Global Occurrence of C. gattii | CDC EID

EID Journal Home > Volume 16, Number 1–January 2010

Volume 16, Number 1–January 2010
Synopsis
Projecting Global Occurrence of Cryptococcus gattii
Deborah J. Springer and Vishnu Chaturvedi
Author affiliations: New York State Department of Health, Albany, New York, USA; and University at Albany School of Public Health, Albany

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Abstract
Cryptococcus gattii and C. neoformans cause pulmonary and systemic cryptococcosis. Recently, C. gattii was recognized as a distinct pathogen of humans and animals. We analyzed information from 400 publications (1948–2008) to examine whether the fungus occurs globally. Known distribution of C. gattii is possibly limited because specialized reagents for differentiation from C. neoformans are not readily available and not always used, and environmental surveys are patchy. However, autochthonous reports of C. gattii cryptococcosis have now been recognized from tropical and temperate regions. An ongoing outbreak in western Canada strengthens the case that the range of the pathogen has expanded. A few studies have highlighted differences in cryptococcosis between C. gattii and C. neoformans. More than 50 tree species have yielded C. gattii especially from decayed hollows suggesting a possible ecologic niche. This pathogen merits more attention so its environmental occurrence and role in cryptococcosis can be accurately determined.

The yeast genus Cryptococcus has been recognized for >125 years, first from fruit juice, milk, humans, soil, and pigeon droppings and from roosting areas (1). Although C. neoformans human infections were reported early in the 1900s, the overall number of cryptococcosis cases was extremely low. Cryptococcosis cases increased in Africa during 1947–1968, presumedly in association with the emergence of AIDS in the Congo River basin (2); however, no independent confirmation or laboratory data are available for this hypothesis. A unique variant, C. neoformans var. gattii, manifested by the unusual presence of elongated and cigar-shaped yeast morphology in cerebrospinal fluid, was first described in a Congolese Bantu boy (3,4).

Evans described and differentiated C. neoformans into 3 serologic types (A, B, and C) by agglutination (5). Diagnosis of cryptococcosis progressed further with identification of C. neoformans antibodies in body fluids and development of a latex agglutination test (1). Staib (6) developed a Guizotia abyssinica (Nigerseed) creatinine agar medium to distinguish pigment-producing C. neoformans from other Cryptococcus spp., which facilitated rapid screening of clinical and environmental samples for pathogenic C. neoformans isolates. A major advance in the classification and taxonomy of C. neoformans occurred with the discovery of a heterothallic, bipolar mating involved in the production of the perfect state for C. neoformans var. gattii (serotypes B and C). It was termed Filobasidiella bacillispora and differentiated from F. neoformans by production of smooth, elongate cylinder- to rod-shaped basidiospores (7).

Currently, C. neoformans is recognized as a species complex comprising C. neoformans var. grubii (serotype A) and C. neoformans var. neoformans (serotype D), which have distinct clinical manifestations and biological characteristics (1,8). C. gattii (serotypes B and D) was recognized as a species distinct from C. neoformans because of differences in basidiospore morphology, environmental niches, morphologic features in vivo, limited molecular identity (55%–61% relatedness of DNA), multiple gene genealogies, unique random amplified polymorphic DNA typing patterns, and inefficient cross-species mating with the production of sterile progeny and no recombination (9). During the previous 2 decades, the increased pace of discovery produced a new appreciation of the 2 major pathogenic species, namely, C. neoformans and C. gattii. This study aimed to critically examine published information about associated tree species, ecology, and geographic occurrence of C. gattii to infer its environmental distribution.

Methods
We comprehensively searched for published reports using the PubMed database (US National Library of Medicine, National Institutes of Health) for 1948–2008. The keywords used in the search were Cryptococcus alone or in combination with Cryptococcus gattii; Cryptococcus neoformans; Cryptococcus neoformans var. neoformans; Cryptococcus neoformans var. grubii; Cryptococcus neoformans serotype A, B, C, D, or AD; and cryptococcosis alone or in combination with human, pigeon, and animal. Additionally, we scrutinized reference lists in publications obtained from PubMed searches for citations that had not been captured with our choice of keywords in PubMed searches. These citations were easily obtained by repeating the search criteria in the Web of Science (Thompson Reuters) and Google Scholar.

One of us (D.J.S.) independently examined the title, abstract, methods, data tables and figures of publications identified in the literature search. Information about Cryptococcus isolates, serotype, mating type, molecular type, geographic location, and other relevant details were entered into a master spreadsheet. All publications with adequate documentation of C. gattii by >1 valid laboratory methods were regarded as acceptable for inclusion.

Results
From 400 potentially useful publications, we shortlisted ≈200 and identified 105 that provided information about primary isolations of C. gattii from clinical, veterinary, and environmental sources. Geographically, the reports originated from a total of 48 countries, although most reports concentrated on few areas (Table 1). Because a certain level of selection bias existed in this search process, we might have missed some relevant publications (10).

Distinguishing Features of C. gattii
C. gattii was easily and reliably differentiated from C. neoformans on creatinine dextrose bromthymol blue (CDB) medium. This work built on the discovery that C. neoformans can assimilate creatinine as sole source of carbon and nitrogen. Further modification in CDB medium led to development of canavanine-glycine-bromthymol blue agar, which has since become the differential medium of choice (1,11,12). Unfortunately, the medium is still not widely used in diagnostic laboratories, most likely because of limited availability from commercial suppliers.

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