| Coccidioides immitis | |
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| Colonies ofCoccidioides immitis growing in petri dish | |
Scientific classification | |
| Kingdom: | Fungi |
| Division: | Ascomycota |
| Class: | Eurotiomycetes |
| Order: | Onygenales |
| Family: | Onygenaceae |
| Genus: | Coccidioides |
| Species: | C. immitis |
| Binomial name | |
| Coccidioides immitis G.W.Stiles (1896) | |
| Synonyms[1] | |
Coccidioides immitis is apathogenicfungus that resides in thesoil in certain parts of thesouthwestern United States, northernMexico, and a few other areas in theWestern Hemisphere.[2]
C. immitis, along with its relativeC. 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]
C. immitis is largely found in California, but also Baja California and Arizona, whileC. posadasii is regularly found in Texas, northern Mexico and in Central and South America. BothC. immitis andC. posadasii are present in Arizona.[5]: 296–297 C. immitis is more common west of theTehachapi Mountains, whileC. posadasii is more common east of it.[6]Coccidioides spp. are found inalkaline, sandy soils from semi-desert regions with hot summers, gentle winters, and annual rainfall between 10 and 50 centimetres (3.9 and 19.7 in). These fungi are usually found 10 to 30 centimetres (3.9 to 11.8 in) beneath the surface.[7]
C. immitis can cause a disease calledcoccidioidomycosis (valley fever).[8][9][10] Its incubation period varies from 7 to 21 days.[11] 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 discoverCoccidioidesantigens. However, because theCoccidioides creates a mass that can mimic a lung tumor, the correct diagnosis may require a tissue sample (biopsy). AGomori methenamine silver stain can then confirm the presence of theCoccidioides organism's characteristic spherules within the tissue. TheC. 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 aselect agent by both theU.S. Department of Health and Human Services and theU.S. Department of Agriculture, and was considered abiosafety level 3 pathogen.
The introduction ofazoles revolutionized treatment for coccidioidomycosis,[14] and these agents are usually the first line of therapy. However, none of these azoles are safe to use in pregnancy and lactation because they have shownteratogenicity in animal studies.
Of theazoles,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-toxictriazoles (fluconazole anditraconazole) 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 andvoriconazole (triazole compounds similar in structure to fluconazole) andcaspofungin (glucan synthesis inhibitor of theechinocandin structural class). However, these drugs have not been FDA approved, and clinical trials are lacking. Susceptibility testing ofCoccidioidesspecies in one report revealed uniform susceptibility to most antifungal agents, including these newer drugs.
In very severe cases, combination therapy withamphotericin 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 asalvage 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 also unsuccessful.
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 classicamphotericin 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).
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.
Along withC. posadasii,C. immitis was featured on theselect agents and toxins list compiled by theU.S. Department of Health and Human Services (HHS), as evident from theCode 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]
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