Coccidioides immitis is a pathogenic fungus that resides in the soil
in certain parts of the southwestern United States, northern Mexico,
and a few other areas in the Western Hemisphere.
1.1 Precise location
2 Clinical manifestation
3.3 Duration of therapy and costs
4 HHS select agents listing
6 External links
C. immitis, along with its relative C. posadasii, is most commonly
seen in the desert regions of the southwestern United States,
including certain areas of Arizona, California, New Mexico, Nevada,
Texas, and Utah; and in Central and South America in Argentina,
Brazil, Colombia, Guatemala, Honduras, Mexico, Nicaragua, Paraguay,
C. immitis is largely found in California, but also Baja California
and Arizona, while C. posadasii is regularly found in Texas, northern
Mexico and in Central and South America. Both C. immitis and C.
posadasii are present in Arizona. C. immitis is more common west of
the Tehachapi mountains, while posadasii east of it. Coccidioides
spp. are found in alkaline, sandy soils from semi-desert regions with
hot summers, gentle winters, and annual rainfall between 10 and
50 cm. These fungi are usually found 10 to 30 cm beneath the
C. immitis can cause a disease called coccidioidomycosis (valley
fever). Its incubation period varies from 7 to 21 days.
Coccidioidomycosis is not easily diagnosed on the basis of vital signs
and symptoms, which are usually vague and nonspecific. Even a chest
X-ray or CT scan cannot reliably distinguish it from other lung
diseases, including lung cancer. Blood or urine tests are
administered, which aim to discover
Coccidioides antigens. However,
Coccidioides creates a mass that can mimic a lung tumor,
the correct diagnosis may require a tissue sample (biopsy). A Gomori
methenamine silver stain can then confirm the presence of the
Coccidioides organism's characteristic spherules within the tissue.
The C. immitis fungus can be cultured from a patient sample, but the
culture can take weeks to grow and requires special precautions on a
part of the laboratory staff while handling it (screw cap vials and
sterile transfer hoods are recommended. It is reported as the
tenth-most often acquired infection in the laboratory conditions with
two documented deaths. Until October 2012, C. immitis had been
listed as a select agent by both the U.S. Department of Health and
Human Services and the U.S. Department of Agriculture, and was
considered a biosafety level 3 pathogen.
Coccidioides infections have an incubation period from one to
four weeks and resolve without specific therapy; few clinical
trials have assessed outcomes in less-severe disease.
Commonly used indicators to judge the severity of illness include:
Continuous fever for longer than 1 month
Body-weight loss of more than 10%
Intense night sweats that persist for more than 3 weeks
Infiltrates that involve more than half of one lung or portions of
Prominent or persistent hilar adenopathy
Anticoccidioidal complement fixation IgG titers of 1:16 or higher
Absence of dermal hypersensitivity to coccidioidal antigens
Inability to work
Symptoms that persist for more than 2 months
Risk factors for dissemination (for which treatment should be
Primary infection during infancy
Primary infection during pregnancy, especially in the third trimester
or immediately post partum
Immunosuppression (e.g., patients with HIV/AIDS, transplant
recipients, patients receiving high-dose corticosteroids, those
receiving antitumor necrosis factor medications)
Chronic debilitation or underlying disease, including diabetes
mellitus or preexisting cardiopulmonary disease
High inoculum exposures
Certain ethnicities, such as Filipino, Black, or Hispanic
Age greater than 55 years
The introduction of azoles revolutionized treatment for
coccidioidomycosis, and these agents are usually the first line of
therapy. However, none of the azoles is safe to use in pregnancy and
lactation because they have shown teratogenicity in animal studies.
Of the azoles, ketoconazole is the only one approved by the U.S. Food
and Drug Administration (FDA) for treatment of coccidioidomycosis.
Nevertheless, although it was initially used in the long-term
treatment of nonmeningeal extrapulmonary disease, more-potent,
less-toxic triazoles (fluconazole and itraconazole) have replaced it.
Itraconazole (400 mg/day) appears to have efficacy equal to that
of fluconazole in the treatment of nonmeningeal infection and have the
same relapse rate after therapy is discontinued. However, itraconazole
seems to perform better in skeletal lesions, whereas fluconazole
performs better in pulmonary and soft tissue infection. Serum levels
of itraconazole are commonly obtained at the onset of long-term
therapy because its absorption is sometimes erratic and unpredictable.
Complications can include hepatic dysfunction.
For patients who are unresponsive to fluconazole, options are limited.
Several case reports have studied the efficacy of three newer
antifungal agents in the treatment of disease that is refractory to
first-line therapy: posaconazole and voriconazole (triazole compounds
similar in structure to fluconazole) and caspofungin (glucan synthesis
inhibitor of the echinocandin structural class). However, these drugs
have not been FDA approved, and clinical trials are lacking.
Susceptibility testing of
Coccidioides species in one report revealed
uniform susceptibility to most antifungal agents, including these
In very severe cases, combination therapy with amphotericin B and an
azole have been postulated, although no trials have been conducted.
Caspofungin in combination with fluconazole has been cited as
beneficial in a case report of a 31-year-old Asian patient with
coccidioidal pneumonia. In a case report of a 23-year-old Black male
with HIV and coccidioidal meningitis, combination therapy of
amphotericin B and posaconazole led to clinical improvement.
Posaconazole has been approved by the European Commission as a salvage
therapy for refractory coccidioidomycosis. Clinical trials are now
ongoing for further evaluation.
Voriconazole is also being studied in
salvage therapy for refractory cases. A case report indicated that
voriconazole in combination with amphotericin B as salvage therapy for
disseminated coccidioidomycosis was successful.
Several case reports have studied caspofungin, with differing results.
Caspofungin 50 mg/day following administration of amphotericin B
in a patient with acute pulmonary coccidioidomycosis who had undergone
transplantation showed promising results. In a patient with
disseminated coccidioidomycosis, first-line therapy with amphotericin
B and caspofungin alone failed to elicit a response, but the patient
was then given caspofungin combined with fluconazole, with good
results. A published report described a patient with disseminated and
meningeal coccidioidomycosis in whom conventional therapy with
fluconazole, voriconazole, and amphotericin B failed; caspofungin
50 mg/day after a loading dose of 70 mg intravenously was
Amphotericin B, introduced in 1957, remains the treatment of choice
for severe infections. It is usually reserved for worsening disease or
lesions located in vital organs such as the spine. It can be
administered either in the classic amphotericin B deoxycholate
formulation or as a lipid formulation. No studies have directly
compared amphotericin B with azole therapy. Complications include
renal toxicity, bone marrow toxicity, and local systemic effects
Duration of therapy and costs
The objectives of treatment are resolution of infection, decrease of
antibody titers, return of function of involved organs, and prevention
of relapse. The duration of therapy is dictated by the clinical course
of the illness, but it should be at least 6 months in all patients and
often a year or longer in others. Therapy is tailored based on a
combination of resolution of symptoms, regression of radiographic
abnormalities, and changes in CF IgG titers. Immunocompromised
patients and patients with a history of meningeal involvement require
The cost of antifungal therapy is high, from $5,000 to $20,000 per
year. These costs increase for critical patients in need of intensive
care. Arizona spent an average of $33,762 per patient with
coccidioidomycosis between 1998 and 2001.
HHS select agents listing
Along with C. posadasii, C. immitis was featured on the select agents
and toxins list compiled by the U.S. Department of Health and Human
Services (HHS), as evident from the
Code of Federal Regulations
Code of Federal Regulations (42
CFR 73). However, on October 5, 2012 due to advances in medical
research and development of a number of licensed treatments, both
pathogens were removed from the HHS select agents listing.
^ "GSD Species Synonymy:
Coccidioides immitis G.W. Stiles". Species
Fungorum. CAB International. Retrieved 2016-02-06.
^ a b c "Infectious Disease Index:
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"Operational Guidelines (version 1.0) for Geological Fieldwork in
Areas Endemic for
Coccidioidomycosis (Valley Fever)" (PDF). U.S.
Geological Survey Open-
File Report 00-348 Version 1.0. U.S. Department
of the Interior. Retrieved 12 July 2013.
^ Hospenthal, Duane R., and Michael G. Rinaldi. Diagnosis and
Treatment of Human Mycoses. Totowa, N.J.: Humana Press, 2007, p.
^ Garcia Garcia SC, Salas Alanis JC, Flores MG, Gonzalez Gonzalez SE,
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Coccidioidomycosis and the
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Coccidioidomycosis (Valley Fever)". Centers for Disease Control and
Prevention (CDC). Retrieved 11 July 2013.
^ "Fungal pneumonia: a silent epidemic -
fever)" (PDF). Centers for Disease Control and Prevention (CDC).
Retrieved 11 July 2013.
^ Loretta S. Chang; Tom M. Chiller. "Infectious Diseases Related To
Travel". Centers for Disease Control and Prevention (CDC). Retrieved
12 July 2013.
Coccidioides immitis". Tom Volk's
Fungus of the Month. Tom Volk's
Fungi. Retrieved 11 July 2013.
^ "Symptoms of
Coccidioidomycosis (Valley Fever)". Centers for Disease
Control and Prevention (CDC). Retrieved 11 July 2013.
^ "Treatment and Outcomes for
Coccidioidomycosis (Valley Fever)".
Centers for Disease Control and Prevention (CDC). Retrieved 11 July
^ "HHS select agents and toxins" (PDF). Code of Federal Regulations
(CFR), Title 42 - Public Health. Office of the Federal Register.
Archived from the original (PDF) on 20 October 2013. Retrieved 11 July
^ "HHS select agents and toxins".
Code of Federal Regulations
Code of Federal Regulations (CFR),
Title 42, Part 73 (Volume 77, Number 194) - Public Health. Office of
the Federal Register. Retrieved 11 July 2013.
Coccidioides immitis and
Coccidioides posadasii, a
presentation by Nancy L Wengenack, PhD, Director of the Mycology and
Mycobacteriology Laboratories and Associate Professor of Laboratory
Medicine and Pathology in the Division of Clinical Microbiology at
Fungal infection and mesomycetozoea (B35–B49, 110–118)
Tinea = skin;
endothrix) = hair
Tinea barbae/tinea capitis
Tinea pedis (athlete's foot)
White superficial onychomycosis
Distal subungual onychomycosis
Proximal subungual onychomycosis
Tinea corporis gladiatorum
Primary cutaneous coccidioidomycosis. Primary pulmonary
Primary cutaneous histoplasmosis
Primary pulmonary histoplasmosis
Progressive disseminated histoplasmosis
North American blastomycosis
South American blastomycosis
Congenital cutaneous candidiasis
Erosio interdigitalis blastomycetica
Allergic bronchopulmonary aspergillosis
Primary cutaneous aspergillosis
Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa
Conidiobolus coronatus/Conidiobolus incongruus
Enterocytozoon bieneusi/Encephalitozoon intestinalis
Granuloma gluteale infantum