Pathogenic fungi

Pathogenic fungi tend to be ones that cause infections to the surface of the body. Their fibres grow in the upper layer of the skin which causes inflammation and damage. This can also provide a route into the body for other opportunistic infections. Diseases such as athlete's foot, ringworm, oral and vaginal thrush are examples of fungal infections.

This photo of a slide was sent to The 'X' Zone for our broadcast on Morgellons on Friday night, November 10 2006.

A request for assistance was sent to medical learning institutions around the world and his is the email that came back to us from the University of Texas:

Rob:
Our expert, Dr Adelaide Herbert, contends that Morgellons disease exists only in the patient’s mind -- “… it is actually not uncommon to have patients come in and describe the sensation that something is crawling on their skin,” she says. See:
http://www.khou.com/news/local/stories/khou060505_gj_morgellonsdisease.20ff957e.html However, she is not available to review content online.


David R. Bates
Executive Director of Media Relations
Office of Institutional Advancement
UT Health Science Center at Houston
Phone: 713-500-3050
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Encyclopedia of Medicine | Cryptococcosis

Definition
Cryptococcosis is an infection caused by inhaling the fungus Cryptococcus neoformans. It is one of the diseases most often affecting AIDS patients. Cryptococcosis may be limited to the lungs, but frequently spreads throughout the body. Although almost any organ can be infected, the fungus is often fatal if it infects the nervous system where it causes an inflammation of the membranes covering the brain and spinal cord (meningitis).

Description
The fungus causing cryptococcus, C. neoformans, is found worldwide in soil contaminated with pigeon or other bird droppings. It has also been found on unwashed raw fruit. Cryptococcosis is a rare disease in healthy individuals, but is the most common fungal infection affecting people with AIDS.

People with Hodgkin's disease or who are taking large doses of drugs that suppress the functioning of the immune system (corticosteroids, chemotherapy drugs) are also more susceptible to cryptococcal infection. Cryptococcosis is also called cryptococcal meningitis (when the brain is infected), Busse-Buschke disease, European blastomycosis, torular meningitis, or torulosis.

Causes and symptoms
Once the cryptococcal fungus reaches the lungs, three things can happen. The immune system can heal the body without medical intervention, the disease can stay localized in the lungs, or it can spread throughout the body. In healthy people with normally functioning immune systems, the body usually heals itself, and the infected person notices no symptoms and has no complications (asymptomatic). The disease does not spread from one person to another.

Cryptococcosis is an opportunistic infection that puts people with immune system diseases at higher risk of developing more serious forms of the disease. In the United States, 6–10% of all patients with AIDS get cryptococcosis.

If the body does not heal itself, the fungus begins to grow in the lungs and form nodules that can be seen on chest x rays. In the early stages of infection, an individual usually only exhibits symptoms of a respiratory infection, such as a dry cough, so the disease is rarely diagnosed.

The fungus can remain dormant in the lungs and produce an active infection later if the immune system is weakened. If the disease becomes active, it can cause cryptococcal pneumonia in the lungs. Unfortunately, however, cryptococcal pneumonia has symptoms similar to other pneumonias (cough, chest pain, difficulty breathing), making it difficult to accurately diagnose. The infection can spread to other parts of the body, particularly the brain and central nervous system.

Most patients are not diagnosed as having cryptococcosis until they show signs of cryptococcal meningitis, or infection of the membranes surrounding the brain and spinal cord. Symptoms appear gradually over a period of two to four weeks. Fever and headache are the most common symptoms, occurring in about 85% of patients. Nausea, vomiting, unwanted weight loss, and fatigue are also common. Other symptoms seen in 25–30% of patients are blurred vision, stiff neck, aversion to light, and seizures. Since the symptoms of classic meningitis, such as stiff neck and aversion to light, do not occur in many patients, diagnosis is often delayed. In addition to meningitis, inflammation of the brain (encephalitis) and brain lesions called cryptococcomas or tortulomas can also develop.

In addition to the brain, the cryptococcal infection can spread to the kidneys, bone marrow, heart, adrenal glands, lymph nodes, urinary tract, blood, and skin. Often times preceding the development of cryptococcal meningitis, painless rashes and lesions that mimic other skin diseases, such as molluscum contagiosum, may develop. A small percentage of patients with brain infections show infections in other organs as well.

Diagnosis
Physicians who regularly work with AIDS patients have the most experience in diagnosing cryptococcosis. The preferred methods of diagnosis use simple and very accurate blood and cerebrospinal fluid (CSF) tests that detect the presence of an antigen produced by the fungus. The cerebrospinal fluid test is generally more sensitive to detecting the meningitis form of the infection. CSF is collected during a procedure called a lumbar puncture, during which an anesthetic is applied to a small area of the back near the spine and a needle is used to withdraw a sample of cerebrospinal fluid from the space between the vertebrae and the spinal cord. Once obtained, a small amount of ink (called India ink) is added to a sample of CSF or a sample prepared from skin lesions. If the fungus is present, it will become visible when the ink binds to the capsule or covering that surrounds the fungus. Faster results are obtained with the India ink test, but it is less accurate than the blood test (75–85% accuracy compared to 99% accuracy with the blood test) because some strains are not visible using this method. Antigen tests are routinely recommended for non-symptomatic patients with advanced AIDS.

Another way to diagnose cryptococcosis is to culture a sample of sputum, tissue from a lung biopsy,or CSF in the laboratory to isolate the fungus. Cultures are also done to assess the effectiveness of treatment.

Chest x rays are useful in assessing lung damage and may reveal a single mass or multiple distinct nodules, but the x ray alone does not lead to a definitive diagnosis of cryptococcosis.

Treatment
Once cryptococcosis is diagnosed, treatment begins with amphotericin B (Fungizone), sometimes in combination with 5-flucytosine (Ancobon). Amphotericin B is a powerful fungistatic drug with potentially toxic side effects, such as kidney toxicity and lower concentrations of an important blood component called hemoglobin. This medication can also cause fever, chills, nausea and vomiting, diarrhea, headache, and muscle aches. Treatment is generally given intravenously during a hospital stay and continues until the patient is stable or improving (no more than two to three weeks). 5-flucytosine is given orally. Patients may also receive other medication to minimize the side effects from these drugs.

Amphotericin B, with or without 5-flucytosine, is given for several weeks until the patient is stable, after which the patient receives oral fluconazole (Diflucan). Fluconazole is a broad-spectrum antifungal drug with few serious side effects. Patient with AIDS must continue taking fluconazole for the rest of their lives to prevent a relapse of cryptococcosis. Sometimes fluconazole is given to patients with advanced AIDS as a preventative (prophylactic) measure.

Because of the high cost of fluconazole, the manufacturer of the drug, Pfizer, has established a financial assistance plan to make the drug available at lower cost to those who meet certain criteria. Patients needing this drug should ask their doctors about this program.

Prognosis
Untreated cryptococcosis is always fatal. The acute mortality rate for patients with AIDS is 10–25%. Most deaths are attributable to cryptococcal meningitis and occur within two weeks after diagnosis. For AIDS patients who do not receive continued suppressive therapy (fluconazole), the relapse rate is 50–60% within six months and a shortened life expectancy. Once the cryptococcosis infection has been successfully treated, individuals may be left with a variety of neurologic symptoms, such as weakness, headache, and hearing or visual loss. In addition, fluid may accumulate around the brain (hydrocephalus).

Prevention
The best way to prevent cryptococcosis is to stay free of HIV infection. People with suppressed immune systems should try to stay away from areas contaminated with pigeon or other bird droppings, such as the attics of old buildings, barns, and areas under bridges where pigeons roost.

Resources

ORGANIZATIONS
Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. <http://www.cdc.gov>.

National Aids Clearinghouse. 800-458-5231.

National Aids Hotline. 800-342-AIDS.

Project Inform. 205 13th Street, #2001, San Francisco, CA 94103. (800) 822-7422. <http://www.projinf.org>.

OTHER
Powderly, William G. "Cryptococcosis." Journal of the International Association of Physicians in AIDS Care. July 1996 <http://www.iapac.org/diseases/fungi/cocc.html>.

"Project Inform Cryptococcal Infections Fact Sheet." Project Inform. 21 May 1996 <http://www.projinf.org>.

Tish Davidson

KEY TERMS

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Adrenal gland—A pair of organs located above the kidneys. The outer tissue of the gland produces the hormones epinephrine (adrenaline) and norepinephrine, while the inner tissue produces several steroid hormones.

Amphotericin B (Fengizone)—An antifungal medication, prescribed for topical or systemic use in treating fungal infections.

Antibody—A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.

Antigen—A foreign protein or particle capable of eliciting an immune response.

Asymptomatic—Persons who carry a disease but who do not exhibit symptoms of the disease are said to be asymptomatic.

Biopsy—The removal of a tissue sample for diagnostic purposes.

Cerebrospinal fluid (CSF)—The clear fluid that surrounds the spinal cord and brain and acts as a shock absorber.

Corticosteroids—A group of hormones produced naturally by the adrenal gland or manufactured synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.

Encephalitis—Inflammation of the brain.

Hodgkin's disease—A disease that causes chronic inflammation of the lymph nodes, spleen, liver and kidneys. It is also called malignant lymphoma.

Hydrocephalus—Build-up of fluid around the brain.

Immunocompromised—A state in which the immune system is suppressed or not functioning properly.

India ink test—A diagnostic test used to detect the cyptococcal organism C. neoformans. A dye, called India ink, is added to a sample of CSF fluid, and if the fungi is present, they will become visible as the dye binds to the capsule surrounding the fungus.

Lumbar puncture—Also called a spinal tap, a procedure in which a thin needle is used to withdraw a sample of cerebrospinal fluid for diagnostic purposes from the area surrounding the spine.

Meningitis—Inflammation of the membranes covering the brain and spinal cord called the meninges.

Molluscum contagiosum—A disease of the skin and mucuous membranes, caused by a poxvirus and found all over the world.

Opportunistic infection—An infection that is normally mild in a healthy individual, but which takes advantage of an ill person's weakened immune system to move into the body, grow, spread, and cause serious illness.

Pneumonia—Inflammation of the lungs, typically caused by a virus, bacteria, or other organism.

Superficial - localised to the skin, the hair, and the nails.
Subcutaneous - infection confined to the dermis, subcutaneous tissue or adjacent structures.
Systemic - deep infections of the internal organs.
Opportunistic - cause infection only in the immunocompromised.

Human fungal infections in the United Kingdom are uncommon in normally healthy persons, being confined to conditions such as candidiasis (thrush) and dermatophyte skin infections such as athlete's foot. However, in the immunocompromised host, a variety of normally mild or nonpathogenic fungi can cause potentially fatal infections. Furthermore, the relative ease with which people can now visit "exotic" countries provides the means for unusual fungal infections to be imported into this country.

Superficial Mycoses
As listed above, in superficial mycoses infection is localised to the skin, the hair, and the nails. An example is "ringworm" or "tinea", an infection of the skin by a dermatophyte. Ringworm refers to the characteristic central clearing that often occurs in dermatophyte infections of the skin. Dermatophyte members of the genera Trycophyton, Microsporum and Epidermophyton are responsible for the disease. Tinea can infect various sites of the body, including the scalp (tinea capitis), the beard (tinea barbae) the foot (tinea pedis: "athlete's foot") and the groin (tinea cruris). All occur in the United Kingdom although tinea infections, other than pedis, are now rare.
Candida albicans is a yeast causing candidiasis or "thrush" in humans. As a superficial mycoses, candidiasis typically infects the mouth or vagina. C. albicans is part of the normal flora of the vagina and gastrointestinal tract and is termed a "commensal". However, during times of ill health or impaired immunity the balance can alter and the organism multiplies to cause disease. Antibiotic treatment can also alter the normal bacterial flora allowing C. albicans to flourish.

Subcutaneous Mycoses
These are infections confined to the dermis, subcutaneous tissue or adjacent structures. Infection may arise following the wounding of the skin and the introduction of vegetable matter. These mycoses are rare and confined mainly to tropical regions. They tend to be slow in onset and chronic in duration. An example is sporotrichosis caused by Sporothrix schenckii. The fungus is dimorphic, being a mould that can convert to a yeast form at 37°C on rich laboratory media or in infection. Sporotrichosis was once common in Europe but cases are now rare. The disease is most prevalent the Americas, South Africa and Australia. Infection usually follows and insect bite, thorn prick or scratch from a fish spine. Certain occupation groups appear to have increased risk from infection. These include florists, farm workers and others who handle hay and moss. The most common symptom is a ulcerative lesion that may develop into lymphangitis.

Systemic Mycoses (primary and opportunistic)
These are invasive infections of the internal organs with the organism gaining entry by the lungs, gastrointestinal tract or through intravenous lines. They may be caused by: (i) primary pathogenic fungi or (ii) by opportunistic fungi that are of marginal pathogenicity but can infect the immunocompromised host.

Primary Pathogenic Fungi
Infection occurs in previously healthy persons and arises through the respiratory route. Examples include histoplasmosis, blastomycosis, coccidiomycosis and paracoccidiodomycosis. The fungi occur throughout the world but not in the United Kingdom.

Histoplasmosis. This is caused by Histoplasma capsulatum. The organism is dimorphic (being a mould that can convert to a yeast form). H. capsulatum is endemic in many parts of the world including North and South America. It is found in the soil and growth is enhanced by the presence of bird and bat excreta. Environments containing such material are often implicated as sources of human infection. The lungs are the main site of infection but dissemination to the liver, heart and central nervous system can occur. Pulmonary infection can resemble symptoms seen in tuberculosis.

Opportunistic Fungi
Here, patients usually have some serious immune or metabolic defect, or have undergone surgery. The diseases include aspergillosis, systemic candidosis and cryptococcosis. Exceptionally, other fungi that are normally not pathogenic, such as Trichosporon, Fusarium or Penicillium, may cause systemic infections.
Aspergillosis. This is the name given to a number of different diseases caused by the mould Aspergillus. It produces large numbers of spores and occurs world-wide. In the United Kingdom, A. fumigatus is the most common species causing disease. The organism can infect the lungs, inner ear, sinuses and, rarely, the eye of previously healthy persons. In the immunosuppressed host, Aspergillus can disseminate throughout the body.

Candidosis. In severely immunocompromised patients (e.g. those receiving chemotherapy) C. albicans, that is part of the normal human flora (see above), can proliferate and disseminate throughout the body.

Cryptococcosis. This is a systemic infection caused by the yeast Cryptococcus neoformans. The commonest manifestation is a subacute or chronic form of meningitis resulting from the inhalation of the organism. Pulmonary infection can also occur. The disease affects both healthy and immunosuppressed individuals and occurs world-wide. C. neoformans can be isolated in large numbers from pigeon droppings in the environment, although such birds do not appear to harbour the yeast.

Other Fungal Related Disease
Constant exposure to fungal spores in the atmosphere can induce respiratory allergies. Elevated antibodies to a range of common spore forming fungi have been demonstrated in occupational diseases such as Humidifier fever, Malt workers' lung and Wheat threshers' disease.

Certain fungi, such as mushrooms, can produce poisonous toxins that may prove fatal if ingested (e.g. Amanita phalloides: "death cap"). Others (Psilocybe) affect the central nervous system inducing hallucinogenic responses.

Many moulds produce secondary metabolites (mycotoxins) that are highly toxic to humans. Ergotism is caused by eating bread prepared from rye infected with the fungus Claviceps purpurea. Historically, several large scale outbreaks of madness in local populations have been attributed to ergotism.

Pneumocystis.

This is an infection of the lung caused by Pneumocystis carinii. The organism is a common cause of fatal pneumonia in AIDS patients. An intracellular parasite, with a life cycle of trophozoite and cyst, it was formerly considered to be a protozoan. However, comparison of DNA and RNA sequences have established that it is one of the group of ustomycetous red yeast fungi. The cysts contain 8 nuclei which can be seen in smears of pulmonary aspirates. P. carinii is a commensal of many wild and domestic animals and evidence suggests that human infection is commonly derived from dogs.

References
Peters, W. and Gilles, H.M. (1995). Colour Atlas of Tropical Medicine and Parasitology. Mosby-Wolfe.
Roberts, S.O.B., Hay, R.J. and Mackenzie, D.W.R. (1984). A Clinician's Guide to Fungal Disease. (Infectious Diseases and Antimicrobial agents: 5). Marcel Dekker, Inc. New York.