Cryptococcus neoformans infections at Vancouver Hospital and Health Sciences Centre (1997–2002): epidemiology, microbiology and histopathology

Abstract
An outbreak of infections due to a rare subspecies of Cryptococcus neoformans (var. gattii) was recognized on Vancouver Island (VI), British Columbia, in 2002, which had affected 59, mostly immunocompetent, individuals since 1999. The objectives of this study were to: (1) determine if the outbreak had spread to Vancouver and its surrounding communities and (2) review the epidemiological, clinical and pathological features of all cryptococcal infections in patients admitted to the Vancouver Hospital and Health Sciences Centre (VHHSC) over a 5 year period. VHHSC microbiology and pathology databases were searched for cryptococcal infections from 1 June 1997 to 31 December 2002. Hospital charts of all identified patients were reviewed. Available cryptococcal isolates and histopathological specimens were reviewed. Twenty-six cases of cryptococcosis were identified in both HIV-positive (n = 15) and HIV-negative (n = 11) patients. C. neoformans var. grubii was cultured from 13 patients, of whom 10 were HIV-positive. The outbreak strain, C. neoformans var. gattii, was detected in three patients; all had travelled to VI. C. neoformans var. neoformans was cultured from two patients, Cryptococcus laurentii was cultured from one, and seven patients had cryptococcosis based on histopathology alone, without cultures. The majority (10/15) of the HIV-positive patients developed systemic disease whilst HIV-negative patients (8/11) presented with pulmonary cryptococcosis. Lung biopsies revealed necrotizing and/or fibrosing granulomas, with cryptococcal cells in 5 of 10 specimens. Brain biopsies showed cryptococcal organisms within leptomeninges and deeper structures with minimal associated inflammation. This retrospective study demonstrated a sharp increase in the total number of C. neoformans infections in both immunocompromised and immunocompetent patients at the VHHSC in 2002. There was no evidence of spread of the outbreak strain to the Greater Vancouver area. This is the first correlation of clinical and investigational findings of cryptococcosis in a region in North America where C. neoformans varieties gattii and grubii are endemic.