Histoplasmosis

Question 1

What is histoplasmosis?

Answer 1

A fungal infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum)

Question 2

Where is histoplasmosis endemic?

Answer 2

Central and south-central United States, especially in the Ohio and Mississippi River valleys

Question 3

What is the association between CD4 T lymphocyte count and histoplasmosis in people with HIV?

Answer 3

A CD4 count <150 cells/mm3 is associated with an increased risk of symptomatic illness

Question 4

How is histoplasmosis acquired?

Answer 4

By the inhalation of microconidia that form in the mycelial phase of the fungus

Question 5

What are common clinical manifestations of progressive disseminated histoplasmosis in people with advanced HIV?

Answer 5

Fever, fatigue, weight loss, hepatosplenomegaly, cough, and dyspnea

Question 6

What gastrointestinal symptoms are associated with histoplasmosis?

Answer 6

Fever, nausea and vomiting, diarrhea, abdominal pain, and weight loss

Question 7

What is the preferred method for diagnosing disseminated histoplasmosis in people with HIV?

Answer 7

Detection of Histoplasma antigen in blood or urine

Question 8

What percentage of urine samples from people with AIDS and disseminated histoplasmosis tested positive for Histoplasma antigen in a study?

Answer 8

100%

Question 9

What are the usual cerebrospinal fluid findings for Histoplasma meningitis?

Answer 9

Lymphocytic pleocytosis, elevated protein, and low glucose

Question 10

What activities should individuals with HIV and low CD4 counts minimize to reduce the risk of histoplasmosis?

Answer 10

Creating dust, cleaning chicken coops, disturbing bird/bat droppings, remodeling buildings, exploring caves

Question 11

What is the preferred therapy for primary prophylaxis of histoplasmosis in high-risk individuals?

Answer 11

Itraconazole 200 mg PO once daily

Question 12

What are the criteria for discontinuing primary prophylaxis for histoplasmosis?

Answer 12

• Stable ART
• CD4 count ≥150 cells/mm3 for 6 months
• Undetectable HIV-1 viral load

Question 13

What is the preferred therapy for induction treatment of severe disseminated histoplasmosis?

Answer 13

Liposomal amphotericin B 3 mg/kg IV daily

Question 14

What is the maintenance therapy for severe disseminated histoplasmosis?

Answer 14

Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO two times a day

Question 15

What is the preferred therapy for treating histoplasma meningitis?

Answer 15

Liposomal amphotericin B 5 mg/kg IV daily

Question 16

What are the criteria for discontinuing long-term suppressive therapy for histoplasmosis?

Answer 16

• 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

Question 17

What should be measured in patients receiving itraconazole therapy after 2 weeks?

Answer 17

Random itraconazole serum concentrations

Question 18

What is the preferred initial regimen for treating histoplasmosis in pregnant patients?

Answer 18

Amphotericin B or its lipid formulations

Question 19

True or False: Azole antifungals should be avoided during the first trimester of pregnancy.

Answer 19

True

Question 20

Fill in the blank: The preferred therapy for maintenance treatment of histoplasma meningitis is _______.

Answer 20

Itraconazole 200 mg PO two or three times a day

Question 21

What is the indication for restarting primary prophylaxis for histoplasmosis?

Answer 21

CD4 count <150 cells/mm3

Question 22

What is the alternative therapy for maintenance treatment in patients who cannot tolerate itraconazole?

Answer 22

• Voriconazole 400 mg PO twice daily for 1 day, then 200 mg PO twice daily
• Fluconazole 800 mg PO once daily

Question 23

What is the recommended dose of intravenous liposomal amphotericin B for treating severe disseminated histoplasmosis?

Answer 23

3 mg/kg daily for ≥2 weeks or until clinical improvement.

This treatment is recommended for patients with symptomatic severe disseminated histoplasmosis.

Question 24

What should be done if a patient cannot tolerate liposomal amphotericin B?

Answer 24

IV amphotericin B lipid complex at 5 mg/kg daily can be used.

This is an alternative if cost is a concern.

Question 25

What is the step-down therapy for patients after intravenous treatment for histoplasmosis?

Answer 25

Oral itraconazole, 200 mg three times a day for 3 days, followed by 200 mg two times a day for ≥12 months. ## Footnote This is recommended for ongoing treatment after initial therapy.

Question 26

Why should serum concentrations of itraconazole be monitored?

Answer 26

To check for erratic absorption and potential drug interactions. ## Footnote It is important due to interactions with CYP3A4 inducers or inhibitors.

Question 27

What is the preferred formulation of itraconazole for better absorption?

Answer 27

The liquid formulation, taken on an empty stomach. ## Footnote It does not require gastric acid for absorption.

Question 28

In patients with acute pulmonary histoplasmosis and CD4 count <300 cells/mm3, what therapy should be administered?

Answer 28

Therapy similar to that of mild-to-moderate disseminated disease. ## Footnote This is to ensure adequate treatment for compromised immune systems.

Question 29

What is the initial therapy for confirmed meningitis caused by histoplasmosis?

Answer 29

Liposomal amphotericin B at a dose of 5 mg/kg IV daily for 4 to 6 weeks. ## Footnote This treatment duration depends on symptom resolution.

Question 30

How long should maintenance therapy with oral itraconazole be continued after initial IV therapy for meningitis?

Answer 30

For ≥12 months. ## Footnote Dose adjustments may be necessary based on ART interactions.

Question 31

What is the alternative to itraconazole for Histoplasma meningitis?

Answer 31

Voriconazole. ## Footnote This is recommended if itraconazole is not tolerated.

Question 32

What should be monitored when using oral voriconazole?

Answer 32

Trough serum concentrations after 5 days of therapy. ## Footnote The goal is to achieve a serum concentration of 1 to 5 µg/mL.

Question 33

Is fluconazole effective for treating histoplasmosis?

Answer 33

Less effective than itraconazole, but moderately effective at 800 mg daily. ## Footnote It can be considered when other treatments are not suitable.

Question 34

How should antigen levels be monitored during histoplasmosis therapy?

Answer 34

Check monthly for the first 3 months, then every 3–4 months until negative. ## Footnote A rise in antigen levels may indicate relapse.

Question 35

When should ART be started for people with HIV diagnosed with histoplasmosis?

Answer 35

As soon as possible after initiating antifungal therapy. ## Footnote This is crucial to prevent complications like IRIS.

Question 36

What is the preferred antifungal treatment for pregnant patients with histoplasmosis?

Answer 36

Amphotericin B or its lipid formulations. ## Footnote They are preferred especially during the first trimester.

Question 37

What potential risks are associated with itraconazole during pregnancy?

Answer 37

Embryotoxic and teratogenic effects in rodents. ## Footnote Major skeletal defects and encephaloceles have been observed.

Question 38

What is the recommendation for using fluconazole during the first trimester of pregnancy?

Answer 38

Should generally be avoided. ## Footnote Higher doses have been associated with increased risk of congenital malformations.

Question 39

What should be done if a patient has a CD4 count <150 cells/mm3 after discontinuing suppressive therapy?

Answer 39

Suppressive therapy should be resumed. ## Footnote This is important to prevent relapse.

Question 40

What are the common adverse reactions associated with itraconazole?

Answer 40

Worsening heart failure, adrenal insufficiency, and transaminitis. ## Footnote These are serious side effects that require monitoring.