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Histoplasmosis

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Diagnosis and Treatment of Fungal Infections

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Abstract

Histoplasmosis, among the endemic mycoses, is the leading cause of hospitalization and death in the USA. The infection is asymptomatic in most otherwise healthy individuals who experience low inoculum exposure but may cause severe pneumonia following a heavy exposure. Patients with underlying obstructive pulmonary disease typically develop chronic pulmonary disease, which is progressive if not treated. Progressive disseminated disease may occur, usually in patients who are immunocompromised, and is generally fatal if not diagnosed and treated correctly and in a timely fashion.

The diagnosis can be established without difficulty in most patients by use of a battery of mycologic and serologic tests. Antigen detection is the most sensitive method for diagnosing acute diffuse pulmonary histoplasmosis, and progressive disseminated histoplasmosis. Serologic tests are particularly helpful in patients with subacute and chronic pulmonary histoplasmosis.

Treatment is indicated in most patients with acute diffuse pulmonary histoplasmosis and all patients with chronic pulmonary histoplasmosis or progressive disseminated histoplasmosis. Liposomal Amphotericin B is the treatment of choice for patients with severe manifestations of histoplasmosis requiring hospitalization. Itraconazole is recommended for mild cases not requiring hospitalization and for continued therapy following response to liposomal Amphotericin B.

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References

  1. Chu JH, Feudtner C, Heydon K, Walsh TJ, Zaoutis TE. Hospitalizations for endemic mycoses: a population-based national study. Clin Infect Dis. 2006;42(6):822–5.

    Article  PubMed  Google Scholar 

  2. Mittal J, Ponce MG, Gendlina I, Nosanchuk JD. Histoplasma Capsulatum: mechanisms for pathogenesis. Curr Top Microbiol Immunol. 2019;422:157–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Arango M, Castaneda E, Agudelo CI, De Bedout C, Agudelo CA, Tobon A, et al. Histoplasmosis: results of the Colombian National Survey, 1992-2008. Biomedica. 2011;31(3):344–56.

    Article  PubMed  Google Scholar 

  4. Mata-Essayag S, Colella MT, Rosello A, de Capriles CH, Landaeta ME, de Salazar CP, et al. Histoplasmosis: a study of 158 cases in Venezuela, 2000-2005. Medicine. 2008;87(4):193–202.

    Article  PubMed  Google Scholar 

  5. Baker J, Setianingrum F, Wahyuningsih R, Denning DW. Mapping histoplasmosis in South East Asia—implications for diagnosis in AIDS. Emerg Microb Infect. 2019;8(1):1139–45.

    Article  Google Scholar 

  6. Ashraf N, Kubat RC, Poplin V, Adenis AA, Denning DW, Wright L, et al. Re-drawing the maps for endemic mycoses. Mycopathologia. 2020;185(5):843–65.

    Article  PubMed  PubMed Central  Google Scholar 

  7. McKinsey DS, Pappas PG. Histoplasmosis: time to redraw the map and up our game. Clin Infect Dis. 2020;70(6):1011–3.

    PubMed  Google Scholar 

  8. Maiga AW, Deppen S, Scaffidi BK, Baddley J, Aldrich MC, Dittus RS, et al. Mapping histoplasma capsulatum exposure, United States. Emerg Infect Dis. 2018;24(10):1835–9.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Klein M, Khan M, Salinas JL, Sanchez R. Disseminated pulmonary histoplasmosis in immunocompetent patients: a common epidemiological exposure. BMJ Case Rep. 2019;12(3):e227994.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Azar MM, Loyd JL, Relich RF, Wheat LJ, Hage CA. Current concepts in the epidemiology, diagnosis, and management of histoplasmosis syndromes. Semin Respir Crit Care Med. 2020;41(1):13–30.

    Article  PubMed  Google Scholar 

  11. Canteros CE, Toranzo AI, Levis S, Salas HD, Lopez-Joffre MC, Suarez-Alvarez RO. Use of an Argentinean wildlife tissue collection for epidemiological studies of histoplasmosis. Mycopathologia. 2020;185(5):905–15.

    Article  CAS  PubMed  Google Scholar 

  12. Newman SL. Interaction of histoplasma capsulatum with human macrophages, dendritic cells, and neutrophils. Methods Mol Med. 2005;118:181–91.

    PubMed  Google Scholar 

  13. Deepe GS Jr. Modulation of infection with histoplasma capsulatum by inhibition of tumor necrosis factor-alpha activity. Clin Infect Dis. 2005;41(Suppl 3):S204–7.

    Article  CAS  PubMed  Google Scholar 

  14. Tristao FS, Leonello PC, Nagashima LA, Sano A, Ono MA, Itano EN. Carbohydrate-rich high-molecular-mass antigens are strongly recognized during experimental histoplasma capsulatum infection. Rev Soc Bras Med Trop. 2012;45(2):232–7.

    Article  PubMed  Google Scholar 

  15. Friedrich D, Zapf D, Lohse B, Fecher RA, Deepe GS Jr, Rupp J. The HIF-1alpha/LC3-II axis impacts fungal immunity in human macrophages. Infect Immun. 2019;87(7):e00125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Assi M, Martin S, Wheat LJ, Hage C, Freifeld A, Avery R, et al. Histoplasmosis after solid organ transplant. Clin Infect Dis. 2013;57(11):1542–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hage CA, Bowyer S, Tarvin SE, Helper D, Kleiman MB, Wheat LJ. Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy. Clin Infect Dis. 2010;50(1):85–92.

    Article  CAS  PubMed  Google Scholar 

  18. Wheat LJ, Conces D, Allen SD, Blue-Hnidy D, Loyd J. Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management. Semin Respir Crit Care Med. 2004;25(2):129–44.

    Article  PubMed  Google Scholar 

  19. Wheat J, French ML, Kohler RB, Zimmerman SE, Smith WR, Norton JA, et al. The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak. Ann Intern Med. 1982;97(5):680–5.

    Article  CAS  PubMed  Google Scholar 

  20. Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am. 2003;17(1):1–19. vii

    Article  PubMed  Google Scholar 

  21. Freifeld AG, Iwen PC, Lesiak BL, Gilroy RK, Stevens RB, Kalil AC. Histoplasmosis in solid organ transplant recipients at a large Midwestern university transplant center. Transpl Infect Dis. 2005;7(3–4):109–15.

    Article  CAS  PubMed  Google Scholar 

  22. Wood KL, Hage CA, Knox KS, Kleiman MB, Sannuti A, Day RB, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279–82.

    Article  PubMed  Google Scholar 

  23. Wheat J. Histoplasmosis in the acquired immunodeficiency syndrome. Curr Top Med Mycol. 1996;7(1):7–18.

    CAS  PubMed  Google Scholar 

  24. Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM, Levitz SM. Idiopathic CD4+ T-lymphocytopenia—four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med. 1993;328(6):393–8.

    Article  CAS  PubMed  Google Scholar 

  25. Zerbe CS, Holland SM. Disseminated histoplasmosis in persons with interferon-gamma receptor 1 deficiency. Clin Infect Dis. 2005;41(4):e38–41.

    Article  PubMed  Google Scholar 

  26. Adderson EE. Histoplasmosis in a pediatric oncology center. J Pediatr. 2004;144(1):100–6.

    Article  PubMed  Google Scholar 

  27. Bhatti S, Vilenski L, Tight R, Smego RA Jr. Histoplasma endocarditis: clinical and mycologic features and outcomes. J Infect. 2005;51(1):2–9.

    Article  PubMed  Google Scholar 

  28. Kraskovsky V, MacKenzie B, Arshad A, Mador MJ. Flip flop fungus sign: an FDG PET sign of benign pulmonary nodules. BMJ Case Rep. 2020;13(11):e236231.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Deppen SA, Massion PP, Blume J, Walker RC, Antic S, Chen H, et al. Accuracy of a novel histoplasmosis enzyme immunoassay to evaluate suspicious lung nodules. Cancer Epidemiol Biomarkers Prev. 2019;28(2):321–6.

    Article  CAS  PubMed  Google Scholar 

  30. Roxas MCA, Sandoval MAS, Salamat MS, Matias PJ, Cabal NP, Bartolo SS. Bilateral adrenal histoplasmosis presenting as adrenal insufficiency in an immunocompetent host in the Philippines. BMJ Case Rep. 2020;13(5):e234935.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mendez-Tovar LJ, Rangel-Delgado PM, Hernandez-Hernandez F, Flores-Garcia A, Galicia-Castelan G, Manzano-Gayosso P, et al. First report of infectious endocarditis due to histoplasma capsulatum in Mexico. Rev Med Inst Mex Seguro Soc. 2019;57(3):181–6.

    PubMed  Google Scholar 

  32. Singh A, Gauri M, Gautam P, Gautam D, Haq M, Handa AC, et al. Head and neck involvement with histoplasmosis; the great masquerader. Am J Otolaryngol. 2019;40(5):678–83.

    Article  CAS  PubMed  Google Scholar 

  33. Singh SRK, Thanikachalam K, Donthireddy V. Desperate times, desperate measures: successful use of chemotherapy in treatment of haemophagocytic lymphohistiocytosis (HLH) due to disseminated histoplasmosis. BMJ Case Rep. 2020;13(9):e235144.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hage CA, Carmona EM, Epelbaum O, Evans SE, Gabe LM, Haydour Q, et al. Microbiological laboratory testing in the diagnosis of fungal infections in pulmonary and critical care practice. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2019;200(5):535–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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(5):448–54.

    Article  PubMed  Google Scholar 

  36. 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(12):1878–82.

    Article  CAS  PubMed  Google Scholar 

  37. Persaud SP, Lawton T, Burnham CD, Anderson NW. Comparison of urine antigen assays for the diagnosis of Histoplasma capsulatum infection. J Appl Lab Med. 2019;4(3):370–82.

    Article  CAS  PubMed  Google Scholar 

  38. Hage CA, Davis TE, Fuller D, Egan L, Witt JR 3rd, Wheat LJ, et al. Diagnosis of histoplasmosis by antigen detection in BAL fluid. Chest. 2010;137(3):623–8.

    Article  CAS  PubMed  Google Scholar 

  39. Bloch KC, Myint T, Raymond-Guillen L, Hage CA, Davis TE, Wright PW, et al. Improvement in diagnosis of histoplasma meningitis by combined testing for histoplasma antigen and immunoglobulin G and immunoglobulin M anti-histoplasma antibody in cerebrospinal fluid. Clin Infect Dis. 2018;66(1):89–94.

    Article  CAS  PubMed  Google Scholar 

  40. Wheat J, Myint T, Guo Y, Kemmer P, Hage C, Terry C, et al. Central nervous system histoplasmosis: multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine (Baltimore). 2018;97(13):e0245.

    Article  CAS  PubMed  Google Scholar 

  41. 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 Vaccine Immunol. 2011;18(4):661–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Joseph WL. Current diagnosis of histoplasmosis. Trends Microbiol. 2003;11(10):488–94.

    Article  Google Scholar 

  43. Almeida MA, Damasceno LS, Pizzini CV, Muniz MM, Almeida-Paes R, Zancope-Oliveira RM. Role of western blot assay for the diagnosis of histoplasmosis in AIDS patients from a National Institute of infectious diseases in Rio de Janeiro, Brazil. Mycoses. 2019;62(3):261–7.

    Article  CAS  PubMed  Google Scholar 

  44. 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(7):896–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 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(9):3204–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bialek R, Feucht A, Aepinus C, Just-Nubling G, Robertson VJ, Knobloch J, et al. Evaluation of two nested PCR assays for detection of histoplasma capsulatum DNA in human tissue. J Clin Microbiol. 2002;40(5):1644–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zatti MDS, Arantes TD, Fernandes JAL, Bay MB, Milan EP, Naliato GFS, et al. Loop-mediated isothermal amplification and nested PCR of the internal transcribed spacer (ITS) for Histoplasma capsulatum detection. PLoS Negl Trop Dis. 2019;13(8):e0007692.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Chen J, Li Y, Li Z, Chen G, Liu X, Ding L. Metagenomic next-generation sequencing identified histoplasma capsulatum in the lung and epiglottis of a Chinese patient: a case report. Int J Infect Dis. 2020;101:33–7.

    Article  PubMed  Google Scholar 

  49. Zhang HC, Zhang QR, Ai JW, Cui P, Wu HL, Zhang WH, et al. The role of bone marrow metagenomics next-generation sequencing to differential diagnosis among visceral leishmaniasis, histoplasmosis, and Talaromycosis marneffei. Int J Lab Hematol. 2020;42(2):e52–e4.

    Article  PubMed  Google Scholar 

  50. Rubio-Carrasquilla M, Santa CD, Rendon JP, Botero-Garces J, Guimaraes AJ, Moreno E, et al. An interferon gamma release assay specific for histoplasma capsulatum to detect asymptomatic infected individuals: a proof of concept study. Med Mycol. 2019;57(6):724–32.

    Article  CAS  PubMed  Google Scholar 

  51. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, 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.

    Article  PubMed  Google Scholar 

  52. Hoz RL, Loyd JE, Wheat LJ, Baddley JW. How I treat histoplasmosis. Curr Fungal Infect Rep. 2013;7(1):36–43.

    Article  Google Scholar 

  53. Johnson PC, Wheat LJ, Cloud GA, Goldman M, Lancaster D, Bamberger DM, et al. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med. 2002;137(2):105–9.

    Article  CAS  PubMed  Google Scholar 

  54. Goldman M, Zackin R, Fichtenbaum CJ, Skiest DJ, Koletar SL, Hafner R, et al. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis. 2004;38(10):1485–9.

    Article  PubMed  Google Scholar 

  55. Myint T, Anderson AM, Sanchez A, Farabi A, Hage C, Baddley JW, et al. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse. Medicine. 2014;93(1):11–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Connolly P, Wheat LJ, Schnizlein-Bick C, Durkin M, Kohler S, Smedema M, et al. Comparison of a new triazole, posaconazole, with itraconazole and amphotericin B for treatment of histoplasmosis following pulmonary challenge in immunocompromised mice. Antimicrob Agents Chemother. 2000;44(10):2604–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Restrepo A, Tobon A, Clark B, Graham DR, Corcoran G, Bradsher RW, et al. Salvage treatment of histoplasmosis with posaconazole. J Infect. 2007;54(4):319–27.

    Article  PubMed  Google Scholar 

  58. Wheat LJ, Connolly P, Smedema M, Brizendine E, Hafner R, Group ACT, et al. Emergence of resistance to fluconazole as a cause of failure during treatment of histoplasmosis in patients with acquired immunodeficiency disease syndrome. Clin Infect Dis. 2001;33(11):1910–3.

    Article  CAS  PubMed  Google Scholar 

  59. Wheat LJ, Connolly P, Smedema M, Durkin M, Brizendine E, Mann P, et al. Activity of newer triazoles against histoplasma capsulatum from patients with AIDS who failed fluconazole. J Antimicrob Chemother. 2006;57(6):1235–9.

    Article  CAS  PubMed  Google Scholar 

  60. Kohler S, Wheat LJ, Connolly P, Schnizlein-Bick C, Durkin M, Smedema M, et al. Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model. Antimicrob Agents Chemother. 2000;44(7):1850–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hage CA, Connolly P, Horan D, Durkin M, Smedema M, Zarnowski R, et al. Investigation of the efficacy of micafungin in the treatment of histoplasmosis using two north American strains of histoplasma capsulatum. Antimicrob Agents Chemother. 2011;55(9):4447–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Infectious Diseases, Emory University School of Medicine, Atlanta, USA

    Wassim Abdallah

  2. Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh - School of Medicine, Pittsburgh, USA

    Chadi Hage

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  1. Wassim Abdallah
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Correspondence to Wassim Abdallah .

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Editors and Affiliations

  1. Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Duane R. Hospenthal

  2. Departments of Pathology, Microbiology, and Clinical Laboratory Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Michael G. Rinaldi

  3. Departments of Medicine and Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

    Thomas J. Walsh

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Dr. Abdallah is an Internal Medicine Resident Physician at Indiana University School of Medicine. Dr. Hage is an Associate Professor of Clinical Medicine at Indiana University School of Medicine and faculty in the thoracic transplantation program at Indiana University Health.

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Abdallah, W., Hage, C. (2023). Histoplasmosis. In: Hospenthal, D.R., Rinaldi, M.G., Walsh, T.J. (eds) Diagnosis and Treatment of Fungal Infections. Springer, Cham. https://doi.org/10.1007/978-3-031-35803-6_20

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