Describe the bimorphic behavior exhibited by most pulmonary mycoses.
At room temperature, exist as molds (mycelia); at body temperature, exist as yeasts.
"Yeast in the heat, mold in the cold".
Who is susceptible to infection by pulmonary mycoses?
The immunocompromised at at greater risk, but these can cause illness in the immunocompetent!
Describe the natural setting and distribution of Histoplasma.
Found in rich, moist soil (with bird & bat feces) in the Mississippi and Ohio river valleys.
Distinguish a Histoplasma mold from a Blastomyces mold.
Both form branched hyphae, but histoplasma is multinucleate while blastomyces is uninucleate.
Which are more infectious, microconidia or macroconidia? Why?
What occurs upon inhalation of the infectious agent?
Microconidia--smaller, so better alveolar penetration.
Upon inhalation, microconidia are phagocytized (via CD2/18 antigens) and transform into yeasts.
Distinguish Histoplasma, Blastomyces, and Coccidiodes based on their appearance at body temperature.
Histoplasma forms yeast with narrow bud necks.
Blastomyces forms much larger yeast with broad bud necks.
Coccidioides forms spherules filled with endospores.
Describe the time progression of pulmonary infection in the three major mycoses
Histoplasma and Coccidiodes cause pulmonary illness about 1-3 weeks following exposure. Blastomyces takes about 4-6 weeks.
What are the pulmonary symptoms of histoplasmosis?
What does imaging reveal?
Non-specific flu-like syndrome.
Resembles miliary TB. Latent infection yields multiple calcified lesions & granulomas.
What complications can be seen in severe histoplasmosis?
Pericarditis, ocular fibrosis, and fibrosing mediastinitis (causes SVC syndrome, cor pulmonale, and mitral stenosis).
What are the treatment indications for Histoplasma?
Often, no treatment is necessary. Itraconazole can be given as an adjunct.
If severe/disseminated, give Itraconazole + Amphotericin B.
Describe the natural setting and distribution of Blastomyces.
Found in rich/moist and acidic soil along rivers. Prevalent in mississippi & Ohio river valleys (like Histo), but also around the Great Lakes.
How does primary Blastomyces infection occur?
What doesn't occur in the lung?
Inhalation of microconidia.
Unlike histo, Blasto microconidia do not require phagocytosis to transform. They form yeasts extracellularly, and are too large to be phagocytosed.
What are the most common clinical syndromes seen in Blastomycosis?
Flu-like pulmonary infection (usually benign & self-limiting, sometimes granulomatous)
Sometimes skin infection (primary or disseminated) yielding SubQ nodules or papules.
What are the treatment indications for Blastomyces?
Treat with Itraconazole; add Amphotericin B if severe/disseminated.
More aggressive therapy than with Histo?
Describe the natural setting and distribution of Coccidioides.
When are flares of infection seen?
Found in mineral-rich soils in hot & arid climates (San Joaquin valley).
Incidence highest in late summer & autumn (driest season). Spikes with storms, construction, or anything that can kick up the mold.
Describe the two morphs of Coccidioides.
Outside: Multicellular hyphae form barrel-shaped arthroconidia.
Inside: Spherules with endospores.
What special populations must be considered in evaluating Coccidioides infection?
Pregnant women, construction workers, agricultural workers, ranchers.
Note: Incidence higher in darker-skinned ethnicities.
What are the treatment indications (and CONTRAINDICATIONS) for Coccidioides?
Usually no antifungals necessary. If severe: Itraconazole + Amphotericin B.
Note: Azoles are TERATOGENIC
Which mycosis is often coincident with bronchogenic carcinoma, TB, and other severe pulmonary diseases?
Recall the mechanism of action of Itraconazole and Amphotericin B.
Itraconazole (and most azoles) block ergosterol synthesis from lanosterol by blocking 14a-demethylase.
Amphotericin B binds Ergosterol in the cell wall.