09. Coccidioidomycosis

Overview

Coccidioides spp are dimorphic fungi found in Arizona, California (Central Valley), New Mexico, west Texas, and northern Mexico, with Coccidioides immitis predominately found in California and Coccidioides posadasii in all other endemic regions. The most common presentation is “Valley Fever” which presents like CAP. Disseminated disease (<1% cases) often affects skin/soft tissue, bones/joints, and CNS.

Risk Factors for Severe Disease

  • Immunosuppression: advanced HIV, transplantation, corticosteroids, TNF alpha inhibitors
  • Pregnancy, especially third trimester
  • Diabetes
  • Cardiopulmonary disease
  • Age > 65

Evaluation

  • Most Coccidioides infections (1/2 to 2/3 cases) have unapparent or mild symptoms that do not require medical attention; 95% of symptomatic infections self-resolve after several weeks
  • Primary infection often presents similarly to community-acquired pneumonia with development of cough, SOB, and chest pain 1-3 weeks after exposure. Other features include fevers, arthralgias, rash, and fatigue, which may persist for months. This is a common presentation in endemic areas but rare in San Francisco
  • Extrapulmonary disease affects skin/soft tissue, CNS (meningitis) and bones (e.g. mono/polyarticular arthritis and vertebral osteomyelitis)
  • Diagnosis can be made by biopsy, culture, or serology
    • Biopsy: presence of spherules in tissue is pathognomonic
    • Culture: isolation of Coccidioides in culture from clinical specimen is diagnostic
    • Serology: complement fixation and immunodiffusion
      • Most frequent means for diagnosing Coccidioides infections; however, must consider the patient context as serologic testing may be falsely negative (insensitive due to early disease or immunosuppression) or falsely positive (resolved infection)
      • Immunodiffusion: qualitative test for IgM and IgG (IgM detectable from 1-2 weeks after onset of symptoms to several months afterwards, IgG detected months to years after infection). Overall sensitivity is ~70% (but only 20-40% if immunocompromised)
      • Complement fixation: quantitative test for IgG, reported as titer
        • Serum titer > 1:16 suggests disseminated infection
        • Useful for monitoring disease activity during therapy
        • Overall sensitivity is ~60-70% (but only 30% if immunocompromised)
      • Diagnosis of cocci meningitis: in addition to serum studies, check CSF fungal culture, CSF complement fixation, and CSF cocci antigen

Management

  • Uncomplicated pulmonary infection: treatment not needed in low risk individuals
  • Complicated or uncomplicated pulmonary infection in vulnerable host: fluconazole 200-400 mg/day for 3-6 months (depending on degree of illness, patient factors)
  • Severe pulmonary or disseminated infection: fluconazole or liposomal amphotericin B (consider the latter especially if respiratory failure, rapid progression of disease, or spinal involvement). Surgical debridement or stabilization may be important in certain cases. Treatment duration ranges from months to years depending on host, symptoms, and clinical severity
  • Meningitis: fluconazole is first line (800-1200mg IV/PO q24hrs). Hydrocephalus is a frequent complication (may need VP shunt or intrathecal amphotericin in severe cases). Patients should continue on lifelong fluconazole suppression.
  • See also the IDSA guidelines on the management of coccidioidomycosis: https://doi.org/10.1093/cid/ciw360

Galgiani JN, Ampel NM, Blair JE, et al. Coccidioidomycosis. Clin Infect Dis 2005;41:1217-1223. 

Pappagianis D, Zimmer BL. Serology of coccidioidomycosis. Clin Microbiol Rev 1990; 3:247.

Rosenstein NE, Emery KW, Werner SB, et al. Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995-1996. Clin Infect Dis. 2001;32(5):708‐715. doi:10.1086/319203

Malo J, Luraschi-Monjagatta C, Wolk DM, Thompson R, Hage CA, Knox KS. Update on the diagnosis of pulmonary coccidioidomycosis. Ann Am Thorac Soc. 2014;11(2):243‐253. doi:10.1513/AnnalsATS.201308-286FR

Bennett, John E., Raphael Dolin, and Martin J. Blaser. Mandell, douglas, and bennett's principles and practice of infectious diseases: 2-volume set. Vol. 1 & 2. Elsevier Health Sciences, 2019

Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112‐e146. doi:10.1093/cid/ciw360