OBJECTIVE: Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases. However, studies on Talaromyces marneffei detection using mNGS remain scarce. Therefore, this study aimed to explore the diagnostic performance of mNGS in T. marneffei.
METHODS: Between March 2021 and June 2023, patients who were discharged with a final diagnosis of talaromycosis, or confirmed T. marneffei infection by mNGS, culture or pathological examination were included in the study. Culture and mNGS were performed simultaneously for all patients. Clinical data were retrieved for analysis.
RESULTS: A total of 78 patients were enrolled, with 40 in the talaromycosis group and 38 in the suspected-talaromycosis group. In the talaromycosis group, mNGS showed a higher positivity rate(40/40, 100.0%) compared to culture(34/40, 85.0%)(P = 0.111). All patients in the suspected-talaromycosis group tested negative via culture, while mNGS yielded positive results. The T. marneffei reads in the talaromycosis group were significantly higher than in the suspected-talaromycosis group (4399 vs. 28, P < 0.001). In the suspected-talaromycosis group, of the four patients with low reads who did not receive antifungal therapy, one died and one lung lesion progressed; most patients(31/34, 91.2%) recovered after receiving appropriate antifungal therapy.
CONCLUSIONS: mNGS proves to be a rapid and highly sensitive method for detecting T. marneffei. Higher reads of T. marneffei correspond to a higher likelihood of infection. However, cases with low reads necessitate a comprehensive approach, integrating clinical manifestations, laboratory tests, and imaging examinations to confirm T. marneffei infection.

UNASSIGNED: Talaromycosis is a serious opportunistic infectious disease caused by Talaromyces marneffei, which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death.
UNASSIGNED: Both patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for T. marneffei. T. marneffei was detected in the blood culture of case 2, with infection of Candida parapsilosis and Pneumocystis jirovecii. Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy.
UNASSIGNED: Talaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.

UNASSIGNED: A high aspartate aminotransferase/platelet ratio index (APRI) predicts mortality in patients with severe infection. This study aims to assess the potential of APRI as a predictor for mortality in patients with HIV-associated Talaromyces marneffei (HTM).
UNASSIGNED: Associations between APRI and CD4 count, white blood cell count, C-reactive protein (CRP) level, procalcitonin (PCT) level, and cytokines were assessed in 119 patients. Univariate and multivariate Cox regression models were used to predict APRI on 24-week mortality.
UNASSIGNED: APRI was positively associated with CRP (r = 0.190, P = .039), PCT (r = 0.220, P = .018), interleukin 6 (r = 0.723, P < .001), interleukin 10 (r = 0.416, P = .006), and tumor necrosis factor α (r = 0.575, P < .001) and negatively associated with CD4 count (r = -0.234, P = .011). In total, 20.2% (24/119) of patients died within the 24-week follow-up. The 24-week survival rate was 88.0% for patients with APRI <5.6% and 61.1% for those with APRI ≥5.6 (log-rank P < .001). After adjustment for sex, age, body mass index, and CD4 count, as well as serum levels of hemoglobin, APRI ≥5.6 (adjusted hazard ratio [95% CI]; 3.0 [1.2-7.1], P = .015), PCT ≥1.7 ng/mL (3.7 [1.5-9.6], P = .006), and non-amphotericin B deoxycholate treatment (2.8 [1.2-6.6], P = .018) were independent risk factors for 24-week mortality.
UNASSIGNED: For patients with HTM, APRI is associated with severity and is an independent risk factor for 24-week mortality.

BACKGROUND: This study\'s objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis.
METHODS: A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020.
RESULTS: Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine level > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level < 100 × 109 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia. There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the patients with or without fungal clearance at 2 weeks. 10 mg on the first day of amphotericin B deoxycholate was calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206). The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3%, which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, and 25 mg, daily) (62.9%).
CONCLUSIONS: The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance.
BACKGROUND: ChiCTR1900021195. Registered 1 February 2019.

Underrated and neglected, talaromycosis is a life-threatening fungal disease endemic to the tropical and subtropical regions of Asia. In China, it has been reported that talaromycosis mortality doubles from 24 to 50% when the diagnosis is delayed, and reaches 100% when the diagnosis is missed. Thus, the accurate diagnosis of talaromycosis is of utmost importance. Herein, in the first part of this article, we provide an extensive review of the diagnostic tools used thus far by physicians in the management of cases of talaromycosis. The challenges encountered and the perspectives which may aid in the discovery of more accurate and reliable diagnostic approaches are also discussed. In the second part of this review, we discuss the drugs used to prevent and treat T. marneffei infection. Alternative therapeutic options and potential drug resistance reported in the contemporary literature are also discussed. We aim to guide researchers towards the discovery of novel approaches to prevent, diagnose, and treat talaromycosis, and therefore improve the prognosis for those afflicted by this important disease.

The increased levels of IL-1β and IL-18 cytokines have been associated with the severity of sepsis and outcomes of patients infected with Talaromyces marneffei. Previous studies have suggested that NLRP3 plays an important role in caspase-1 activated secretion of IL-1β and IL-18 in fungal-infected macrophages. In the present study, the role of the NLRP3 inflammasome in talaromycosis is investigated in an in vitro assay and in vivo with a mice systemic infection model. We found that the NLRP3 inflammasome pathway in infected mice is activated along with increased production of IL-1β. Such an activation of the NLRP3 inflammasome is also observed in either mice or human macrophages challenged with T. marneffei conidia. Our results indicate that IL-1β release by infected macrophages is NLRP3 inflammasome-dependent and NLRP3 contributes to death of mice at the early stage of pulmonary infection. Moreover, a greater number of MPO-positive cells are found in the lungs of infected Nlrp3-/- mice and WT mice with reduced LDH levels, especially at the last stage of infection. Therefore, we conclude that the NLRP3 Inflammasome activation is important for fungal clearance, neutrophil recruitment and lung injury during T. marneffei Infection.

BACKGROUND: Cryptococcosis and talaromycosis are known as \'neglected epidemics\' due to their high case fatality rates and low concern. Clinically, the skin lesions of the two fungal diseases are similar and easily misdiagnosed. Therefore, this study aims to develop an algorithm to identify cryptococcosis/talaromycosis skin lesions.
METHODS: Skin images of tararomiasis and cryptococcosis were collected from published articles and augmented using the Python Imaging Library (PIL). Then, five deep artificial intelligence models, VGG19, MobileNet, InceptionV3, Incept ResNetV2 and DenseNet201, were developed based on the collected datasets using transfer learning technology. Finally, the performance of the models was evaluated using sensitivity, specificity, F1 score, accuracy, AUC and ROC curve.
RESULTS: In total, 159 articles (79 for cryptococcosis and 80 for talaromycosis), including 101 cryptococcosis skin lesion images and 133 talaromycosis skin lesion images, were collected for further mode construction. Five methods showed good performance for prediction but did not yield satisfactory results for all cases. Among them, DenseNet201 performed best in the validation set, followed by InceptionV3. However, InceptionV3 showed the highest sensitivity, accuracy, F1 score and AUC values in the training set, followed by DenseNet201. The specificity of DenseNet201 in the training set is better than that of InceptionV3.
CONCLUSIONS: DenseNet201 and InceptionV3 are equivalent to the optimal model in these conditions and can be used in clinical settings as decision support tools for the identification and classification of skin lesions of cryptococcus/talaromycosis.

Talaromycosis is an invasive mycosis endemic in tropical and subtropical Asia and is caused by the pathogenic fungus Talaromyces marneffei. Approximately 17,300 cases of T. marneffei infection are diagnosed annually, and the reported mortality rate is extremely high (~1/3). Despite the devastating impact of talaromycosis on immunocompromised individuals, particularly HIV-positive persons, and the increase in reported occurrences in HIV-uninfected persons, diagnostic and therapeutic approaches for talaromycosis have received far too little attention worldwide. In 2021, scientists living in countries where talaromycosis is endemic raised a global demand for it to be recognized as a neglected tropical disease. Therefore, T. marneffei and the infectious disease induced by this fungus must be treated with concern. T. marneffei is a thermally dimorphic saprophytic fungus with a complicated mycological growth process that may produce various cell types in its life cycle, including conidia, hyphae, and yeast, all of which are associated with its pathogenicity. However, understanding of the pathogenic mechanism of T. marneffei has been limited until recently. To achieve a holistic view of T. marneffei and talaromycosis, the current knowledge about talaromycosis and research breakthroughs regarding T. marneffei growth biology are discussed in this review, along with the interaction of the fungus with environmental stimuli and the host immune response to fungal infection. Importantly, the future research directions required for understanding this serious infection and its causative pathogenic fungus are also emphasized to identify solutions that will alleviate the suffering of susceptible individuals worldwide.

Talaromycosis is an invasive endemic mycosis caused by the dimorphic fungus Talaromyces marneffei (T. marneffei, TM). It mainly affects immunodeficient patients, especially HIV-infected individuals, which causes significant morbidity and mortality. Culture-based diagnosis takes a long turnaround time with low sensitivity, leading to treatment delay. In this study, we aimed to evaluate the performance of Metagenomic Next-Generation Sequencing (mNGS) for the rapid diagnosis of talaromycosis in HIV-infected patients.
Retrospectively analysis was conducted in HIV-infected cases at Changsha First Hospital (China) from January 2021 to March 2022. Patients who underwent routine microbiological examination and mNGS testing in parallel were enrolled. The clinical final diagnosis was used as a reference standard, and cases were classified into the TM group (60 cases) and the non-TM group (148 cases). The clinical performances of mNGS were compared with culture and serum Galactomannan (GM). The mixed infections detected by mNGS were analyzed. The impact of mNGS detection on treatment was also investigated.
The sensitivity of mNGS test reached 98.3% (95% CI, 89.8-99.9), which was significantly higher than culture (66.7% [95% CI, 53.2-77.9], P < 0.001) and serum GM (83.3% [95% CI, 71.0-91.2], P < 0.05). The specificity of 98.6% (95% CI, 94.7-99.7) was similar to culture (100.0% [95% CI, 96.8-100.0], P = 0.156), and superior to serum GM (91.9% [95% CI, 85.9-95.5], P < 0.05). In bronchoalveolar lavage fluid (BALF) samples, the positive rate of mNGS was 97.6%, which was significantly higher than culture (28.6%, P <0.001). mNGS has excellent performance in the identification of mixed infection in TM group patients. Cytomegalovirus, Epstein-Barr virus and Pneumocystis jirovecii were the most common concurrent pathogens. In summary, 60.0% (36/60) patients were added or adjusted to antimicrobial therapy after mNGS test.
mNGS is a powerful technique with high specificity and sensitivity for the rapid diagnosis of talaromycosis. mNGS of BALF samples may be a good option for early identification of T. marneffei in HIV-infected individuals with manifestations of infection. Moreover, mNGS shows excellent performance in mixed infection, which benefits timely treatment and potential mortality reduction.

Talaromyces marneffei is a thermally dimorphic fungus that affects multiple organs and frequently invades immunocompromised individuals. However, only a few studies have reported the presence of intestinal infection associated with T. marneffei. Herein, we reported a case of intestinal T. marneffei infection in a man who complained of a 1-month history of intermittent fever, abdominal pain, and diarrhea. The result of the human immunodeficiency virus antibody test was positive. Periodic acid-Schiff and Gomorrah\'s methylamine silver staining of the intestinal biopsy tissue revealed T. marneffei infection. Fortunately, the patient\'s symptoms rapidly resolved with prompt antifungal treatment. In addition, we summarized and described the clinical characteristics, management, and outcomes of patients with intestinal T. marneffei infection. A total of 29 patients were identified, the majority of whom (65.52%) were comorbid with acquired immunodeficiency syndrome. The main clinical features included anemia, fever, abdominal pain, diarrhea, weight loss, and lymphadenopathy. The transverse and descending colon, ileocecum, and ascending colon were the most common sites of lesions. A considerable number of patients (31.03%) developed intestinal obstruction, intestinal perforation, and gastrointestinal bleeding. Of the 29 patients, six underwent surgery, 23 survived successfully with antifungal treatment, five died of T. marneffei infection, and one died of unknown causes. T. marneffei intestinal infection should be considered when immunodeficient patients in endemic areas present with non-specific symptoms, such as fever, abdominal pain, and diarrhea. Appropriate and timely endoscopy avoids delays in diagnosis. Early aggressive antifungal therapy improves the clinical outcomes of patients.