Panel’s Recommendations

Routine use of antifungal medications for primary prophylaxis of histoplasmosis in children is not recommended (BIII). Amphotericin B is preferred for initial treatment of moderately severe to severe infections (AI*). Itraconazole is the azole preferred for treatment of histoplasmosis (AIII). In manifestations of histoplasmosis in which antigenuria is demonstrated, antigen levels should be monitored during therapy and for 1 year thereafter to identify relapse (AIII). For severe or moderately severe acute primary pulmonary histoplasmosis, amphotericin B should be administered for at least 1 to 2 weeks (and clinical improvement) (AIII). After treatment with amphotericin, patients with intact immunity should receive itraconazole for at least 12 weeks (AIII). Adults with CD4 T lymphocyte (CD4) cell counts <150 cells/mm3 and HIV-infected children with severe immunosuppression should receive itraconazole consolidation therapy for at least 12 months (AIII). The preferred treatment for severe or moderately severe progressive disseminated histoplasmosis is initial (induction) therapy with amphotericin B for ≥2 weeks (and favorable clinical response), followed by consolidation therapy with itraconazole for at least 12 months (AI*). Itraconazole monotherapy for 12 months is recommended for HIV-infected children with mild to moderate progressive disseminated histoplasmosis (AII*). Liposomal amphotericin B for 4 to 6 weeks is the preferred initial treatment in the presence of focal brain lesions (BIII*). Thereafter, children should receive itraconazole consolidation therapy for at least 12 months and until cerebrospinal fluid abnormalities, including histoplasma antigen, have resolved (AII*). In the event of immune reconstitution inflammatory syndrome, antiretroviral therapy should be continued along with antifungal therapy (AIII). Longer-term suppressive therapy (secondary prophylaxis) with itraconazole may be required in HIV-infected children who are severely immunosuppressed (meaning CD4 percentage <15% at any age or CD4 count <150 cells/mm3 in children aged ≥6 years) and patients who experience relapse despite receipt of appropriate therapy (AIII).

Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = One or more randomized trials in children^† with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children^† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children^† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children^† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

^†Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents