Risk Factors forCryptococcus gattiiInfection, British Columbia, Canada

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 Infections

“…Notably, C. gattii is overrepresented in Australian Aborigines (29), in whom diabetes is common. Diabetes was not a risk factor for C. gattii in British Columbia (230).…”

“…However, following the North American outbreaks and, more recently, outbreaks in Australia, new risk groups have been recognized. These groups include patients with underlying HIV infection, cancer, solid organ transplantation, and other immunodeficiencies (96,98,130,132,198,230) (Table 4). In an Australian study of 86 patients, HIV was rare (1 of 79 patients tested for antibodies to HIV), but 7% of patients had underlying idiopathic CD4 lymphopenia, 3% had previously received kidney transplants, 8.1% had a malignancy, and 14% had received corticosteroids or immunosuppressive drugs (130).…”

“…In British Columbia, only 62% of patients were considered previously healthy (198); a case-control analysis identified oral corticosteroid use, smoking, older age, HIV infection, and malignancy as risk factors (230). The proportion of patients who had predisposing conditions or who were taking immunosuppressive medications was even higher (76%) in U.S. cases (n ϭ 76 patients) infected with "outbreak" strains.…”

“…In the U.S. Pacific Northwest, the distribution of molecular types was as follows: 50% VGIIa, 32% VGIIc, 10% VGIIb, 5% VGI, and 3% VGIII (86). It is possible that the VGII genotype has a propensity to cause respiratory disease (see above) and that it is associated with host immunocompromise or predisposing medical conditions (40 to 73% of patients) (86,132,230). Although features of infection differ between "outbreak" and "nonoutbreak" disease, the reason for the difference has not been determined.…”

Impact of HIV infection and smoking on lung immunity and related disorders

“…This was associated with a higher frequency of influenza B than influenza A, a greater risk of pneumococcal co-infection and a higher mortality; however, there was no difference in smoking prevalence between the two groups of patients [130]. With respect to fungal infections, strong associations between smoking and infection with Cryptococcus neoformans and C. gattii have been described in both HIV-infected and -uninfected individuals [131,132].…”