''Cryptococcus gattii'', formerly known as ''Cryptococcus neoformans'' var. ''gattii'', is an encapsulated

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

found primarily in

tropical The tropics are the regions of Earth surrounding the equator, where the sun may shine directly overhead. This contrasts with the temperate or polar regions of Earth, where the Sun can never be directly overhead. This is because of Earth's ax ...

and

subtropical The subtropical zones or subtropics are geographical zone, geographical and Köppen climate classification, climate zones immediately to the Northern Hemisphere, north and Southern Hemisphere, south of the tropics. Geographically part of the Ge ...

climates. Its

teleomorph In mycology, the terms teleomorph, anamorph, and holomorph apply to portions of the life cycles of fungi in the phyla Ascomycota and Basidiomycota: *Teleomorph: the sexual reproductive stage (morph), typically a fruiting body. *Anamorph: an ase ...

is ''Filobasidiella bacillispora'', a filamentous

fungus A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

belonging to the

class Class, Classes, or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used d ...

Tremellomycetes The Tremellomycetes are a class of dimorphic fungi in the Agaricomycotina. Some species have gelatinous basidiocarps (fruiting bodies) or (microscopically) a sacculate parenthesome. There are six orders, 17 families, and 39 genera in the Trem ...

. ''C. gattii'' is one of two organisms causing the infectious disease

cryptococcosis Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and in the brain, where it appears as a meningitis. Coughing, difficulty breathing, chest pain and fever are seen when the lungs are infect ...

(along with ''C. neoformans''). Clinical manifestations of ''C. gattii'' infection include pulmonary

(lung infection), basal

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

, and cerebral cryptococcomas. Occasionally, the fungus is associated with skin, soft tissue,

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

, bone, and joint infections. In recent years, it has appeared in

British Columbia British Columbia is the westernmost Provinces and territories of Canada, province of Canada. Situated in the Pacific Northwest between the Pacific Ocean and the Rocky Mountains, the province has a diverse geography, with rugged landscapes that ...

Canada Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, making it the world's List of coun ...

and the Pacific Northwest. It has been suggested that

tsunami A tsunami ( ; from , ) is a series of waves in a water body caused by the displacement of a large volume of water, generally in an ocean or a large lake. Earthquakes, volcanic eruptions and underwater explosions (including detonations, ...

s, such as the

1964 Alaska earthquake The 1964 Alaska earthquake, also known as the Great Alaska earthquake and Good Friday earthquake, occurred at 5:36 PM Alaska Standard Time, AKST on Good Friday, March 27, 1964.

and tsunami, might have been responsible for carrying the fungus to North America and its subsequent spread there. From 1999 through to early 2008, 216 people in British Columbia have been infected with ''C. gattii'', and eight died from complications related to it. The fungus also infects animals, such as

dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the gray wolf. Also called the domestic dog, it was selectively bred from a population of wolves during the Late Pleistocene by hunter-gatherers. ...

koala The koala (''Phascolarctos cinereus''), sometimes inaccurately called the koala bear, is an arboreal herbivorous marsupial native to Australia. It is the only Extant taxon, extant representative of the Family (biology), family ''Phascolar ...

s, and

dolphin A dolphin is an aquatic mammal in the cetacean clade Odontoceti (toothed whale). Dolphins belong to the families Delphinidae (the oceanic dolphins), Platanistidae (the Indian river dolphins), Iniidae (the New World river dolphins), Pontopori ...

s. In 2007, the fungus appeared for the first time in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, in

Whatcom County, Washington Whatcom County (, ) is a County (United States), county located in the northwestern corner of the U.S. state of Washington (state), Washington, bordered by the Lower Mainland (the Metro Vancouver and Fraser Valley Regional Districts) of the ...

and in April 2010 had spread to Oregon. The most recently identified strain, designated VGIIc, is particularly virulent, having proved fatal in 19 of 218 known cases.

Nomenclature

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

Environmental microbiology

''C. gattii'' occupies an environmental niche in decaying hollows of trees native to tropical as well as subtropical and temperate regions. It may then contaminate nearby soil or persist in wood products.

Distribution

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 ''Liquidambar styraciflua'', commonly known as the American sweetgum among other names, is a deciduous tree in the genus ''Liquidambar'' native to warm temperate areas of eastern North America and tropical montane regions of Mexico and Central A ...

''), and Pohutukawa tree (''

Metrosideros excelsa ''Metrosideros'' is a genus of approximately 60 trees, shrubs, and vines in the family Myrtaceae, mostly found in the Pacific region. Most of the tree forms are small, but some are exceptionally large, the New Zealand species in particular. The ...

''). One study concluded " st 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."

Epidemiology

''C. gattii'' infections were initially thought to be restricted to tropical and subtropical regions. C. gattii is the predominant cause of cryptococcosis in

sub-Saharan Africa Sub-Saharan Africa is the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the list of sovereign states and ...

. 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 The Pacific Northwest (PNW; ) is a geographic region in Western North America bounded by its coastal waters of the Pacific Ocean to the west and, loosely, by the Rocky Mountains to the east. Though no official boundary exists, the most common ...

of North America. 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 Sexual reproduction is a type of reproduction that involves a complex life cycle in which a gamete ( haploid reproductive cells, such as a sperm or egg cell) with a single set of chromosomes combines with another gamete to produce a zygote tha ...

occurring within the highly sexual VGII population. VGII ''C. gattii'' have probably undergone either bisexual or unisexual reproduction in multiple different locales, thus giving rise to novel virulent

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

Pathology

''C. gattii'' is notable for causing cryptococcosis in otherwise healthy persons. Unlike ''

Cryptococcus neoformans ''Cryptococcus neoformans'' is an encapsulated basidiomycetous yeast belonging to the class Tremellomycetes and an obligate aerobe that can live in both plants and animals. Its teleomorph is a filamentous fungus, formerly referred to ''Filob ...

'', ''C. gattii'' is not particularly associated with human immunodeficiency virus infection or other forms of immunosuppression. Increased virulence may be related to a capability to rapidly proliferate within

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

s. ''C. gattii'' infection is more likely to be limited to the lung (rather than disseminating to the CNS). When CNS infection does occur, it may involve more localised lesions (cryptococcomas) rather than the diffuse infection characteristic of ''C. neoformans''.

Diagnosis

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. The optimal growth temperature of ''C. gattii'' is 30 C.

Treatment

Medical treatment consists of prolonged

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

therapy (for 6–8 weeks or longer) with the antifungal drug

amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococ ...

, either in its conventional or lipid formulation. The addition of oral or intravenous

flucytosine Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...

improves response rates. Oral

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. These include candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to pr ...

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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

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 Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...

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.