Cryptococcus gattii infection: Clinical features and diagnosis
- Sharon Chen, PhD, MBBS, FRACP, FRCPA
Sharon Chen, PhD, MBBS, FRACP, FRCPA
- Clinical Associate Professor
- Sydney Medical School, University of Sydney
- Kieren A Marr, MD
Kieren A Marr, MD
- Section Editor — Compromised Host Infections; Fungal Infections
- Professor of Medicine and Oncology
- Johns Hopkins University School of Medicine
- Tania C Sorrell, MD
Tania C Sorrell, MD
- Professor of Clinical Infectious Diseases and Director of the Centre for Infectious Diseases and Microbiology
- Sydney Medical School, University of Sydney
Cryptococcus gattii has emerged as an important fungal pathogen. Infection manifests most often as potentially fatal meningoencephalitis and/or pulmonary disease. The emergence of clusters of cryptococcosis due to C. gattii in British Columbia, Canada in 1999, with subsequent spread to the United States Pacific Northwest, challenged our understanding of this disease [1,2]. With more robust microbial testing, we now appreciate its presence as an important pathogen in North America, especially in western regions. C. gattii infection had previously been detected infrequently and was thought to be largely restricted to tropical and subtropical regions, including Australia and Papua New Guinea. It is now clear that sporadic cases occur in various regions around the world.
The clinical manifestations, complications, and diagnosis of C. gattii infection will be reviewed here. The microbiology, epidemiology, pathogenesis, and treatment of C. gattii infection are discussed separately; C. neoformans infection is also reviewed elsewhere. (See "Cryptococcus gattii infection: Microbiology, epidemiology, and pathogenesis" and "Cryptococcus gattii infection: Treatment" and "Microbiology and epidemiology of Cryptococcus neoformans infection" and "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients" and "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-seronegative patients" and "Cryptococcus neoformans infection outside the central nervous system" and "Cryptococcus neoformans: Treatment of meningoencephalitis and disseminated infection in HIV seronegative patients".)
Incubation period — The incubation period of C. gattii infection in humans is uncertain. A study of seven travelers to Vancouver Island, British Columbia, revealed a median time to clinical presentation of six to seven months (range 2 to 11 months) . A subsequent report of a traveler to British Columbia suggested a shorter incubation of six weeks , whereas other reports have described patients who developed infection 13 months and 36 months after exposure, respectively [5,6]. The proportion of C. gattii disease representing acute infection versus reactivation of latent infection remains unknown; however, most reported cases of C. gattii infection appear to be primary infections.
Clinical features — C. gattii infection often presents as an indolent illness and most commonly involves the central nervous system (CNS), the lungs, or both. Neurologic infection is more common in cases of C. gattii infection that occur in endemic areas (eg, Australia), compared with the Vancouver outbreak setting, where pulmonary manifestations were more frequent. As with C. neoformans, HIV-infected patients with C. gattii infection overwhelmingly present with meningoencephalitis (up to 97 percent of cases) [7,8]. Systemic features including fever, chills, and weight loss were reported in 17 to 47 percent of patients in the North American Pacific Northwest outbreak [9-11]. Fever was reported in 54 percent of HIV-infected patients with C. gattii infection in South Africa  and in 37 percent of patients in Columbia , but was uncommon (10 percent) in patients with C. gattii infection in Australia .
Neurologic features — Headache and neck stiffness are common neurologic symptoms at diagnosis. Other neurologic deficits that may be present, or evolve during the course of illness, include seizures, cranial nerve deficits, cerebellar abnormalities, focal limb weakness, and abnormal mentation (eg, confusion and personality change) [12-16].
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- CLINICAL MANIFESTATIONS
- Incubation period
- Clinical features
- - Neurologic features
- - Papilledema
- - Pulmonary features
- - Other features
- Comparison of C. gattii and C. neoformans infection
- - IRIS-like syndrome
- Chest imaging
- Brain imaging
- Approach to diagnosis
- Diagnostic tests
- - Culture and histopathology
- - Cryptococcal antigen
- Lateral flow assay
- - Molecular tests
- DIFFERENTIAL DIAGNOSIS