Talaromyces marneffei Mp1p Antigen Detection may Play an Important Role in the Early Diagnosis of Talaromycosis in Patients with Acquired Immunodeficiency Syndrome

Abstract

Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with Talaromyces marneffei (TSM group, n = 93) and those without Talaromyces marneffei (non-TSM group, n = 190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4? counts of \ 50 cells/lL compared to those with CD4? counts ranged from 50-100 cells/lL. The Mp1p EIA has the advantage of assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4? counts.

Advances in diagnosis and treatment of talaromycosis in patients with AIDS

“…A commercial Mp1p antigen detection assay for clinical use was approved in China in 2018. In a recent study of 283 patients with AIDS, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of Mp1p enzyme immunoassay within 3 days after admission were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively, which was consistent with the gold standard (kappa, 0.729) and superior to GM determination (kappa, 0.603) [15] . The GM and M1p1 antigen tests have been listed as the auxiliary diagnostic methods in the Chinese AIDS diagnosis and treatment guideline in 2021 [16]…”

“…In a recent study of 283 patients with AIDS, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of Mp1p enzyme immunoassay within 3 days after admission were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively, which was consistent with the gold standard (kappa, 0.729) and superior to GM determination (kappa, 0.603). [15] The GM and M1p1 antigen tests have been listed as the auxiliary diagnostic methods in the Chinese AIDS diagnosis and treatment guideline in 2021. [16] T. marneffei can be detected in blood samples of patients using several quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays, which show specificity near 100% and sensitivity equal to blood cultures at approximately 70%.…”

Clinical performance of metagenomic next-generation sequencing for the rapid diagnosis of talaromycosis in HIV-infected patients

“…The specificity of PCR-based detection methods varies greatly, ranging from 63.0 to 100.0% (Hien et al, 2016;Lu et al, 2016;Li et al, 2020). MP1P antigen of T. marneffei was developed for rapid detection and showed a sensitivity of only 86.3% (n=372) and 72.0% (n=93), respectively, in two studies of relatively large sample size (Thu et al, 2021;Chen et al, 2022). Compared with the detection methods mentioned above, mNGS demonstrates better sensitivity and specificity in the rapid diagnosis of talaromycosis in HIV patients.…”

“…Currently, the culture and species identification of clinical specimens is the golden standard for the diagnosis (Ning et al, 2018). However, it takes 10-14 days to yield a positive result, delaying the early diagnosis and timely treatment (Andrianopoulos, 2020;Chen et al, 2022). In addition, the culture results may be negative because of the low fungal loads in the early stage of infection, which will lead to a missed diagnosis.…”

Voriconazole trough concentration and clinical outcomes in patients with Talaromycosis

“…Talaromycosis is an endemic mycosis mainly prevalent in tropical and subtropical Asia regions and is caused by Talaromyces marneffei (T. marneffei) infection and can cause life-threatening disseminated infections [1,2] . The mortality-related talaromycosis is up to 30%, and it can reach up to 91% if treatment is delayed [3,4] .…”