Abstract
Increasing attention has been directed to Talaromyces marneffei (T. marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. marneffei infection in HIV-negative patients.
Highlights
Talaromyces marneffei (T. marneffei) is a dimorphic fungus causing life-threatening opportunistic infections that is endemic in southern China, southeastern Asia, and northeastern India, and it was previously considered the agent of a common infectious disease complication of HIV patients (Le et al, 2017; Guo et al, 2020)
Patients enrolled in this study included patients suffering from T. marneffei infection, pulmonary aspergillosis, or bacterial or viral pneumonia, and they were admitted for hospitalization during sample collection
Among the 33 patients, 16 had a definite diagnosis of T. marneffei infection (TM group), all without fungemia, and 2 patients were simultaneously infected with Staphylococcus aureus; 10 were confirmed to have pulmonary aspergillosis (PA group), and all had chronic pulmonary aspergillosis; 2 were diagnosed with viral pneumonia (VP group), and the pathogen was identified as an influenza virus; and 5 patients had bacterial pneumonia (BP group), and the pathogen was unclear, it was confirmed to be unrelated to T. marneffei, aspergillosis, or influenza virus infection
Summary
Talaromyces marneffei (T. marneffei) is a dimorphic fungus causing life-threatening opportunistic infections that is endemic in southern China, southeastern Asia, and northeastern India, and it was previously considered the agent of a common infectious disease complication of HIV patients (Le et al, 2017; Guo et al, 2020). Similar to other pulmonary mycoses, histopathology or a positive culture of T. marneffei with sterile body fluids are the gold standard methods to diagnose T. marneffei infection. These diagnostic methods are typically time consuming and laborious, and the possible invasiveness and complications of these methods limit their application by physicians. Some studies have found that Mp1p protein (Wang et al, 2011), galactomannan (GM) antigen (Li et al, 2020) or T. marneffei antigen (Prakit et al, 2016) can assist in diagnosing T. marneffei infection, these diagnosis determinants lack sensitivity or specificity or are useful preferentially in only HIV-positive patients. It is essential to explore promising serum biomarkers to diagnose T. marneffei infection in HIV-negative patients
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