- •
Although histoplasmosis is highly endemic in certain regions of the Americas, disease may be seen globally and should not be overlooked in patients with unexplained pulmonary or systemic illnesses.
- •
Most patients exhibit pulmonary signs and symptoms, accompanied by radiographic abnormalities, which often are mistaken for community-acquired pneumonia caused by bacterial or viral agents.
- •
Once a diagnosis is considered, a panel of mycologic and non–culture-based assays is adequate to establish a
Histoplasmosis
Section snippets
Key points
Epidemiology
Histoplasmosis is most commonly understood as intensely endemic in the Ohio and Mississippi River Valleys in the United States and much of Latin America (Fig. 1),3, 4 although it has been known for some time that other areas around the world saw cases as well.5 The HIV pandemic and the increasing use of other immunosuppressive medications, such as calcineurin and tumor necrosis factor inhibitors, has resulted in more cases of histoplasmosis and thus improved understanding of the distribution of
Pathogenesis
Infection with H capsulatum occurs by inhaling microconidia after disturbance of environmental sites containing the organism.32 Infection is usually asymptomatic in healthy individuals unless a large inoculum has been inhaled.25 In the absence of immunocompromising conditions, acute infection resolves with the development of cell-mediated immunity.33 As a consequence of production of T lymphocytes that recognize the organism, tumor necrosis factor α and interferon gamma are induced, activating
Acute Pulmonary Histoplasmosis
After inhalation of Histoplasma microconidia, a majority (90%) of patients develop subclinical, self-limited, and most often unrecognized disease (Table 1). Symptoms are more likely to manifest after high-inoculum exposures, in immunocompromised patients, in those at the extremes of age, and possibly with more intrinsically virulent strains.34, 35 The overt acute pulmonary syndrome occurs after a median incubation period of 14 days and is characterized by fever, chills, dyspnea, and cough.
Pathology
Rapid identification of H capsulatum var. capsulatum is facilitated by visualization of ovoid yeast cells measuring 2 μm to 4 μm in greatest dimension in tissue and/or body fluid specimens. The average size of H capsulatum var. duboisii (range, approximately 6–12 μm or greater), however, is often much larger than that of H capsulatum var. capsulatum, so presumptive identification should not rely solely on microscopic morphology. Budding yeast is connected at a narrow base, which helps
Treatment
Histoplasmosis resolves without treatment in most healthy individuals, in whom treatment is usually not recommended. The main exception is healthy individuals with recent exposure to a site contaminated with the organism, in whom early treatment is usually recommended to shorten the duration of illness and prevent the rare occurrence of PDH. In contrast, histoplasmosis is progressive in most immunocompromised patients, in whom PDH is highly likely and treatment is always recommended. Rare
References (107)
- et al.
AIDS on Trinidad
Lancet
(1984) - et al.
Clinicopathological features of cutaneous histoplasmosis in human immunodeficiency virus-infected patients in Zimbabwe
Trans R Soc Trop Med Hyg
(2001) - et al.
Histoplasmosis among hospitalized febrile patients in northern Tanzania
Trans R Soc Trop Med Hyg
(2012) - et al.
Burden of serious fungal infections in Spain
Clin Microbiol Infect
(2015) - et al.
Endemic mycoses: overlooked causes of community acquired pneumonia
Respir Med
(2012) - et al.
FDG-PET imaging and the diagnosis of non-small cell lung cancer in a region of high histoplasmosis prevalence
Lung Cancer
(2002) - et al.
Broncholithiasis
J Thorac Cardiovasc Surg
(1971) - et al.
Haemophagocytic syndrome associated with infections
Baillieres Best Pract Res Clin Haematol
(2000) - et al.
Infections associated with haemophagocytic syndrome
Lancet Infect Dis
(2007) - et al.
Diagnosis of histoplasmosis by antigen detection in BAL fluid
Chest
(2010)
Detection of Histoplasma capsulatum DNA in human samples by real-time polymerase chain reaction
Diagn Microbiol Infect Dis
Urine polymerase chain reaction is not as sensitive as urine antigen for the diagnosis of disseminated histoplasmosis
Diagn Microbiol Infect Dis
Acute histoplasmosis presenting as the adult respiratory distress syndrome
Chest
Itraconazole therapy for blastomycosis and histoplasmosis
Am J Med
Follow-up of patients with chronic pulmonary histoplasmosis treated with amphotericin B
Chest
Blastomycosis in indiana: digging up more cases
Chest
Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group
Am J Med
Salvage treatment of histoplasmosis with posaconazole
J Infect
Hospitalizations for endemic mycoses: a population-based national study
Clin Infect Dis
The incidence of hospitalized cases of systemic mycotic infections
Sabouraudia
An atlas of sensitivity to tuberculin, PPD-B and histoplasmin in the United States
Am Rev Respir Dis
Epidemiology of endemic systemic fungal infections in Latin America
Med Mycol
Systemic histoplasmosis in South Africa. A review of the previous cases and a report of an additional case–the first successfully treated
S Afr Med J
Disseminated histoplasmosis in HIV-infected patients in South America: a neglected killer continues on its rampage
PLoS Negl Trop Dis
Histoplasmosis after solid organ transplant
Clin Infect Dis
A multinational outbreak of histoplasmosis following a biology field trip in the ugandan rainforest
J Travel Med
Erythema nodosum and erythema multiforme as clinical manifestations of histoplasmosis in a community outbreak
N Engl J Med
Leads from the MMWR. Cave-associated histoplasmosis–Costa Rica
JAMA
Histoplasmosis in idaho and montana, USA, 2012-2013
Emerg Infect Dis
Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients
Medicine (Baltimore)
Disseminated histoplasmosis, invasive pulmonary aspergillosis, and other opportunistic infection in a homosexual patient with acquired immune deficiency syndrome
Sex Transm Dis
Homosexuality, steroid therapy, and histoplasmosis
Ann Intern Med
Bone marrow examination and culture in the diagnosis of acquired immunodeficiency syndrome (AIDS)
Arch Intern Med
Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks
Medicine (Baltimore)
Immunologic diversity among serogroup 1 Legionella pneumophila urinary antigens demonstrated by monoclonal antibody enzyme-linked immunosorbent assays
J Clin Microbiol
Histoplasmosis: results of the Colombian national survey, 1992-2008
Biomedica
Histoplasmosis: a new endemic fungal infection in China? Review and analysis of cases
Mycoses
Detection of environmental sources of histoplasma capsulatum in Chiang Mai, Thailand, by nested PCR
Myco
Chronic cavitary pulmonary histoplasmosis in a non-HIV and immunocompromised patient without overseas travel history
Yonsei Med J
Occurrence of histoplasmosis in Asia
Mycopathol Mycol Appl
Literature review and case histories of Histoplasma capsulatum var. duboisii infections in HIV-infected patients
Emerg Infect Dis
Progressive disseminated histoplasmosis among human immunodeficiency virus-infected patients from West-Africa: report of four imported cases in Italy
Infez Med
Histoplasmosis among human immunodeficiency virus-infected people in Europe: report of 4 cases and review of the literature
Medicine (Baltimore)
Challenges in the management of disseminated progressive histoplasmosis in human immunodeficiency virus-infected patients in resource-limited settings
Open Forum Infect Dis
Histoplasma capsulatum, lung infection and immunity
Future Microbiol
Histoplasmosis
Proc Am Thorac Soc
Correlation between pathogenicity and temperature sensitivity in different strains of Histoplasma capsulatum
J Clin Invest
Comparison of phylogenetically distinct histoplasma strains reveals evolutionarily divergent virulence strategies
MBio
Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic
Arthritis Rheum
Cited by (250)
Haemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis in an immunocompetent patient
2024, Medical Mycology Case Reports50-Year-Old Man With Fevers, Cough, and Night Sweats
2024, Mayo Clinic ProceedingsConstitutional syndrome and miliary pattern in an HIV-positive patient
2023, Enfermedades Infecciosas y Microbiologia ClinicaRe-estimation of the burden of serious fungal diseases in Uganda
2024, Therapeutic Advances in Infectious Disease