Histoplasmosis and blastomycosis are the two most common midwestern endemic mycoses. A history of exposure to the geographic areas in which these organisms occur is central to raising suspicion for an endemic fungal infection. For infection with these organisms, the diagnosis is definitively established by recovery of the organism in tissue or body fluids, which may take weeks. A rapid diagnosis can be made by finding the distinctive yeasts in tissues or body fluids. Antigen testing allows a presumptive diagnosis of these endemic fungal infections while awaiting culture results, but cross-reactivity between assays for Histoplasma and Blastomyces is routinely seen. Antibody tests provide supportive evidence for infection with either of these endemic mycoses but are less useful in immunosuppressed patients.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance
Chapman SW, Lin AC, Hendricks KA, Nolan RL, Currier MM, Morris KR, et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect. 1997;12:219–28.
Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23:367–81.
De Groote MA, Bjerke R, Smith H, Rhodes LV. Expanding epidemiology of blastomycosis: clinical features and investigation of 2 cases in Colorado. Clin Infect Dis. 2000;30:582–4.
Smith JA, Kauffman CA. Blastomycosis. Proc Am Thorac Soc. 2010;7:173–80.
Crampton TL, Light RB, Berg GM, Meyers MP, Schroeder GC, Hershfield ES, et al. Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals. Clin Infect Dis. 2002;34:1310–6.
Carlos WG, Rose AS, Wheat LJ, Norris S, Sarosi GA, Knox KS, et al. Blastomycosis in Indiana: digging up more cases. Chest. 2010;138:1377–82.
Anderson JL, Dieckman JL, Reed KD, Meese JK. Canine blastomycosis in Wisconsin: a survey of small-animal veterinary practices. Med Mycol. 2014;52:774–9.
Gray NA, Baddour LM. Cutaneous inoculation blastomycosis. Clin Infect Dis. 2002;34:e44–9.
Smith JA, Riddell J, Kauffman CA. Cutaneous manifestations of endemic mycoses. Curr Infect Dis Rep. 2013;15:440–9.
Martynowicz MA, Prakash UB. Pulmonary blastomycosis: an appraisal of diagnostic techniques. Chest. 2002;121:768–73.
Durkin M, Witt J, LeMonte A, Wheat B, Connolly P. Antigen assay with the potential to aid in diagnosis of blastomycosis. J Clin Microbiol. 2004;42:4873–5.
Connolly P, Hage CA, Bariola JR, Bensadoun E, Rodgers M, Bradsher RW, et al. Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay. Clin Vacc Immunol. 2012;19:53–6.
Bariola JR, Perry P, Pappas PG, Proia L, Shealey W, Wright PW, et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010;50:797–804.
Hage CA, Davis TE, Egan L, Parker M, Fuller D, Demonte AM, et al. Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay. Respir Med. 2007;101:43–7.
Hage CA, Knox KS, Davis TE, Wheat LJ. Antigen detection in bronchoalveolar lavage fluid for diagnosis of fungal pneumonia. Curr Opin Pulm Med. 2011;17:167–71.
Bariola JR, Hage CA, Durkin M, Bensadoun E, Gubbins PO, Wheat LJ, et al. Detection of Blastomyces dermatitidis antigen in patients with newly diagnosed blastomycosis. Diagn Microbiol Infect Dis. 2011;69:187–91.
Frost HM, Novicki TJ. Blastomyces antigen detection for diagnosis and management of blastomycosis. J Clin Microbiol. 2015;53:3660–2. Report on the effectiveness of the Blastomyces EIA assay for detecting B. dermatitidis antigen. Sensitivity was lower than previously reported. The authors report that the EIA test in urine can be followed to assess response to therapy.
Van Der Veer J, Lewis RJ, Emtiazjoo AM, Allen SD, Wheat J, Hage CA. Cross-reactivity in the Platelia™ Aspergillus enzyme immunoassay caused by blastomycosis. Med Mycol. 2012;50:396–8.
Cummmings JR, Jamison GR, Boudreaux JW, Howles MJ, Walsh TJ, Hayden RT. Cross-reactivity of non-Aspergillus fungal species in the Aspergillus galactomannan enzyme immunoassay. Diagn Microbiol Infect Dis. 2007;59:113–5.
Soufleris AJ, Klein BS, Courtney BT, Proctor MA, Jones JM. Utility of anti-WI-1 serological testing in the diagnosis of blastomycosis in Wisconsin residents. Clin Infect Dis. 1994;19:87–91.
Klein BS, Jones JM. Isolation, purification, and radiolabeling of a novel 120-kD surface protein on Blastomyces dermatitidis yeasts to detect antibody in infected patients. J Clin Invest. 1990;85:152–61.
Richer SM, Smedema ML, Durkin MM, Brandhorst TT, Hage CA, Connolly PA, et al. Development of a highly sensitive and specific blastomycosis antibody enzyme immunoassay using Blastomyces dermatitidis surface protein BAD-1. Clin Vacc Immunol. 2014;21:143–6. Report of a recently developed antibody assay that might prove to be more specific for blastomycosis than prior assays.
Babady NE, Buckwalter SP, Hall L, Le Febre KM, Binnicker MJ, Wengenack NL. Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol. 2011;49:3204–8.
Sidamonidze K, Peck MK, Perez M, Baumgardner D, Smith G, Chaturvedi V, et al. Real-time PCR assay for identification of Blastomyces dermatitidis in culture and in tissue. J Clin Microbiol. 2012;50:1783–6.
Bialek R, Cirera AC, Herrmann T, Aepinus C, Shearn-Bochsler VI, Legendre AM. Nested PCR assays for detection of Blastomyces dermatitidis in paraffin-embedded canine tissue. J Clin Microbiol. 2003;41:205–8.
Cano M, Hajjeh RA. The epidemiology of histoplasmosis: a review. Semin Respir Infect. 2001;16:109–18.
Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007;20:115–32.
Kauffman CA, Freifeld AG, Andes DR, Baddley JW, Herwaldt L, Walker RC, et al. Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET). Transpl Infect Dis. 2014;16:213–24.
Limaye AP, Connolly PA, Sagar M, Fritsche TR, Cookson BT, Wheat LJ, et al. Transmission of Histoplasma capsulatum by organ transplantation. N Engl J Med. 2000;343:1163–6.
Cuellar-Rodriquez J, Avery RK, Lard M, Budev M, Gordon SM, Shrestha NK, et al. Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area. Clin Infect Dis. 2009;49:710–6.
Benedict K, Thompson GR, Deresinski S, Chiller T. Mycotic infections acquired outside areas of known endemicity, United States. Emerg Infect Dis. 2015;21:1935–41. Interesting review of cases of endemic mycoses reported in patients and animals living outside the areas endemic for these fungi.
Connolly PA, Durkin MM, LeMonte AM, Hackett E, Wheat LJ. Detection of Histoplasma antigen by a quantitative immunoassay. Clin Vacc Immunol. 2007;14:1587–91.
Hage CA, Ribes JA, Wengenack NL, Baddour LM, Assi M, McKinsey DS, et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis. 2011;53:448–54.
Wheat LJ. Approach to the diagnosis of the endemic mycoses. Clin Chest Med. 2009;30:379–90.
Hage CA, Davis TE, Fuller D, Egan L, Witt JR, Wheat LJ, et al. Diagnosis of histoplasmosis by antigen detection in BAL fluid. Chest. 2010;137:623–8.
Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. 2005;40:844–52.
Swartzentruber S, LeMonte A, Witt J, Fuller D, Davis T, Hage C, et al. Improved detection of Histoplasma antigenemia following dissociation of immune complexes. Clin Vacc Immunol. 2009;16:320–2.
Swartzentruber S, Rhodes L, Kurkjian K, Zahn M, Brandt ME, Connolly P, et al. Diagnosis of acute pulmonary histoplasmosis by antigen detection. Clin Infect Dis. 2009;49:1878–82.
Scheel CM, Samayoa B, Herrera A, Lindsley MD, Benjamin L, Reed Y, et al. Development and evaluation of an enzyme-linked immunosorbent assay to detect Histoplasma capsulatum antigenuria in immunocompromised patients. Clin Vacc Immunol. 2009;16:852–8.
Cloud JL, Bauman SK, Neary BP, et al. Performance characteristics of a polyclonal enzyme immunoassay for the quantitation of Histoplasma antigen in human urine samples. Am J Clin Pathol. 2007;128:18–22.
Theel ES, Harring JA, Dababneh AS, Rollins LO, Bestrom JE, Jespersen DJ. Re-evaluation of commercial regents for detection of Histoplasma capsulatum antigen in urine. J Clin Microbiol. 2015;53:1198–203.
Zhang C, Lei G-S, Lee CH, Hage CA. Evaluation of two new enzyme immunoassay reagents for diagnosis of histoplasmosis in a cohort of clinically characterized patients. Med Mycol. 2015;53:868–73.
Wheat J, Wheat H, Connolly P, Kleiman M, Supparatpinyo K, Nelson K, et al. Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses. Clin Infect Dis. 1997;24:1169–71.
Hage CA, Kirsch EJ, Stump TE, Kauffman CA, Goldman M, Connolly P, et al. Histoplasma antigen clearance during treatment of histoplasmosis in patients with AIDS determined by a quantitative antigen enzyme immunoassay. Clin Vacc Immunol. 2011;18:661–6.
Wheat LJ, Hackett E, Durkin M, Connolly P, Petraitiene R, Walsh TJ, et al. Histoplasmosis-associated cross-reactivity in the BioRad Platelia Aspergillus enzyme immunoassay. Clin Vacc Immunol. 2007;14:638–40.
Vergidis P, Walker RC, Kaul DR, Kauffman CA, Freifeld AG, Slagle D, et al. Histoplasmosis may be misdiagnosed as aspergillosis due to false-positive Aspergillus galactomannan assay. Transpl Infect Dis. 2012;14:213–7.
Richer SM, Smedema ML, Durkin MM, Herman KM, Hage CA, Fuller D, et al. Improved diagnosis of acute pulmonary histoplasmosis by combining antigen and antibody detection. Clin Infect Dis. 2016;62:896–902. Report of a new antibody assay for histoplasmosis which, when combined with antigen assays in urine and serum, appears to increase the sensitivity of non-culture techniques for the diagnosis of acute pulmonary histoplasmosis.
Koepsell SA, Hinrichs SV, Iwen PC. Applying a real-time PCR assay for Histoplasma capsulatum to clinically relevant formalin-fixed paraffin-embedded human tissue. J Clin Microbiol. 2012;50:3395–7.
Bracca A, Tosello ME, Girardini JE, Amigot SL, Gomez C, Serra E. Molecular detection of Histoplasma capsulatum var. capsulatum in human clinical samples. J Clin Microbiol. 2003;41:1753–5.
Rickerts V, Bialek R, Tintelnot K, Jacobi V, Just-Nubling G. Rapid PCR-based diagnosis of disseminated histoplasmosis in an AIDS patient. Eur J Clin Microbiol Infect Dis. 2002;21:821–3.
Moncada PA, Budvytiene I, Ho DY, Deresinski SC, Montoya JG, Banaei N. Utility of DNA sequencing for direct identification of invasive fungi from fresh and formalin-fixed specimens. Am J Clin Pathol. 2013;140:203–8.
Conflict of Interest
Marisa H. Miceli, Caroline G. Castillo, and Carol A. Kauffman declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Advances in Diagnosis of Invasive Fungal Infections
About this article
Cite this article
Miceli, M.H., Castillo, C.G. & Kauffman, C.A. Diagnosis of Midwestern Endemic Mycoses. Curr Fungal Infect Rep 10, 87–95 (2016). https://doi.org/10.1007/s12281-016-0260-7
- Endemic mycoses
- Antigen tests
- Antibody tests