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''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. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
found primarily in
tropical The tropics are the regions of Earth surrounding the Equator. They are defined in latitude by the Tropic of Cancer in the Northern Hemisphere at N and the Tropic of Capricorn in the Southern Hemisphere at S. The tropics are also referred to ...
and
subtropical The subtropical zones or subtropics are geographical and climate zones to the north and south of the tropics. Geographically part of the temperate zones of both hemispheres, they cover the middle latitudes from to approximately 35° north a ...
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 asex ...
is ''Filobasidiella bacillispora'', a filamentous
fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
belonging to the
class Class 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 differently ...
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 Tremell ...
. ''Cryptococcus gattii'' causes the human diseases of pulmonary
cryptococcosis Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and brain, where it appears as a meningitis. Cough, difficulty breathing, chest pain and fever are seen when the lungs are infected. When the ...
(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, headache, and neck stiffness. Other symptoms include confusion or ...
, 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 (commonly abbreviated as BC) is the westernmost province of Canada, situated between the Pacific Ocean and the Rocky Mountains. It has a diverse geography, with rugged landscapes that include rocky coastlines, sandy beaches, for ...
,
Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by to ...
and the Pacific Northwest. It has been suggested that
global warming In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to ...
may have been a factor in its emergence in British Columbia. It has also been suggested that
tsunami A tsunami ( ; from ja, 津波, lit=harbour wave, ) 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 other underwater exp ...
s, such as the
1964 Alaska earthquake The 1964 Alaskan earthquake, also known as the Great Alaskan earthquake and Good Friday earthquake, occurred at 5:36 PM AKST on Good Friday, March 27.
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 dogs,
koala The koala or, inaccurately, koala bear (''Phascolarctos cinereus''), is an arboreal herbivorous marsupial native to Australia. It is the only extant representative of the family Phascolarctidae and its closest living relatives are the ...
s, and
dolphin A dolphin is an aquatic mammal within the infraorder Cetacea. Dolphin species belong to the families Delphinidae (the oceanic dolphins), Platanistidae (the Indian river dolphins), Iniidae (the New World river dolphins), Pontoporiidae (the b ...
s. In 2007, the fungus appeared for the first time in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
, in
Whatcom County, Washington Whatcom County is a county located in the northwestern corner of the U.S. state of Washington, bordered by the Canadian Lower Mainland (the Metro Vancouver and Fraser Valley Regional Districts of British Columbia) to the north, Okanogan ...
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''.


Disease summary

Cryptococcal disease is an uncommon disease that can affect the lungs (
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
) 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 Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary i ...
, seizures, and focal neurological deficit.


Environmental occurrence

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 ''Pinus canariensis'', the Canary Island pine, is a species of gymnosperm in the conifer family Pinaceae. It is a large, evergreen tree, native and endemic to the outer Canary Islands of the Atlantic Ocean. Description ''Pinus canariensis'' is a ...
''), American sweetgum (''
Liquidambar styraciflua American sweetgum (''Liquidambar styraciflua''), also known as American storax, hazel pine, bilsted, redgum, satin-walnut, star-leaved gum, alligatorwood, or simply sweetgum, is a deciduous tree in the genus ''Liquidambar'' native to warm temper ...
''), and Pohutukawa tree (''
Metrosideros excelsa ''Metrosideros excelsa'', commonly known as pōhutukawa ( mi, pōhutukawa), New Zealand Christmas tree, New Zealand Christmas bush, and iron tree, is a coastal evergreen tree in the myrtle family, Myrtaceae, that produces a brilliant display o ...
''). 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

The highest incidences of ''C. gattii'' infections occur in Papua New Guinea and Northern Australia. Though cases have been reported in various other regions including Brazil, India and the
Pacific Northwest The Pacific Northwest (sometimes Cascadia, or simply abbreviated as 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. Thou ...
of North America. Unlike ''
Cryptococcus neoformans ''Cryptococcus neoformans'' is an encapsulated 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 ''Filobasidiella 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, potentially due to its ability to grow extremely rapidly within white blood cells. 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 from Washington, and one each from Idaho and California. Slightly more than half of these case 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 th ...
occurring within the highly sexual VGII population.Billmyre RB, Croll D, Li W, Mieczkowski P, Carter DA, Cuomo CA, Kronstad JW, Heitman J. Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution. MBio. 2014 Jul 29;5(4):e01494-14. doi: 10.1128/mBio.01494-14. 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 (biology), morphology or physical form and structure, its Developmental biology, developmental proc ...
s.


Transmission

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.


Symptoms

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 Night sweats, also referred to as nocturnal hyperhidrosis (Hyperhidrosis - a medical term for excessive sweating + nocturnal - night), is the repeated occurrence of excessive sweating during sleep Sleep is a sedentary state of mind and bo ...
* Weight loss * Nausea (with or without vomiting) * Skin lesions (rashes, scaling, plaques, papules, nodules, blisters, subcutaneous tumors or ulcers) * Lethargy * Apathy


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. 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''.


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 nutrie ...
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 cryptococcosis ...
, 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. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...
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 Lobectomy means ''surgical excision of a lobe''. This may refer to a lobe of the lung (also simply called a lobectomy), a lobe of the thyroid ( hemithyroidectomy), a lobe of the brain (as in anterior temporal lobectomy), or a lobe of the liver ...
) 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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
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 In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered a ...
infections or mild-to-moderate pulmonary infections, the treatment is usually fluconazole. *For people who have severe
lung infections The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...
, or infections in the central nervous system (brain and spinal cord), the treatment is amphotericin B in combination with flucytosine.


See also

*


References


Further reading

* * {{Taxonbar, from=Q149791 Animal fungal diseases Fungal plant pathogens and diseases Fungi and humans Fungi of Africa Fungi of Asia Tremellomycetes Yeasts