosis diagnosis . The sensitivity of the GM assay in that study seemed to be much higher than that in our study; however, their sample size was small, which may increase the risk of sampling errors. In addition, the selection of the cut-off values and the different inclusion criteria could have affected the results.
There have been no reports related to combined approaches for talaromycosis diagnosis. Combined approaches seemed to have a diagnostic advantage over Mp1p antigen detection alone in our study. In addition, the sensitivity of combined approaches was superior to that of blood culture, although the PPV was not high enough. This suggests that combined approaches have the potential for application and are worth further in-depth studies to establish a better diagnostic model.
In our study, more than 90% of the patients with AIDS with talaromycosis had a CD4 + T cell count of < 50 Nr/µL. We found that the number of patients with talaromycosis and the positivity rates in the Mp1p assay increased with decreases in the CD4 + T cell counts. In addition, the Mp1p assay showed a superior diagnostic efficacy in the patients with CD4 + T cell counts of < 50 Nr/µL. It is known that lower CD4 + T cell counts are associated with more severe OIs and generally indicate more severe disseminated infections in patients with AIDS. We speculated that in patients with lower CD4 + T cell counts, the increased growth of T. marneffei strains may cause them to secrete more Mp1p antigens into the blood, which makes them easier to detect.
This study identified the clinical value of Mp1p antigen detection, which could assist in the early diagnosis of talaromycosis. Although a small number of studies have explored the diagnostic value of Mp1p antigen detection, these were only preliminary explorations [14–16]. The relatively large sample size is a strength of our study. Furthermore, in contrast to the study conducted in Vietnam , we selected hospitalised patients with AIDS as the control group, which more closely matched the clinical needs. We also compared between the different assays simultaneously, especially the Mp1p and GM assays. Few studies have compared the diagnostic efficacy of Mp1p and GM antigen detections simultaneously. Only Wang et al.  used both approaches to investigate Mp1p antigenaemia in patients with HIV infection. However, in their study, the GM assay was used only as a gold standard method for talaromycosis diagnosis.
This study had some limitations. Our study population included hospitalised patients with AIDS, and the PPV and NPV were not based on the general population. Therefore, our results are only applicable to the identification of talaromycosis in patients with AIDS but not in the general population. Another limitation of our study is that some of our patients lacked records of antifungal treatment before admission; thus, we cannot exclude such confounding factors. Nevertheless, our study offers application value. We believe that Mp1p antigen detection can be used for the diagnosis of talaromycosis in clinical settings to promote its early diagnosis and treatment and reduce mortality. To further optimise the clinical application of Mp1p antigen detection, we will further detect and quantify Mp1p levels, determine the best cut-off value, and build a diagnostic model for early diagnosis in a larger prospective group.
In summary, it is difficult to achieve an early diagnosis of talaromycosis relying on the diagnostic gold standard of culture or histopathology. Mp1p antigen detection has a superior advantage in assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4 + T cell counts of 50 Nr/µL.