Febrile Syndromes

Febrile Syndromes is a topic covered in the Washington Manual of Medical Therapeutics.

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Histoplasma capsulatum Infections

General Principles

  • The severity of infection depends on the degree of the patient’s immunosuppression.
  • Histoplasmosis often occurs in AIDS patients who live in endemic areas such as the Mississippi and Ohio River Valleys.
  • Such infections are usually disseminated at the time of diagnosis.


  • Suspect histoplasmosis in patients with fever, hepatosplenomegaly, and weight loss.
  • Pancytopenia develops because of bone marrow involvement.
  • Diagnosis is made by a positive culture or biopsy demonstrating 2–4 μm budding yeast, but the urine and serum Histoplasma antigens can also be used for diagnosis and to monitor treatment.


  • Disseminated disease is treated with liposomal amphotericin B, 3 mg/kg IV daily for 2 weeks or until the patient clinically improves, followed by itraconazole, 200 mg PO bid indefinitely.
  • CNS disease is initially treated with liposomal amphotericin B, 5 mg/kg IV daily for 4–6 weeks, before starting itraconazole.
  • Itraconazole absorption should be documented by a serum drug level. Liquid itraconazole is preferred because of improved absorption; however, it can be expensive and difficult to obtain.
  • Discontinuation of itraconazole is possible if sustained increase in CD4 count is observed >100–200 cells/μL for more than 6 months.

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