Histoplasmosis Flashcards
What is histoplasmosis?
A fungal infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum)
Where is histoplasmosis endemic?
Central and south-central United States, especially in the Ohio and Mississippi River valleys
What is the association between CD4 T lymphocyte count and histoplasmosis in people with HIV?
A CD4 count <150 cells/mm3 is associated with an increased risk of symptomatic illness
How is histoplasmosis acquired?
By the inhalation of microconidia that form in the mycelial phase of the fungus
What are common clinical manifestations of progressive disseminated histoplasmosis in people with advanced HIV?
Fever, fatigue, weight loss, hepatosplenomegaly, cough, and dyspnea
What gastrointestinal symptoms are associated with histoplasmosis?
Fever, nausea and vomiting, diarrhea, abdominal pain, and weight loss
What is the preferred method for diagnosing disseminated histoplasmosis in people with HIV?
Detection of Histoplasma antigen in blood or urine
What percentage of urine samples from people with AIDS and disseminated histoplasmosis tested positive for Histoplasma antigen in a study?
100%
What are the usual cerebrospinal fluid findings for Histoplasma meningitis?
Lymphocytic pleocytosis, elevated protein, and low glucose
What activities should individuals with HIV and low CD4 counts minimize to reduce the risk of histoplasmosis?
Creating dust, cleaning chicken coops, disturbing bird/bat droppings, remodeling buildings, exploring caves
What is the preferred therapy for primary prophylaxis of histoplasmosis in high-risk individuals?
Itraconazole 200 mg PO once daily
What are the criteria for discontinuing primary prophylaxis for histoplasmosis?
- Stable ART
- CD4 count ≥150 cells/mm3 for 6 months
- Undetectable HIV-1 viral load
What is the preferred therapy for induction treatment of severe disseminated histoplasmosis?
Liposomal amphotericin B 3 mg/kg IV daily
What is the maintenance therapy for severe disseminated histoplasmosis?
Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO two times a day
What is the preferred therapy for treating histoplasma meningitis?
Liposomal amphotericin B 5 mg/kg IV daily
What are the criteria for discontinuing long-term suppressive therapy for histoplasmosis?
- Receipt of azole treatment for >1 year
- Negative fungal blood cultures
- Serum or urine Histoplasma antigen below quantification
- Undetectable HIV viral load on stable ART
- CD4 count ≥150 cells/mm3 and on ART for ≥6 months
What should be measured in patients receiving itraconazole therapy after 2 weeks?
Random itraconazole serum concentrations
What is the preferred initial regimen for treating histoplasmosis in pregnant patients?
Amphotericin B or its lipid formulations
True or False: Azole antifungals should be avoided during the first trimester of pregnancy.
True
Fill in the blank: The preferred therapy for maintenance treatment of histoplasma meningitis is _______.
Itraconazole 200 mg PO two or three times a day
What is the indication for restarting primary prophylaxis for histoplasmosis?
CD4 count <150 cells/mm3
What is the alternative therapy for maintenance treatment in patients who cannot tolerate itraconazole?
- Voriconazole 400 mg PO twice daily for 1 day, then 200 mg PO twice daily
- Fluconazole 800 mg PO once daily
What is the recommended dose of intravenous liposomal amphotericin B for treating severe disseminated histoplasmosis?
3 mg/kg daily for ≥2 weeks or until clinical improvement.
This treatment is recommended for patients with symptomatic severe disseminated histoplasmosis.
What should be done if a patient cannot tolerate liposomal amphotericin B?
IV amphotericin B lipid complex at 5 mg/kg daily can be used.
This is an alternative if cost is a concern.
What is the step-down therapy for patients after intravenous treatment for histoplasmosis?
Oral itraconazole, 200 mg three times a day for 3 days, followed by 200 mg two times a day for ≥12 months.
This is recommended for ongoing treatment after initial therapy.
Why should serum concentrations of itraconazole be monitored?
To check for erratic absorption and potential drug interactions.
It is important due to interactions with CYP3A4 inducers or inhibitors.
What is the preferred formulation of itraconazole for better absorption?
The liquid formulation, taken on an empty stomach.
It does not require gastric acid for absorption.
In patients with acute pulmonary histoplasmosis and CD4 count <300 cells/mm3, what therapy should be administered?
Therapy similar to that of mild-to-moderate disseminated disease.
This is to ensure adequate treatment for compromised immune systems.
What is the initial therapy for confirmed meningitis caused by histoplasmosis?
Liposomal amphotericin B at a dose of 5 mg/kg IV daily for 4 to 6 weeks.
This treatment duration depends on symptom resolution.
How long should maintenance therapy with oral itraconazole be continued after initial IV therapy for meningitis?
For ≥12 months.
Dose adjustments may be necessary based on ART interactions.
What is the alternative to itraconazole for Histoplasma meningitis?
Voriconazole.
This is recommended if itraconazole is not tolerated.
What should be monitored when using oral voriconazole?
Trough serum concentrations after 5 days of therapy.
The goal is to achieve a serum concentration of 1 to 5 µg/mL.
Is fluconazole effective for treating histoplasmosis?
Less effective than itraconazole, but moderately effective at 800 mg daily.
It can be considered when other treatments are not suitable.
How should antigen levels be monitored during histoplasmosis therapy?
Check monthly for the first 3 months, then every 3–4 months until negative.
A rise in antigen levels may indicate relapse.
When should ART be started for people with HIV diagnosed with histoplasmosis?
As soon as possible after initiating antifungal therapy.
This is crucial to prevent complications like IRIS.
What is the preferred antifungal treatment for pregnant patients with histoplasmosis?
Amphotericin B or its lipid formulations.
They are preferred especially during the first trimester.
What potential risks are associated with itraconazole during pregnancy?
Embryotoxic and teratogenic effects in rodents.
Major skeletal defects and encephaloceles have been observed.
What is the recommendation for using fluconazole during the first trimester of pregnancy?
Should generally be avoided.
Higher doses have been associated with increased risk of congenital malformations.
What should be done if a patient has a CD4 count <150 cells/mm3 after discontinuing suppressive therapy?
Suppressive therapy should be resumed.
This is important to prevent relapse.
What are the common adverse reactions associated with itraconazole?
Worsening heart failure, adrenal insufficiency, and transaminitis.
These are serious side effects that require monitoring.
