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.

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.

BACKGROUND: Current guidelines recommend amphotericin B as the preferred drug for induction therapy; however, amphotericin B is not available in certain settings. Induction therapy with amphotericin B deoxycholate or voriconazole has been shown to be an effective treatment for talaromycosis. However, prospective clinical trials comparing these two antifungal drugs are absent from the literature.
METHODS: In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors.
RESULTS: We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291-0.696, p < 0.001; OR 0.443, 95% CI 0.261-0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333-0.793, p = 0.003; OR 0.542, 95% CI 0.318-0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4-36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1-34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup.
CONCLUSIONS: Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup.
BACKGROUND: ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

Talaromycosis is a fatal opportunistic infection prevalent in human immunodeficiency virus (HIV)-infected patients, previous studies suggest environmental humidity is associated with monthly talaromycosis hospitalizations of HIV-infected patients, but the acute risk factor remains uncertain. In this study, we evaluated the associations between talaromycosis hospitalizations of HIV-infected patients (n = 919) and environmental factors including meteorological variables and air pollutants at the event day (assumed \"lag 0\" since the exact infection date is hard to ascertain) and 1-7 days prior to event day (lag 1-lag 7) in conditional logistics regression models based on a case crossover design. We found that an interquartile range (IQR) increase in temperature at lag 0-lag 7 (odds ratio [OR] [95% CI] ranged from 1.748 [1.345-2.273] to 2.184 [1.672-2.854]), and an IQR increase in humidity at lag 0 (OR [95% CI] = 1.192 [1.052-1.350]), and lag 1 (OR [95% CI] = 1.199 [1.056-1.361]) were significantly associated with talaromycosis hospitalizations of HIV-infected patients. Besides, temperature was also a common predictor for talaromycosis in patients with co-infections including candidiasis (n = 386), Pneumocystis pneumonia (n = 183), pulmonary tuberculosis (n = 141), and chronic hepatitis (n = 158), while humidity was a specific risk factor for talaromycosis in patients with candidiasis, and an air pollutant, SO2, was a specific risk factor for talaromycosis in patients with Pneumocystis pneumonia. In an age stratified evaluation (cutoff = 50 years old), temperature was the only variable positively associated with talaromycosis in both younger and older patients. These findings broaden our understanding of the epidemiology and pathogenesis of talaromycosis in HIV-infected patients.

OBJECTIVE: Talaromyces marneffei (TM) is a pathogenic fungus endemic in Southeast Asia and human immunodeficiency virus (HIV)-positive populations, but studies related to non-endemic areas and HIV-negative populations are still limited. Therefore, this study aims to provide more additional evidence for clinical work of talaromycosis.
METHODS: To collect clinical information of patients with talaromycosis admitted to hospitals in Zhejiang Province, China from January 1, 2010 to May 31, 2020, retrospectively analyzed clinical characteristics and prognosis, COX multivariate regression analysis was used for survival analysis.
RESULTS: A total of 92 patients were enrolled, including 76 males, 73 HIV-positive patients, with an average age of 40.1 ± 13.0. Compared to HIV-positive group, the negative group had higher admission age (47.7 ± 14.6 vs 38.1 ± 11.9, p = 0.003) and lower proportion of male (89.0% vs 57.9%, p = 0.004), there was no significant difference in imaging of lungs. There were significantly more HIV-positive patients in those with pleural effusion (100% vs 69.4%, p = 0.001). COX multivariate regression analysis suggested pleural effusion (HR = 3.220; 95% CI 1.117-9.287; p = 0.030) and HIV infection (HR = 0.057; 95% CI 0.009-0.370; p = 0.003) which were independent predictors of prognosis in patients with talaromycosis.
CONCLUSIONS: In non-endemic areas, clinical symptoms, signs, and laboratory tests of patients with talaromycosis are similar to those in endemic areas. Patients with pleural effusion have lower survival rate, HIV-infected people are less likely to relapse, and there is no significant correlation between extent of lung involvement and survival of infected patients.