Coccidioidomycosis: Laboratory diagnosis and screening
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
Coccidioides spp (C. immitis and C. posadasii), which are fungi endemic in desert regions of the southwestern United States and Central and South America, cause coccidioidomycosis. Coccidioidomycosis has protean manifestations and is frequently unrecognized, especially in travelers to endemic areas who return to locations where the disease is not typically encountered. Without specific laboratory tests, it is generally not possible to differentiate coccidioidal infections from numerous other illnesses. This is especially true for the initial respiratory illness .
Several routine tests are commonly abnormal, especially with early coccidioidal pneumonia, but all are nonspecific. These include a slight increase in the peripheral white blood cell count, peripheral eosinophilia, and an elevated erythrocyte sedimentation rate . Notably, serum procalcitonin levels are often normal . Similarly, chest radiographs or other imaging procedures may also reveal abnormalities. Although occasionally suggestive of the precise diagnosis , confirmatory tests are nearly always needed.
Conventional approaches to diagnosing coccidioidomycosis involve identification or recovery of Coccidioides spp from clinical specimens and detection of specific anticoccidioidal antibodies in serum or other body fluids. The laboratory diagnosis of coccidioidomycosis will be reviewed here. The epidemiology, clinical manifestations, and treatment of coccidioidomycosis are discussed separately. (See "Primary coccidioidal infection" and "Coccidioidal meningitis" and "Coccidioidomycosis in compromised hosts" and "Management of pulmonary sequelae and complications of coccidioidomycosis" and "Manifestations and treatment of extrapulmonary coccidioidomycosis".)
DIAGNOSING PATIENTS WITH SYMPTOMATIC DISEASE
Approach to diagnosis — A variety of different tests can be used to diagnose coccidioidal infection. Which test to use depends in part upon the patient's signs and symptoms. Specific considerations for immunocompromised hosts and those with complications are presented elsewhere. (See "Coccidioidomycosis in compromised hosts" and "Manifestations and treatment of extrapulmonary coccidioidomycosis" and "Coccidioidal meningitis" and "Management of pulmonary sequelae and complications of coccidioidomycosis".)
Most ambulatory patients who are suspected of having coccidioidomycosis are evaluated with serologic testing. There are several serologic tests available:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Kim MM, Blair JE, Carey EJ, et al. Coccidioidal pneumonia, Phoenix, Arizona, USA, 2000-2004. Emerg Infect Dis 2009; 15:397.
- Lundergan LL, Kerrick SS, Galgiani JN. Coccidioidomycosis at a university outpatient clinic: A clinical description. In: Coccidioidomycosis: Proceedings of the Fourth International Conference, Einstein HE, Catanzaro, A (Eds), National Foundation for Infectious Diseases, Washington 1985. p.47.
- Sakata KK, Grys TE, Chang YH, et al. Serum procalcitonin levels in patients with primary pulmonary coccidioidomycosis. Ann Am Thorac Soc 2014; 11:1239.
- Yozwiak ML, Lundergan LL, Kerrick SS, Galgiani JN. Symptoms and routine laboratory abnormalities associated with coccidioidomycosis. West J Med 1988; 149:419.
- 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:e112.
- Kuberski T, Myers R, Wheat LJ, et al. Diagnosis of coccidioidomycosis by antigen detection using cross-reaction with a Histoplasma antigen. Clin Infect Dis 2007; 44:e50.
- Durkin M, Connolly P, Kuberski T, et al. Diagnosis of coccidioidomycosis with use of the Coccidioides antigen enzyme immunoassay. Clin Infect Dis 2008; 47:e69.
- Kassis C, Zaidi S, Kuberski T, et al. Role of Coccidioides Antigen Testing in the Cerebrospinal Fluid for the Diagnosis of Coccidioidal Meningitis. Clin Infect Dis 2015; 61:1521.
- Wieden MA, Lundergan LL, Blum J, et al. Detection of coccidioidal antibodies by 33-kDa spherule antigen, Coccidioides EIA, and standard serologic tests in sera from patients evaluated for coccidioidomycosis. J Infect Dis 1996; 173:1273.
- Blair JE, Coakley B, Santelli AC, et al. Serologic testing for symptomatic coccidioidomycosis in immunocompetent and immunosuppressed hosts. Mycopathologia 2006; 162:317.
- Pappagianis D, Zimmer BL. Serology of coccidioidomycosis. Clin Microbiol Rev 1990; 3:247.
- Zartarian M, Peterson EM, de la Maza LM. Detection of antibodies to Coccidioides immitis by enzyme immunoassay. Am J Clin Pathol 1997; 107:148.
- Oubsuntia, V, Bogul, N, Lancaster, M. Utility of positive enzyme immunoassay results for detection of Coccidioides specific IGM. Proceedings of the Fifty-fourth Annual Coccidioidomycosis Study Group. In press.
- Blair JE, Currier JT. Significance of isolated positive IgM serologic results by enzyme immunoassay for coccidioidomycosis. Mycopathologia 2008; 166:77.
- Blair JE, Mendoza N, Force S, et al. Clinical specificity of the enzyme immunoassay test for coccidioidomycosis varies according to the reason for its performance. Clin Vaccine Immunol 2013; 20:95.
- Kuberski T, Herrig J, Pappagianis D. False-positive IgM serology in coccidioidomycosis. J Clin Microbiol 2010; 48:2047.
- Lindsley MD, Ahn Y, McCotter O, et al. Evaluation of the Specificity of Two Enzyme Immunoassays for Coccidioidomycosis by Using Sera from a Region of Endemicity and a Region of Nonendemicity. Clin Vaccine Immunol 2015; 22:1090.
- Johnson SM, Pappagianis D. The coccidioidal complement fixation and immunodiffusion-complement fixation antigen is a chitinase. Infect Immun 1992; 60:2588.
- Yang MC, Magee DM, Cox RA. Mapping of a Coccidioides immitis-specific epitope that reacts with complement-fixing antibody. Infect Immun 1997; 65:4068.
- Pishko EJ, Kirkland TN, Cole GT. Isolation and characterization of two chitinase-encoding genes (cts1, cts2) from the fungus Coccidioides immitis. Gene 1995; 167:173.
- Huppert M, Bailey JW, Chitjian P. Immunodiffusion as a substitute for complement fixation and tube precipitin tests in coccidioidomycosis. In: Coccidioidomycosis. The Second Symposium on Coccidioidomycosis, Ajello L (Ed), University of Arizona Press, Tucson 1967. p.221.
- SMITH CE, SAITO MT, SIMONS SA. Pattern of 39,500 serologic tests in coccidioidomycosis. J Am Med Assoc 1956; 160:546.
- Huppert M, Bailey JW. Immunodiffusion as a screening test for coccidioidomycosis serology. Sab 1963; 2:284.
- Huppert M, Peterson ET, Sun SH, et al. Evaluation of a latex particle agglutination test for coccidioidomycosis. Am J Clin Pathol 1968; 49:96.
- Pappagianis D. Coccidioidomycosis (San Joaquin or Valley Fever). In: Occupational Mycoses, DiSalvo A (Ed), Lea and Febiger, Philadelphia 1983. p.13.
- Monheit JE, Cowan DF, Moore DG. Rapid detection of fungi in tissues using calcofluor white and fluorescence microscopy. Arch Pathol Lab Med 1984; 108:616.
- Sobonya RE, Barbee RA, Wiens J, Trego D. Detection of fungi and other pathogens in immunocompromised patients by bronchoalveolar lavage in an area endemic for coccidioidomycosis. Chest 1990; 97:1349.
- Hagman HM, Madnick EG, D'Agostino AN, et al. Hyphal forms in the central nervous system of patients with coccidioidomycosis. Clin Infect Dis 2000; 30:349.
- Muñoz-Hernández B, Martínez-Rivera MA, Palma Cortés G, et al. Mycelial forms of Coccidioides spp. in the parasitic phase associated to pulmonary coccidioidomycosis with type 2 diabetes mellitus. Eur J Clin Microbiol Infect Dis 2008; 27:813.
- Nicolasora N, Cinti SK, Riddell Iv J, Kauffman CA. Photo quiz. A 53-year-old man with a large air bubble in his chest. Clin Infect Dis 2008; 47:823.
- Bialek R. Amplification of coccidioidal DNA in clinical specimens by PCR. J Clin Microbiol 2005; 43:1492; author reply 1492.
- Bialek R, González GM, Begerow D, Zelck UE. Coccidioidomycosis and blastomycosis: advances in molecular diagnosis. FEMS Immunol Med Microbiol 2005; 45:355.
- Binnicker MJ, Buckwalter SP, Eisberner JJ, et al. Detection of Coccidioides species in clinical specimens by real-time PCR. J Clin Microbiol 2007; 45:173.
- Stevens DA, Clemons KV, Levine HB, et al. Expert opinion: what to do when there is Coccidioides exposure in a laboratory. Clin Infect Dis 2009; 49:919.
- Huppert M, Sun SH, Rice EH. Specificity of exoantigens for identifying cultures of Coccidioides immitis. J Clin Microbiol 1978; 8:346.
- Sandhu GS, Kline BC, Stockman L, Roberts GD. Molecular probes for diagnosis of fungal infections. J Clin Microbiol 1995; 33:2913.
- Fisher MC, Koenig GL, White TJ, Taylor JW. Molecular and phenotypic description of Coccidioides posadasii sp. nov., previously recognized as the non-California population of Coccidioides immitis. Mycologia 2002; 94:73.
- Bridget M Barker, personal communication.
- Coccidioides immitis spherule-derived skin test antigen – Spherusol. Highlights of prescribing information. http://nielsenbio.com/files/Spherusol-full-prescribing.pdf (Accessed on October 27, 2014).
- Johnson R, Kernerman SM, Sawtelle BG, et al. A reformulated spherule-derived coccidioidin (Spherusol) to detect delayed-type hypersensitivity in coccidioidomycosis. Mycopathologia 2012; 174:353.
- Wack EE, Ampel NM, Sunenshine RH, Galgiani JN. The Return of Delayed-Type Hypersensitivity Skin Testing for Coccidioidomycosis. Clin Infect Dis 2015; 61:787.
- Levine HB, Restrepon A, Eyck DR, Stevens DA. Spherulin and coccidioidin: cross-reactions in dermal sensitivity to histoplasmin and paracoccidioidin. Am J Epidemiol 1975; 101:512.
- Stevens DA, Levine HB, Deresinski SC, Blaine LJ. Spherulin in clinical coccidioidomycosis: Comparison with coccidioidin. Chest 1975; 68:697.
- Stevens DA, Levine HB, TenEyck DR. Dermal sensitivity to different doses of spherulin and coccidioidin. Chest 1974; 65:530.
- SMITH CE, WHITING EG. The use of coccidioidin. Am Rev Tuberc 1948; 57:330.
- Padua y Gabriel A, Martínez-Ordaz VA, Velasco-Rodreguez VM, et al. Prevalence of skin reactivity to coccidioidin and associated risks factors in subjects living in a northern city of Mexico. Arch Med Res 1999; 30:388.
- DIAGNOSING PATIENTS WITH SYMPTOMATIC DISEASE
- Approach to diagnosis
- Diagnostic tests
- - Detection of anticoccidioidal antibodies
- Enzyme-linked immunoassays
- Complement fixing antibodies
- Tube precipitin-type antibodies
- Latex tests
- - Recovery of Coccidioides spp from clinical specimens
- Staining characteristics
- - Antigen detection
- SCREENING ASYMPTOMATIC PATIENTS
- Immunocompetent patients
- Immunocompromised hosts
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS