Current Infectious Disease Reports

, Volume 15, Issue 6, pp 536–543

Endemic Mycoses in Immunocompromised Hosts

Transplant Oncology (M Ison and N Theodoropoulos, Section Editors)


Endemic mycoses remain a significant cause of morbidity and mortality among immunocompromised patients. As the number of immunosuppressed individuals increases worldwide, the incidence of endemic mycoses is also expected to rise. In immunocompromised patients, endemic mycoses can present in atypical fashion, cause more severe and/or disseminated disease, and result in higher mortality. Despite several noteworthy advances over the past decade, significant challenges remain with regard to the prevention, diagnosis, and therapy of endemic mycoses in immunocompromised hosts. This review highlights important developments related to the epidemiology, diagnosis, treatment, and prevention of commonly encountered endemic mycoses. We also discuss emerging topics, knowledge gaps, and areas of future research.


Endemic fungi Endemic mycoses Blastomyces dermatitidis Coccidioides immitis Coccidioides posadasii Histoplasma capsulatum Paracoccidioides brasiliensis Penicillium marneffei Sporothrix schenkii Immunocompromised Immunosuppressed 


  1. 1.
    Hsu LY, Ng ES, Koh LP. Common and emerging fungal pulmonary infections. Infect Dis Clin North Am. 2010;24(3):557–77.PubMedCrossRefGoogle Scholar
  2. 2.
    Kauffman CA. Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis. Infect Dis Clin North Am. 2006;20(3):645–62. vii.PubMedCrossRefGoogle Scholar
  3. 3.
    Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol. 2010;36(1):1–53.PubMedGoogle Scholar
  4. 4.
    Grim SA et al. A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation. Transpl Infect Dis. 2012;14(1):17–23.PubMedCrossRefGoogle Scholar
  5. 5.
    Ramos-e-Silva M et al. Systemic mycoses in immunodepressed patients (AIDS). Clin Dermatol. 2012;30(6):616–27.PubMedCrossRefGoogle Scholar
  6. 6.
    Smith JA, Kauffman CA. Endemic fungal infections in patients receiving tumour necrosis factor-alpha inhibitor therapy. Drugs. 2009;69(11):1403–15.PubMedCrossRefGoogle Scholar
  7. 7.
    Hu Y et al. Penicillium marneffei infection: an emerging disease in mainland China. Mycopathologia. 2013;175(1–2):57–67.PubMedCrossRefGoogle Scholar
  8. 8.
    Le T et al. Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis. 2011;52(7):945–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Baddley JW et al. Histoplasmosis in HIV-infected patients in a southern regional medical center: poor prognosis in the era of highly active antiretroviral therapy. Diagn Microbiol Infect Dis. 2008;62(2):151–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Chapman SW et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12):1801–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Huang JY et al. Coccidioidomycosis-associated Deaths, United States, 1990–2008. Emerg Infect Dis. 2012;18(11):1723–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Pappas PG et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010;50(8):1101–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Blair JE et al. Serologic testing for symptomatic coccidioidomycosis in immunocompetent and immunosuppressed hosts. Mycopathologia. 2006;162(5):317–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Centers for Disease Control and Prevention (CDC). Increase in reported coccidioidomycosis--United States, 1998–2011. MMWR Morb Mortal Wkly Rep. 2013;62(12):217–21.Google Scholar
  15. 15.
    Dasmasceno LS et al. Disseminated histoplasmosis and aids: relapse and late mortality in endemic area in North-Eastern Brazil. Mycoses. 2013;56(5):520–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Taroumian S et al. Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs. Arthritis Care Res (Hoboken). 2012;64(12):1903–9.CrossRefGoogle Scholar
  17. 17.
    Rangwala F et al. Histoplasmosis and penicilliosis among HIV-infected Thai patients: a retrospective review. Southeast Asian J Trop Med Public Health. 2012;43(2):436–41.PubMedGoogle Scholar
  18. 18.
    Cuellar-Rodriguez J 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(5):710–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Freifeld AG et al. Histoplasmosis in solid organ transplant recipients at a large Midwestern university transplant center. Transpl Infect Dis. 2005;7(3–4):109–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Gauthier GM et al. Blastomycosis in solid organ transplant recipients. Transpl Infect Dis. 2007;9(4):310–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Kontoyiannis DP et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50(8):1091–100.PubMedCrossRefGoogle Scholar
  22. 22.
    Edwards LB et al. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States. Am Rev Respir Dis. 1969;99(4):1–132.PubMedGoogle Scholar
  23. 23.
    Gautam R et al. Identifying areas of high risk of human exposure to coccidioidomycosis in Texas using serology data from dogs. Zoonoses Public Health. 2013;60(2):174–81.PubMedCrossRefGoogle Scholar
  24. 24.
    Singh N et al. Donor-derived fungal infections in organ transplant recipients: guidelines of the American Society of Transplantation, infectious diseases community of practice. Am J Transplant. 2012;12(9):2414–28.PubMedCrossRefGoogle Scholar
  25. 25.
    Dierberg KL et al. Donor-derived organ transplant transmission of coccidioidomycosis. Transpl Infect Dis. 2012;14(3):300–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Tang YW et al. Urine polymerase chain reaction is not as sensitive as urine antigen for the diagnosis of disseminated histoplasmosis. Diagn Microbiol Infect Dis. 2006;54(4):283–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Connolly P et al. Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay. Clin Vaccine Immunol. 2012;19(1):53–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Hage CA et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis. 2011;53(5):448–54.PubMedCrossRefGoogle Scholar
  29. 29.
    Mendoza N, Blair JE. The utility of diagnostic testing for active coccidioidomycosis in solid organ transplant recipients. Am J Transplant. 2013;13(4):1034–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Babady NE et al. Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol. 2011;49(9):3204–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Koepsell SA, Hinrichs SH, 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(10):3395–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Sidamonidze K et al. Real-time PCR assay for identification of Blastomyces dermatitidis in culture and in tissue. J Clin Microbiol. 2012;50(5):1783–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Elias NA et al. Rapid identification of Histoplasma capsulatum directly from cultures by multiplex PCR. Mycopathologia. 2012;174(5–6):451–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Dantas KC et al. The use of nested Polymerase Chain Reaction (nested PCR) for the early diagnosis of Histoplasma capsulatum infection in serum and whole blood of HIV-positive patients*. An Bras Dermatol. 2013;88(1):141–3.PubMedCrossRefGoogle Scholar
  35. 35.
    Liao MH, Lin JF, Li SY. Application of a multiplex suspension array for rapid and simultaneous identification of clinically important mold pathogens. Mol Cell Probes. 2012;26(5):188–93.PubMedCrossRefGoogle Scholar
  36. 36.
    Liu X, Zhang Z, Hou B, Wang D, Sun T, Li F, et al. Rapid identification of Sporothrix schenckii in biopsy tissue by PCR. J Eur Acad Dermatol Venereol. 2012. doi:10.1111/jdv.12030
  37. 37.
    Inglis DO et al. Comparative transcriptomics of infectious spores from the fungal pathogen Histoplasma capsulatum reveals a core set of transcripts that specify infectious and pathogenic states. Eukaryot Cell. 2013;12(6):828–52.PubMedCrossRefGoogle Scholar
  38. 38.
    Galgiani JN et al. Coccidioidomycosis. Clin Infect Dis. 2005;41(9):1217–23.PubMedCrossRefGoogle Scholar
  39. 39.
    Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007;20(1):115–32.PubMedCrossRefGoogle Scholar
  40. 40.
    Wheat LJ et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807–25.PubMedCrossRefGoogle Scholar
  41. 41.
    Abadio AK et al. Comparative genomics allowed the identification of drug targets against human fungal pathogens. BMC Genomics. 2011;12:75.PubMedCrossRefGoogle Scholar
  42. 42.
    Brilhante RS et al. Ciprofloxacin shows synergism with classical antifungals against Histoplasma capsulatum var. capsulatum and Coccidioides posadasii. Mycoses. 2013;56(3):397–401.PubMedCrossRefGoogle Scholar
  43. 43.
    Brilhante RS et al. Effect of farnesol on growth, ergosterol biosynthesis, and cell permeability in Coccidioides posadasii. Antimicrob Agents Chemother. 2013;57(5):2167–70.PubMedCrossRefGoogle Scholar
  44. 44.
    Cole GT et al. A vaccine against coccidioidomycosis is justified and attainable. Med Mycol. 2004;42(3):189–216.PubMedCrossRefGoogle Scholar
  45. 45.
    Deepe Jr GS. Preventative and therapeutic vaccines for fungal infections: from concept to implementation. Expert Rev Vaccines. 2004;3(6):701–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Deepe Jr GS, Wuthrich M, Klein BS. Progress in vaccination for histoplasmosis and blastomycosis: coping with cellular immunity. Med Mycol. 2005;43(5):381–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Hung CY et al. An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection. Vaccine. 2012;30(31):4681–90.PubMedCrossRefGoogle Scholar
  48. 48.
    Magalhaes A et al. Prophylactic and therapeutic vaccination using dendritic cells primed with peptide 10 derived from the 43-kilodalton glycoprotein of Paracoccidioides brasiliensis. Clin Vaccine Immunol. 2012;19(1):23–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Travassos LR, Taborda CP. New advances in the development of a vaccine against paracoccidioidomycosis. Front Microbiol. 2012;3:212.PubMedCrossRefGoogle Scholar
  50. 50.
    Wuthrich M et al. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest. 2011;121(2):554–68.PubMedCrossRefGoogle Scholar
  51. 51.
    Xue J et al. A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB/c mice against coccidioidomycosis. Infect Immun. 2009;77(8):3196–208.PubMedCrossRefGoogle Scholar
  52. 52.
    Brown GD, Denning DW, Levitz SM. Tackling human fungal infections. Science. 2012;336(6082):647.PubMedCrossRefGoogle Scholar
  53. 53.
    Nanjappa SG et al. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. PLoS Pathog. 2012;8(7):e1002771.PubMedCrossRefGoogle Scholar
  54. 54.
    Nanjappa SG et al. Protective antifungal memory CD8(+) T cells are maintained in the absence of CD4(+) T cell help and cognate antigen in mice. J Clin Invest. 2012;122(3):987–99.PubMedCrossRefGoogle Scholar
  55. 55.
    Ison MG et al. Donor-derived disease transmission events in the United States: data reviewed by the OPTN/UNOS Disease Transmission Advisory Committee. Am J Transplant. 2009;9(8):1929–35.PubMedCrossRefGoogle Scholar
  56. 56.
    Blodget E et al. Donor-derived Coccidioides immitis fungemia in solid organ transplant recipients. Transpl Infect Dis. 2012;14(3):305–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Brugiere O et al. Coccidioidomycosis in a lung transplant recipient acquired from the donor graft in France. Transplantation. 2009;88(11):1319–20.PubMedCrossRefGoogle Scholar
  58. 58.
    Carvalho C et al. Cerebral coccidioidomycosis after renal transplantation in a non-endemic area. Transpl Infect Dis. 2010;12(2):151–4.PubMedCrossRefGoogle Scholar
  59. 59.
    Wright PW et al. Donor-related coccidioidomycosis in organ transplant recipients. Clin Infect Dis. 2003;37(9):1265–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Vikram HR, Dosanjh A, Blair JE. Coccidioidomycosis and lung transplantation. Transplantation. 2011;92(7):717–21.PubMedCrossRefGoogle Scholar
  61. 61.
    Tripathy U et al. Donor transfer of pulmonary coccidioidomycosis in lung transplantation. Ann Thorac Surg. 2002;73(1):306–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Garzoni C, Ison MG. Uniform definitions for donor-derived infectious disease transmissions in solid organ transplantation. Transplantation. 2011;92(12):1297–300.PubMedCrossRefGoogle Scholar
  63. 63.
    Ison MG, Nalesnik MA. An update on donor-derived disease transmission in organ transplantation. Am J Transplant. 2011;11(6):1123–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Anstead GM, Graybill JR. Coccidioidomycosis. Infect Dis Clin North Am. 2006;20(3):621–43.PubMedCrossRefGoogle Scholar
  65. 65.
    Travassos LR, Taborda CP, Colombo AL. Treatment options for paracoccidioidomycosis and new strategies investigated. Expert Rev Anti Infect Ther. 2008;6(2):251–62.PubMedCrossRefGoogle Scholar
  66. 66.
    Vasquez-del-Mercado E, Arenas R, Padilla-Desgarenes C. Sporotrichosis. Clin Dermatol. 2012;30(4):437–43.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Transplant and Immunocompromised Host Infectious Disease Program, Department of MedicineUniversity of California, San Francisco (UCSF)San FranciscoUSA
  3. 3.UCSFSan FranciscoUSA

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