This document provides an overview of histoplasmosis, including its epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment. It describes how histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum, which exists as a mold in the environment and a yeast in tissues. Most infections are asymptomatic, but symptomatic cases can range from mild acute pulmonary infection to potentially fatal disseminated infection. Diagnosis involves antigen detection, culture, histopathology, or serologic testing. Treatment with antifungals is recommended for severe or disseminated cases.

1. Overview of Histoplasmosis
B. Keith English, M.D.
Chair, Department of Pediatrics
and Human Development

2. Nothing to Disclose

3. Thank You!
 Many thanks to my long-time colleague Dr.
Sandy Arnold, Chief of Pediatric Infectious
Diseases at Le Bonheur Children’s Hospital and
the University of Tennessee Health Science
Center in Memphis for sharing her slides with me
(I have modified them for this presentation)

4. Diagnosing Pulmonary
Histoplasmosis in Children
 A child living in Nashville
presents with cough for
several weeks, low grade
fever and dyspnea. The
CXR is shown.
 What is the best test to
confirm the diagnosis of
subacute pulmonary
histoplasmosis?

5. A. Histoplasma urine
antigen
B. Complement fixation
antibody titers
C. BAL and culture
D. Histoplasma serum
antigen
E. Cold agglutinins

6. Treating Mediastinal
Histoplasmosis?
 A 6 year old boy in Memphis is discovered
to have a large right paratracheal mass
deviating the trachea on a CXR done during
influenza A infection. He became
asymptomatic after the flu resolved.
 What is the best treatment for this patient?

7. A. Itraconazole
B. Amphotericin B
C. Steroids
D. Steroids & itraconazole
E. No treatment

8. Dimorphic Fungi 101
 Thermally dimorphic fungi
 Yeast form at body temperature i.e. isolated from tissues
 Mold at lower temps – found in the environment
– Endemic mycoses – geographically distinct and thermally
dimorphic
 Histoplasmosis
 Blastomycosis
 Coccidioidomycosis
 Exist in nature as spore forming molds
 Inhaled spores are infectious
 Not contagious from person to person

9. Histoplasmosis
 Caused by the dimorphic fungus Histoplasma
capsulatum
 Found in soil as mold with microconidia
(infectious spores)
 Climate and specific soil conditions thought to
account for areas of endemnicity
 May also be found in higher concentrations in
certain microfoci

10. Histoplasmosis
in North and
South America

11. Histo in the U.S.

12. Epidemiology: high
risk activities
Caves Spelunking
Chicken coops Cleaning, demolition, use of droppings for fertilizer
Bird roosts Excavation, camping
Bamboo canebrakes Cutting cane, recreation
School yards Routine activities, cleaning
Prison grounds Routine activities, cleaning
Decayed wood piles Transporting or burning wood
Dead trees Recreational, cutting wood
Contaminated chimneys Cleaning, demolition
Old building Demolition, remodeling, cleaning
Laboratories Research with H capsulatum
Ship hatch cover Cleaning off sea gull guano
Microfocus Activities

13. Clinical manifestations
 In endemic areas, over half of adults have
evidence of infection (by histoplasmin skin
testing) by young adulthood
 Most infections asymptomatic
 Severity of disease depends on:
 Inoculum size (intense exposure in closed space)
 Cell-mediated immune function
 Virulence of specific strain
 Pre-existing immunity

15. Pathophysiology
 Inhaled microconidia germinate in lungs
 Local infection occurs (pneumonitis)
 Fungi phagocytosed as part of acute inflammation
 Dissemination via lymphohematogenous route
occurs early (in first 2 weeks)
 Cell mediated immunity required for phagocytic
cells to become fungicidal
 Granulomatous inflammation develops as cell
mediated immunity controls infection
 Antibodies produced but not part of effective
immune response

16. Pathophysiology
 Re-infection can occur but usually mild due to
pre-existing cell-mediated immunity
 Most likely to occur in setting of high inoculum
exposure
 Reactivation/reinfection may also occur in the
setting of immunosuppression (HIV, organ
transplant)

17. Clinical manifestations
Clinical syndrome Percent of total
Asymptomatic infection 50–90
Symptomatic infection 10–50
Self-limited syndromes % of symptomatic
Acute pulmonary 60
Rheumatologic 10
Pericarditis 10
Chronic pulmonary 10
Disseminated 10
Histoplasmomas <1
Fibrosing mediastinitis <1

18. Case
A 15 year old boy presents with diffuse
pneumonitis (CXR on next slide). In the ER he is
profoundly hypoxic and is intubated for
respiratory failure. His father is at the adult ER
for similar symptoms. You suspect
histoplasmosis because the mother tells you
they were hiking and exploring caves a few
weeks ago.

19. Diagnosis? Treatment?
 What is the best way
to make the
diagnosis?
 What treatment is
recommended?

20. Pulmonary histoplasmosis
 Flu-like illness with cough, fatigue, fever
CXR findings
– normal to patchy infiltrates or miliary pattern with mediastinal
lymph nodes
– "Buckshot" appearance on chest radiograph with subsequent
calcification in cases of very heavy exposure
 More severe with heavy inoculum, respiratory failure and
death can occur without treatment
 Disseminated - diffuse reticulonodular pattern (like miliary
TB) – no adenopathy
 Extrapulmonary disease may coexist as may
rheumatologic manifestations: arthritis/arthralgia,
erythema nodosum (or these can occur alone)

21. Histoplasma pneumonia

23. Subacute Pulmonary Histo
 A child living in Nashville
presents with cough for
several weeks, low grade
fever and dyspnea. The
CXR is shown.
 What is the best test to
confirm the diagnosis of
subacute pulmonary
histoplasmosis?

25. Mediastinal granuloma
 A 6 year old boy in Memphis is discovered
to have a large right paratracheal mass
deviating the trachea on a CXR done during
influenza A infection. He became
asymptomatic after the flu resolved.
 What is the best treatment for this patient?

26. Mediastinal histoplasmosis
 Exuberant granulomatous response may result in
compression of mediastinal structures by lymph
nodes
 Tracheobronchi, esophagus, pulmonary
vessels, SVC
 May have associated granulomatous* lesions in
lungs, liver, spleen
*Acute histoplasmosis may heal with calcification of granulomata

27. Mediastinal histoplasmosis
 Masses may persist for years but do
eventually resolve; may wax and wane over
time
 Symptoms may develop months or years after
infection
 Generally treatment for the histoplasmosis is
not needed unless there are prolonged
symptoms (and even then if of uncertain
value)

28. Post-obstructive pneumonia
 Masses have very few organisms so response
to antifungal therapy unlikely
 Steroids may help – data are limited
 For post-obstructive pneumonia, treat for
community-acquired pneumonia, not
Histoplasma pneumonia

29. Treatment of mediastinal granuloma?
A. Itraconazole
B. Amphotericin B
C. Steroids
D. Steroids & itraconazole
E.No treatment

31. histo

33. Clinical Infectious Diseases

34. Disseminated histoplasmosis
 Occurs in patients with depressed CMI
 Risk correlates with CD4 count in HIV in
endemic areas (was once leading “AIDS-
defining illness” in certain parts of U.S.)
 Also occurs in infants under one year of age
with diffuse reticuloendothelial involvement -
may cause pneumonitis, hepatosplenomegaly,
bone marrow suppression; may be fulminant,
fatal

38. Clinical Infectious Diseases

39. Laboratory diagnosis
Culture/Histopathology
 Lung biopsy or BAL specimen will be positive
in acute pulmonary with high inoculum or
disseminated, not mild acute pulmonary
 Use lysis centrifugation (Isolator) for blood
culture in disseminated disease
 May take 4 to 6 weeks to grow
 Tissue specimens can be stained for fungus
with silver stain or GMS, peripheral blood with
Wright’s stain

40. Laboratory diagnosis
Antigen detection
 Detected in urine, serum, CSF, BAL fluid
 Most likely to be positive in disseminated
disease (90% positive) or severe acute
pulmonary (75% positive)
 Urine > sensitive than serum
 May cross react with blastomyces,
paracoccidiodes

41. Laboratory diagnosis
Serologic testing
 For yeast and mycelial antigens
 Complement Fixation more sensitive [>1:8 in 90%
of acute pulmonary cases; immunodiffusion more
specific [76% M band +, 23% H band +]
 Develop 2 to 6 weeks after infection
 May be elevated from past or asymptomatic
infection
 Low titer or false negative if immunocompromised

42. Clinical Infectious Diseases

43. Treatment of Histoplasmosis
in Children
 Antifungal therapy (itraconazole, Ampho B)
strongly recommended for severe pulmonary
disease, disseminated disease, CNS disease
 IDSA guidelines recommend antifungal therapy
(with steroids) for severe pericarditis, prolonged
or severe symptoms associated with mediastinal
granuloma, etc – but evidence supporting this
recommendation weak to non-existent
 Anecdotal evidence of dramatic response to
steroids in patients with bronchial/tracheal
obstruction, etc, but weak overall evidence