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Home , Coccidioidomycosis, Fungemia, Histoplasmosis, Sporotrichosis, Tinea capitis, Tinea corporis

Fungal

• 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 • AbiAerobic • Saphrophytic or parasitic • Cell wall contains glucan and chitin • Cell membrane contains ergosterol

Fungal cell structure Pathogenesis

• (unicellular, Toxins: produced, but not relevant to budding) human infections

Disease from: • (hyphae, mycelia, ) Bulk of organisms Immune response to them or their byproducts • Dimorphs (both)

MID 25 & 26 Overview of fungal infections

• Superficial or cutaneous (, , nails) • Subcutaneous • Systemic – “true ” 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 pedis Tinea unguum •

MID 25 & 26 Superficial fungal infections

Malassezia furfur: lipophilic (derives nourishment from skin lipids) Pathogenesis: lives on skin, causes pigment changes and underneath Diseases: • • Occasionally with lipid infusion

MID 25 & 26 Subcutaneous fungal : • Organism: Sporothrix schenkii – Dimorphic ( in environment, yeast in body) • Habitat: soil, worldwide • Pathogenesis: splinters or thorns inoculate organism into subcutaneous tissues

Subcutaneous fungal infections

• Pathogenesis: introduced through skin by foreign body, grow in subcutaneous tissues, spread via lymphatics • Disease; usual local; may disseminate to adjacent , . • Most common in nonindustrialized world (mycetoma of feet)

MID 25 & 26 Sporotrichosis

Pathophysiology: Clinical: • inoculated by • Gardeners and foreign body outdoorspersons • Yeasts travel along • Ulcerating nodules lymphatics along hard cord • Elicit mixed pyogenic- • and granulomatous destruction reaction • Dissemination rare

MID 25 & 26 Systemic fungal infections: the “true pathogens” , , • Dimorphic • RitRespiratory acqu iitiisition • Restricted geographic distribution • Infect normal hosts • Disease reminiscent of TB

Histoplasmosis Histoplasmosis

Organism: capsulatum Pathophysiology: Clinical: – Soil dimorph (yeast in body, mold in • Mold spores transform Mimics TB. Usually environment) into yeast in , elicit latent disease, but cellular as per Habitat: with high N content • may cause /chronic TB cavitary lung disease – Ohio-Mississippi valley; Caribbean; Central • Hematogenous and S. America • may disseminate after dissemination infection (infancy, – of , birds, poultry (chicken coops • Skin test reactivity immunocompromise) and caves • Walled off granulomata • may reactivate years later Pathogenesis: inhalation of spores

MID 25 & 26 MID 25 & 26 Coccidioidomycosis

Organism: immitis – Dimorph: mold in soil, spherules and endospores in

Habitat: lower Sonoral life zone (arid): Southwest US, , Central and

Pathogenesis: inhalation of spores

Cocci

Pathophysiology: Clinical: • Spores transform into • Acute self-limited flu-like spherules in lung, elicit seroconversion syndrome cellular immunity as per (“Valley ”) TB • Acute or chronic lung • Hematogenous disease dissemination • Dissemination • Skin test reactivity (pregnancy, dark skin, • Walled off immunocompromise) –Skin – Bone – CNS

MID 25 & 26 Blastomycosis

Organism: Blastomyces dermatiditis dimorph: mold to yeast Habitat: humid woodlands – MidAtlan tic zone – Beaver dams, peanut farms – Organic debris rather than soil Pathogenesis: inhalation of spores

MID 25 & 26 Blastomycosis

Pathophysiology: Clinical: • Spores transform into • Acute or chronic lung yeast in lung, disease disseminate ((y)nodular/cavitary) • No good test • Disseminated to define exposed disease: population –Skin – Bone – Urinary tract in men

MID 25 & 26 Systemic fungal infections: B. “the opportunists” Histo, Blasto, Cocci Opportunists • Geographic • Omnipresent distribution • Yeasts or molds • Dimorphic • Various routes of • Infection by inhalation infection • Pyogenic/- • Host response varies tous host response • Clinical syndromes • Similar to TB vary • Infection =~ immunity • No lasting immunity

Cryptococcosis

Organism: neoformans yeast with a thick polysaccharide capsule

Habitat: bioterrorists (of a sort), worldwide

Pathogenesis: inhalation of yeasts

MID 25 & 26

Pathophysiology: Clinical • Inhalation leads to • OR • Transient colonization • Meningoencephalitis OR • Acute or chronic • Acute/chronic lung • Fever, , stiff disease OR neck, fever, • CNS invasion • Hydrocephalus

MID 25 & 26 Cryptococcal

• India ink preparation of CSF may show organisms • Serum or CSF antigen assay diagnostic in >95% cases of CNS disease

Candidiasis

• Organism: albicans et al (yeasts with hyphal forms) • Habitat: normal human flora • PthPathogenesi s: – Colonized areas: change in environment leads to overgrowth – Noncolonized areas: change in immunity leads to invasion

MID 25 & 26 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)

MID 25 & 26 Pathogenesis of invasive Candida infections • Breach in anatomic integrity (often biofilm on catheter) • Defective PML function (first line of defense) – Myeloperoxidase, complement necessary but not sufficient defense – Cytokines also essential for recruiting phagocytes in disseminated disease – may or may not be present; may or may not be protective

Invasive

• 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

MID 25 & 26 “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 Pathophysiology Clinical identify Spores in lung may: • Allergic • Infection and – Elicit allergy bronchopulmonary colonization are – Grow in ppgreexisting asppgergillosis difficult to distinguish cavity • • Best treatment – Invade vasculature, • Invasive aspergillosis restores missing disseminate with local and distant disease with pneumonia, other defense – Neutrophils prime end-organ disease defenders

Aspergillosis

• Organism: fumigatus and others – Mold without a yeast phase

• Habitat: everywhere, worldwide

• Pathogenesis: inhalation of spores

MID 25 & 26

• Organism: species of , genera Rhizopus and Mucor (Zygomycetes) – Molds without a yeast phase

• Habitat: everywhere, worldwide

• Pathogenesis: inhalation of spores

MID 25 & 26 Mucormycosis

Pathophysiology: Clinical: Alveolar MPH/PML clear The most acute and organisms, BUT: fulminant fungal infection • Metabolic acidosis known • Dia be tes Lower airways: pneumonia • Neutrophil dysfunction progressing to infarction • Iron overload Upper airways: sinusitis progressing to brain May enable relentless growth

MID 25 & 26 Summary: Fungal “opportunism”

• Metabolic (, M. furfur, mucor) • Dimorphism (sporo, histo, blasto, cocci) • Cl(tCapsule (cryptococcus ) • Adherence (candida)

Summary: defenses

• Intact skin (dermatophytes, Candida) • Lymphocyte function (dimorphs, cryptococcus, candida) • Neu trophil func tion (can dida, asperg illus, mucor) • Body milieu (candida, mucor)

MID 25 & 26