Risk Factors for Cryptococcus gattii Infection | CDC EID

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Volume 17, Number 2–February 2011
Research
Risk Factors for Cryptococcus gattii Infection, British Columbia, Canada
Laura MacDougall, Murray Fyfe, Marc Romney, Mike Starr, and Eleni Galanis

Author affiliations: British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada (L. MacDougall, M. Fyfe, M. Romney, M. Starr, E. Galanis); Public Health Agency of Canada, Ottawa, Ontario (L. MacDougall); Vancouver Island Health Authority, Victoria, British Columbia, Canada (M. Fyfe); University of British Columbia, Vancouver (M. Fyfe, M. Romney, E. Galanis); St. Paul's Hospital, Vancouver (M. Romney); and Royal Children's Hospital, Melbourne, Victoria, Australia (M. Starr)


Suggested citation for this article

Abstract

To determine whether particular environmental, medical, or behavioral risk factors existed among Cryptcoccus gattii–infected persons compared with the general population, we conducted a sex-matched case–control study on a subset of case-patients in British Columbia (1999–2001). Exposures and underlying medical conditions among all case-patients (1999–2007) were also compared with results of provincial population–based surveys and studies. In case–control analyses, oral steroids (matched odds ratio [MOR] 8.11, 95% confidence interval [CI] 1.74–37.80), pneumonia (MOR 2.71, 95% CI 1.05–6.98), and other lung conditions (MOR 3.21, 95% CI 1.08–9.52) were associated with infection. In population comparisons, case-patients were more likely to be >50 years of age (p<0.001), current smokers (p<0.001), infected with HIV (p<0.001), or have a history of invasive cancer (p<0.001). Although C. gattii is commonly believed to infect persons with apparently healthy immune systems, several immunosuppressive and pulmonary conditions seem to be risk factors. Cryptococcus gattii emerged on Vancouver Island, British Columbia (BC), Canada, in 1999, resulting in one of the highest incidences of this infection worldwide (1,2). The natural reservoir of C. gattii seems to be soil and plant debris, and it has been associated with numerous tree species (3,4). When inhaled, this encapsulated basidiomycetous yeast may infect humans as well as diverse animal species (5). Infected humans may be asymptomatic but usually exhibit pulmonary infection characterized by cough, shortness of breath, and single or multiple pulmonary nodules visible on radiographs of the lung. Body sites such as brain, skin, and bone are affected less commonly (6,7). Approximately 18% of patients in British Columbia have disseminated disease, including meningitis and brain cryptococcomas (1). The case-fatality rate among BC residents during 1999–2007 was 8.7% (1). C. gattii is believed to infect persons with uncompromised immune systems (8,9), unlike C. neoformans, a relatively common opportunistic pathogen in HIV-infected patients and other immunocompromised patients. Although true differences in species-specific pathogenicity may exist, C. gattii may also commonly infect persons with undetected immune deficiencies. Early studies have identified several risk factors for Cryptococcus spp. infection; however, these do not distinguish between species. In experimental studies, steroids have been shown to decrease host resistance to infection (10). Case-series investigations have linked corticosteroid use with an increased risk of dying from cryptococcal meningitis (11) and with an increased risk for disseminated disease (12). A nationwide survey of 163 HIV-negative cryptococcosis patients in France (1985–1993) showed that having malignancies (32%), undergoing organ transplantation (19%), and receiving corticosteroid therapy (33%) were the main predisposing factors (13). Other frequently identified predisposing conditions for cryptococcosis include sarcoidosis, hyper-immunoglobulin (Ig) M and hyper–IgE syndromes, and CD4+ T-cell lymphopenia in those who are HIV negative (14). Case reports have also suggested that cirrhosis is a risk factor for cryptococcal peritonitis (15). Compared with results for adults, cryptococcal infections are rare in children, no matter their HIV status (16). Historical studies of cryptococcosis patients have shown that higher proportions of male patients had the disease, both before and after the HIV epidemic (14). The risk for disseminated infection among HIV-positive persons with cryptococcal infection was almost 4× higher for those who smoked at the time of diagnosis than for those who did not (17). Many studies that examined predisposing factors for Cryptococcus infection in humans have done so in selected populations (e.g., HIV-positive patients), and assessment has been frequently limited to medical rather than behavioral or environmental exposures. Often laboratory testing was not undertaken to distinguish patients with C. gattii infection from those with C. neoformans infection. In newer studies, which have obtained subtyping information, typically, the number of C. gattii isolates was insufficient to determine risk factors. Risk factors suggested in the medical literature have arisen from case reports and case series that described the proportion of patients with particular underlying conditions. Although some investigations have compared risk factors between patients with C. gattii and those with C. neoformans infections (8,9), we could find no examples in which case-patients were compared with healthy controls to determine risks for disease acquisition. Ecologically, epidemiologically, and clinically, C. gattii is sufficiently different from its fungal relative C. neoformans (including C. neoformans var. grubii and C. neoformans var. neoformans) to warrant its own species designation (18). It therefore seems reasonable to assume that the risk factors for disease acquisition may not be the same. We undertook this current investigation to determine whether, compared with the general population, particular medical, behavioral, or environmental risk factors existed among case-patients with C. gattii infection in British Columbia, Canada. full-text: Risk Factors for Cryptococcus gattii Infection | CDC EID



Suggested Citation for this Article
MacDougall L, Fyfe M, Romney M, Starr, Galanis E. Risk factors for Cryptcoccus gattii infection, British Columbia, Canada. Emerg Infect Dis [serial on the Internet]. 2011 Feb [date cited].
http://www.cdc.gov/EID/content/17/2/193.htm


DOI: 10.3201/eid1702.101020


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Laura MacDougall, British Columbia Centre for Disease Control, 655 W 12th Ave, Vancouver, BC V5Z 4R4, Canada; email: laura.macdougall@bccdc.ca