Coccidioides
Coccidioides immitis
is on the U.S. Government Occupational Safety and Health Administration [OSHA] list of biological agents and toxins that
have the potential to pose a severe threat
to public health and safety and that can potentially be utilized
by terrorists.
Species
Coccidioides immitis is the only species included in the
genus Coccidioides.
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Taxonomic
Classifications
Kingdom: Fungi
Phylum: Ascomycota
Class: Euascomycetes
Order: Onygenales
Family: Onygenaceae
Genus: Coccidioides |
Culture of Coccidioides immitis
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Toxic Mould Species:
Mould Pictures
Absidia Mould
Alternaria Mould
Aspergillus Mould
Aureobasidium Mould
Blastomyces Mould
Candida Mould
Coccidioides
Cryptococcus Mould
Curvularia Mould
Histoplasma Mould
Mucor Mould
Penicillium Mould
Pseudallescheria
Sporothrix Mould
Stachybotrys Mould
Verticillium Mould
Yeast
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Description and Habitat On Sabouraud's dextrose agar at 25C, C. immitis
colonies are initially moist and smooth, but rapidly become suede-like
to downy greyish white with a tan to brown underside.
Coccidioides immitis is a
thermally
dimorphic
fungus, existing in
mycelial
form in soil, particularly at warm and dry
areas with low rain fall, high summer temperatures, and low altitude. It
specifically inhabits alkaline soil. It is isolated in rodent burrows at
desert-like areas of southwest United States. It is endemic at southwest
United States, (Southern
California, Arizona, Nevada, New Mexico and West Texas),
Northern Mexico, and certain areas in
Central and South America. The
largest South American endemic region is in Argentina where the climate
is dry and the soil conditions are similar to those in the desert
Southwest.
As an invading organism in a living tissue,
it is seen as
spherules and endospores - tiny round bodies embedded in the tissues that
function
like a sac or case
to enclose or contain the spores. In the laboratory, Coccidioides immitis
continues to grow as a filamentous mould and does not produce spherules at any
temperature unless special growth medium is provided. This indicates
that temperature is not the only variable that controls the spherule formation. |
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Coccidioides
immitis is distinguished from other fungal pathogens by the unique
morphogenetic features of its growth in host tissue.
Microscopic
morphology shows typical single-celled, hyaline, rectangular to
barrel-shaped, thick-walled
arthroconidia.
Typically, these arthroconidia alternate
with empty disjunctor cells.
Culture identification by the
exoantigen test is now the method of choice.
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Arthroconidia of C. immitis |
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WARNING: Cultures of Coccidioides immitis represent
a severe biohazard to laboratory personnel and must be handled
with extreme caution in an appropriate pathogen handling
cabinet. |
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Health Effects
Coccidioides immitis has the highest virulence among all known
fungi. Healthy persons may be infected with it and the disease is
sometimes fatal. |
The
hypha of the fungi in the soil
will change into
arthroconidia, which are light and easily
dispersed in the air by natural processes, such as storms or by
environmental disruption, such as building constructions.
Arthroconidia are inhaled and swell in the lung and develop into
tissue spherules that are filled by numerous endospores. At
maturity, a part of the spherule wall ruptures, and endospores
are released into the surrounding tissue, where they enlarge to
form new spherules. The fungus proliferates in the body by
repeating the same cycle. The incubation period is between 7 days
and one month.
Symptoms of acute coccidioidomycosis include
fever, headache, rash, muscle aches, dry cough, weight loss, and
malaise. Most infections are asymptomatic or self-limited and
resolve without antimicrobial treatment in patients with healthy
immune systems. In rare instances, severe lung disease or
disseminated infection can develop in patients; susceptibility is
higher in immunocompromised persons, pregnant women, and persons
of African or Asian descent
The symptoms often resemble those of common cold
and pneumonia. When lung infection is in its chronic phase, bloody
phlegm and
hemoptysis may develop. According to the studies in
USA, 30-40% of those infected will become ill, about 9% of
patients will deteriorate into serious conditions and about 3%
will be fatal.
Nat'l Center of Biotechnology Information.
In the U.S., the disease is often called
'Valley Fever', because the organism is prevalent in the
San Joaquin Valley of Central California and
in Mexico (though it is strangely absent from the
deserts of Africa and Asia).
Outbreaks of coccidioidomycosis
have occurred among archaeology students digging in prehistoric
Indian sites in Northern California.
In 1977, a major dust
storm blew soil from the San Joaquin Valley up into Northern
California, including San Francisco, Marin County, Santa Clara,
and Monterey County. Immediately following the storm,
numerous cases of coccidioidomycosis were reported in non-endemic
regions of middle and Northern California. At the time,
there was some concern that C. immitis might be able to
seed and persist in the soil in these areas, but that has not
occurred.
Millions of people in the
U.S. Southwest have contracted the disease. Fortunately, most cases are benign, and healing is spontaneous. A few become
systemic, and are usually fatal if untreated or misdiagnosed. The
disseminated form of this disease is commoner among males than
females, and among people with darkly pigmented skin. Coccidioidomycosis can also present as
erythema nodosum, or as a reactive arthritic condition which is
commonly referred to as desert rheumatism.
Imported cases may be observed following
travel to endemic areas.
Physicians outside the endemic regions should consider coccidioidomycosis as a possible diagnosis of a respiratory
infection if the patient has ever traveled through the
desert Southwest or lived in an endemic area. Reactivation
of a prior asymptomatic C. immitis infection is potential
concern for immunocompromised individuals.
(Source:
http://www.tigr.org/tdb/tgi/cigi/cimmitis_doc.html)
It has been estimated,
primarily on the basis of skin tests, that there are between
25,000 and 100,000 new cases of human C. immitis infections
each year in United States. Approximately 10 in 200 of these
progress to disseminated disease. A history of recurrent
epidemics of coccidioidal infections, primarily in recreational
and urban areas of the San Joaquin Valley, has focused attention
on the need for both improved therapy and vaccine development.
A
recent Tucson news report claimed a 50% increase in the number of
reported C. immitis infections during 1999 in Pima County,
Arizona, and a 30% rise in the disease statewide. The direct cost
of medical supplies and sick leave for patients with Valley Fever
has also escalated. In Kern County, California, located near the
epicenter of the endemic region in that state, the accrued cost of
the disease from 1991 to 1995 was estimated at more than $66
million.
Vaccination of persons at risk of contacting coccidioidomycosis is a feasible approach to the control of this
insidious fungal disease. The rationale for immunoprotection is
based on the observation that natural infection by C. immitis
almost always confers lifelong immunity against the disease.
The year 2001 has
seen an interesting outbreak of this disease in Dinosaur National
Monument, Utah. Ten people who had been working at a 'dig'
developed acute respiratory coccoidioidomycosis
within two weeks of exposure. All were treated with
fluconazole, with an average hospital stay of 1.5 days, and
released, apparently none the worse for their experience. New
regulations for digs at Dinosaur call for watering down of the
soil before digging, and use of approved respirators (N95). [from
Bryce Kendrick's The Fifth Kingdom]
Visit the web site:
Center for Disease Control and Prevention.
Histopathology of coccidioidomycosis of
lung. Mature spherule with endospores of Coccidioides immitis, intense infiltrate of
neutrophils. CDC/Dr. Lucille K. Georg (Above photo and caption is courtesy of:
Mycology Online)
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Disseminated
coccidioidomycosis, caused by Coccidioides immitis. |
Macroscopic
Features
Coccidioides
immitis
colonies grow rapidly. The colony morphology may be very
variable. At 25 or 37°C and on Sabouraud dextrose agar, the
colonies are moist, glabrous, membranous, and grayish initially,
later producing white and cottony aerial mycelium. With age,
colonies become tan to brown in color.
Microscopic
Features
Microscopic
appearance of the fungus depends on the temperature of
isolation:
1. At 25°C
Hyphae and arthroconidia
are produced. Hyphae are hyaline, septate and thin. Racquet
hyphae may occasionally be observed on slides prepared from
young cultures. Arthroconidia are thick-walled, barrel-shaped,
and 2-4 x 3-6 µm in size. Typically, these arthroconidia
alternate with empty disjunctor cells. On the released
arthroconidia, annular frills that are the remnants of the
disjunctor cells are observed.
2. At 37°C
Large, round, thick-walled
spherules (10-80 µm in diameter) filled with endospores (2-5 µm
in diameter) are observed. Production of spherules in vitro
requires inoculation into a special synthetic medium, such as
converse liquid medium, an incubation temperature of 37-40°C
and presence of CO2 at a concentration as high as 20%.
Coccidioides immitis
continues to grow as a mould and does not produce spherules at
any temperature unless special growth medium is provided in
vitro. This finding indicates that temperature is not the only
variable that controls the spherule formation. Thus, some
authorities prefer not to classify this fungus as thermally
dimorphic. Nevertheless, Coccidioides immitis is commonly
classified among the thermally dimorphic fungi.
The definitive
identification of an isolated Coccidioides immitis strain
requires demonstration of spherule production in vitro, use of
DNA probes, application of exoantigen tests, or demonstration of
spherule production in vivo by animal experiments. Molecular
typing studies have also been initiated and appear useful in
identification.
Laboratory
Precautions
The
arthroconidia of Coccidioides immitis are very
infectious. All manipulations should be done in a biological
safety cabinet.
Therapy
Amphotericin
B, itraconazole,
and voriconazole
appear active in vitro against Coccidioides immitis.
However, amphotericin B is less active against some of the
isolates for which it fails to exert fungicidal activity.
Itraconazole and voriconazole, on the other hand, do not have
any fungicidal activity at all against Coccidioides immitis.
Nikkomycins are additive to synergistic in vitro with fluconazole
or itraconazole against Coccidioides immitis.
Patients with self-limited
disease or relatively localized acute pulmonary infections
usually do not require antifungal therapy. Antifungal therapy
should be given to patients who have disseminated disease or are
under risk of complications due to their underlying
immunosuppression and other factors. Amphotericin B and azoles,
such as fluconazole, itraconazole, and ketoconazole
are used for treatment of coccidioidomycosis. However, clinical
failure during antifungal therapy is not uncommon. Azoles,
particularly fluconazole, is preferred for treatment of cases
with meningitis. Available data suggest that the azole therapy
should be continued life long in cases with meningitis to
prevent relapses. Amphotericin B, if used for treatment of
meningitis, should be given via intrathecal route and for a
prolonged duration.
Animal experiments suggest
that caspofungin,
sordarins, and nikkomycins are also promising in treatment of
coccidioidomycosis.
Concomitant surgical
interventions may be required for some patients with pulmonary
coccidioidomycosis as well as cases with bone and joint
involvement.
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