Fungal Infections

Disease name and synonyms

Coccidioidomycosis (Valley Fever) Link to article

Fungi responsible (links to these)

Coccidioides immitis and Coccidioides posadasii (no difference in disease or diagnostic performance between species)

Disease description

Initial infection results in symptoms in 40% of individuals which are self-limited in 80% of these people. Typical features are a ‘short-lived ‘flu-like’ syndrome (fever, cough and pleurisy), sometimes associated with erythema nodosum or erythema multiforme (especially in women).

In those whose disease is not self-limited, most progressive disease involves the lungs. A progressive pneumonia (primary pulmonary coccidioidomycosis) may occur with continuing fever, pulmonary symptoms and eosinophilia. This may also resolve spontaneously, and varies in severity. In immunocompromised individuals and rarely in previously well individuals, a milary, reticulonodular type of pulmonary disease that is characteristic of early disseminated coccidioidomycosis.

Following a primary infection pulmonary nodules or cavitation may occur, which may or may not progress. Patients with nodules are usually asymptomatic. Upper lobe cavitation may resemble chronic pulmonary aspergillosis or tuberculosis. Patients develop chronic productive cough, haemoptysis, weight loss and chest pains.

Dissemination, which is usually clinically silent, may occur to any body site, the more common locations being the skin, meninges, bones or joints, lymph nodes and other soft tissues. The clinical presentation may be delayed weeks or months after the primary infection. Localised swelling, sometimes with a discharging sinus, is common for many sites. Bone infection may present with a pathological fracture. Joint infection is typically a monoarthritis. Coccidioidal meningitis presents sub-acutely, similarly to tuberculous meningitis, with headache, lethargy and declining mental status.

Frequency and global burden

Coccidioidomycosis is restricted to the Americas (see map). An estimated 150,000 infections occur annually in the USA, and an unknown number in central and South America. Approximately 25,000 new, clinical cases of coccidioidomycosis are reported annually in the USA leading to ~75 deaths per year. Occasional epidemics occur. Case numbers have been rising in Arizona, possibly related to immigration to the state and building on previously wild desert areas, with 7 cases per 100,000 persons in 1990, increasing~75 cases per 100,000 persons in 2007. The most affected countries outside the USA are Mexico, Guatemala, Brazil, Paraguay and Argentina.

Underlying problems and at risk patients

Most patients with coccidioidomycosis are previously healthy. Dissemination is more common in certain racial groups including Filipinos and African-Americans, as well as men. Pregnancy (second or third trimester) increases the risk of dissemination. Immunocompromised patients, especially those on corticosteroids or with advanced HIV infection or AIDS, are at particular risk of dissemination. Patients who do not produce interleukin 12 and/or gamma interferon are more likely to develop disseminated coccidioidomycosis, as are those with a STAT3 genetic defect (Hyper IgE syndrome or Job’s syndrome).

Diagnostic testing

As C. immitis is never a commensal organism or a laboratory contaminant, isolation of the organism in culture is diagnostic. C. immitis is a Biosafety level 3 pathogen and must be managed accordingly. C. immitis grows on many fungal media, but poorly, or not at all, on standard bacterial media such as blood agar. C. immitis is difficult to culture from blood and cerebrospinal fluid, even in the context of disseminated disease or meningitis. The highly characteristic appearance of spherules in direct microscopy or histological sections confirms infection.

Serology with IgG or IgM antibody detection is sensitive and usually signifies infection, if detectable.  Falling titres is indicative of an improvement.

In meningitis, the cerebrospinal fluid usually has features similar to those of tuberculosis, namely an elevate protein, reduced glucose and many lymphocytes visible. The key diagnostic test is detection of anti-coccidioidal antibodies in CSF. 1,3-β-D-glucan is detectable in CSF and in endemic areas is likely to distinguish coccidioidal meningitis from tuberculous meningitis and cryptococcal meningitis, especially if cryptococcal antigen is negative.

In nodular or chronic cavitary pulmonary coccidioidomycosis, the radiology is not usually distinctive and a history of travel or residence in an endemic area important to considering the diagnosis.


Pulmonary nodules do not usually require treatment, as long as they remain stable and patients are asymptomatic. Oral itraconazole or fluconazole are currently the preferred agents, usually in doses of 400mg daily. Posaconazole is also very active. Fluconazole is preferred for meningitis. Itraconazole is preferred for bone and joint infection.

For coccidioidal meningitis, either high dose (800mg/d) fluconazole or intrathecal amphotericin B.

Outlook and prognosis

Coccidioidal meningitis needs to be treated lifelong, as it is incurable. Complications including communicating hydrocephalus. The relapse rate for chronic cavitary pulmonary coccidioidomycosis after 12 months of azole treatment is about 50%. Other forms of coccidioidomycosis are usually curable if treatment is given over several months, with relapse rates of 10-30%.


IDSA Coccidioidomycosis guidelines (2016)

DiCaudo 2014

Johnson 2014

Jude 2014


Natural history of primary infection with Coccidioides immitis

An example of primary pulmonary coccidioidomycosis in California, with ongoing fever, night sweats, cough and weight loss after 4 weeks, and increasing right lower lobe shadowing.

An example of a small pulmonary cavity in the right upper lobe in pulmonary coccidioidomycosis.

Severe chronic cavitary pulmonary coccidioidomycosis of the right lung, showing one very large pulmonary cavity, with some pleual thickening and smaller cavities in the right apex.





Lymph node localization of coccidioidomycosis in a Mexican immigrant to the USA.

Cutaneous coccidioidomycosis in a 17 year old Caucasian living in the Bay Area.

Destruction of the elbow with a pathological fracture all related to longstanding bone and joint coccidioidomycosis.

Bone scan showing disseminated coccidioidomycosis to multiple sites.






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