Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization.

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

Development of IL-17A inhibitor-induced atopic dermatitis-like rash in psoriasis patients: Insights into immune shift.

Cases of atopic dermatitis (AD)-like rash induced by IL-17A inhibitor secukinumab treatment (SI-AD) have been recently reported in psoriasis patients. To identify immune and inflammatory factors expression in SI-AD. A panel of 15 immune and inflammatory factors in peripheral blood samples from various groups, including patients with patients with SI-AD, psoriasis with secukinumab (S-stable), advanced psoriasis patients (Advanced) and healthy controls (HC). Interleukin-10 (IL-10), IL-4 and IL-17A were detected in skin tissue biopsy samples by immunohistochemistry and real-time quantitative polymerase chain reaction. The immunoglobulin E levels in the SI-AD patients exceeded normal values. The IL-10 levels in SI-AD patients were higher than those in S-stable patients, advanced patients and HC. The IL-4 levels in SI-AD patients were higher than that in S-stable patients and HC. The IL-17A levels in SI-AD patients were higher than those in advanced psoriasis patients and HC, but no significant differences were observed between SI-AD patients and S-stable patients. IL-10 and IL-4 levels were higher in AD-like rashes than in healthy skin, while IL-17A did not differ significantly between the two. Upon discontinuing secukinumab, and switching to oral cyclosporine, antihistamines, Janus kinase 1 inhibitor and topical glucocorticoids, SI-AD patients experienced significant improvement in their skin lesions. Upon reexamination, all 15 immune and inflammatory factors returned to normal levels. Immune shift from Th17 towards Th2 may occur in SI-AD, as indicated by abnormal expression of multiple immune and inflammatory factors observed in peripheral blood and skin tissues.

Co-Infection Talaromyces marneffei and Pneumocystis jirovecii in a Patient with Systemic Lupus Erythematosus.

Talaromyces marneffei (TM) and Pneumocystis jirovecii (PJ) infection are opportunistic infections that typically affect individuals with compromised immune systems, such as those with HIV or immunodeficiency. However, these infections are rarely seen in patients with systemic lupus erythematosus (SLE). We present a case study of a 52-year-old woman diagnosed with SLE who developed a co-infection of TM and PJ after receiving glucocorticoids, mycophenolate mofetil (MMF), and belimumab therapy. The patient's pneumonia improved following treatment with voriconazole, clarithromycin, and compound sulfamethoxazole. This case highlights the potential risk of serious opportunistic infections in SLE patients receiving a combination of glucocorticoids, MMF, and belimumab. Close monitoring of lymphocyte count, immunoglobulin levels, and chest computed tomography scans can aid in the early detection of infections. To the best of our knowledge, this is the first reported case of TM and PJ co-infection in an SLE patient.

The Epidemiology and Clinical Characteristics of Fungemia in a Tertiary Hospital in Southern China: A 6-Year Retrospective Study.

Knowledge of the epidemiology and clinical characteristics of fungemia in southern China is limited. We conducted a six-year retrospective descriptive study to analyze the epidemiological and clinical characteristics of fungemia at the largest tertiary hospital in Guangxi, southern China. Data were obtained from the laboratory registry of patients with fungemia between January 2014 and December 2019. Demographic characteristics, underlying medical conditions, and outcomes for each case were analyzed. A total of 455 patients with fungemia were identified. Unexpectedly, Talaromyces marneffei (T. marneffei) was the most frequently isolated agent causing fungemia in the region (149/475, 31.4%), and Candida albicans (C. albicans) was the most commonly isolated Candida spp. (100/475, 21.1%). We identified that more than 70% of talaromycosis fungemia developed in AIDS patients, whereas candidemia was most commonly associated with a history of recent surgery. Notably, the total mortality rate of fungemia and the mortality rate in patients with T. marneffei and Cryptococcus neoformans (C. neoformans) fungemia were significantly higher in HIV-uninfected patients than in HIV-infected patients. In conclusion, the clinical pattern of fungemia in Guangxi is different from that in previous studies. Our study may provide new guidance for the early diagnosis and prompt treatment of fungemia in similar geographic regions.

The Epidemiology of Tinea Capitis in Guangxi Province, China.

The aim of this study was to analyze the epidemiological characteristics and pathogen spectrum of tinea capitis in Guangxi, southern China. A multicenter prospective descriptive study was conducted in 8 hospitals across Guangxi. From January 2019 to July 2022, one hundred seventy-one (171) patients diagnosed with tinea capitis were included. Demographic data, risk factors, and fungal data were collected. If necessary, species were further identified by morphological or molecular sequencing in the central laboratory. Of the 171 cases of tinea capitis, 74.3% occurred in patients aged 2-8 years. Children with tinea capitis were mainly boys (59.6%) and were more likely than adults to have a history of animal contact (44.2% vs. 33.3%) and zoophilic dermatophyte infection (76.9% vs. 46.7%, P = 0.008). The adults were mainly female (53%) and were more likely than children to have a history of infection with anthropophilic organisms (53.3% vs. 18.9%). The causative agents of tinea capitis in Guangxi were diverse, and the most common pathogen was Microsporum canis (M. cani, n = 98, 62%), followed by Trichophyton mentagrophytes (T. mentagrophytes n = 18, 11.4%) and Trichophyton tonsurans (T. tonsurans n = 12, 7.6%). In addition, tinea capitis caused by Nannizzia incurvata (N. incurvata) and Trichophyton verrucosum (T. verrucosum) was detected in the study. Notably, the proportion of patients with kerion in the study was 41.5% (n = 71), and most of those patients were children (n = 68), especially neglected children living in the rural mountainous areas of Guangxi, where they were unable to receive timely diagnosis and appropriate treatment. In conclusion, the causative agents of tinea capitis in Guangxi, South China, are diverse, and the incidence of kerion is high, indicating that diagnosis and treatment modalities in the region remain grossly inadequate. Clinicians and policy-makers should collaborate to adopt public health strategies to control the disease.

Apophysomyces variabilis as an emerging pathogen in Mainland China.

BACKGROUND: Mucormycosis is a rare form of invasive, rapidly progressive and lethal opportunistic fungal infection caused by Mucorales. Although Rhizopus arrhizus (R. arrhizus) is the most commonly isolated Mucorales worldwide, infections caused by Apophysomyces variabilis (A. variabilis) are increasing. OBJECTIVES AND METHODS: We present a case of necrotizing fasciitis caused by A. variabilis in an immunocompetent woman. In order to further understand the characteristics of the strain isolated from the patient, we identified the strain through ITS sequencing, assessed the ability to tolerate salt concentrations and temperature conditions, in addition to performing in vitro drug susceptibility testing against common antifungal agents. RESULTS: The strain showed 98.76% identity with A. variabilis in the NCBI database, and it was found to tolerate higher temperatures and salt concentrations than previously reported strains. The strain was sensitive to amphotericin B and posaconazole, but not to voriconazole, itraconazole, 5-fluorocytosine and echinocandins. CONCLUSIONS: This case indicates that Mucorales caused by A. variabilis should be recognised as an emerging pathogen that can cause a high mortality rate in the absence of prompt diagnosis and proper treatment in China, aggressive surgical debridement combined with prompt and appropriate antifungal treatment may improve outcomes.

Prevalence and clinical characteristics of methicillin-resistant Staphylococcus aureus infections among dermatology inpatients: A 7-year retrospective study at a tertiary care center in southwest China.

Background: Increased rates of methicillin-resistant Staphylococcus aureus (MRSA) antibiotic resistance and the associated morbidity have increased dermatologists' attention to skin and soft tissue MRSA infections. However, the clinical characterization of MRSA skin and soft tissue infections (SSTIs) in Southwest China is lacking, which precludes optimal prevention and treatment of these infections. Objectives: This study was conducted to characterize the prevalence, clinical comorbidities and antibiotic susceptibility of MRSA isolates from SSTIs, including community-associated (CA) and healthcare-associated (HA) isolates. Methods: In the Dermatology Inpatient Department of the First Affiliated Hospital of Guangxi Medical University, a retrospective study was conducted on data, including patient demographics and clinical information, from culture-confirmed S. aureus isolated from skin and soft tissue between January 1, 2015, and December 31, 2021. Isolate susceptibility to 13 antibiotics was determined using the Vitek 2 system. Results: From among 864 S. aureus strains, we identified 283 MRSA (32.75%) isolates comprising 203 CA-MRSA and 80 HA-MRSA isolates. The average rate of CA-MRSA isolation for MRSA SSTIs was 71.73%. The HA-MRSA isolation rate for MRSA SSTIs increased significantly. HA-MRSA-infected patients were older. The most common dermatological presentation of CA-MRSA infection was staphylococcal scalded skin syndrome, while the comorbidity severe drug eruption was significantly associated with HA-MRSA infection. One CA-MRSA strain was resistant to linezolid, and one HA-MRSA strain had an intermediate phenotype for vancomycin; both strains had low sensitivity to clindamycin and erythromycin (3.70%~19.40%). However, HA-MRSA isolates were more susceptible to trimethoprim/sulfamethoxazole. Conclusions: CA-MRSA is a predominant pathogen causing SSTIs, and HA-MRSA infection incidence is increasing gradually. Both strains showed increasing antibiotic resistance. Our data on MRSA susceptibility may guide dermatologist antibiotic treatment decisions. Dermatologists should consider these identified comorbidities of MRSA SSTIs when patients are admitted and initiate early prevention and treatment of MRSA.

Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis.

The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0-5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h-1, and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP > 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP > 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of Cmin > 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC.

Experimental Phaeohyphomycosis of Curvularia lunata.

Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to Curvularia lunata (C. lunata) in animals and humans are increasing. However, studies on the pathogenesis, virulence, and epidemiology of C. lunata have rarely been discussed. In the present study, BALB/c mice were experimentally inoculated with C. lunata suspension by different routes and the course of infection was evaluated. In addition, the in vitro antifungal susceptibility of C. lunata against six commonly used antifungals was evaluated using the microdilution method. Inoculation resulted in skin lesions in animals inoculated intraperitonially and subcutaneously. Infection was confirmed by both mycological and histopathologic examination. C. lunata spores and hyphae were detected in the histopathologic sections stained with hexamine silver staining. In addition, voriconazole (VRC) demonstrated greater activity against C. lunata when compared to the other antifungals, whereas fluconazole (FLC) was the least active antifungal with a minimum inhibitory concentration (MIC) range of 8-16 µg/mL. Further studies are necessary to understand the pathogenicity of C. lunata and uncover the mystery of this fungus.

The Relationship Between the Effectiveness of HMME-PDT and the Dermoscopic Features of Port-wine Stains in Chinese Pediatric Patients: A Retrospective Study.

INTRODUCTION: Although pulsed dye laser (PDL) remains the gold standard for the treatment of port-wine stains (PWS), hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) is another treatment modality that has been shown to be effective in the treatment of PWS. This study aimed to observe the clinical efficacy and therapeutic response of HMME-PDT in the treatment of pediatric Chinese patients with PWS and to analyze the association between the efficacy of therapy and the dermoscopic features of PWS. METHODS: Pediatric patients with PWS and negative HMME skin test were enrolled between December 2017 and May 2021. Patients received an intravenous injection of 5 mg/kg HMME, and lesions were irradiated with 532-nm LED green light with a power density of 70-80 mW/cm2 for 20-25 min. Digital photographs and dermoscopic images were taken before and after two treatment sessions, and the clinical response was observed. The relationship between the efficacy of HMME-PDT and the dermoscopic features of PWS was retrospectively analyzed. RESULTS: A total of 216 pediatric patients (1-14 years) were recruited. Sixty-six patients had the pink type, while 150 had the purple type. After two HMME-PDT sessions, 55 patients showed excellent efficacy (25.46%), 77 patients showed good efficacy (35.65%), 69 patients showed fair efficacy (31.94%), and 15 patients showed no improvement (6.95%). Dotted and globular vessels were highly associated with excellent efficacy (41.82%); linear vessels were mainly associated with good efficacy (54.55%); reticular vessels were mainly associated with fair (55.07%) and mixed vessels were mainly associated with no improvement (26.66%). CONCLUSION: HMME-PDT is an effective and safe treatment for pediatric patients with PWS. Dotted and globular vessels as well as linear vessels showed better efficacy compared to the other dermoscopic patterns in patients with PWS. Dermoscopy can provide useful clinical information about treatment outcomes.

A Special Tinea Nigra Caused by Curvularia lunata: Case Report and Literature Review.

Tinea nigra is a superficial fungal infection usually caused by Hortaea werneckii (H. werneckii). We report a special case of tinea nigra in an immunocompetent child who developed a unilateral, rapidly growing pigmented lesion on her palm. Interestingly, Curvularia lunata (C. lunata) was isolated from the lesion scrapes and was identified by both morphological features and molecular biology methods. The lesion was completely cleared by topical naftifine hydrochloride and ketoconazole cream. We present-to the best of our knowledge-the first case of tinea nigra where the causative pathogen was identified as C. lunata. We therefore provide a brief literature review of previously reported cases of tinea nigra to broaden the knowledge of the potential causative pathogens. The etiology, demography, clinical features, diagnostic methods, and treatment of the reviewed cases are summarized and analyzed.

In vitro Antifungal Susceptibility Profiles of Cryptococcus neoformans var. grubii and Cryptococcus gattii Clinical Isolates in Guangxi, Southern China.

This study analyzed the in vitro drug sensitivity of Cryptococcus spp. from Guangxi, Southern China. One hundred three strains of Cryptococcus were recovered from 86 patients; 14 were HIV positive and 72 were HIV negative. Ninety-two strains were identified as Cryptococcus neoformans var. grubii, while 11 strains were identified as Cryptococcus gattii (5 C. gattii sensu stricto and 6 Cryptococcus deuterogattii). The recovered strains were tested against commonly used antifungal drugs (fluconazole, amphotericin B, 5-fluorocytosine, itraconazole, and voriconazole) and to novel antifungal drugs (posaconazole and isavuconazole) using CLSI M27-A4 method. The results showed that all isolates were susceptible to most antifungal drugs, of which the minimum inhibitory concentration (MIC) ranges were as follows: 0.05-4 µg/ml for fluconazole, 0.25-1 µg/ml for amphotericin B; 0.0625-2 µg/ml for 5-fluorocytosine, 0.0625-0.25 µg/ml for itraconazole, 0.0078-0.25 µg/ml for voriconazole, 0.0313-0.5 µg/ml for posaconazole, 0.0020-0.125 µg/ml for isavuconazole for C. neoformans var. grubii isolates, and 1-16 µg/ml for fluconazole, 0.125-1 µg/ml for 5-fluorocytosine, 0.25-1 µg/ml for amphotericin B, 0.0625-0.25 µg/ml for itraconazole, 0.0156-0.125 µg/ml for voriconazole, 0.0156-0.25 µg/ml for posaconazole, and 0.0078-0.125 µg/ml for isavuconazole for C. gattii isolates. Furthermore, some C. neoformans var. grubii isolates were found to be susceptible-dose dependent to 5-fluorocytosine and itraconazole. In addition, a reduction in the potency of fluconazole against C. gattii is possible. We observed no statistical differences in susceptibility of C. neoformans var. grubii and C. gattii in the tested strains. Continuous observation of antifungal susceptibility of Cryptococcus isolates is recommended to monitor the emergence of resistant strains.

Voriconazole Versus Amphotericin B as Induction Therapy for Talaromycosis in HIV/AIDS Patients: A Retrospective Study.

Disseminated talaromycosis caused by Talaromyces marneffei is a life-threatening opportunistic infection. Although amphotericin B deoxycholate (dAmB) remains the first-line induction treatment, voriconazole can also be used. However, no clinical trials have compared dAmB and voriconazole in the administration of talaromycosis. We retrospectively evaluated the efficacy and safety of voriconazole or dAmB as induction therapy for talaromycosis in HIV-infected patients. We enrolled HIV-infected patients with a confirmed Talaromyces marneffei infection who received intravenous dAmB (0.6 to 0.7 mg/kg daily for 2 weeks) or voriconazole (6 mg/kg every 12 h on day 1 and 4 mg/kg every 12 h afterward) as induction therapy, followed by oral itraconazole as consolidation and maintenance therapy. Drug efficacy was evaluated based on response rate. Drug safety was evaluated based on the occurrence of adverse events. In total, 58 patients who received voriconazole and 82 who received dAmB were enrolled from two hospitals. The voriconazole and dAmB treatment groups had similar response rates at the primary and follow-up efficacy evaluations. However, the durations of induction antifungal therapy and hospital stay were shorter for patients in the voriconazole group than in the dAmB group. Few adverse reactions occurred in either the voriconazole or dAmB group. Our retrospective study indicated that voriconazole is an effective and safe induction antifungal drug for HIV-associated disseminated talaromycosis. The duration of induction treatment with voriconazole was shorter, indicating its potential as a better choice in clinical practice. The duration of voriconazole induction therapy is 11 to 13 days.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.

Emerging Cryptococcus gattii species complex infections in Guangxi, southern China.

The emergence and spread of cryptococcosis caused by the Cryptococcus gattii species complex has become a major public concern worldwide. C. deuterogattii (VGIIa) outbreaks in the Pacific Northwest region demonstrate the expansion of this fungal infection to temperate climate regions. However, infections due to the C. gattii species complex in China have rarely been reported. In this study, we studied eleven clinical strains of the C. gattii species complex isolated from Guangxi, southern China. The genetic identity and variability of these isolates were analyzed via multi-locus sequence typing (MLST), and the phylogenetic relationships among these isolates and global isolates were evaluated. The mating type, physiological features and antifungal susceptibilities of these isolates were also characterized. Among the eleven isolates, six belonged to C. deuterogattii, while five belonged to C. gattii sensu stricto. The C. deuterogattii strains from Guangxi, southern China were genetically variable and clustered with different clinical isolates from Brazil. All strains were MATα, and three C. deuterogattii isolates (GX0104, GX0105 and GX0147) were able to undergo sexual reproduction. Moreover, most strains had capsule and were capable of melanin production when compared to the outbreak strain from Canada. Most isolates were susceptible to antifungal drugs; yet one of eleven immunocompetent patients died of cryptococcal meningitis caused by C. deuterogattii (GX0147). Our study indicated that the highly pathogenic C. deuterogattii may be emerging in southern China, and effective nationwide surveillance of C. gattii species complex infection is necessary.

Evaluation of quantitative real-time PCR and Platelia galactomannan assays for the diagnosis of disseminated Talaromyces marneffei infection.

Talaromyces (Penicillium) marneffei is an emerging pathogen that causes significant morbidity and mortality in immunocompromised patients in endemic regions such as southeast Asia. The diagnosis of disseminated T. marneffei infection remains challenging in clinical practice. In the study, a well-validated real-time quantitative polymerase chain reaction (qPCR) target region of ITS1-5.8S-ITS2 and a Platelia galactomannan (GM) assay were compared for their diagnostic performance using serum samples from patients with or without human immunodeficiency virus (HIV). The results showed that this novel qPCR method is highly sensitive and specific for T. marneffei DNA detection in serum samples, and the limit of detection and species-specificity of qPCR were five copies of DNA and 100%, respectively. For detection in serum samples from 36 talaromycosis patients, the sensitivity of qPCR was 86.11% (31/36), including 20/20 (100%) patients with fungemia and 11/16 (68.75%) patients without fungemia. For the GM assay, the sensitivity was 80.56% (29/36) when the GM optical density cutoff index was ≥0.5, including 19/20 (95%) patients with fungemia and 10/16 (62.5%) patients without fungemia. These results indicate that the novel qPCR and GM assays can be used as a valuable tool in the diagnosis of T. marneffei infection. Serum samples are convenient hematological specimens for T. marneffei DNA quantification. Combining the GM assay and qPCR is more scientific and appropriate for diagnosing T. marneffei infection in endemic areas.

Talaromycosis (Penicilliosis) Due to Talaromyces (Penicillium) marneffei: Insights into the Clinical Trends of a Major Fungal Disease 60 Years After the Discovery of the Pathogen.

Talaromycosis (penicilliosis) is a major fungal disease endemic across a narrow band of tropical countries of South and Southeast Asia. The etiologic agent is a thermally dimorphic fungus Talaromyces (Penicillium) marneffei, which was first isolated from a bamboo rat in Vietnam in 1956, but no formal description was published. In 1959, Professor Gabriel Segretain formally described it as a novel species Talaromyces (Penicillium) marneffei, and the human pathogenic potential of the fungus in Mycopathologia. The first natural human case of talaromycosis (penicillosis) was reported in 1973 and involved an American minister with Hodgkin's disease who lived in Southeast Asia. Sixty years after the discovery of the pathogen, talaromycosis caused by T. marneffei is recognized as an important human disease with the potential to cause high mortality in the absence of proper diagnosis and prompt treatment. Talaromycosis remains a significant infectious complication in HIV/AIDS patients and in patients with other immune defects. The disease is being recognized with an increasing frequency well beyond the traditional endemic areas. The natural reservoirs of T. marneffei in wild rodents are well-defined, which links the ecology with the epidemiology of talaromycosis in endemic areas. There is an urgent unmet need for rapid and affordable point-of-care diagnostic tests. We also need more clinical studies to define the best therapeutic options for the management of talaromycosis patients.