Coccidioides immitis
| Ascomycota | |
|---|---|
| Scientific classification | |
| Kingdom: | Fungi |
| Division: | Ascomycota |
| Class: | Euascomycetes |
| Order: | Onygenales |
| Family: | Onygenaceae |
| Genus: | Coccidioides |
| Binomial name | |
| Coccidioides immitis G.W. Stiles |
|
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.
It, along with its relative Coccidioides posadasii, is most commonly seen in the desert regions of the southwestern United States, and in Central and South America. It can cause a disease called coccidioidomycosis (Valley Fever). Coccidioidomycosis is not diagnosed on the basis of signs and symptoms, which are usually vague and nonspecific, or on a chest X-ray, which cannot distinguish valley fever from other lung diseases, including lung cancer. Blood tests are available that test for antibodies against the organism. However, because the organisms create a mass that can mimic a lung tumor, the diagnosis may require a tissue sample (biopsy). A Gomori methenamine silver (GMS) stain can then confirm the presence of the organism's characteristic spherules within the tissue. The Coccidioides immitis organism can be cultured from a patient sample, but the culture can take weeks to grow and requires special precautions by the laboratory. It has been declared a select agent by both the U.S. Department of Health and Human Services and the U.S. Department of Agriculture, and is considered a biosafety level 3 pathogen.
Contents |
Treatment [edit]
- Most Coccidioides infections resolve without specific therapy; few clinical trials have assessed outcomes in less-severe disease.
- Commonly used indicators to judge the severity of illness:
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- 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 (CF) 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):
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- Primary infection during infancy
- Primary infection during pregnancy, especially in the third trimester or immediately postpartum
- Immunosuppression (e.g., patients with HIV/AIDS, transplant recipients, patients receiving high-dose corticosteroids, those receiving anti–tumor necrosis factor [TNF] 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 therapy 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.
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- Of the azoles, ketoconazole is the only one that is approved by the US 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.
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- 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,[64] 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.
- Dosages vary. Common dosages:
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- Ketoconazole - 400 mg/day orally
- Itraconazole - 200 mg 2-3 times/day orally
- Fluconazole - 400-800 mg/day orally or IV
- Complications:
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- Hepatic dysfunction
- For patients who are unresponsive to fluconazole, options are limited. Several case reports have studied the efficacy of 3 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).[65, 66, 67] 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 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 Korean man 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 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 third 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 IV 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.
- Dosage:
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- Amphotericin B deoxycholate - 0.5-1.5 mg/kg/day IV
- Lipid formulations of amphotericin B - 2-5 mg/kg/day IV
- Complications:
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- Renal toxicity, bone marrow toxicity, 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.
In popular culture [edit]
Coccidioides immitis is used as a plot device in Thunderhead, a novel by Douglas Preston and Lincoln Child. The fungus (prepared from infected victims) is revealed to be the principal agent in corpse powder (based on corpse poison used by Witch). It was also mentioned by the fictional antihero Dr. Gregory House (played by actor James Hugh Calum Laurie) on the Television Series, House MD (episode Lines in the Sand).
