Histoplasmosis

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Histoplasmosis

• Cause and Treatment

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What is Histoplasmosis?

• Fungal Infection
• Caused by Histoplasma capsulatum
• Variety duboisii
• Occurs in Africa
• Not as severe of an infection
• Variety capsulatum
• Occurs in America
• Common cause of histoplasmosis

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Histoplasma capsulatum Infection

• Histoplasma capsulatum is a dimorphic fungi
• The concentration of Histoplasma capsulatum will
  often increase in bird and bat droppings
• Infection occurs when airborne spores enter a
  host organisms respiratory tract

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Risk of Infection

• Location
• Ohio river valley
• Throughout the US and South America
• Through Africa
• Profession/Hobby
• Dealing with avian livestock, zoos, or caves
• Immune System Disease
• More likely to be infected from other diseases
• Previous Lung Damage

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Progress of Infection

• Histoplasmosis first affects the lungs and can
  spread to other organs, including the brain
• Dormant Stage
• Acute Stage
• Chronic Stage
• Systemic Stage (Disseminated Histoplasmosis)

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Dormant Stage

• No symptoms exist
• Fungi survives in spore form within the lungs

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Acute Stage

• Characterized by short bursts of activity
• Symptoms
• Flu
• Lung Issues
• Cough
• Chest pain
• Inflammation of infected areas
• Fever
• Chills

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Chronic Stage

• Histoplasma capsulatum becomes established in the
  body
• The fungus goes through alternations of activity
  and dormancy
• Symptoms
• Increase in frequency of previous symptoms
• Shortness of breath
• Excessive sweating
• Liver infection or spleen infection

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Systemic Stage

• Occurs as the fungus reaches all parts of the
  host organism, including most organs and the
  central nervous system
• Symptoms
• Increase in frequency of previous symptoms
• Skin and mouth sores, including rashes
• Joint and muscle pain
• Headache
• Neck stiffness

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Detection

• Lung X-Ray
• Tissue Samples
• Blood, Bone Marrow, Skin
• Cultures
• Blood, Sputum
• Testing
• Antigen Testing
• CD4 Count

• Early Detection Saves Lives!

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Treatment

• Antifungal Medications
• Amphotericin B
• Azoles
• Fluconazole
• Itraconazole
• Ketonazole

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Amphotericin B Deoxycholate

• Discovered as a byproduct of a microorganism
• Administered by IV
• Toxic at low doses
• Low brain fluid penetration
• Broadly applied to fungal infections

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Forms of Amphotericin B

• Abelcet
• Amphotericin B Lipid Complex
• Bilayer membrane/drug complex
• Amphotec
• Liposomal Amphotericin B
• Vesicle/drug complex
• AmBisome
• Amphotericin B Colloidal Dispersion
• Cholesterol sulfate/drug complex

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Amphotericin B Mechanism

• Acts by forming clusters of drug molecules that
  form tunnels in ergosterol containing membranes
• These tunnels propagate unregulated movement of
  polar molecules out of the cell

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Fluconazole

• Diflucan
• High blood-brain barrier passage
• Has low reactivity
• Often leads to resistant forms of fungus

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Itraconazole

• Sporanox
• Highly effective
• But
• Passes into brain poorly
• Has antagonistic effect with amphotericin B
• Good drugs, but should be administered after
  amphotericin treatment

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Ketonazole

• Broad application towards fungus, but has not
  been used extensively
• Has a variety of side effects, but may be useful
  against resistant fungi

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Azole Mechanism

• Drugs based on azole ring skeleton
• Inhibits a cytochrome enzyme involved with the
  synthesis of ergosterol
• Cytochrome P450 14-alpha-demethylase

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Further Research

• History of drug design/discovery
• Detail of mechanism for azole-protein
  interactions
• Novel Treatments