Medscape is available in 5 Language Editions – Choose your Edition here.


Pediatric Histoplasmosis

  • Author: James S Hagood, MD; Chief Editor: Russell W Steele, MD  more...
Updated: Jan 14, 2015


Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum. The fungus grows saprophytically and develops mycelia with macroconidia and microconidia. The parasitic form is characterized by the production of yeasts 2-4 μm in diameter. Histoplasmosis is endemic in the central United States and in other parts of the world with warm humid soil and large populations of migratory birds. It is the most common pulmonary and systemic mycosis of humans. Clinical manifestations vary from a mild flulike illness that often goes unnoticed to rapidly progressive, often fatal, disseminated disease.[1] The presentation varies depending on the host's immunity and the size of the inoculum.

The principal challenges to the clinician caring for patients with histoplasmosis are to recognize the disease, which can mimic a number of processes, and to rationally use a confusing array of tests for diagnosis and treatment. In 1905, Samuel Darling described histoplasmosis in a patient working in the Panama Canal Zone. As early as the 1940s, Amos Christie, MD, and colleagues used the histoplasmin skin test to demonstrate that numerous patients with abnormal chest radiographs but negative tuberculin results actually had self-limited infection with histoplasmosis.



Five serotypes of capsulatum are known, including some avirulent strains. Histoplasma species have a mycelial form at ambient temperatures. The spores of H capsulatum (microconidia) become airborne when soil is disturbed (see Causes).

The initial neutrophil response is ineffective against the yeast form. Macrophages ingest the yeast, but they continue to proliferate. Specific immunity, which occurs 10-21 days after infection, is needed to kill the organisms. Specific helper T cells are able to activate macrophages to form the granulomas that are characteristic of the disease. Natural killer cells mediate extracellular killing, which antibodies enhance.

Pneumonitis, with a predominant mononuclear infiltrate, peaks 2 weeks after infection. Granulomas can form in the pulmonary parenchyma and in the hilar and mediastinal lymph nodes. These lesions can be caseating and may develop calcification and fibrosis over time. In most infections, fungemia likely occurs at some point because splenic granulomas have been observed after asymptomatic infection. In individuals with impaired T cell–mediated immunity, other sites of infection include the bone marrow, liver, adrenal glands, CNS, joint spaces, heart valves, and blood vessels.

Reports describe infectious complications in almost every tissue. Reactivation of infection may occur in individuals who become immunosuppressed long after a primary infection; this reactivation accounts for many of the cases observed in nonendemic areas. Reinfection can occur in the setting of heavy conidial burdens but is generally mild because of specific immunity.

Recent animal studies have revealed that interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and GR 1(+) cells are important in localizing and controlling Histoplasma infection. YPS3 and cell wall alpha-(1,3)-glucan of Histoplasma are also associated with virulence.




United States

An estimated 50 million individuals have been infected with H capsulatum. Nationwide, approximately 22% of the population have positive skin-test results for histoplasmin, though the rate may be as high as 80% in endemic areas in the central United States, specifically the Ohio and Mississippi River Valleys (see the image below). Of the 500,000 individuals who are exposed annually, 50,000-200,000 develop symptoms, and 1500-4000 require hospitalization.

Map demonstrates the distribution of histoplasmin Map demonstrates the distribution of histoplasmin skin-test positivity by region. Used with permission from the American Thoracic Society.


Endemic regions for histoplasmosis are found in Central and South America, in the Caribbean, in Africa, and in Asia. However, microfoci are believed to occur anywhere soil conditions are appropriate to support the growth of H capsulatum.


The overall mortality rate of histoplasmosis is low; most cases spontaneously resolve. In individuals with immunosuppression, progressive disseminated disease has a high mortality rate of 7-23%. Without treatment, disseminated disease is usually fatal. Disseminated infection can localize in any tissue, leading to various complications. Pericarditis and obstruction of mediastinal structures are the principal complications in individuals who are immunocompetent.


No racial predilection to infection or to disease presentation is apparent.


Among adults, histoplasmosis is described more commonly in men than in women. However, certain clinical manifestations, such as erythema nodosum, are described most commonly in women. These sex differences in infection and disease are not observed in children.


Histoplasmosis occurs at any age. Disseminated disease is more likely to occur in individuals at the extremes of life, unless a person has immunodeficiency. The incidence of disseminated histoplasmosis in children appears to have decreased in the last 30 years. The sex-related differences observed in infection and disease among adults are not observed in children.

Contributor Information and Disclosures

James S Hagood, MD Professor of Pediatrics and Chief, Division of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, School of Medicine and Rady Children's Hospital of San Diego

James S Hagood, MD is a member of the following medical societies: American Thoracic Society

Disclosure: Nothing to disclose.


Gulnur Com, MD Pediatric Pulmonologist, University of Arkansas for Medical Sciences Children's Hospital

Gulnur Com, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, Cystic Fibrosis Foundation

Disclosure: Nothing to disclose.

Asad Ansari, MD, MPH Attending Physician, Pediatric Pulmonology and Infectious Diseases, Memorial Children's Hospital

Asad Ansari, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Glenn Fennelly, MD, MPH Director, Division of Infectious Diseases, Lewis M Fraad Department of Pediatrics, Jacobi Medical Center; Clinical Associate Professor of Pediatrics, Albert Einstein College of Medicine

Glenn Fennelly, MD, MPH is a member of the following medical societies: Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

  1. Lo MM, Mo JQ, Dixon BP, Czech KA. Disseminated histoplasmosis associated with hemophagocytic lymphohistiocytosis in kidney transplant recipients. Am J Transplant. 2010 Mar. 10(3):687-91. [Medline].

  2. Chamany S, Mirza SA, Fleming JW, Howell JF, Lenhart SW, Mortimer VD, et al. A large histoplasmosis outbreak among high school students in Indiana, 2001. Pediatr Infect Dis J. 2004 Oct. 23(10):909-14. [Medline].

  3. McKinsey DS, McKinsey JP. Pulmonary histoplasmosis. Semin Respir Crit Care Med. 2011 Dec. 32(6):735-44. [Medline].

  4. Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am. Mar 2003. 17(1):1-19, vii. [Medline].

  5. Rosenthal J, Brandt KD, Wheat LJ, Slama TG. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum. 1983 Sep. 26(9):1065-70. [Medline].

  6. AETC. Clinical Manual for Management of the HIV-Infected Adult. AETC National Resource Center [serial online]. Available at Accessed: January 11, 2007.

  7. Mandell GL, Bennett JE, Dolin R. Histoplasmosis. Principles and Practice of Infectious Diseases. 6th ed. Oxford, England: Churchill Livingstone; 2004.

  8. Cionni DA, Lewis SA, Petersen MR, Foster RE, Riemann CD, Sisk RA, et al. Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis. Ophthalmology. 2012 Feb. 119(2):327-32. [Medline].

  9. Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. 2005 Mar 15. 40(6):844-52. [Medline].

  10. Rangel-Castilla L, Hwang SW, White AC, Zhang YJ. Neuroendoscopic Diagnosis of Central Nervous System Histoplasmosis with Basilar Arachnoiditis. World Neurosurg. 2011 Nov 7. [Medline].

  11. Wheat LJ. Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host. Transpl Infect Dis. 2006 Sep. 8(3):128-39. [Medline].

  12. 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 Vaccine Immunol. 2009 Mar. 16(3):320-2. [Medline].

  13. Wheat LJ, Garringer T, Brizendine E, Connolly P. Diagnosis of histoplasmosis by antigen detection based upon experience at the histoplasmosis reference laboratory. Diagn Microbiol Infect Dis. May 2002. 43(1):29-37. [Medline].

  14. O'Shaughnessy EM, Shea YM, Witebsky FG. Laboratory diagnosis of invasive mycoses. Infect Dis Clin North Am. Mar 2003. 17(1):135-58. [Medline].

  15. Maubon D, Simon S, Aznar C. Histoplasmosis diagnosis using a polymerase chain reaction method. Application on human samples in French Guiana, South America. Diagn Microbiol Infect Dis. 2007 May 15. [Medline].

  16. Adderson EE. Histoplasmosis in a pediatric oncology center. J Pediatr. 2004 Jan. 144(1):100-6. [Medline].

  17. Johnson PC, Wheat LJ, Cloud GA, 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. Jul 16 2002. 137(2):105-9. [Medline]. [Full Text].

  18. Pitisuttithum P, Negroni R, Graybill JR, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother. 2005 Oct. 56(4):745-55. [Medline].

  19. Raad II, Graybill JR, Bustamante AB, et al. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis. Jun 15 2006. 42(12):1726-34. [Medline].

  20. Restrepo A, Tobon A, Clark B, et al. Salvage treatment of histoplasmosis with posaconazole. J Infect. 2007 Apr. 54(4):319-27. [Medline].

  21. 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 (Baltimore). 2014 Jan. 93(1):11-8. [Medline].

  22. Antachopoulos C, Walsh TJ. New agents for invasive mycoses in children. Curr Opin Pediatr. 2005 Feb. 17(1):78-87. [Medline].

  23. Edwards LB, Acquaviva FA, Livesay VT, Cross FW, Palmer CE. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States. Am Rev Respir Dis. 1969 Apr. 99(4):Suppl:1-132. [Medline].

  24. George R, Penn R. Histoplasmosis. Sarosi GA, Davies SF, eds. Fungal Diseases of the Lung. New York, NY: Raven; 1993. 39-50.

  25. Guimaraes AJ, Pizzini CV, De Matos Guedes HL, et al. ELISA for early diagnosis of histoplasmosis. J Med Microbiol. Jun 2004. 53(Pt 6):509-14. [Medline].

  26. Hamilton AJ. Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei; current status and future trends. Med Mycol. Dec 1998. 36(6):351-64. [Medline].

  27. Joseph Wheat L. Current diagnosis of histoplasmosis. Trends Microbiol. 2003 Oct. 11(10):488-94. [Medline].

  28. Keating GM. Posaconazole. Drugs. 2005. 65(11):1553-67. [Medline].

  29. Kumar N, Singh S, Govil S. Adrenal histoplasmosis: clinical presentation and imaging features in nine cases. Abdom Imaging. 2003 Sep-Oct. 28(5):703-8. [Medline].

  30. Kurowski R, Ostapchuk M. Overview of histoplasmosis. Am Fam Physician. 2002 Dec 15. 66(12):2247-52. [Medline].

  31. Levitz SM. Overview of host defenses in fungal infections. Clin Infect Dis. 1992 Mar. 14 Suppl 1:S37-42. [Medline].

  32. Mathisen DJ, Grillo HC. Clinical manifestation of mediastinal fibrosis and histoplasmosis. Ann Thorac Surg. Dec 1992. 54(6):1053-7; discussion 1057-8. [Medline].

  33. Mocherla S, Wheat LJ. Treatment of histoplasmosis. Semin Respir Infect. 2001 Jun. 16(2):141-8. [Medline].

  34. Murray JF, Nadel JA. Histoplasmosis. Textbook of Respiratory Medicine. 4th ed. 2005. 1045-55.

  35. Wheat J. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore). 1997 Sep. 76(5):339-54. [Medline].

  36. [Guideline] Wheat J, Sarosi G, McKinsey D, et al. Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America. Clin Infect Dis. 2000 Apr. 30(4):688-95. [Medline].

  37. Wiedermann BL. Histoplasmosis. Feigin RD, Cherry JD, Fletcher J, eds. Textbook of Pediatric Infectious Diseases. WB Saunders; 1998. 2337-50.

Hilar lymphadenopathy in an 11-year-old child.
Map demonstrates the distribution of histoplasmin skin-test positivity by region. Used with permission from the American Thoracic Society.
Hematoxylin and eosin stain of infected lung tissue. Histoplasma organisms appear to have a false capsule.
Starling roost in Alabama.
Acute pulmonary syndrome in a 16-year-old female adolescent.
Fibrosing mediastinitis with mediastinal widening and tracheal deviation.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.