Cryptococcus gattii

Cryptococcus gattii has recently been divided into five species.[9] These are C. gattii, C. bacillisporus, C. deuterogattii, C. tetragattii, and C. decagattii.

Cryptococcal disease is an uncommon disease that can affect the lungs (pneumonia) and nervous system (causing meningitis and focal brain lesions called cryptococcomas) in humans. The main complication of lung infection is respiratory failure. Central nervous system infection may lead to hydrocephalus, seizures, and focal neurological deficit.

Soil debris associated with certain tree species has been found frequently to contain C. gattii VGIII MATα and MATa, and less commonly VGI MATα, in Southern California. These isolates were fertile, were found to be indistinguishable from the human isolates by genome sequence, and were virulent in in vitro and animal tests. Isolates were found associated with Canary Island pine (Pinus canariensis), American sweetgum (Liquidambar styraciflua), and Pohutukawa tree (Metrosideros excelsa).[10]

One study concluded "[j]ust as people who travel to South America are told to be careful about drinking the water, people who visit other areas like California, the Pacific Northwest, and Oregon need to be aware that they are at risk for developing a fungal infection, especially if their immune system is compromised."[11]

The highest incidences of C. gattii infections occur in Papua New Guinea and Northern Australia. However cases have been reported in various other regions including Brazil, India and the Pacific Northwest of North America.

Unlike Cryptococcus neoformans, C. gattii is not particularly associated with human immunodeficiency virus infection or other forms of immunosuppression. The fungus can cause disease in healthy people, perhaps because it can grow extremely rapidly within white blood cells.[12]

In the United States, C. gattii serotype B, subtype VGIIa, is largely responsible for clinical cases. The VGIIa subtype was responsible for the outbreaks in Canada; it then appeared in the U.S. Pacific Northwest.

According to a CDC summary, from 2004 to 2010, 60 cases were identified in the U.S.: 43 in Oregon, 15 in Washington, and one each in Idaho and California. Slightly more than half of these cases were immunocompromised; 92% of all isolates were of the VGIIa subtype. In 2007, the first case in North Carolina was reported, subtype VGI, which is identical to the isolates found in Australia and California.

The multiple clonal clusters in the Pacific Northwest likely arose independently of each other as a result of sexual reproduction occurring within the highly sexual VGII population.[13] VGII C. gattii have probably undergone either bisexual or unisexual reproduction in multiple different locales, thus giving rise to novel virulent phenotypes.

The infection is caused by inhaling yeasts or spores. The fungus is not transmitted from person to person or from animal to person. A person with cryptococcal disease is not contagious.[14]

Most people who are exposed to the fungus do not become ill. In people who become ill, symptoms appear many weeks to months after exposure. Symptoms of cryptococcal disease include:

• Prolonged cough (lasting weeks or months)
• Sputum production
• Sharp chest pain
• Shortness of breath
• Sinusitis (cottony drainage, soreness, pressure)
• Severe headache (meningitis, encephalitis, meningoencephalitis)
• Stiff neck (prolonged and severe nuchal rigidity)
• Muscle soreness (mild to severe, local or diffuse)
• Photophobia (excessive sensitivity to light)
• Blurred or double vision
• Eye irritation (soreness, redness)
• Focal neurological deficit
• Fever (delirium, hallucinations)
• Confusion (abnormal behavior changes, inappropriate mood swings)
• Seizures
• Dizziness
• Night sweats
• Weight loss
• Nausea (with or without vomiting)
• Skin lesions (rashes, scaling, plaques, papules, nodules, blisters, subcutaneous tumors or ulcers)
• Lethargy
• Apathy

Culture of sputum, bronchoalveolar lavage, lung biopsy, cerebrospinal fluid or brain biopsy specimens on selective agar allows differentiation between the five members of the C. gattii species complex and the two members of the C. neoformans species complex.

Molecular techniques may be used to speciate Cryptococcus from specimens that fail to culture.

Cryptococcal antigen testing from serum or cerebrospinal fluid is a useful preliminary test for cryptococcal infection, and has high sensitivity for disease. It does not distinguish between different species of Cryptococcus.

Medical treatment consists of prolonged intravenous therapy (for 6–8 weeks or longer) with the antifungal drug amphotericin B, either in its conventional or lipid formulation. The addition of oral or intravenous flucytosine improves response rates. Oral fluconazole is then administered for six months or more.

Antifungals alone are often insufficient to cure C. gattii infections, and surgery to resect infected lung (lobectomy) or brain is often required. Ventricular shunts and Ommaya reservoirs are sometimes employed in the treatment of central nervous system infection.

People who have C. gattii infection need to take prescription antifungal medication for at least 6 months; usually the type of treatment depends on the severity of the infection and the parts of the body that are affected.

• For people who have asymptomatic infections or mild-to-moderate pulmonary infections, the treatment is usually fluconazole.
• For people who have severe lung infections, or infections in the central nervous system (brain and spinal cord), the treatment is amphotericin B in combination with flucytosine.[15]

• Jenney A, Pandithage K, Fisher DA, Currie BJ (2004). "Cryptococcus infection in Tropical Australia". Journal of Clinical Microbiology. 42 (8): 3865–3868. CiteSeerX 10.1.1.627.3222. doi:10.1128/jcm.42.8.3865-3868.2004. PMC 497626. PMID 15297551.

• Buchanan, Kent; Murphy, Juneann W. (1998). "What Makes Cryptococcus neoformans a Pathogen?". Emerging Infectious Diseases. Centers for Disease Control and Prevention (CDC). 4 (1): 71–83. doi:10.3201/eid0401.980109. ISSN 1080-6040. PMC 2627665. PMID 9452400.
• Datta, Kausik; Bartlett, Karen H.; Baer, Rebecca; Byrnes, Edmond; Galanis, Eleni; Heitman, Joseph; Hoang, Linda; Leslie, Mira J.; MacDougall, Laura; Magill, Shelley S.; Morshed, Muhammad G.; Marr, Kieren A. (2009). "Spread of Cryptococcus gattii into Pacific Northwest Region of the United States". Emerging Infectious Diseases. Centers for Disease Control and Prevention (CDC). 15 (8): 1185–1191. doi:10.3201/eid1508.081384. ISSN 1080-6040. PMC 2815957. PMID 19757550.