Fungus Flashcards

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Fungus Characteristics

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Eukaryotic
Membrane-Bound Organelles
Mitochondria
Nucleus

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Fungal Cell Wall

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Polysaccharides/Peptides:
Chitin
1,3-β-Glucans & 1,6-β-Glucans
Mannan
NOTE: “Galactomannan = Aspergillus”

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Fungal Cell Membrane

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Ergosterol
1,3-β-Glucans

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4 Classes of Fungi
That cause infection in humans

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Zygomycetes
Basidiomycetes
Ascomycetes
Deuteromycetes
“Zee BAD Mothers…”

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Dimorphism

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Most common:
Yeast in humans, Hyphae in environment

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Hyphae Types

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Branching:
Dichotomous (Y-Shaped, Aspergillus)
Right-Angle (T-Shaped)
Septate/Non-Septate:
Septate (Aspergillus)
Non-Septate (Zygomycetes)
Pseudohyphae?

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Microscopic form of Candida

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Appears as:
YEAST, PSEUDOHYPHAE, HYPHAE
(the ONLY one that appears as all 3 at once)
NOTE: If “GERM TUBE +”, then C. Albicans

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Microscopic form of Malassezia Furfur

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Appears as:
Spaghetti and Meatballs

Causes: Tinea Versicolor

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Microscopic form of Aspergillus

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Appears as:
Septate Hyphae with Branching (Y)

Treat with: Voriconazole

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Classic Dimorphic Fungi

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Blastomyces (Large Yeast)
Coccidio (Spherules in vivo)
Paracoccidio (Yeast Aggregates)
Histoplasma (Typical)
Penicillium
Sporothrix (Typical)

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Endemic Dimorphic Fungi

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Blastomyces (SE U.S., Miss. River Basin)
Coccidio (SW U.S.)
Histo (Mississippi River Basin)

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Capsules

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ONLY seen with Cryptococcus Neoformans
Composed of: Glucuronoxylomannan

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Fungal Receptors on Host Cells

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There are MANY
TLR2/TLR4 are MOST important
Initiate NF-κB sequence

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Receptor Polymorphisms

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TLR4 = ↑ Aspergillus/Candida Infection
MBL = ↑ Candida Infection
Dectin-1 = ↑ Candida Infection

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Septation by Fungi Class

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Zygomycetes = Few to No Septa
Ascomycetes = Simple Septa

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Conidia/Sporangiospores

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Fungal “buds” that are inhaled. Usually not a problem unless immunocompromised.
Conidia = Aspergillus
Sporangiospores = Zygomycetes

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Fungal Spread

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Typically only effective against compromised hosts
Variable clinical phenotype
Almost never human-human transmission

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Fungi that form ONLY Yeast in Tissue:

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Cryptococcus
Histoplasma
Blastomycetes
Sporothrix

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Fungi that form Yeast AND Hyphae in vivo:

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Candida
Malassezia

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Fungi that form ONLY Hyphae in vivo:

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Aspergillus
Zygomycetes
Dermatophytes

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Fungi that form Spherules in vivo:

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Coccidioides

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Dermatophytes

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Microsporum (Multi-Septal, Macro-Conidia)
Epidermophyton
Trichophyton (Delicate Hyphae w/ micro-conidia)

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Staining Techniques

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H&E: Differentiates immune response
Not sensitive for Fungi
PAS: Stains cell wall of Fungi
GM Silver: Stains cell wall even better than PAS

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Levels of Fungal Infection w/in the body

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Superficial (tine versicolor)
Mucocutaneous (dermatophytosis)
Subcutaneous (sporotrichosis, chromoblasto, etc.)
Deep Mycoses (Candidiasis, Aspergillosis)

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Subcutaneous Mycoses

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Chromoblastomycosis
Mycetoma (infect muscle, tendon, bone)
Sporotrichosis (rose thorns)

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Deep Mycoses

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Opportunistic:
Candidiasis
Apergillosis
Zygomycosis

Pathogenic:
Histoplasmosis

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Distinguish b/w Budding Yeasts in vivo

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Crypto = CAPSULE
Blasto = BIG yeast
Histo = Normal yeast

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Drugs Targeting Ergosterol

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Polyenes (AmB, Nystatin)
Azoles (target 14-Demethylase)
Allylamines (target squalene epoxidase)

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Topical Azoles

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Clotrimazole
Miconazole

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Fluconazole

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EXCEPTION to the rules:
Renally Excreted
Not broad spectrum (Candida, Crypto)

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Voriconazole

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Aspergillus infection

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Echinocandins

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Target synthesis of 1,3-β-Glucans
Any drug that ends in “fungin” is an echinocandin
Work against: CANDIDA & ASPERGILLUS

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5-Fluourocytosine (5-FC)

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Targets CRYPTOCOCCUS
Can cross the BBB
Used w/ AmB
Is taken up by fungus and converted to a metabolite that inhibits DNA Synthesis (chemo)

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Superficial Mycoses

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Fungal Infections of:
Stratum Corneum
Do NOT elicit host-response, non-symptomatic except for color change of skin

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Cutaneous Mycoses

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Fungal Infection of:
Epidermis/Dermis
Elicit inflammatory reaction by host. (eg. Ringworm/dermatophytoses)

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Dermatophyte Infection by Body Region

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Tinea Capitis - Head
Tinea Barbae - Beard
Tinea Corporus - Body
Tinea Cruris - Groin
Tinea Pedis - Feet
Tinea Unguium/Onychomycosis – Nails
Tinea Manuum - Hand

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Human-Human Transmissible Fungi
(EXCEPTIONS!)

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Dermatophytes (as in wrestling, babies being cradled, etc.)
Penile/Vaginal Candidiasis (you know how… dirty)

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Dermatophyte Classes

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Anthrophilic = Live in humans (T. Tonsurans)
Zoophilic = Live in animals (M. Canis)
Geophilic = Live in soil (M. Gypseum)

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Hair Follicle Invasion Styles

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Ectothrix = Fungus attacks hair AT the level of the skin. Lumberjack model
(M. Canus, M. Gypseum, T. Equinum)
Endothrix = Fungus goes INTO follicle and grows back up INSIDE hair shaft. Much more devastating
(T. Tonsurans)

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Infection Areas of the body by Dermatophyte Genus

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Trycophoton = Infects EVERYTHING
Microsporum = Everything EXCEPT NAILS
Epidermophyton (floccosum) = GROIN

Dermatophyte Genera = M, E, T

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Tinea Capitis

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Mostly in babies and children
Hispanic/AA most common
T. Tonsurans in U.S., M. Canis worldwide
EXCEPTION: Treated w/ Systemic Anti-Fungals as well as Topical Shampoo and object disinfection

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Tinea Capitis Diagnosis

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Diagnosis made by culture and KOH/Calcofluor staining

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Treatment of Dermatophytoses
(EXCEPT Tinea Capitis)

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TOPICAL THERAPY:
Miconazole, Clotrimazole, Terbinafine

Oral medication may be used if infection is severe or resistant

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Onychomycosis

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Infection of Nail/Nail Bed
Caused by: T. Rubrum, T. Mentagrophytes, T. Tonsurans

Causes Pain and Paronychia

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Types of Onychomycosis
(Tinea Unguium)

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DSO = Distal to Proximal progression
Most common type
PSO = Prox. To distal progression
Early indicator of AIDS
WSO = Stays on dorsal aspect of nail
T. Mentagrophytes

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Onychomycosis Treatment

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Terbinafine
Itraconazole

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Tinea Versicolor

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Caused by Malassezia Furfur
Usually in upper trunk, neck, arms

Infection resides in stratum corneum of skin
Spaghetti and meatballs on histology

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Opportunistic Mycoses

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Infections in Immunocompromised Hosts:
Hosts have altered CMI (T-Cell Function)
Prone to: Mucocutaneous Candidiasis, Crypto, Pneumocystosis
Altered Mφ Function
Invasive Candidiasis, Aspergillosis, Zygomycosis

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Pathogenic/Deep/Systemic Mycoses

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Infections Can Occur in Normal Hosts:
Histo, Blasto, Coccidio
“Mr. Fungus COCKs his gun and BLASTs and HITs Lung, Meninges, Bone, and Organs

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Candidiasis

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Opportunistic
C. Albicans is most virulent species
Mucocutaneous Examples
Oral Thrush, Onychomychosis, Vaginal Candidiasis
Deeply Invasive Examples
Candidemia, Endocarditis, Renal Candidiasis

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Mucocutaneous v. Invasive Candidiasis
Risk Factor Comparison

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Mucocutaneous:
Underlying Disease, Steroid Use, Age, Pregnancy, Antibacterial Use

Invasive:
Trauma/Catheters, Neutropenia (chemo), Transplantation, Surgery, Hemodialysis

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Chronic Mucocutaneous Candidiasis
(APECED)

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INHERITED disorder which results in susceptibility to Candidiasis
Resistant infection of oropharynx, digits, face

May also see:
Endocrinopathy (Hypoparathyroid, T1-DM, Hypothyroid, etc.)

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Mucocutaneous v. Invasive Candidiasis
Treatment Comparison

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Mucocutaneous:
Topical Azoles (clotrim-, micon-)
Nystatin, Oral Fluconazole
IV echinocandin in severe cases

Invasive:
Fluconazole
Echinocandins
AmB Formulations

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Invasive Candidiasis:
Pathogenesis

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Adherence and Colonization of Host
Penetration through mucosa via trauma or catheter, etc.
Dissemination through blood
Replication in tissues

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Candida Endophthalmitis

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Candida Infection of the eye
Seen as white spots in the retina

NOTE: ESPECIALLY dangerous when involving Macula

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Invasive Aspergillus:
Radiologic Signs

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Halo Sign in lungs
Granuloma w/ poorly demarcated borders
Air Crescent Sign

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Invasive Aspergillus:
Treatment

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Voriconazole
Liposomal AmB

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Mucormycosis
(Zygomycosis)

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Opportunistic
Rhizopus most common
ESPECIALLY seen in diabetes patients

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Rhinocerebral Zygomycosis

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Inhaled spores lodge in paranasal sinuses
Invade tissues through membrane/bone
Track along ocular muscles/nerves to brain, cranial nerves, ICA, etc!
Very deadly and dangerous for brain

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Mucormycosis Appearance

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WIDE, Ribbon-Like
NON-Septate Hyphae
Right-Angle Branching
Invades blood vessel walls and nerves

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Invasive Zygomycosis:
Treatment

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AmB (all kinds)

Possibly with Surgery and stimulation of Host Defenses

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Cryptococcus Neoformans

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Opportunistic
ENCAPSULATED YEAST
Neurotrophic

Can present in: Lungs/CNS/Diffuse

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Cryptococcus:
At Risk Hosts

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T-Cell Compromised Patients
High Dose Corticosteroids
Organ Transplant Recipients
HIV+ Patients w/ ↓ CD4 count

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Cryptococcus:
Pathogenesis

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Yeast Inhalation
Replication in Lung w/ T-Cell recruitment
Hematogenous dissemination across BBB
Replication w/ Capsule

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Cryptococcus:
Normal v. Immune Deficient Hosts

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Normal:
Chronic Inflammation development of granuloma

Immune Deficient:
Little inflammatory reaction, possible ↑ cranial pressure, CNS involvement

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Cryptococcus:
Treatment

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AmB + 5-FC w/ long-term Fluconazole

May require release of Intracranial pressure

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Pneumocytosis
(Pneumocystis Carnii)

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Opportunistic
Predominantly attacks lungs
Pt’s have fever, dyspnea, cough

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Pneumocytosis and Oxygen Exchange

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Opportunistic
Has GREATEST effect on lung oxygenation

SHUNT: Lung is Perfused, but not Ventilated

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Pneumocystis:
Treatment

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Trimethoprim-Sulfamethoxazole
Antibacterial antibiotic

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Histoplasmosis

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Most common in Central USA
Pulmonary Entry
Disseminated infection w/ T-Cell Compromise

Reticuloendothelial System:
Liver, Spleen, Lymph Nodes, Bone Marrow
(due to intracellular nature of histo)

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Histoplasmosis:
Pathogenesis

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Enters via lungs
Abides INSIDE Mφ’s and Monocytes
Granuloma formation (poor in Immunocompromised patients)
Dissemination to Primary Lymph Tissues

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Coccidioidomycosis:
Characteristic Structure &
Susceptible Hosts

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SPHERULES in vivo
Pulmonary Symptoms
w/ Cutaneous infection/meningitis

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Treatment:
Pathogenic Fungi
(Histo, Blasto, Coccidio)

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ITRACONAZOLE

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21 yo old student w/ non-pruritic discoloration on upper back and chest

Disease, Organism, Treatment

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Tinea Versicolor
Malassezia Furfur
Spaghetti & Meatballs on histo
Topical Ketaconazole Shampoo, Clotrimazole
CAN give Itraconazole if necessary

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13 yo male wrestler w/ pruritic thoraco-abdominal lesions

Disease, Organism(s), Treatment

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Tinea Corporis (Gladiatorum)
Annular, erythematous lesions w/ central clearing
Dermatophyte (M, E, T. Tonsurans)
Topical Azoles/Nystatin

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10 yo boy w/ pruritic scalp lesions

Disease, Organism(s), Treatment

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Tinea Capitis
T. Tonsurans (M. Canus possibly)
Systemic AND Topical Treatment:
Ketaconazole Shampoo & Itraconazole

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Oncology pt is profoundly neutropenic. c/o chest pain, cough, and w/ blood tinged sputum.
CT shows nodular lesions with halo.

Organism, Diagnosis Method, Treatment

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Halo Sign = Angioinvasive Organism:
Aspergillus, Zygomycetes
Diagnose w/ Bronchial Lavage & Culture
Treat w/ Fluconazole or AmB

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Surgical pt s/p bowel resection due to carcinoma. Blood cultures yield Hyphae, PseudoH., and Yeast

Organism, Treatment

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Hyphae, Pseudohyphae, and Yeast = Candida
Germ Tube+ = C. Albicans
Treat w/ Fluconazole or Echinocandins if pt is unstable (in event of liver toxicity)

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A Lumbar Puncture shows encapsulated yeasts in the CNS.

Organism, Treatment, Side Effects of Treatment

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CAPSULE = Cryptococcus Neoformans

Treatment: AmB + 5-FC, possible CSF drain
Watch for liver toxicity and pancytopenia

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Most kidney Toxic “azole”?

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Fluconazole
ALL other azoles go through Liver.

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Which drugs interfere w/ Cyclosporin A Treatment and why?

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Azoles (except fluconazole)

They are broken down by p450 system the same as Cyclosporin A. Both last in system longer than expected and can cause toxicity.

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16 yo male w/ T1-DM is chronicall non-compliant. Presents w/ DKA and zygomycosis of ethmoid sinus.
Treatment, Important Phys. Exam point…

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AmB

Check for EYE involvement (diplopia)

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8 yo w/ CGD suffers from invasive pulmonary Aspergillosus. Which azole will NOT treat this?

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Fluconazole

ONLY effective against Crypto & Candida

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14 yo w/ cryptococcal meningitis. Can this be treated with Caspofungin?

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NO
Echinocandins ONLY have activity against Candida and Aspergillus
“Caspofungin is for Candida and Aspergillus”

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Which anti-fungal agent causes pancytopenia/neutropenia?

Back 85

5-FC
Can enter into bone marrow and prevent DNA Txn and production of new blood cells.