Coccidioides immitis

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Coccidioides immitis
Coccidioides immitis.jpg
colonies of Coccidioides immitis growing in petri dish
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
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]
  • Zymonema immitis(G.W.Stiles) Mello (1918)
  • Mycoderma immite(G.W.Stiles) Verdun & Mandoul (1924)
  • Blastomycoides immitis(G.W.Stiles) Castell. (1928)
  • Geotrichum immite(G.W.Stiles) A.Agostini (1932)
  • Aleurisma immite(G.W.Stiles) Bogliolo & J.A.Neves (1952)
Sputum culture of Coccidioides immitis on Sabouraud's medium, showing white, cottony fungus growth Coccidioides immitis on Sabouraud's medium.jpg
Sputum culture of Coccidioides immitis on Sabouraud's medium, showing white, cottony fungus growth
Microscopic appearance of an old culture of Coccidioides immitis, showing fragmented chlamydospores. This is the infective form of the fungus occurring in nature Coccidioides immitis microscopy.jpg
Microscopic appearance of an old culture of Coccidioides immitis, showing fragmented chlamydospores. This is the infective form of the fungus occurring in nature
Septate hyphae of Coccidioides immitis with 90-degree branching and thick-walled barrel-shaped arthroconidia alternating with empty cells Arthroconidia of Coccidioides immitis 39G0040 lores.jpg
Septate hyphae of Coccidioides immitis with 90-degree branching and thick-walled barrel-shaped arthroconidia alternating with empty cells

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

Epidemiology

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

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. [5] :296–297C. immitis is more common west of the Tehachapi Mountains, while C. posadasii is more common 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 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]

Clinical manifestation

C. immitis can cause a disease called coccidioidomycosis (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 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). [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

Azoles

The introduction of azoles 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 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.

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 also unsuccessful.

Amphotericin

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

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

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 (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]

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any species of the genus Candida. When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers along with other symptoms depending on the parts involved.

<span class="mw-page-title-main">Coccidioidomycosis</span> Fungal infection

Coccidioidomycosis, commonly known as cocci, Valley fever, as well as California fever, desert rheumatism, or San Joaquin Valley fever, is a mammalian fungal disease caused by Coccidioides immitis or Coccidioides posadasii. Coccidioidomycosis is endemic in certain parts of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico.

<span class="mw-page-title-main">Histoplasmosis</span> Human disease

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; called disseminated histoplasmosis, it can be fatal if left untreated.

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<span class="mw-page-title-main">Itraconazole</span> Chemical compound used as medication to treat fungal infections

Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth or intravenously.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc. discovered by James Balkovec, Regina Black and Frances A. Bouffard. It is a member of a new class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall. Caspofungin was the first inhibitor of fungal (1→3)-β-D-glucan synthesis to be approved by the United States Food and Drug Administration. Caspofungin is administered intravenously.

<span class="mw-page-title-main">Sporotrichosis</span> Medical condition

Sporotrichosis, also known as rose handler's disease, is a fungal infection that may be localised to skin, lungs, bone and joint, or become systemic. It presents with firm painless nodules that later ulcerate. Following initial exposure to Sporothrix schenckii, the disease typically progresses over a period of a week to several months. Serious complications may develop in people who have a weakened immune system.

<span class="mw-page-title-main">Esophageal candidiasis</span> Medical condition

Esophageal candidiasis is an opportunistic infection of the esophagus by Candida albicans. The disease usually occurs in patients in immunocompromised states, including post-chemotherapy and in AIDS. However, it can also occur in patients with no predisposing risk factors, and is more likely to be asymptomatic in those patients. It is also known as candidal esophagitis or monilial esophagitis.

<span class="mw-page-title-main">Posaconazole</span> Pharmaceutical drug

Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.

<span class="mw-page-title-main">Aspergillosis</span> Medical condition

Aspergillosis is a fungal infection of usually the lungs, caused by the genus Aspergillus, a common mould that is breathed in frequently from the air, but does not usually affect most people. It generally occurs in people with lung diseases such as asthma, cystic fibrosis or tuberculosis, or those who are immunocompromized such as those who have had a stem cell or organ transplant or those who take medications such as steroids and some cancer treatments which suppress the immune system. Rarely, it can affect skin.

<i>Coccidioides</i> Genus of fungi

Coccidioides is a genus of dimorphic ascomycetes in the family Onygenaceae. Member species are the cause of coccidioidomycosis, also known as San Joaquin Valley fever, an infectious fungal disease largely confined to the Western Hemisphere and endemic in the Southwestern United States. The host acquires the disease by respiratory inhalation of spores disseminated in their natural habitat. The causative agents of coccidioidomycosis are Coccidioides immitis and Coccidioides posadasii. Both C. immitis and C. posadasii are indistinguishable during laboratory testing and commonly referred in literature as Coccidioides.

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

Exophiala jeanselmei is a saprotrophic fungus in the family Herpotrichiellaceae. Four varieties have been discovered: Exophiala jeanselmei var. heteromorpha, E. jeanselmei var. lecanii-corni, E. jeanselmei var. jeanselmei, and E. jeanselmei var. castellanii. Other species in the genus Exophiala such as E. dermatitidis and E. spinifera have been reported to have similar annellidic conidiogenesis and may therefore be difficult to differentiate.

<i>Coccidioides posadasii</i> Species of fungus

Coccidioides posadasii is a pathogenic fungus that, along with Coccidioides immitis, is the causative agent of coccidioidomycosis, or valley fever in humans. It resides in the soil in certain parts of the Southwestern United States, northern Mexico, and some other areas in the Americas, but its evolution was connected to its animal hosts.

<i>Prototheca wickerhamii</i> Species of alga

Prototheca wickerhamii is a ubiquitous green alga that does not have chlorophyll. It is widely present in the environment but is a rare cause of opportunistic infection in humans (protothecosis).

Fungistatics are anti-fungal agents that inhibit the growth of fungus. The term fungistatic may be used as both a noun and an adjective. Fungistatics have applications in agriculture, the food industry, the paint industry, and medicine.

Invasive candidiasis is an infection (candidiasis) that can be caused by various species of Candida yeast. Unlike Candida infections of the mouth and throat or vagina, invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood (fungemia), heart, brain, eyes, bones, and other parts of the body.

<i>Candida tropicalis</i> Species of fungus

Candida tropicalis is a species of yeast in the genus Candida. It is a common pathogen in neutropenic hosts, in whom it may spread through the bloodstream to peripheral organs. For invasive disease, treatments include amphotericin B, echinocandins, or extended-spectrum triazole antifungals.

<span class="mw-page-title-main">Trichosporon asteroides</span> Fungus of the genus Trichosporon

Trichosporon asteroides is an asexual basidiomycetous fungus first described from human skin but now mainly isolated from blood and urine. T. asteroides is a hyphal fungus with a characteristically yeast-like appearance due to the presence of slimy arthroconidia. Infections by this species usually respond to treatment with azoles and amphotericin B.

References

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  11. Loretta S. Chang; Tom M. Chiller. "Infectious Diseases Related To Travel". Centers for Disease Control and Prevention (CDC). Retrieved 12 July 2013.
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  14. "Treatment and Outcomes for Coccidioidomycosis (Valley Fever)". Centers for Disease Control and Prevention (CDC). Retrieved 11 July 2013.
  15. "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.
  16. "HHS select agents and toxins". Code of Federal Regulations (CFR), Title 42, Part 73 (Volume 77, Number 194) - Public Health. Office of the Federal Register. Retrieved 11 July 2013.