Genotypic diversity and antifungal susceptibility of <i>Cryptococcus neoformans</i> isolates from paediatric patients in China

Hong, Nan; Chen, Min; Xu, Nan; Al‐Hatmi, Abdullah M. S.; Zhang, Chao; Pan, Wei; Hagen, Ferry; Boekhout, Teun; Xu, Jianping; Zou, Xian B; Wan-qin, Liao

doi:10.1111/myc.12863

Cited by 12 publications

(8 citation statements)

References 48 publications

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“…In our study, ST5 and ST31 were the most common epidemic genotypes, similar to results from domestic research reports [ 16 , 35 ]. Notably, in the adjacent province of Sichuan, the ST5 prevalence is 82.9% (34/41) [ 36 ].…”

Section: Discussionsupporting

confidence: 90%

“…Candida parapsilosis ATCC 22019 was used as the control strain for the susceptibility assays. Based on domestic and foreign research reports, we set the epidemiological cut-off values (ECVs) at 8 mg/L for 5-FC and FLU, 0.25 mg/L for ITR and VOR, and 1 mg/L for AMB for Cryptococcus neoformans [ 16 – 18 ]. In the present study, isolates with minimum inhibitory concentration values above the ECVs were considered resistant.…”

Section: Methodsmentioning

confidence: 99%

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Risk Factors for Cryptococcal Meningitis Recurrence in Human Immunodeficiency Virus (HIV)-Infected Patients in a Large Chinese Acquired Immune Deficiency Syndrome (AIDS) Treatment Center

Zhou

et al. 2021

Med Sci Monit

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Background Cryptococcal meningitis (CM) is one of the most common opportunistic neuroinfections in patients with HIV. Most studies have focused on non-HIV CM and there are only a few studies on HIV CM in China. The purpose of the present study was to evaluate the characteristics and risk factors for CM recurrence in patients infected with HIV in the Chongqing Public Health Treatment Center in China. Material/Methods From January 2014 to December 2017, all patients with CM aged 18 years or older were enrolled and a case-control study was performed to determine the risk factors associated with recurrence of CM. Antimicrobial susceptibility was determined with a fungal drug sensitivity kit and the sequence types (STs) were analyzed with multilocus sequence typing. Results The incidence of CM in the 5185 HIV-infected patients was 3.5% (179). Follow-up data were available for 82 of the patients for whom complete medical records were available and they were included in the present study. There were 7 STs among 82 Cryptococcus neoformans isolates; ST5 and ST31 were the most prevalent genotypes. Testing showed that C. neoformans had high sensitivity to 5 antifungal drugs and no differences in resistance were observed, even when different STs were tested. Risk factors for recurrence were analyzed in 69 patients, excluding those who died. The results of multivariate analysis showed that only hospital stay was associated with recurrence of CM. Conclusions Our results indicated that combining education about medication with clinical treatment could help prevent recurrence of CM.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Risk Factors for Cryptococcal Meningitis Recurrence in Human Immunodeficiency Virus (HIV)-Infected Patients in a Large Chinese Acquired Immune Deficiency Syndrome (AIDS) Treatment Center

Zhou

et al. 2021

Med Sci Monit

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“…A total of 4200 isolates from 41 studies were included in our population genetic analyses. The detailed descriptions of these isolates and their genotype data, including their protocols for DNA extraction, amplification and sequencing and allelic profiling can be found in the original reports [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Methodsmentioning

confidence: 99%

Analyses of the Global Multilocus Genotypes of the Human Pathogenic Yeast Cryptococcus neoformans Species Complex

Hitchcock

2022

Genes

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Cryptococcus neoformans species complex (CNSC) is a globally distributed human opportunistic yeast pathogen consisting of five major molecular types (VNI, VNII, VNB, VNIII and VNIV) belonging to two species, C. neoformans (VNI, VNII and VNB, collectively called serotype A) and C. deneoformans (VNIV, commonly called serotype D), and their hybrids (VNIII, serotype AD). Over the years, many studies have analyzed the geographical distribution and genetic diversity of CNSC. However, the global population structure and mode of reproduction remain incompletely described. In this study, we analyze the published multilocus sequence data at seven loci for CNSC. The combined sequences at the seven loci identified a total of 657 multilocus sequence types (STs), including 296 STs with known geographic information, representing 4200 non-redundant isolates from 31 countries and four continents. Among the 296 STs, 78 and 52 were shared among countries and continents, respectively, representing 3643 of the 4200 isolates. Except for the clone-corrected serotype D sample among countries, our analysis of the molecular variance of the 4200 isolates revealed significant genetic differentiations among countries and continents in populations of CNSC, serotype A, and serotype D. Phylogenetic analyses of the concatenated sequences of all 657 STs revealed several large clusters corresponding to the major molecular types. However, several rare but distinct STs were also found, representing potentially novel molecular types and/or hybrids of existing molecular types. Phylogenetic incompatibility analyses revealed evidence for recombination within all four major molecular types—VNI, VNII, VNIV and VNB—as well as within two VNB subclades, VNBI and VNBII, and two ST clusters around the most common STs, ST5 and ST93. However, linkage disequilibrium analyses rejected the hypothesis of random recombination across most samples. Together, our results suggest evidence for historical differentiation, frequent recent gene flow, clonal expansion and recombination within and between lineages of the global CNSC population.

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“…Antifungal agents fluconazole (FLC), fluorocytosine (5FC), amphotericin B (AMB), itraconazole (ITC), voriconazole (VOR), posaconazole (POS) and isavuconazole (ISA) were used in the susceptibility tests. The broth microdilution method was performed following the CLSI M27-A3 guidelines [32] to assess the antifungal susceptibility of all clinical isolates in vitro. The concentration ranges were 0.125-64 μg/mL for FLC, 0.008-4 μg/mL for 5FC, 0.016-8 μg/mL for AMB and 0.002-1 μg/mL for ITC, VOR, POS and ISA.…”

Section: Antifungal Susceptibility Testingmentioning

confidence: 99%

Emerging Cryptococcus gattii species complex infections in Guangxi, southern China

et al. 2020

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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.

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Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans isolates from paediatric patients in China

Cited by 12 publications

References 48 publications

Risk Factors for Cryptococcal Meningitis Recurrence in Human Immunodeficiency Virus (HIV)-Infected Patients in a Large Chinese Acquired Immune Deficiency Syndrome (AIDS) Treatment Center

Risk Factors for Cryptococcal Meningitis Recurrence in Human Immunodeficiency Virus (HIV)-Infected Patients in a Large Chinese Acquired Immune Deficiency Syndrome (AIDS) Treatment Center

Analyses of the Global Multilocus Genotypes of the Human Pathogenic Yeast Cryptococcus neoformans Species Complex

Emerging Cryptococcus gattii species complex infections in Guangxi, southern China

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