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.

BackgroundCryptococcosis 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.MethodsThe 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.ResultsA 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 MIC50 ≥ 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.ConclusionsThe 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.