Abstract
Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia.
Highlights
Cryptococcosis is one of the main fungal diseases in Asia due to the AIDS pandemic and is caused by members of the Cryptococcus neoformans/C. gattii species complex [1,2]
Different colors correspond to different countries; (B) Same as A, but showing the genotypes from clinical and environmental sources; (C) Same as A and B, but with the addition of the genotypes of 179 C. neoformans var. grubii isolates from different continents. doi:10.1371/journal.pone.0072222.g001
The 476 C. neoformans var. grubii isolates in our dataset were obtained from 228 HIV-positive patients, 134 HIV-negative patients, and 47 from individuals with unknown HIV status (Table A in Supplementary Tables S1), as well as 67 isolates from avian droppings from Chiang Mai, Thailand and Tokyo, Japan (Table B in Supplementary Tables S1)
Summary
Cryptococcosis is one of the main fungal diseases in Asia due to the AIDS pandemic and is caused by members of the Cryptococcus neoformans/C. gattii species complex [1,2]. The number of HIV-infected patients that annually acquire cryptococcosis is estimated to be over 140,000 [3], with the majority of cases being caused by C. neoformans var. Grubii has been reported to occur in immunocompetent individuals in the Asian region, e.g. from China, Japan, Korea and Taiwan [8,13,14,15,16]. In Vietnam, cryptococcosis in both immunocompromised and immunocompetent individuals was found to be mainly caused by C. neoformans var.
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