Clinical Overview of Valley Fever

What to know

  • About 40% of cases of Valley fever develop lung infection symptoms.
  • Infections are usually self-limiting but 5-10% develop complications. Disseminated disease is rare.
  • Serologic tests to detect IgM and IgG antibodies are the most common diagnostics.
  • Infections are usually treated with fluconazole or amphotericin B.
Two healthcare providers having a discussion

Etiology

Two species of Coccidioides cause infection: Coccidioides immitis (typically in California) and Coccidioides posadasii (typically outside of California). Clinical differences between the two species have not been observed.

Coccidioide lives in the soil in the southwestern United States and parts of Mexico, Central America, and South America. Valley fever is considered highly endemic in southern Arizona and California’s southern San Joaquin Valley.

At-risk populations

Risk factors for severe or disseminated coccidioidomycosis include:

  • African-American race or Filipino ethnicity
  • HIV/AIDS
  • Organ transplant
  • Diabetes mellitus
  • Pregnancy
  • Use of immunosuppressive medications

Exposure risks

In endemic areas, risk factors include occupations and activities that increase exposure to dust, such as:

  • Construction
  • Agricultural work
  • Archaeology
  • Military training

How it spreads

Coccidioidomycosis is typically acquired via inhalation of airborne arthroconidia. Arthroconidia often become airborne after contaminated soil is disturbed. Disturbance can result from small-scale activities including construction or excavation, or large-scale events such as dust storms and earthquakes.

Primary cutaneous coccidioidomycosis, solid organ donor-derived coccidioidomycosis, and fomite-transmitted coccidioidomycosis can also occur but are very uncommon.

Clinical features

Symptomatic persons (approximately 40% of cases) usually present 1 to 3 weeks after exposure. Typical symptoms include fatigue, cough, dyspnea, headache, night sweats, myalgias, and rash.

Primary pulmonary disease is often self-limiting. However, approximately 5 to 10% of patients fail to recover and develop complications or chronic pulmonary disease. Disseminated disease occurs in an estimated 1% of cases. Higher rates of dissemination are observed in certain risk groups, with bones/joints, soft tissues, and meninges most commonly affected.

In persons who develop progressive, chronic, or disseminated disease, symptoms may persist for months or even longer. Meningitis can lead to permanent neurologic damage. Mortality is high in HIV-infected persons with diffuse lung disease.

Diagnosis

Serologic tests to detect IgM and IgG antibodies are most often used to diagnose coccidioidomycosis. Other methods include culture and microscopy.

Enzyme immunoassay (EIA)

EIA is a very sensitive and commonly used method for diagnosing coccidioidomycosis. Two EIAs for detection of specific IgM and IgG antibodies against Coccidioides are currently available:

  • Premier ® Coccidioides EIA – Meridian Bioscience, Inc.
  • Enzyme Immunoassay for detection of specific antibodies against Coccidioides spp – Immuno Mycologics, Inc. (IMMY)

Immunodiffusion (ID)

ID detects IgM antibodies; positive early in the course of infection.

Complement Fixation (CF)

CF etects IgG antibodies and allows for assessment of disease severity.

Lateral Flow Assay (LFA)

The Sona Coccidioides Antibody LFA (Immuno Mycologics, Inc. [IMMY]) is a rapid test (~30 minutes). It detects the presence of total antibodies against Coccidioides spp (IgM or IgG).

Culture can be performed on tissue and respiratory specimens. However, sputum can be difficult to obtain for culture since patients' coughs are often non-productive. Processing and manipulation of cultures should be done in a biosafety level 3 laboratory.

Microscopy can be used for detection of spherules in tissue or respiratory secretions; low sensitivity.

Urinary antigen detection is not widely used. They may have some utility in diagnosing coccidioidomycosis in immunocompromised patients with severe forms of the disease.

FDA approved a PCR for detection of Coccidioides directly from lower respiratory specimens (GeneSTAT.MDx Coccidioides – DxNA, LLC). Other PCR tests are still experimental but appear promising.

Treatment and recovery

No evidence from randomized trials exists to determine whether antifungal treatment for uncomplicated coccidioidal infections reduces symptom duration or prevents complications. Some infections will resolve without antifungal treatment. Infectious Diseases Society of America (IDSA) guidelines suggest treatment for primary pulmonary coccidioidomycosis in patients who:

  • Are immunosuppressed
  • Have severe or significantly debilitating illness
  • Have diabetes or are frail because of age or comorbidities
  • Are pregnant
  • Are of African or Filipino ancestry

Disseminated coccidioidomycosis requires antifungal treatment, typically fluconazole or amphotericin B. For more detailed treatment guidelines, please refer to the Infectious Diseases Society of America's Practice Guidelines for the Treatment of Coccidioidomycosis.

Surveillance and statistics

Coccidioidomycosis is reportable in certain states. Check with your health department for more information about disease reporting requirements and procedures in your area. See facts and stats about coccidioidomycosis.

Areas for further research

Many aspects of coccidioidomycosis are being researched to better understand risk and distribution, and improve surveillance, testing and treatment.

Research areas to better understand risk include identifying:

  • Host factors in select racial and ethnic groups that increase risk
  • Influence of climate change on Coccidioides' geographic distribution.
  • Improved methods for environmental detection.

To improve patient outcomes researchers are working to:

  • Establish optimal treatment regimen for primary pulmonary infections.
  • Develop an effective vaccine.