Mycology 3: Systemic Dimorphs

Question 1

Common features of endemics:
What is environmental / infectious form?
What is pathogenic form?

Answer 1

• Environmental / infectious form is mold. Found in soil. Saprobic
• Pathogenic form in host is yeast (Hc and Bd) or endosporulating spherule (Coccidioides)

Question 2

Histoplasma capsulatum
Geography / environment
How common?
Method of infection
Morphology
Immune response

Answer 2

• Found in Mississippi and Ohio River valleys. Midwest / South. Associated w/ bird / bat guano (starlings, grackles, chickens, pigeons).
• Most common fungal respiratory infection in the world. Most common systemic mycosis in US.
• Spores are inhaled. Dimorphism is thermally regulated. Extracellular or intracellular parasite w/in macrophages.
• Mold – multinucleate branched hyphae, tuberculate macroconidia / microcondita.
• Yeast – Uninucleate oval yeast w/ narrow neck budding. Pathogenic. May be found extracellularly or intracellulartly. Grow at 37 degrees.
• CMI achieves fungistasis but not fungal eradication. Lifelong latent infection.

Question 3

Histoplasma diseases:
Immunocompetent?
What percentage of infections cause sxs?
Lung diseases?
Disseminated disease?
Diagnosis (2)
Treatment (severe, less severe, prophylaxis, suppression)

Answer 3

• Most immunocompetent individuals just get flu-like sxs (fatigue, fever, headache). Self limiting.
• Just 5% of infections cause sxs.
• Lung diseases
• Focal, nodular, diffuse, and cavitary lung diseases, especially in emphysema pxs.
• Granulomas may undergo central caseous necrosis and later calcification.
• Hematogenous dissemination to sites rich in macrophages (blood, bone marrow, liver, spleen, brain, etc). Nodular lesions on hands / tongue,
• Ocular sxs due to inflammatory response and neovascularization.
• Skin reaction test to histoplasmin: CMI / DTH. Not super useful b/c exposure is almost universal.
• Urine antigen test is better, indicating active infection.
• Calcified granulomas on CXR
• Tx – Amphotericin B (IV) is DOC for severe infections. Itraconazole (solution) is used for immunocompetent pxs, less severe disease, prophylaxis, and suppression for immunocompromised pxs.

Question 4

What is the most common endemic mycosis in AIDS pxs?

Answer 4

Histoplasma

Question 5

Blastomyces dermatitidis
Geography
Morphology / size
Disease
Diagnosis
Treatment (severe, less severe, immunocompetent, HIV)

Answer 5

• Eagle River (beaver dams), Mississippi / Ohio river valleys, northern Midwest (MN / WI)
• Organisms are larger than Histo but smaller than Coccidioides. Larger than WBCs. Broad based budding. Possible to see Blasto in sputum (not Histo).
• Main disease is in lungs (pneumonia). Most common disseminates sites are skin, bone, and urogenital tract.
• Diagnosis – antigen test, but there is cross-reactivity for Histo
• Calcofluor white (fluorescent stain) in sputum or BAL (better).
• Tx – Amphotericin B (IV) is DOC for severe infections. Itraconazole (solution) is used for immunocompetent pxs and less severe disease in immunocompromised. Incidence is not high enough to warrant prophylaxis in HIV pxs.

Question 6

Coccidioides
Which 2 species?  Where are they found?
What time of year is infection most common?
Morphology
How often does infection cause sxs?
Symptoms
Risk Factors
Treatment

Answer 6

• C immitis found in California. C posadasii found outside of California
• Incidence is highest in late summer fall w/ dusty conditions
• Environmental / infectious form – Mold. Barrel-shaped hyphae (arthroconidia) w/ alternating nonviable “disjunctor cells”, which break to release arthroconidia, which are inhaled.
• Pathogenic form in host – Endosporulating spherule. VERY large
• Infection is asymptomatic in 50-70% of cases. Symptomatic in 30-50% of cases
• Pulmonary infection (99.5% of cases). May range from flu-like sxs to pneumonia.
• CXR shows consolidation, hilar lymphadenopathy, “egg shell cavities”, or pulmonary nodules.
• 50% of symptomatic pxs have maculopapular rash due to hypersensitivity rxn (NOT fungal spread). Erythema nodosum / erythema multiforme.
• Disseminated infection - Rare. Skin is most commonly affected organ, but can occur anywhere.
• Risk factors – Males, pregnant females, young / old, Filipino, AA, Mexican, Native American, immunocompromise.
• Treatment is difficult. Amphotericin B, fluconazole, and itraconazole are only partially effective

Question 7

2 general methods of diagnosis for endemics

What are the downsides of each?

Answer 7

• Culture is gold standard, but it may have low sensitivity and be slow
• Serological Ab tests are available for all 3 diseases, however sensitivity may be low in immunocompromised pxs (no humoral response).

Question 8

General treatment for endemics:
Mild disease, immunocompetent, prophylaxis
Severe diseases / immunocompromised

Answer 8

• Mild disease, immunocompetent, prophylaxis – Itraconazole

* Severe disease / immunocompromised – Amphotericin B (IV)