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Background: Cryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors., Methods: The data of cryptococcal infections in China during 11 years were retrospectively analyzed. According to the position of infection, the patients were categorized into the pulmonary infection group and extrapulmonary infection group. The composition of the two groups was compared, and the potential risk factors of disseminated infection were analyzed. Logistic regression was used to analyze the prognostic risk factors of the disease., Results: A total of 165 patients were enrolled. 113 (68.5%) were male, and the age was 47.49 (18-82) years. 101 cases (61.2%) had a normal immune function and 64 cases (38.8%) had impaired immune function. 45 patients had extrapulmonary infection, involving the central nervous system, bone and joint, skin and bloodstream, and 120 patients had simple pulmonary infection. The mortality of the extrapulmonary infection group (48.9%) was significantly higher than that of the pulmonary infection group (0.8%). According to univariate logistic regression analysis, immune status (hazard ratio [HR], 4.476; 95% confidence interval [CI], 1.725-11.618; P = 0.002), infection position ([HR], 113.826; [CI], 14.607-886.967; P < 0.001), white blood cell count, ([HR],1.209;[CI], 1.054-1.386; P = 0.007), hemoglobin ([HR], 0.970; [CI], 0.955-0.986; P < 0.001), platelet count ([HR], 0.993; [CI], 0.987-0.999; P = 0.026), neutrophil percentage ([HR], 1.115; [CI], 1.065-1.168; P < 0.001), lymphocyte percentage ([HR], 0.875; [CI], 0.827-0.927; P < 0.001), neutrophil-to-lymphocyte Ratio (NLR) ([HR], 1.144; [CI], 1.072-1.221; P < 0.001), monocyte percentage ([HR], 0.752; [CI], 0.618-0.915; P = 0.004) were related to the prognosis. Multivariate logistic regression analysis showed that the infection position was remained related to the prognosis with statistical significance ([HR], 0.018; [CI], 0.001-0.384; P = 0.001)., Conclusion: Extrapulmonary infection of Cryptococcosis is an important risk factor for prognosis. High levels of neutrophils and NLR, and low levels of lymphocytes and monocytes may lead to disseminated infection of Cryptococcosis. Further studies are needed to reduce the occurrence rate of extrapulmonary infection and mortality., (© 2024. The Author(s).)

Objective: The incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients., Methods: This is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed., Results: 255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)]., Conclusion: The immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Cryptococcosis is an invasive fungal disease with increased morbidity in China over the past two decades. Cryptococci can infect immunocompromised hosts as well as immunocompetent ones. In this study, we reviewed data of 71 inpatients with cryptococcosis at Ningbo First Hospital from May 2010 to May 2020 and compared the clinical profiles of pulmonary cryptococcosis (PC) and extrapulmonary cryptococcosis (EPC). Of 71 patients (38 males, 33 females), 70 were non-HIV. The annual inpatient population increased dramatically, especially in the PC group. PC was confirmed in 77.46% (55/71) of cases by pathology. The rest were EPC including intracranial infection (15.49%, 11/71) and cryptococcemia (7.04%, 5/71). Compared with PC, a larger proportion of EPC patients were found to have immunocompromised conditions judged by predisposing factors (p < 0.01), or detectable humoral or cellular immunodeficiency. Fever and headache were more common in EPC patients (p < 0.001). Patients with EPC had lower serum sodium level (p = 0.041), lower monocyte counts (p = 0.025) and higher C-reactive protein (p = 0.012). In our study, the sensitivity of cryptococcus antigen detection for EPC was 100% regardless of sample type, while serum lateral flow assay (LFA) tested negative in 25% (5/20) of PC. Immunocompromised hosts are more likely to suffer from EPC than PC., (© 2023. The Author(s).)

Background: Cryptococcosis is caused by a fungi of the Cryptococcus neoformans/Cryptococcus gattii complex and is a severe concern for public health worldwide. C. neoformans species are globally distributed, and C. gattii species are mostly found in America, Australia, and Sub-Saharan Africa. Cryptococcus usually infects an immunocompromised population; however, the majority of cryptococcosis in China has been reported in patients without any recognizable immunosuppression, i.e., HIV infection. To date, very few studies investigated this disease in South Central China., Methods: The present study recruited 230 clinically suspected cryptococcosis cases in the last 5 years at two hospitals in Jiangxi Province, South Central China. All isolated strains were subjected to multilocus sequence typing (MLST) and phylogenetic analysis. Serotype and mating type were assessed by PCR, in vitro antifungal susceptibility was assessed by the CLSI-M27-A3 protocol., Results: A total of 230 patients were identified as infected by C. neoformans , including 12 cases with Talaromyces marneffei coinfection. All seven MLST markers were successfully amplified and used to identify the ST genotype in 199 strains. C. gattii strains were not detected. In contrast to previous studies, 59.3% of the patients had an immunocompromised status, and 61.9% of these patients were infected with HIV. All isolates manifested serotype A and mating type α. The ST5 genotype was common (89.5%) in the Jiangxi region, and three novel genotypes (ST656, ST657, and ST658 in six isolates) were detected in the present study. A total of 86 of the isolates (43.2%) were not sensitive to fluconazole at a MIC 50 ≥ 8 μg/ml, most of the isolates were resistant to amphotericin B, and nearly all isolates were resistant to itraconazole and posaconazole. Resistances to 5-Flucytosine and voriconazole were very rare., Conclusions: The results of the present study indicated that C. neoformans is the predominant species for cryptococcosis in Jiangxi Province, and a large proportion of the strains were not sensitive to fluconazole, which may be related to treatment failure and relapse. A high percentage of HIV-related C. neoformans infections was reported in Jiangxi, supporting a previous hypothesis that cryptococcosis is more frequent among the HIV-infected population in China. Continuous monitoring of species distribution and antifungal sensitivity is important for the investigation of this severe disease in the Jiangxi region., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Bian, Blechert, Deng, Chen, Li, Yang, Chen and Zhan.)

Background: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat., Methods: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression)., Results: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015)., Conclusions: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients., (© 2021. The Author(s).)

Cryptococcus neoformans is an environmental fungal pathogen that causes opportunistic infections and severe disseminated meningoencephalitis, mainly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS). In this study, the clinical characteristics, treatment protocols, and outcomes of 70 patients with AIDS and Cryptococcus neoformans infection at Beijing Ditan Hospital were retrospectively analyzed. We performed antimicrobial sensitivity tests and multilocus sequence typing (MLST) on C. neoformans isolates from these patients. The most common symptoms were headache (58.6%), fever (54.3%), and high cerebrospinal fluid pressure (≥200 mm H 2 O) (71.4%). All patients were positive for C. neoformans antigen in blood or cerebrospinal fluid. The CD4 cell counts of 92.8% (65/70) of patients were <100 cells/µL. In total, 74 C. neoformans isolates were obtained from the 70 patients. The 65 isolates that could be typed fell into 12 sequence types (STs) by MLST: ST5, ST31, ST63, ST202, ST237, ST289, ST295, ST296, ST298, ST324, ST337, and ST359. ST5 was the major type, accounting for 78.5% of isolates (51/65). This study comprehensively assessed the clinical and molecular epidemiology of C. neoformans in patients with AIDS and may inform the development of targeted prevention and treatment strategies for immunocompromised patients with C. neoformans infection.

To investigated the molecular epidemiology and in vitro antifungal susceptibility of Cryptococcus isolates from West China Hospital from HIV and non-HIV patients between 2009 and 2015. A total of 132 C. neoformans and C. gattii were subjected to antifungal susceptibility testing by E-test method. Among the 132 isolates, 42 C. neoformans and C. gattii were analyzed by mating type and URA5-RFLP. A total of 113 C. neoformans and C. gattii were subjected to multi-locus sequence typing (MLST). MLST results revealed that ST5 was the major molecular type. The wild-type (WT) phenotype was seen in 91.5-100% of C. neoformans isolates for amphotericin B, 5-flucytosine, fluconazole, and voriconazole. However, 72.3% (94/130) of C. neoformans isolates were non-wild-type (non-WT) to itraconazole by E-test method. In the sixth study year, the geometric mean, MIC 50 and MIC 90 of fluconazole were the highest (P < 0.001). Among 132 patients. 52 were coinfected with HIV and 80 were HIV-negative. Isolates from HIV and non-HIV patients showed no differences in susceptibility to amphotericin B (P = 0.544), 5-flucytosine (P = 0.063), fluconazole (P = 0.570), voriconazole (P = 0.542), and itraconazole (P = 0.787). Our study showed that Cryptococcus in southwest China showed a low degree of genetic diversity. The increased MIC values of fluconazole are noted. Cryptococcus isolates from HIV and non-HIV patients have shown no differences in susceptibility to five antifungal agents.

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.

Objectives: To explore the clinical features and associated factors of cryptococcosis in patients with connective tissue disease (CTD) from Southern China., Methods: Demographic and clinical data were collected between 2007 and 2018. Associated factors were analyzed by logistic regression analysis., Results: A total of 6809 inpatients with CTD were included. Cryptococcosis was diagnosed in 30 patients (prevalence, 0.4%). Cryptococcosis was predominant in patients with ANCA-associated vasculitis (AAV) (prevalence, 6/530, 1.1%). Lung was commonly involved (18/30, 60.0%), followed by meninges (6/30, 20.0%), blood stream (5/30, 16.7%), and disseminated cryptococcosis (involved blood stream and meninges) (1/30, 3.3%). Infiltrates (10/18, 55.6%) and small nodules (8/18, 44.4%) were the main radiographic manifestation of pulmonary cryptococcosis (PC). The positive rate of serum cryptococcal antigen (CrAg) in patients with PC was 88.2%. Cryptococcus spp. were found in 75% (3/4) patients who underwent lung biopsy. Most of the patients with cryptococcal meningitis (CM) had elevated cerebrospinal fluid (CSF) opening pressure (6/7, 85.7%) and decreased CSF glucose level (5/7, 71.4%). Positive blood culture confirmed the diagnosis of cryptococcal sepsis (CS). Three patients died (10.0%), including one with CM and two with PC. Multivariate logistic regression analysis showed that accumulated dose of glucocorticoid (GC) [odds ratio (OR) = 1.42, 95% confidence interval (CI) 1.04-1.93, P = 0.03] was associated with cryptococcosis in patients with CTD., Conclusions: Cryptococcosis develops in various organs. Typical radiological manifestation accompanied with positive serum CrAg provides helpful clues for the diagnosis. Lumbar puncture is a critical diagnostic method to distinguish CM. The accumulated dose of GC is associated with cryptococcosis in patients with CTD. Key Points • Pulmonary cryptococcosis is suspected if pulmonary nodules adjacent to the pleura are present, with serum CrAg positive. • Cryptococcal meningitis has insidious onset and the diagnosis mainly depends on lumber puncture. • Cryptococcal sepsis is not rare and needs timely blood culture in suspected patients.

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., Competing Interests: The authors have declared that no competing interests exist.

Cryptococcosis is a systemic infection and it may occur in immunocompromised and immunocompetent hosts. In order to better understand the clinical characteristics of patients with PC in different immune status, we retrospectively investigated the clinical, radiological, and treatment profiles of immunocompetent and immunocompromised patients with PC during a 10-year period (2008-2017). As a result, out of 136 patients, 94 (69.1%) were immunocompromised hosts. For the PC patients without CNS involvement, higher percentage of immunocompetent patients (39.5%, 15/38) had asymptomatic presentation than immunocompromised patients (6.3%, 3/48) (P < 0.05). Multiple pulmonary nodules (72.7%, 56/77), ground-glass attenuation/interstitial changes (94.4%, 17/18) and cavitation (88.6%, 31/35) were significantly frequent in immunocompromised patients (P < 0.05). A total of 47 patients were misdiagnosed as tuberculosis or tumors based on CT signs. PC was likely to be misdiagnosed as tuberculosis in immunocompromised patients (88.2%, 15/17), and tumor was more likely to be considered in immunocompetent patients (43.3%, 13/30). Immunocompetent patients accounted for 80% (24/30) of patients with definite diagnosis on surgical lung biopsy. Fluconazole monotherapy can achieve good clinical outcome in most PC patients without central nervous system (CNS) involvement (91.5%, 54/59). After 3 months of treatment, 92.7% (38/41) patients have improved imaging findings. In conclusion, PC has diverse imaging manifestations and it is easily misdiagnosed. Lobectomy should be carefully selected in immunocompetent patients with a single lung lesion. Fluconazole monotherapy is preferred for PC patients without CNS involvement.

Background: This study aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis from 2013 to 2017 in a major teaching hospital in China., Methods: Trends in antifungal drug susceptibility of 217 consecutive non-repetitive cryptococcal isolates collected from patients of an university hospital in China were analyzed between 2013 and 2017. Of those, 98 isolates were conserved for identification by internal transcribed spacer (ITS) sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Multilocus sequence typing (MLST) was used to designate molecular types. Clinical characteristics of the 98 patients with cryptococcosis during the period of 2013-2017 were retrospectively evaluated., Results: There was a trend for gradual increase in the MIC range of fluconazole was from 2013 to 2017. The conserved 98 clinical cryptococcal isolates included 97 C. neoformans and one C. gattii, and 90 (91.8%) isolates belonged to ST5 genotype VNI. Out of the 98 patients with cryptococcosis, 28 (28.6%) were HIV-infected and 32 (32.7%) had no underlying diseases. HIV-infected patients had higher mortality than HIV-uninfected patients (28.6% vs 14.3%, p=0.147)., Conclusions: Most of the patients with cryptococcosis were not HIV-infected in this study, while patients with HIV had a higher mortality. Reduced susceptibility to fluconazole was observed among C. neoformans isolates, most of them belonged to ST5 genotype VNI having an impact on the effective dose of fluconazole., (Copyright © 2019 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Pulmonary cryptococcosis (PC) is not considered an rare, opportunistic infection anymore. The immunocompetent population accounts for an increasing proportion of the morbidity., Objective: This study investigated the clinical characteristics of PC patients spanning 20 years, in a referral centre of China., Patients/methods: We retrospectively investigated the clinical data of 99 patients with PC who were diagnosed at Peking Union Medical College Hospital (PUMCH) from January 1998 to December 2017., Results: Pulmonary cryptococcosis incidence in PUMCH has seen sharp increase in two decades. There were 40.4% (40/99), 17.2% (17/99) and 42.4% (42/99) immunocompetent, mildly immunocompromised and severe immunocompromised patients, respectively. Significantly higher (P = .035) male predominance in immunocompetent and mildly immunocompromised groups (68.4%, 39/57) compared with severe immunocompromised group (45.2%, 19/42) was found. Overall, 27.5% (11/40) immunocompetent patients reported a significant difference (P = .02) in history of more than weekly drinking, higher than mildly or severe immunocompromised. No significant difference occurred in symptoms and radiographic characteristics among the groups. In pulmonary computerised tomography findings, the non-air pathway feature was the dominant distribution characteristics in all patients with PC (P = .002). The gap in body dissemination frequency between immunocompetent combined with mildly immunocompromised (5.26%, 3/57) and severe immunocompromised (19.0%, 8/42) was marginally significant (P = .05)., Conclusions: Gender and alcohol drinking could be PC risk factors of concern in patients without severe immunodeficiency. No significant difference occurred in symptoms or radiographic characteristics between patients with different levels of immune status. The unique radiographic non-air pathway distribution in the lung may be the feature of Cryptococcus invasion that may enhance accurate diagnosis., (© 2019 The Authors. Mycoses published by Blackwell Verlag GmbH.)

Cryptococcosis is a globally distributed infectious fungal disease. However, much remains unknown about its molecular epidemiology in many parts of the world. In this study, we analyzed 86 clinical Cryptococcus neoformans isolates from 14 regions in Jiangxi Province in south central China. Each isolate was from a different patient and 35 of the 86 (40.7%) patients were infected with HIV. All strains belonged to serotype A and mating type α (MATα). Genotyping based on DNA sequences at seven nuclear loci revealed eight sequence types (STs) among the 86 isolates, including two novel STs that have not been reported from other parts of the world. ST5 was the dominant genotype and our comparative analyses showed that these genotypes in Jiangxi likely originated by dispersal from other regions within and outside of China and/or mutations from another genotype within Jiangxi. Though none of the isolates was resistant to the five tested antifungal drugs (flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole), obvious differences in their minimum inhibitory concentrations were observed, even among isolates of the same ST. Our results suggest that continuous monitoring should be conducted to understand the changing dynamics of C. neoformans in this and other regions.

Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly., (© 2017 Blackwell Verlag GmbH.)

Objective: Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome. However, limited data exist for pediatric patients. The aim of this study was to describe the clinical characteristics of cryptococcosis in pediatric patients., Patients and Methods: A retrospective study was conducted at West China Second University Hospital, Sichuan University. Data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis were evaluated. Clinical characteristics associated with cryptococcal meningitis and disseminated cryptococcosis were compared., Results: Twelve cases of cryptococcal meningitis and 11 cases of disseminated cryptococcosis were identified. Seventeen cases had no underlying disease, but 6 cases had malnutrition. Only 6 cases had a history of exposure to pigeon droppings. No cases had pulmonary cryptococcosis alone. Coughing, pulmonary moist rales, swollen lymph nodes, liver and spleen, and skin rashes were seen only in disseminated cryptococcosis. The prevalence of headache and positive meningeal irritation sign was higher in cryptococcal meningitis than disseminated cryptococcosis. The proportion of increase in eosinophils was higher in disseminated cryptococcosis than cryptococcal meningitis. The primary methods used for diagnosis included cerebrospinal fluid ink staining, cerebrospinal fluid culture, blood culture, and lymph node biopsy. Two patients stopped treatment, and 21 patients received antifungal therapy. The mortality rate was 39.13%., Conclusions: Cryptococcosis occurs in non-HIV infected and immunocompetent children. Cryptococcosis lacks specific clinical manifestations. Disseminated cryptococcosis commonly occurs in children. Clinicians should consider a diagnosis of disseminated cryptococcosis for children who present with unexplained long-term fever, mild cough, chest imaging inconsistent with clinical symptoms, lymphadenectasis, hepatosplenomegaly, and eosinophilia.

Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality, primarily caused by Cryptococcus neoformans and Cryptococcus gattii. In China, C. neoformans var. grubii (especially molecular type VNI) is the most common variety in the environment and responsible for the majority of cryptococcal infections. C. gattii infections are quite rare in China and the primary molecular type is VGI, which is closely related to C. gattii isolates in Australia. Interestingly, the majority of cryptococcosis in China were reported in the HIV-uninfected patients (especially immunocompetent hosts). This unique phenomenon may be attributed to multiple polymorphisms in the genes encoding mannose-binding lectin (MBL) and Fc-gamma receptor 2B (FCGR2B) in the Han population, the major ethnic group in China. Compared to immunocompromised patients, immunocompetent patients with cryptococcal meningitis often presented with more intense inflammatory responses and more severe neurological complications, but less fungal burdens and disseminated infection. The overall prognosis, which is independently associated with amphotericin B-based initial therapy, is similar between immunocompetent and immunocompromised patients. In addition, intrathecal administration of amphotericin B has been proved to be an effective adjunctive treatment for cryptococcosis in China., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous reports on the molecular characteristics of clinical isolates of Cryptococcus species in China have focused on isolates from southeast China. To obtain a more detailed molecular epidemiology, a total of 92 cryptococcal isolates were collected from Sichuan province. A total of 24 isolates from 12 other provinces were collected for comparative study. Genotypes and mating types of 116 Cryptococcus isolates were determined. Among the 116 isolates, 43 isolates (19 isolates from Sichuan and 24 isolates outside of Sichuan) were analysed by multi-locus sequence typing (MLST). All 116 clinical isolates were mating type α. Most isolates (114/116) were molecular type VNI and the remaining two isolates were VGI and VGII respectively. MLST results revealed five sequence types (STs) of C. neoformans including two novel STs, with most isolates identified as ST5. The two C. gattii isolates identified in our study were ST44 and ST159. Based on our report and previous studies, there are 15 C. neoformans STs in China which can be divided into three subgroups. The C. gattii isolate from Sichuan could be a scattered subtype of VGII (ST44). Our findings demonstrated that C. neoformans isolates in Sichuan are genetically homogeneous, and ST5 is the epidemic clone of C. neoformans in China., (© 2015 Blackwell Verlag GmbH.)

The purpose of this study was to investigate the molecular characteristics of 83 clinical Cryptococcus neoformans/C. gattii species complex isolated in Beijing, China, between 2007 and 2013. Restriction fragment length polymorphism of the gene URA5 (URA5-RFLP), multilocus sequence typing (MLST), and automated repetitive polymerase chain reaction (rep-PCR; DiversiLab system) were performed to genotype these cryptococcal isolates. There was an excellent correlation amongst the three methods; however, PU157 was assigned as VNII according to URA5-RFLP, while it was classified as VNI by the DiversiLab system analysis. PU157 was finally identified as VNB by seven-locus MLST analysis. Moreover, though AD hybrids could not be processed by MLST, ideal results could be obtained by the DiversiLab system. The genotype VNI accounted for 95.2% (79/83) of isolates. Besides one strain of VNB, VNIII, and VGI each, a strain of VGII was detected in our study, which was isolated from a patient from the temperate region in North China. In addition, the most common MLST sequence type (ST) was ST5, accounting for 91.6% (76/83), followed by ST31, ST63, ST182, ST295, ST296, and ST332. ST295, ST296, and ST332 were new STs. Except for isolate PU157 (VNB), identical results were obtained quickly and accurately through the DiversiLab system compared to MLST and URA5-RFLP. The discovery of VNB and VGII in the temperate climate regions of China suggested that the population structure of C. neoformans and C. gattii should be explored more extensively. Our results also showed that the DiversiLab system can be used in the genotyping of C. neoformans and C. gattii.

Background: Cryptococcosis is a severe fungal infection with a high mortality rate among solid-organ transplant recipients. Today, China is among the countries performing the most kidney transplants worldwide, however data on the association of cryptococcosis with kidney transplantation in mainland China remain scarce and fragmented., Methods: We retrospectively analyzed cases of culture-confirmed cryptococcosis following kidney transplantation that have occurred at our hospital and reviewed the published cases in China over the last 30 years., Results: Cryptococcosis in kidney transplant recipients was mainly caused by Cryptococcus neoformans var. grubii VNI strains and occurred most frequently in patients aged 41-50 years (37.9%, 11/29). The average time to infection after kidney transplantation was 5.16 ± 3.97 years. The clinical manifestations were found to be diverse, with slight to moderate headache and fever, meningeal irritation, and high cerebrospinal fluid pressure being relatively common. Physicians should be alert to these symptoms among kidney transplant recipients., Conclusions: Cryptococcosis is a serious infection among kidney transplant recipients in mainland China. It has unique characteristics, such as a relatively long time to onset after kidney transplantation, and diverse clinical manifestations. Treatment with intrathecal injection of amphotericin B is considered effective for central nervous system involvement. The findings of this study also highlight the urgent need for multicenter, prospective, and multidisciplinary clinical studies and education on cryptococcosis in kidney transplant recipients in China., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cryptococcosis is a potential fatal disease, especially in immunocompromised patients. In China, the profile of cryptococcosis is unclear. Therefore, we summarize the epidemiology and therapy of cryptococcosis in china., Methods: All cases reports about cryptococcosis in China were collected from CBMdisk database (China Biology and Medicine data disc) with key words of cryptococcosis, or cryptococcal infection, or cryptococcus, and case. The features of the cryptococcosis were retrospectively analyzed., Results: There were 1,032 reports about cryptococcosis, including 8,769 cases. Among them, there were 16% patient with AIDS/HIV, and 17% ones without underlying diseases. There were 2,371 cases of CNS infection. Among them of 2,068 cases, the treatment protocols and outcome were clearly described. The percentages of patients who received intrathecal treatment of amphotericin B(AmB), AmB + 5-FC(5-fluorocytosine), AmB + FCZ(fluconazole), and AmB + 5-FU + FCZ in each medication group were 10, 43, 53, and 33%, respectively. The mortalities were significantly lower in the AmB, Amb + 5-FC, AmB + FCZ intrathecal treatment groups compared with their non-intrathecal treatment controls (6% vs. 23%, 25% vs. 35%, 20% vs. 30%, respectively, P < 0.05), but not in the intrathecal AmB + 5-FU + FCZ group (35% vs. 26%, P > 0.05)., Conclusion: The Chinese cryptococcosis had its own special clinical features, such as more patients without identifiable underlying diseases. Intrathecal injection of amphotericin B was effective treatment method for cryptococcal CNS infection in China.

Objective: To characterize the molecular and phenotypic traits of the VGII genotype of Cryptococcus gattii isolate XH91 firstly isolated in China., Methods: The serotype was identified by molecular method; multi-locus sequence typing (MLST) was performed based on 16 gene fragments both of nuclear and mitochondria genomes; the abilities of haploid fruiting, same-sex mating and opposite sex mating were all evaluated; the phenotypic traits including melanin production, capsule size, and growth at 37 degrees C were characterized., Results: The isolate XH91 firstly isolated in China was serotype B. The isolate shared the same MLST genotype with the minor outbreak genotype VGIIb from Vancouver islands. Strain XH91 could mate with the reference strain of opposite mating type and produced basidiospores, but could not mate with the reference strain of same mating type and had no ability of haploid fruiting. We did not observe obvious difference between XH91 and reference strains for melanin production, capsule size, and growth at 37 degrees C., Conclusion: Based on the results from MLST and phenotypic analysis, the Cryptococcus gattii strain XH91 is identical with the minor outbreak genotype VGIIb from Vancouver islands. This study will be critical to gain further insight into the emergence and molecular epidemiology of the VGII genotype of Cryptococcus gattii from China.

Cryptococcosis has been reported to be mostly associated with non-HIV-related patients in China. However, little is known about the molecular characteristics of clinical isolates from the Cryptococcus neoformans species complex in this country. In this study, 115 clinical isolates were included. Molecular type VNI was the most representative (n=103), followed by VGI (n=8), VNIII (n=2), VNIV (n=1), and VGII (n=1). With the exception of a serotype D mating type a isolate, all possessed the MATalpha locus. Multilocus sequence typing (MLST) revealed that most Cryptococcus gattii isolates from China shared identical MLST profiles with the most common MLST genotype reported in the VGI group, and the only one VGII isolate resembled the Vancouver Island outbreak minor genotype. The C. gattii strains involved in this study were successfully grouped according to their molecular type and mating types by PCR-restriction fragment length polymorphism (RFLP) analysis of the GEF1 gene. Our results suggest that (1) in China, cryptococcosis is mostly caused by C. neoformans var. grubii (molecular type VNI), and mating type alpha; (2) The most common causative agents of C. gattii infection in China are closely related to a widely distributed MLST genotype; and (3) The PCR-RFLP analysis of the GEF1 gene has the potential to identify the molecular and mating types of C. gattii simultaneously.

To determine the population structure of the cryptococcosis agents in China, we analyzed the genotype of 120 Cryptococcus neoformans and 9 Cryptococcus gattii strains isolated from 1980 through 2006 from cryptococcosis patients residing in 16 provinces of mainland China. A total of 71% (91/129) of the clinical strains isolated from 1985 through 2006 were from patients without any apparent risk factors. Only 8.5% (11/129) were from AIDS patients; the remaining 20.5% (27/129) were from patients with underlying diseases other than HIV infection. One hundred twenty of the 129 isolates were C. neoformans serotype A, mating type MATalpha strains that exhibited an identical M13-based VNI subtype, which was distinguishable from the reference VNI molecular type. The 9 remaining isolates were serotype B, MATalpha strains of C. gattii and portrayed a typical VGI molecular type. Data analyzed from multilocus sequences showed no variation and that these Chinese C. neoformans isolates belong to a cluster that has phylogenetically diverged from the VNI reference strain. Our finding that most cryptococcosis patients in China had no apparent risk factor is in stark contrast with reports from other countries.

Invasive fungal infections (IFIs) have become a major cause of morbidity and mortality among people with acquired immune deficiency syndrome (AIDS), however, little is known about the clinical features and prognosis of IFI in AIDS in China. This study aimed to characterise the clinical features and prognosis of IFI in AIDS patients in China. We retrospectively reviewed the records of all HIV-infected patients at a Chinese university hospital between December 2004 and May 2006. We identified 35 patients with IFI. IFIs included thrush, oesophageal candidiasis, fungal pneumonia, cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in the digestive tract, 71.8% of IFIs occurred in patients with CD4(+)T-lymphocyte counts <100 cells mm(-3). Candida albicans accounted for 57.4% of fungal pathogens isolated. All the patients received both antiretroviral and antifungal therapy; 27 patients were cured and eight died. IFI is one of the most common opportunistic infections in AIDS patients in China. IFIs mainly occur in patients with low CD4(+)T-lymphocyte counts. The majority of IFIs occur in the digestive tract. The most common pathogen causing IFI is C. albicans. The mortality rate remains high although antiretroviral therapy and many newer antifungals are available in China.