Geographically Structured Populations of <i>Cryptococcus neoformans</i> Variety <i>grubii</i> in Asia Correlate with HIV Status and Show a Clonal Population Structure

<div><p>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. <i>Cryptococcus neoformans</i> variety <i>grubii</i> (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 <i>C</i>. <i>neoformans</i>/<i>C</i>. <i>gattii</i> 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 <i>C</i>. <i>neoformans</i> var. <i>grubii</i> 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.</p>