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Coccidioides
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.[2]

Contents

1 Epidemiology

1.1 Precise location

2 Clinical manifestation 3 Treatment

3.1 Azoles 3.2 Amphotericin 3.3 Duration of therapy and costs

4 HHS select agents listing 5 References 6 External links

Epidemiology[edit] C. immitis, along with its relative C. posadasii,[3] 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, and Venezuela.[4] Precise location[edit] C. immitis is largely found in California, but also Baja California and Arizona, while C. posadasii is regularly found in Texas, northern Mexico
Mexico
and in Central and South America. Both C. immitis and C. posadasii are present in Arizona.[5] C. immitis is more common west of the Tehachapi mountains, while posadasii east of it.[6] 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 surface.[7] Clinical manifestation[edit] C. immitis can cause a disease called coccidioidomycosis (valley fever).[8][9][10] Its incubation period varies from 7 to 21 days.[11] Coccidioidomycosis
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
Coccidioides
antigens. However, because the Coccidioides
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
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.[12] It is reported as the tenth-most often acquired infection in the laboratory conditions with two documented deaths.[2] 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. Treatment[edit]

Most Coccidioides
Coccidioides
infections have an incubation period from one to four weeks[2] 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:[13]

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 both lungs 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 initiated):

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

Azoles[edit] The introduction of azoles revolutionized treatment for coccidioidomycosis,[14] 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
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
Coccidioides
species in one report revealed uniform susceptibility to most antifungal agents, including these newer drugs. In very severe cases, combination therapy with amphotericin B and an azole have been postulated, although no trials have been conducted. Caspofungin
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
Posaconazole
has been approved by the European Commission as a salvage therapy for refractory coccidioidomycosis. Clinical trials are now ongoing for further evaluation. Voriconazole
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
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 also unsuccessful. Amphotericin[edit] 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 (fever, rigors). Duration of therapy and costs[edit] 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 lifelong treatment. 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[edit] 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).[15] 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.[16] References[edit]

^ "GSD Species Synonymy: Coccidioides
Coccidioides
immitis G.W. Stiles". Species Fungorum. CAB International. Retrieved 2016-02-06.  ^ a b c "Infectious Disease Index: Coccidioides
Coccidioides
immitis". MDSC Online. Public Health Agency of Canada (PHAC). Retrieved 16 July 2013.  ^ " Coccidioides
Coccidioides
group database". Broad Institute. Retrieved 11 July 2013.  ^ Frederick S. Fisher; Mark W. Bultman; Demosthenes Pappagianis. "Operational Guidelines (version 1.0) for Geological Fieldwork in Areas Endemic for Coccidioidomycosis
Coccidioidomycosis
(Valley Fever)" (PDF). U.S. Geological Survey Open- File
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. 296-297. ^ http://www.mdpi.com/2309-608X/2/4/34/pdf ^ Garcia Garcia SC, Salas Alanis JC, Flores MG, Gonzalez Gonzalez SE, Vera Cabrera L, Ocampo Candiani J (2015). " Coccidioidomycosis
Coccidioidomycosis
and the skin: a comprehensive review". An Bras Dermatol. 90: 610–9. doi:10.1590/abd1806-4841.20153805. PMC 4631225 . PMID 26560205. CS1 maint: Multiple names: authors list (link) ^ https://www.cdc.gov/fungal/diseases/coccidioidomycosis/symptoms.html ^ " Coccidioidomycosis
Coccidioidomycosis
(Valley Fever)". Centers for Disease Control and Prevention (CDC). Retrieved 11 July 2013.  ^ "Fungal pneumonia: a silent epidemic - Coccidioidomycosis
Coccidioidomycosis
(valley 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
Coccidioides
immitis". Tom Volk's Fungus
Fungus
of the Month. Tom Volk's Fungi. Retrieved 11 July 2013.  ^ "Symptoms of Coccidioidomycosis
Coccidioidomycosis
(Valley Fever)". Centers for Disease Control and Prevention (CDC). Retrieved 11 July 2013.  ^ "Treatment and Outcomes for Coccidioidomycosis
Coccidioidomycosis
(Valley Fever)". Centers for Disease Control and Prevention (CDC). Retrieved 11 July 2013.  ^ "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 2013.  ^ "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. 

External links[edit]

Identification of Coccidioides
Coccidioides
immitis and Coccidioides
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 Mayo Clinic

v t e

Fungal infection and mesomycetozoea (B35–B49, 110–118)

Superficial and cutaneous (dermatomycosis): Tinea
Tinea
= skin; Piedra (exothrix/ endothrix) = hair

Ascomycota

Dermatophyte (Dermatophytosis)

By location

Tinea
Tinea
barbae/tinea capitis

Kerion

Tinea
Tinea
corporis

Ringworm Dermatophytids

Tinea
Tinea
cruris Tinea
Tinea
manuum Tinea
Tinea
pedis (athlete's foot) Tinea
Tinea
unguium/onychomycosis

White superficial onychomycosis Distal subungual onychomycosis Proximal subungual onychomycosis

Tinea
Tinea
corporis gladiatorum Tinea
Tinea
faciei Tinea
Tinea
imbricata Tinea
Tinea
incognito Favus

By organism

Epidermophyton floccosum Microsporum canis Microsporum audouinii Trichophyton
Trichophyton
interdigitale/mentagrophytes Trichophyton
Trichophyton
tonsurans Trichophyton
Trichophyton
schoenleini Trichophyton
Trichophyton
rubrum Trichophyton
Trichophyton
verrucosum

Other

Hortaea werneckii

Tinea
Tinea
nigra

Piedraia hortae

Black piedra

Basidiomycota

Malassezia
Malassezia
furfur

Tinea
Tinea
versicolor Pityrosporum folliculitis

Trichosporon

White piedra

Subcutaneous, systemic, and opportunistic

Ascomycota

Dimorphic (yeast+mold)

Onygenales

Coccidioides
Coccidioides
immitis/ Coccidioides
Coccidioides
posadasii

Coccidioidomycosis Disseminated coccidioidomycosis Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis

Histoplasma capsulatum

Histoplasmosis Primary cutaneous histoplasmosis Primary pulmonary histoplasmosis Progressive disseminated histoplasmosis

Histoplasma duboisii

African histoplasmosis

Lacazia loboi

Lobomycosis

Paracoccidioides brasiliensis

Paracoccidioidomycosis

Other

Blastomyces
Blastomyces
dermatitidis

Blastomycosis North American blastomycosis South American blastomycosis

Sporothrix schenckii

Sporotrichosis

Penicillium marneffei

Penicilliosis

Yeast-like

Candida albicans

Candidiasis Oral Esophageal Vulvovaginal Chronic mucocutaneous Antibiotic candidiasis Candidal intertrigo Candidal onychomycosis Candidal paronychia Candidid Diaper candidiasis Congenital cutaneous candidiasis Perianal candidiasis Systemic candidiasis Erosio interdigitalis blastomycetica

C. glabrata C. tropicalis C. lusitaniae Pneumocystis jirovecii

Pneumocystosis Pneumocystis pneumonia

Mold-like

Aspergillus

Aspergillosis Aspergilloma Allergic bronchopulmonary aspergillosis Primary cutaneous aspergillosis

Exophiala jeanselmei

Eumycetoma

Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa

Chromoblastomycosis

Geotrichum candidum

Geotrichosis

Pseudallescheria boydii

Allescheriasis

Basidiomycota

Cryptococcus neoformans

Cryptococcosis Trichosporon spp Trichosporonosis

Zygomycota (Zygomycosis)

Mucorales (Mucormycosis)

Rhizopus oryzae Mucor indicus Lichtheimia corymbifera Syncephalastrum racemosum Apophysomyces variabilis

Entomophthorales (Entomophthoramycosis)

Basidiobolus ranarum

Basidiobolomycosis

Conidiobolus coronatus/Conidiobolus incongruus

Conidiobolomycosis

Microsporidia (Microsporidiosis)

Enterocytozoon bieneusi/Encephalitozoon intestinalis

Mesomycetozoea

Rhinosporidium seeberi

Rhinosporidiosis

Ungrouped

Alternariosis Fungal folliculitis Fusarium

Fusariosis

Granuloma gluteale infantum Hyalohyphomycosis Otomycosis Phaeohyphomycosis

Taxon identifiers

Wd: Q5139154 EoL: 244854 EPPO: CCDIIM Fungorum: 416228 GBIF: 4911585 MycoBank:

.