Cryptococcosis
Encyclopedia
Cryptococcosis, or cryptococcal disease, is a potentially fatal fungal disease. It is caused by one of two species; Cryptococcus
neoformans and Cryptococcus gattii. These were all previously thought to be subspecies of C. neoformans, but have now been identified as distinct species.
Cryptococcosis is believed to be acquired by inhalation
of the infectious propagule from the environment. Although the exact nature of the infectious propagule
is unknown, the leading hypothesis is the basidiospore
created through sexual or asexual reproduction.
. Other conditions which pose an increased risk include certain lymphoma
s (e.g. Hodgkin's lymphoma
), sarcoidosis
, and patients on long-term corticosteroid
therapy.
Distribution is worldwide in soil. The prevalence of cryptococcosis has been increasing over the past 20 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.
In humans, C. neoformans causes three types of infections:
Cryptococcal meningitis (infection of the meninges
, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Cryptococcus gattii causes infections in immunocompetent people (those having a functioning immune system
), but C. neoformans v. grubii, and v. neoformans usually only cause clinically evident infections in persons who have some form of defect in their immune systems (immunocompromised persons). People who have defects in their cell-mediated immunity
, for example, people with AIDS
, are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, especially if untreated.
Although the most common presentation of cryptococcosis is of C. neoformans infection in an immunocompromised person (such as patients with AIDS), the C. gattii is being increasingly recognised as a pathogen in presumptively immunocompetent hosts, especially in Canada and Australia. This may be due to rare exposure and high pathogenicity, or to unrecognised isolated defects in immunity specific to this organism.
Detection of cryptococcal antigen
(capsular material) by culture
of CSF
, sputum
and urine
provides definitive diagnosis. Blood cultures may be positive in heavy infections.
Cryptococcosis can rarely occur in the immunocompetent person without HIV
, when it usually goes undiagnosed. Less than 250 cases in all are reported in the medical literature, the majority diagnosed postmortem.
combined with oral flucytosine
may be effective. Every attempt should be made to reduce the amount of immunosuppressive medication until the infection is resolved.
AIDS patients often have a reduced response to Amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole
can be used. The decision on when to start treatment for HIV is not yet settled, although one small, under-powered trial suggested that delaying the start of treatment for 10 weeks may be beneficial in avoiding deaths from Immune reconstitution inflammatory syndrome
(IRIS).
The immune reconstitution inflammatory syndrome
(IRIS) has been described in immunocompetent hosts who have meningitis caused by C. gattii and C. grubii. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.
The increasing inflammation can cause brain injury or be fatal.
The mechanism behind IRIS in cryptococcal meningitis may be local or systemic immunosuppression induced by the cryptococcal infection which resolves as the organism is killed by antifungal treatment. This is associated with increased inflammation as the recovering immune system recognises the fungus. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration.
IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom Cryptococcus neoformans is the usual pathogen.
infection in cats.Cryptococcis is most common in dogs and cats but cattle,sheep,goat,horse,wild animals and birds can also be infected.Soil,fowl manure and pigeon droppings are among the sources of infection.
Cryptococcus
Cryptococcus is a genus of fungus. Species grow in culture as yeasts. The perfect forms or teleomorphs of Cryptococcus species are filamentous fungi in the genus Filobasidiella...
neoformans and Cryptococcus gattii. These were all previously thought to be subspecies of C. neoformans, but have now been identified as distinct species.
Cryptococcosis is believed to be acquired by inhalation
Inhalation
Inhalation is the movement of air from the external environment, through the air ways, and into the alveoli....
of the infectious propagule from the environment. Although the exact nature of the infectious propagule
Propagule
In horticulture, a propagule is any plant material used for the purpose of plant propagation. In asexual reproduction, a propagule may be a woody, semi-hardwood, or softwood cutting, leaf section, or any number of other plant parts. In sexual reproduction, a propagule is a seed or spore...
is unknown, the leading hypothesis is the basidiospore
Basidiospore
A basidiospore is a reproductive spore produced by Basidiomycete fungi. Basidiospores typically each contain one haploid nucleus that is the product of meiosis, and they are produced by specialized fungal cells called basidia. In grills under a cap of one common species in the phylum of...
created through sexual or asexual reproduction.
Etiology and Incidence
Cryptococcosis is a defining opportunistic infection for AIDSAIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. Other conditions which pose an increased risk include certain lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s (e.g. Hodgkin's lymphoma
Hodgkin's lymphoma
Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes...
), sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, and patients on long-term corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
therapy.
Distribution is worldwide in soil. The prevalence of cryptococcosis has been increasing over the past 20 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.
In humans, C. neoformans causes three types of infections:
- Wound or cutaneous cryptococcosis
- Pulmonary cryptococcosis, and
- Cryptococcal meningitisMeningitisMeningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
.
Cryptococcal meningitis (infection of the meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...
, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Cryptococcus gattii causes infections in immunocompetent people (those having a functioning immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
), but C. neoformans v. grubii, and v. neoformans usually only cause clinically evident infections in persons who have some form of defect in their immune systems (immunocompromised persons). People who have defects in their cell-mediated immunity
Cell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
, for example, people with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
, are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, especially if untreated.
Although the most common presentation of cryptococcosis is of C. neoformans infection in an immunocompromised person (such as patients with AIDS), the C. gattii is being increasingly recognised as a pathogen in presumptively immunocompetent hosts, especially in Canada and Australia. This may be due to rare exposure and high pathogenicity, or to unrecognised isolated defects in immunity specific to this organism.
Diagnosis
Symptoms include fever, fatigue, chest pain, dry cough, swelling of abdomen, headache, blurred vision and confusion.Detection of cryptococcal antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
(capsular material) by culture
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...
of CSF
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
, sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
and urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
provides definitive diagnosis. Blood cultures may be positive in heavy infections.
Cryptococcosis can rarely occur in the immunocompetent person without HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, when it usually goes undiagnosed. Less than 250 cases in all are reported in the medical literature, the majority diagnosed postmortem.
Treatment
Treatment options in non-AIDS patients who have reduced immune-system function is not well studied. Intravenous Amphotericin BAmphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
combined with oral flucytosine
Flucytosine
Flucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug.It is structurally related to the cytostatic fluorouracil and to floxuridine. It is available in oral and in some countries also in injectable form. A common brand name is Ancobon. Flucytosine was...
may be effective. Every attempt should be made to reduce the amount of immunosuppressive medication until the infection is resolved.
AIDS patients often have a reduced response to Amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole
Fluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
can be used. The decision on when to start treatment for HIV is not yet settled, although one small, under-powered trial suggested that delaying the start of treatment for 10 weeks may be beneficial in avoiding deaths from Immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the...
(IRIS).
IRIS in immunocompetent hosts
The immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the...
(IRIS) has been described in immunocompetent hosts who have meningitis caused by C. gattii and C. grubii. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.
The increasing inflammation can cause brain injury or be fatal.
The mechanism behind IRIS in cryptococcal meningitis may be local or systemic immunosuppression induced by the cryptococcal infection which resolves as the organism is killed by antifungal treatment. This is associated with increased inflammation as the recovering immune system recognises the fungus. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration.
IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom Cryptococcus neoformans is the usual pathogen.
Veterinary cases
Cryptococcosis is also seen in cats and occasionally dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses, and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with FeLVFELV
FELV may refer to:* Functional Extra Low Voltage, see Extra low voltage#Functional Extra Low Voltage * Feline leukemia virus, FeLV...
infection in cats.Cryptococcis is most common in dogs and cats but cattle,sheep,goat,horse,wild animals and birds can also be infected.Soil,fowl manure and pigeon droppings are among the sources of infection.