Coccidioidin

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. 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, and Venezuela. 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 surface. 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, because the 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. The introduction of azoles revolutionized treatment for coccidioidomycosis, 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 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 newer drugs. 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.