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Key sources
The following summarized guidelines for the evaluation and management of histoplasmosis are prepared by our editorial team based on guidelines from the Infectious Diseases Society of America (IDSA/CDC/NIH/HIVMA 2023), the European Confederation of Medical Mycology (ECMM/ISHAM 2021), the Pan American Health Organization (PAHO/WHO 2020), the American Thoracic Society (ATS 2011), and the Infectious Diseases Society of America (IDSA 2007).


1.Classification and risk stratification

Severity assessment
Define severe or moderately severe histoplasmosis as the presence of at least one sign or symptom involving vital organs:
respiratory or circulatory failure
neurological signs
renal failure
coagulation anomalies
general alteration of the WHO performance status > 2, in which the person is confined to a bed or chair for more than half the waking hours and only capable of limited self-care
Define mild-to-moderate histoplasmosis as signs and symptoms not including the above features defining severe or moderately severe histoplasmosis.
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2.Diagnostic investigations

Antigen testing: obtain circulating Histoplasma antigens for the diagnosis of disseminated histoplasmosis in patients with HIV infection.

3.Diagnostic procedures

Histopathological analysis: obtain tissue for the histopathological diagnosis of histoplasmosis using fungal stains (Grocott methenamine silver staining) and fungal culture whenever possible.

4.Medical management

Management of acute pulmonary histoplasmosis, mild-to-moderate, ATS: do not initiate antifungal treatment in asymptomatic patients.
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  • Management of acute pulmonary histoplasmosis (severe)

  • Management of progressive disseminated histoplasmosis

  • Management of chronic cavitary pulmonary histoplasmosis

  • Management of pulmonary nodules

  • Management of broncholithiasis

  • Management of pericarditis

  • Management of mediastinal lymphadenitis

  • Management of mediastinal granuloma

  • Management of fibrosing mediastinitis

  • Management of CNS histoplasmosis

  • Management of rheumatologic syndromes

5.Specific circumstances

Pediatric patients: apply the same treatment indications and regimens in pediatric patients similar to adult patients, except that amphotericin B deoxycholate (1.0 mg/kg/day) is usually well tolerated and lipid preparations are not preferred.
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  • Pregnant patients

  • Patients with HIV (primary prophylaxis)

  • Patients with HIV (management of mild-to-moderate pulmonary disease)

  • Patients with HIV (management of severe pulmonary disease)

  • Patients with HIV (management of chronic pulmonary disease)

  • Patients with HIV (management of meningeal disease)

  • Patients with HIV (therapeutic drug monitoring)

  • Patients with HIV (management of tuberculosis co-infection)

  • Patients with HIV (secondary prophylaxis)

6.Preventative measures

Antifungal prophylaxis: as per ATS 2023 guidelines, initiate primary prophylaxis in patients with a CD25 count < 150 cells/mm³ and at high risk because of occupational exposure or residence in a community with a hyperendemic rate of histoplasmosis (> 10 cases/100 patient-years).
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