Abstract
Cryptococcosis causes approximately 180 000 deaths each year in patients with human immunodeficiency virus (HIV). Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii, responsible for the majority of cases, is distributed globally. We used the consensus ISHAM Multilocus sequence typing (MLST) scheme to define the population structure of clinical C. neoformans var. grubii isolates from Laos (n = 81), which we placed into the global context using published MLST data from other countries (total N = 1047), including a reanalysis of 136 Vietnamese isolates previously reported. We observed a phylogeographical relationship in which the Laotian population was similar to its neighbor Thailand, being dominated (83%) by Sequence Types (ST) 4 and 6. This phylogeographical structure changed moving eastwards, with Vietnam's population consisting of an admixture of isolates dominated by the ST4/ST6 (35%) and ST5 (48%) lineages. The ST5 lineage is the predominant ST reported from China and East Asia, where it accounts for >90% of isolates. Analysis of genetic distance (Fst) between different populations of C. neoformans var. grubii supports this intermediate structure of the Vietnamese population. The pathogen and host diversity reported from Vietnam provide the strongest epidemiological evidence of the association between ST5 and HIV-uninfected patients. Regional anthropological genetic distances suggest diversity in the C. neoformans var. grubii population across Southeast Asia is driven by ecological rather than human host factors. Where the ST5 lineage is present, disease in HIV-uninfected patients is to be expected.
Highlights
Cryptococcus neoformans is the main etiological agent of cryptococcosis
Most cases of cryptococcal meningitis in Laos were associated with human immunodeficiency virus (HIV) infection
The population structure of C. neoformans var. grubii has been described for a number of Asian countries,[17] including Vietnam,[23] Thailand,[10,21] India,[37] China,[36,38,39,40] Japan,[14] and Korea.[13]
Summary
Cryptococcus neoformans is the main etiological agent of cryptococcosis. It is of major significance in patients infected with human immunodeficiency virus (HIV), accounting for an estimated 223 100 cases of meningitis per year globally, and in other individuals with immunosuppression.[1] C. neoformans is an environmental saprophyte associated with bird guano and trees.[2,3,4,5] There is no human to human spread, and human.
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