Treatment Options for Common Fungal Infections and Fungal Sinusitis
Fungal Infections - Columbia University · 1 Fungal Infections • Once exotic and rare; now...
Transcript of Fungal Infections - Columbia University · 1 Fungal Infections • Once exotic and rare; now...
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Fungal Infections• Once exotic and rare; now increasingly common
• Fungi are not “virulent”
• But they are good at taking advantage
• “Opportunistic” in many senses
Fungal biology
• Eukaryotic (organized nucleus and cell structure)
• Non-motile• Aerobic• Saphrophytic or parasitic• Cell wall contains glucan and chitin• Cell membrane contains ergosterol
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Fungal cell structure
• Yeasts (unicellular, budding)
• Molds (hyphae, mycelia, spores)
• Dimorphs (both)
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Pathogenesis
Toxins: produced, but not relevant to human infections
Disease from:Bulk of organismsImmune response to them or their byproducts
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Overview of fungal infections
• Superficial or cutaneous (skin, hair, nails)• Subcutaneous• Systemic
– “true pathogens” may cause disease in normal hosts although worse with immunocompromise
– “opportunists” cause disease almost exclusively in immunocompromised hosts
Superficial fungal infections
Dermatophytes: molds producing keratinase
Pathogenesis: grow as saprophytes on skin/nails; cause inflammation below
Clinical:• Tinea corporis Tinea cruris• Tinea pedis Tinea unguum• Tinea capitis
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Superficial fungal infections
Malassezia furfur: lipophilic yeast (derives nourishment from skin lipids)
Pathogenesis: lives on skin, causes pigment changes and itch underneath
Diseases:• Tinea versicolor• Occasionally fungemia with lipid infusion
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Subcutaneous fungal infections
• Pathogenesis: introduced through skin by foreign body, grow in subcutaneous tissues, spread via lymphatics
• Disease; usual local; may disseminate to adjacent bones, joints.
• Most common in nonindustrialized world (mycetoma of feet)
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Subcutaneous fungal infection: Sporotrichosis
• Organism: Sporothrix schenkii– Dimorphic soil fungus (mold in environment,
yeast in body)• Habitat: soil, worldwide• Pathogenesis: splinters or thorns
inoculate organism into subcutaneous tissues
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Sporotrichosis
Pathophysiology:• Spore inoculated by
foreign body• Yeasts travel along
lymphatics• Elicit mixed pyogenic-
granulomatousreaction
Clinical:• Gardeners and
outdoorspersons• Ulcerating nodules
along hard cord• Bone and joint
destruction• Dissemination rare
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Systemic fungal infections:the “true pathogens”
Histoplasmosis, Coccidioidomycosis, Blastomycosis
• Dimorphic• Respiratory acquisition• Restricted geographic distribution• Infect normal hosts• Disease reminiscent of TB
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Histoplasmosis
Organism: Histoplasma capsulatum– Soil dimorph (yeast in body, mold in
environment)Habitat: soils with high N content
– Ohio-Mississippi valley; Caribbean; Central and S. America
– Guano of bats, birds, poultry (chicken coops and caves
Pathogenesis: inhalation of spores
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HistoplasmosisPathophysiology:• Mold spores transform
into yeast in lung, elicit cellular immunity as per TB
• Hematogenousdissemination
• Skin test reactivity• Walled off granulomata
Clinical:Mimics TB. Usuallylatent disease, but• may cause acute/chronic
cavitary lung disease• may disseminate after
infection (infancy, immunocompromise)
• may reactivate years later
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Coccidioidomycosis
Organism: Coccidioides immitis– Dimorph: mold in soil, spherules and
endospores in host
Habitat: lower Sonoral life zone (arid): Southwest US, Mexico, Central and South America
Pathogenesis: inhalation of spores
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CocciPathophysiology:• Spores transform into
spherules in lung, elicit cellular immunity as per TB
• Hematogenousdissemination
• Skin test reactivity • Walled off granulomas
Clinical:• Acute self-limited flu-like
seroconversion syndrome (“Valley fever”)
• Acute or chronic lung disease
• Dissemination (pregnancy, dark skin, immunocompromise)– Skin– Bone– CNS
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Blastomycosis
Organism: Blastomyces dermatiditisdimorph: mold to yeast
Habitat: humid woodlands– MidAtlantic zone– Beaver dams, peanut farms– Organic debris rather than soil
Pathogenesis: inhalation of spores
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Blastomycosis
Pathophysiology:• Spores transform into
yeast in lung, disseminate
• No good antigen test to define exposed population
Clinical:• Acute or chronic lung
disease (nodular/cavitary)
• Disseminated disease:– Skin– Bone– Urinary tract in men
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Systemic fungal infections: B. “the opportunists”
Histo, Blasto, Cocci• Geographic
distribution• Dimorphic• Infection by inhalation• Pyogenic/granuloma-
tous host response• Similar to TB• Infection =~ immunity
Opportunists• Omnipresent• Yeasts or molds• Various routes of
infection• Host response varies• Clinical syndromes
vary• No lasting immunity
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Cryptococcosis
Organism: Cryptococcus neoformansyeast with a thick polysaccharide capsule
Habitat: bioterrorists (of a sort), worldwide
Pathogenesis: inhalation of yeasts
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Cryptococcosis
Pathophysiology:• Inhalation leads to • Transient colonization
OR• Acute/chronic lung
disease OR• CNS invasion
Clinical• Pneumonia OR• Meningoencephalitis• Acute or chronic• Fever, headache, stiff
neck, fever, delirium• Hydrocephalus
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Cryptococcal meningitis
• India ink preparation of CSF may show organisms
• Serum or CSF antigen assay diagnostic in >95% cases of CNS disease
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Candidiasis
• Organism: Candida albicans et al (yeasts with hyphal forms)
• Habitat: normal human flora• Pathogenesis:
– Colonized areas: change in environment leads to overgrowth
– Noncolonized areas: change in immunity leads to invasion
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Pathogenesis of Candida infections
• Primary host defenses:– Intact skin– Intact mucosa with normal pH and normal
flora– Functioning lymphocytes– Functioning neutrophils
Pathogenesis of local Candida infections
• Environmental changes – Wet skin– Changes in local flora– Hormones, foreign bodies
• Lymphocyte dysfunction– Immaturity– Destruction (HIV)
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Pathogenesis of invasive Candida infections
• Breach in anatomic integrity (often biofilmon catheter)
• Defective PML function (first line of defense)– Myeloperoxidase, complement necessary but
not sufficient defense– Cytokines also essential for recruiting
phagocytes in disseminated disease– Antibody may or may not be present; may or
may not be protective
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Invasive candidiasis
• Usually in critically ill patients with multiple risks (hospitalized, neutropenic, on antibiotics, many catheters)
• Fever, leukocytosis, organ dysfunction• Microabscesses in kidney, liver, skin, eye,
lung, heart• Candida endocarditis
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“Virulence” of Candida?
• Inherent “virulence”– environmental tolerance– Secrete hydrolases, beta proteases,
phospholipases– Can adhere to plastic– Can invade GI, renal epithelium
• Additional hyphal virulence– Protects against phagocytosis– Knockout strains
Additional comments on candidiasis
• Gram stain may help identify
• Infection and colonization are difficult to distinguish
• Best treatment restores missing defense
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Aspergillosis
• Organism: Aspergillus fumigatus and others– Mold without a yeast phase
• Habitat: everywhere, worldwide
• Pathogenesis: inhalation of spores
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Aspergillosis
PathophysiologySpores in lung may:
– Elicit allergy– Grow in preexisting
cavity– Invade vasculature,
disseminate with local and distant disease
– Neutrophils prime defenders
Clinical• Allergic
bronchopulmonaryaspergillosis
• Aspergilloma• Invasive aspergillosis
with pneumonia, other end-organ disease
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Mucormycosis
• Organism: species of Mucorales, genera Rhizopus and Mucor (Zygomycetes)– Molds without a yeast phase
• Habitat: everywhere, worldwide
• Pathogenesis: inhalation of spores
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MucormycosisPathophysiology:Alveolar MPH/PML clear
organisms, BUT:• Metabolic acidosis• Diabetes• Neutrophil dysfunction• Iron overloadMay enable relentless
growth
Clinical:The most acute and
fulminant fungal infection known
Lower airways: pneumonia progressing to infarction
Upper airways: sinusitis progressing to brain abscess
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Summary: Fungal “opportunism”
• Metabolic (dermatophytes, M. furfur, mucor)
• Dimorphism (sporo, histo, blasto, cocci)• Capsule (cryptococcus)• Adherence (candida)
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Summary: antifungal defenses
• Intact skin (dermatophytes, Candida)• Lymphocyte function (dimorphs,
cryptococcus, candida)• Neutrophil function (candida, aspergillus,
mucor)• Body milieu (candida, mucor)