{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:42:30Z","timestamp":1788871350013,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cryptococcosis is caused by a fungi of the <jats:italic>Cryptococcus neoformans\/Cryptococcus gattii<\/jats:italic> complex and is a severe concern for public health worldwide. <jats:italic>C. neoformans<\/jats:italic> species are globally distributed, and <jats:italic>C. gattii<\/jats:italic> species are mostly found in America, Australia, and Sub-Saharan Africa. <jats:italic>Cryptococcus<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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, <jats:italic>in vitro<\/jats:italic> antifungal susceptibility was assessed by the CLSI-M27-A3 protocol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 230 patients were identified as infected by <jats:italic>C. neoformans<\/jats:italic>, including 12 cases with <jats:italic>Talaromyces marneffei<\/jats:italic> coinfection. All seven MLST markers were successfully amplified and used to identify the ST genotype in 199 strains. <jats:italic>C. gattii<\/jats:italic> 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 \u03b1. 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<jats:sub>50<\/jats:sub> \u2265 8 \u03bcg\/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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of the present study indicated that C. <jats:italic>neoformans<\/jats:italic> 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. <jats:italic>neoformans<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.723251","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T06:40:57Z","timestamp":1635748857000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["High Prevalence of HIV-Related Cryptococcosis and Increased Resistance to Fluconazole of the Cryptococcus neoformans Complex in Jiangxi Province, South Central China"],"prefix":"10.3389","volume":"11","author":[{"given":"Chunxi","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyuan","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Blechert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyi","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41579-019-0322-2","article-title":"Drug Resistance and Tolerance in Fungi","volume":"18","author":"Berman","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/myc.12747","article-title":"A Systematic Review of Fluconazole Resistance in Clinical Isolates of Cryptococcus Species","volume":"61","author":"Bongomin","year":"2018","journal-title":"Mycoses"},{"key":"B3","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3201\/eid1405.071312","article-title":"Cryptococcus Neoformans Strains and Infection in Apparently Immunocompetent Patients, China","volume":"14","author":"Chen","year":"2008","journal-title":"Emerging. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s11046-020-00491-4","article-title":"Cryptococcus Neoformans Meningitis Cases Among China\u2019s HIV-Infected Population May Have Been Severely Under-Reported","volume":"185","author":"Chen","year":"2020","journal-title":"Mycopathologia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1038\/s41598-018-20054-4","article-title":"Multilocus Sequence Typing Reveals Both Shared and Unique Genotypes of Cryptococcus Neoformans in Jiangxi Province, China","volume":"8","author":"Chen","year":"2018","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1093\/mmy\/myx026","article-title":"Molecular Characterization of Cryptococcus Neoformans Isolated From the Environment in Beijing, China","volume":"55","author":"Dou","year":"2017","journal-title":"Med. Mycol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s10096-014-2289-2","article-title":"Molecular Epidemiology of Cryptococcus Neoformans and Cryptococcus Gattii in China Between 2007 and 2013 Using Multilocus Sequence Typing and the DiversiLab System","volume":"34","author":"Dou","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1128\/jcm.28.7.1642-1644.1990","article-title":"Natural Habitat of Cryptococcus Neoformans Var. Gattii","volume":"28","author":"Ellis","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"5898","DOI":"10.1128\/AAC.01115-12","article-title":"Cryptococcus Neoformans-Cryptococcus Gattii Species Complex: An International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Fluconazole, Itraconazole, Posaconazole, and Voriconazole","volume":"56","author":"Espinel-Ingroff","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1128\/AAC.06252-11","article-title":"Cryptococcus Neoformans-Cryptococcus Gattii Species Complex: An International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Amphotericin B and Flucytosine","volume":"56","author":"Espinel-Ingroff","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.fgb.2014.10.017","article-title":"Epidemiology of Cryptococcus and Cryptococcosis in China","volume":"78","author":"Fang","year":"2015","journal-title":"Fungal Genet. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.cmi.2016.07.008","article-title":"Predominance of Cryptococcus Neoformans Var. Grubii Multilocus Sequence Type 5 and Emergence of Isolates With Non-Wild-Type Minimum Inhibitory Concentrations to Fluconazole: A Multi-Centre Study in China","volume":"22","author":"Fan","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"B13","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.fgb.2015.02.009","article-title":"Recognition of Seven Species in the Cryptococcus Gattii\/Cryptococcus Neoformans Species Complex","volume":"78","author":"Hagen","year":"2015","journal-title":"Fungal Genet. Biol.: FG. B."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1099\/mic.0.2007\/015594-0","article-title":"Long-Distance Dispersal and Recombination in Environmental Populations of Cryptococcus Neoformans Var. Grubii From India","volume":"154","author":"Hiremath","year":"2008","journal-title":"Microbiol. (Reading England)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008493","article-title":"Emerging Cryptococcus Gattii Species Complex Infections in Guangxi, Southern China","volume":"14","author":"Huang","year":"2020","journal-title":"PloS Neglect. Trop. D."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072222","article-title":"Geographically Structured Populations of Cryptococcus Neoformans Variety Grubii in Asia Correlate With HIV Status and Show a Clonal Population Structure","volume":"8","author":"Khayhan","year":"2013","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s11046-008-9123-2","article-title":"Epidemiological Profile of Cryptococcal Meningitis Patients in Rio Grande do Sul, Brazil","volume":"166","author":"Leal","year":"2008","journal-title":"Mycopathologia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"511","DOI":"10.3760\/cma.j.issn.0366-6999.2012.03.020","article-title":"Ecological Surveys of the Cryptococcus Species Complex in China","volume":"125","author":"Li","year":"2012","journal-title":"Chin. Med. J.-Peking."},{"key":"B19","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nrmicro.2015.6","article-title":"Cryptococcus: From Environmental Saprophyte to Global Pathogen","volume":"14","author":"May","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1080\/13693780902953886","article-title":"Consensus Multi-Locus Sequence Typing Scheme for Cryptococcus Neoformans and Cryptococcus Gattii","volume":"47","author":"Meyer","year":"2009","journal-title":"Med. Mycol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3201\/eid0902.020246","article-title":"Molecular Typing of IberoAmerican Cryptococcus Neoformans Isolates","volume":"9","author":"Meyer","year":"2003","journal-title":"Emerging. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056269","article-title":"Epidemiology of Cryptococcal Meningitis in the US: 1997-2009","volume":"8","author":"Pyrgos","year":"2013","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"9387","DOI":"10.1038\/s41598-020-66094-7","article-title":"Clinical Analysis in Immunocompetent and Immunocompromised Patients With Pulmonary Cryptococcosis in Western China","volume":"10","author":"Qu","year":"2020","journal-title":"Sci. Rep.-UK."},{"key":"B24","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global Burden of Disease of HIV-Associated Cryptococcal Meningitis: An Updated Analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0","volume":"30","author":"Tamura","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.1128\/IAI.00542-09","article-title":"Spores as Infectious Propagules of Cryptococcus Neoformans","volume":"77","author":"Velagapudi","year":"2009","journal-title":"Infect. Immun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1111\/j.1567-1364.2006.00081.x","article-title":"Molecular Analysis of 311 Cryptococcus Neoformans Isolates From a 30-Month ECMM Survey of Cryptococcosis in Europe","volume":"6","author":"Viviani","year":"2006","journal-title":"FEMS Yeast, Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.2147\/IDR.S173805","article-title":"Five-Year China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study of Invasive Fungal Infections Caused by Noncandidal Yeasts: Species Distribution and Azole Susceptibility","volume":"11","author":"Xiao","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"B29","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1128\/JCM.40.3.965-972.2002","article-title":"Geographic Distribution of Mating Type Alleles of Cryptococcus Neoformans in Four Areas of the United States","volume":"40","author":"Yan","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s11046-011-9471-1","article-title":"Cryptococcosis in Chin","volume":"173","author":"Yuchong","year":"2012","journal-title":"Mycopathologia"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.3201\/eid2609.200016","article-title":"Risk-Based Estimate of Human Fungal Disease Burden, China","volume":"26","author":"Zhou","year":"2020","journal-title":"Emerging. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.723251\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T06:41:03Z","timestamp":1635748863000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.723251\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":31,"alternative-id":["10.3389\/fcimb.2021.723251"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.723251","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]},"article-number":"723251"}}