Histoplasmosis

Histoplasma capsulatum

Diagnosis and treatment

Diagnosis:
antigen detection in blood, urine or broncho-alveolar fluid, OR positive microscopy, OR mycological culture of blood, urine, broncho-alveolar fluid, CSF or tissue biopsy, OR PCR in blood or other clinical samples. Aspergillus galactomannan assays may be helpful to diagnose disseminated infections as cross reactivity occurs

Note: CSF, which shows typically a lymphatic pleocytosis, is usually microscopy and culture negative. Detection of histoplasma antigen or antibody is more sensitive. A clinical diagnosis is possible, if disseminated histoplasmosis is present and CNS infection is not explained by another cause

Notes on treatment:

Fluconazole should not be used for treatment of histoplasmosis. Little clinical evidence is available for the use of voriconazole, posaconazole and isavuconazole.
Be aware of interactions of azoles with ARVs,see Drug-drug Interactions Between ARVs and Non-ARVs and Anti-infective/ART interaction table
Measurement of plasma concentration of itraconazole is advised to guide optimal treatment, and itraconazole oral suspension should be preferred due to better bioavailability. Serum itraconazole trough concentration should be at least 1 mcg/mL if measured by high-performance liquid chromatography (HPLC). If levels cannot be measured, consider alternative drugs.

	Drug / Dose	Comments
Severe disseminated histoplasmosis	Induction therapy: liposomal amphotericin B 3 mg/kg/day iv	For 2 weeks or until clinical improvement
Consolidation therapy: itraconazole 200 mg tid po for 3 days, then 200 mg bid po	For at least 12 months
Moderate disseminated histoplamosis	itraconazole 200 mg tid po for 3 days, then 200mg bid po	For at least 12 months
Histoplasma meningitis	Induction therapy: liposomal amphotericin B 5 mg/kg qd iv	For 4-6 weeks
Consolidation therapy: itraconazole 200 mg bid-tid po	For at least 12 months and until resolution of abnormal CSF findings

Drug / Dose

Comments

Severe disseminated histoplasmosis

Induction therapy:
liposomal amphotericin B
3 mg/kg/day iv

For 2 weeks or until clinical improvement

Consolidation therapy:
itraconazole
200 mg tid po for 3 days,
then 200 mg bid po

For at least 12 months

Moderate disseminated histoplamosis

itraconazole
200 mg tid po for 3 days,
then 200mg bid po

For at least 12 months

Histoplasma meningitis

Induction therapy:
liposomal amphotericin B
5 mg/kg qd iv

For 4-6 weeks

Consolidation therapy:
itraconazole
200 mg bid-tid po

For at least 12 months and until resolution of abnormal CSF findings

Secondary Prophylaxis / Maintenance Therapy

Stop: if CD4 count > 150 cells/μL and HIV-VL undetectable over 6 months, negative fungal blood cultures, histoplasma antigen < 2μg/L or neg PCR, if available, and > 1 year treatment

Consider long-term suppressive therapy in severe cases of meningitis and in cases of relapse despite adequate treatment

Drug / Dose
itraconazole 200 mg qd po

Drug / Dose

itraconazole
200 mg qd po