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Foundations of Disease and Therapy > Fungi > Flashcards

Fungi Flashcards

1
Q

Malessezia

Pathogenesis, risk factors, clinical presentation, diagnosis, treatment

A
  • Commensal normally found on skin
  • Degradation of lipids damages melanocytes and causes hyper/hypopigmented and/or pink patches on skin
  • Assocaited with humidity and warm climates
  • Can cause liver spots - Pityrasis Versicolor
  • Also cause of dematitis and dandruff
  • Diagnose with skin scraping and KOH Prep - Spaghetti and Meatball appearance
  • Treat with topical ketoconazole, selenium sulfide
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2
Q

Only drug class that exploits fungal cell wall

A

Echinocandins

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3
Q

Why diagnosing fungi is difficult

A
  • Antibiotics/steroids can worsten infection
  • Blood cultures for systemic infections are often negative
  • Difficult to discriminate b/w colonization and disease
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4
Q

Vaginal Candidiasis

A
  • Presents with itching, soreness, discomfort, white discharge, rash
  • Can correlate with diabetes, contraceptive use, or antibiotics
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5
Q

Subcutaneous Mycoses

A

Chronic, localized infections of skin and subcutaneous tissue that rarely spread systemically

Result of traumatic implantation of environmental fungi (thorn or splinter)

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6
Q

Blastomycosis

A
  • Endemic to Eastern and Central US
  • Histology shows broad-based budding that is the same size as RBC
  • Associated with farmers, hunters, and campers
  • Causes inflammatory lung disease that can disseminate to skin and bone
  • Skin lesions can stimulate squamous cell carcinoma
  • forms granulomatous nodules
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7
Q

Candida virulence factors

A

Adherence to catheters, dentures, etc

Proteolytic Enzymes (nutrient acquisition, penetration)

Biofilm formation

Mofphogenetic transition (yeast –> hyphal)

Immunomodulatory effects

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8
Q

Cryptococcosis

Virulence Factors

A

Polysaccharide capsule (antiphagocytic)

Survives in macrophages

Melanin

Has Alpha Glucan Polymers - Resistant to B-Glucan Drugs (Echinocandins)

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9
Q

Fungal drug resistance (drugs and mechanisms)

A

Resistance to Amphotericin B and Echinocandins is rare

5-FC and Azole resistance is common

Resistance usually due to:

  • efflux pumps
  • upregulation of target enzyme
  • point mutations
  • intrinsic resistance - some species
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10
Q

Dermatophytes (Tinea) Infections - Cutaneous Mycoses

A

Tinea pedia - Athlete’s foot

Tinea cruris - inguinal area

Tinea capitis - head or scalp; associated with lymphadenopathy, alopecia, scaling

Tinea corporis - Occurs on torso; Ringworm; can be acquired from contact with infected dog or cat

Tinea unguium - occurs on nails

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11
Q

Aflatoxin

A

Mycotoxin produced by Aspergillis

Leads to hepatocellular carcinoma

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12
Q

Mucormycosis

Species, risk factors, disease

A

Species: Rhizopus or Mucor

Risk factors:

  • DIABETES - diabetes defining illness (“functional neutropenia”)
  • Ketoacidosis
  • AIDS, steroid use, organ transplant

Disease:

  • Invasive sinusitis with rhonocerebral spread
  • Pulmonary infections in diabetics
  • Skin infections in burn patients
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13
Q

Cryptococcosis

Risk factors and disease

A
  • Caused by yeast
  • Acquired via spores inhaled from pigeon droppings
  • C. gatti associated with Eucalyptus trees
  • Initial disease is flu-like or pneumonia, but can cause meningitis
  • Cryptococcal meningitis is AIDS defining illness
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14
Q

Predisposing factors to Candida diseases

A

CD 4 T Cell Defect –> Oral Candidiasis (thrush)

Neutropenia –> Systemic Candidiasis (high morbidity)

Genetic Defect (Th17 or AIRE) –> Mucocutaneous Candidiasis

Dysregulated Inflammatory Respose (or no defect) –> Vaginitis

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15
Q

Mucormycosis

Pathogenesis, Diagnosis, Treatment

A
  • Pathogenesis*: Iron utilization at acidic pH, proteinases, damages endothelial cells, invades blood vessels and causes thrombosis
  • Diagnosis*: Characteristic aseptate hyphae with right-angle branching
  • Treatment*: Amphotericin B
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16
Q

Aspergillus

Diagnosis

A

Diagnosis:

  • Non-pigmented, septated hyphae with acute-angle branching
  • Aspergilloma: proliferating hyphae from fungal balls
  • Invasive Aspergillosis: Galactomannan Antigen Test (80% sensitive)
  • Chronic Pulmonary Aspergillosis: Often confused with TB
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17
Q

Yeast

A
  • Spheroid/oval shaped cell
  • reproduce asexually
  • Genera-specific bud shapes important for diagnosis
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18
Q

Name the 4 major fungal drug classes and their targets

A
  1. Polyenes –> egosterol
  2. Azoles –> egosterol
  3. Echinocandins –> cell wall
  4. Nucleoside inhibitor –> uracil
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19
Q

Invasive Aspergillosis

A

INflammatory, granulomatous, necrotizing disease of lungs

Can be systemic and fatal

Associated with neutropenia, organ transplant, bone marrow transplant, and immunosuppressive therapy

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20
Q

Azoles

A
  • Inhibit egosterol syntheses - 14-alpha-demethylase
  • Lanosterol -X-> Egosterol
  • Prevent cell from dividing
  • Fungistatic - more likley to build resistance
  • Toxic sterols incorporated into membrane
  • Used for local or less serious infections
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21
Q

Cutaneous Candidiasis

A
  1. Onychomycosis (nails)
  2. Intertrigo (rash of body folds)
  3. Diaper rash

Risk factors: Diabetes, diapers, obesity, alcoholism

Treatment: Itraconazole (oral), topical antifungals

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22
Q

Pneumocystis jirovecii

Diagnosis and treatment

A

Diagnosis:

  • Giemsa Stain - Trophic form; aggregates of 2-8
  • GMS Stain - spores; squashed ping pong balls

Treatment:

  • TMP-SMX
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23
Q

Superficial mycoses

A
  • do not invade living tissue
  • no cellular response from host
  • Malassezia furfur is most common species
  • Easy to diagnose with KOH skin scrapings
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24
Q

Pneumocystis jirovecii

Risk factors, disease

A
  • Causes Pneumocystis Pneumonia in immunocompromised
  • PCP causes interstitial fibrosis of lungs with pulmonary infiltrate
  • Risk factors include: chronic lung disease, HIV, corticosteroids, immunosuppressents, cigarette smoking, low CD 4 Count
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25
Q

4 Types of Mycotic Diseases

A
  1. Superficial
  2. Cutaneous
  3. Subcutaneous
  4. Systemic
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26
Q

Fungal Microscopy methods

A

KOH Wet Mount

  • allows you to visualize hyphae and morphology
  • KOH dissolves skin, hair, and debris
  • Lactophenol blue stain added

GMS - Gormori Methenamine Silver (silver stain)

Calcofluor White (immunofluorescent stain for chitin)

27
Q

Explanation for rise of Opportunistic Fungal Infections

A

Incidence has risen dramatically in recent years due to modern medical techniques and AIDS

28
Q

What characteristic allows a fungi to become a pathogen?

A

Ability to grow at 37°C

29
Q

Disseminated Candidiasis

A
  • Bloodstream infection
  • Most originate from biofilms on IV catheters
  • Acute Stage shows: fever, skin lesions, shock
  • Chronic Shows: slow spread of lesions, hepato-splenic lesions, infrequent fungemia
  • DIFFICULT TO DIAGNOSE
  • Treat with Fluconazole and Echinocandin (First Line), or Amphocerin B as second line (toxic)
30
Q

Fungi that can acheive person-to-person transmission

A
  1. Dermatophytes
  2. Candidiasis (hand hygeine)
  3. Pneumocystosis (unknown, aerosol suspected)
31
Q

Histoplasmosis

A
  • Endemic to Misissippi and Ohio River Valleys
  • Associated with Caves (bat droppings) or Construction
  • You will see Macrophages filled with Histoplasma
  • Cause palatal/tongue ulcers, splenomegaly
32
Q

Paracoccidioidomycosis

A
  • Endemic to Latin America
  • Histology shows Captain’s Wheel budding formation
  • Symtoms similar to Coccidioidomycosis, more common in males
33
Q

What factors determine whether a fungus will cause disease in a host?

A

Size of inoculum and host resistance

34
Q

What are some ways drugs can exploit fungi?

A
  • Fungi have egosterol in their membranes, mammals have cholesterol
  • They have cell walls of glucans and mannans, no peptidoglycan
35
Q

Allergic Bronchopulmonary Aspergillosis (ABPA)

A

Risk to those infected with COPD, cystic fibrosis, emphysema

Type 1 Hypersensitivity

36
Q

Diagnosis of Disseminated Candidiasis

A
  • CHROMagar on culture identifies species
  • Serology only 50% sensitive in blood
  • Direct tissue samples may show organism
37
Q

Non-invasive Aspergillosis

A

Colonization of preexisting cavities in lung (TB)

Pulmonary aspergilloma (fungus balls)

38
Q

Mycetismus

A

Ingestion of preformed fungal toxin (mushroom poisioning)

39
Q

Sporotrichosis

A
  • Caused by Sporothrixi schenckii
  • Rose Grower’s Disease - entry via thorn or splinter
  • Defining Characteristic: Nodular lesions that trace path of lymphatic drainage
  • Gardeners and plant nursery workers at risk
  • Cigar Shaped Yeast
  • Treat with Itraconazole or Potassium Iodide
40
Q

Important immune players against fungi

A
  • PRR’s
  • Neutrophils
  • T Cells
41
Q

Echinocandins

A
  • Blocks B(1,3) glucan synthesase (Inhibits cell wall synthesis)
  • Leads to dissolution of cell wall
  • Only available in IV form - use for life threatening disseminated infection
42
Q

How do we know if an infection is fungal?

A
  • Antibiotics don’t work
  • Duration - Viral infection would have been cleared already
43
Q

Amphotericin B

A
  • Polyene drug class
  • Fungicidal
  • Binds to egosterol and forms holes in fungal membrane
  • Used to treat systemic infections
  • HIGH TOXICITY (especially nephrotoxicity)
44
Q

Chronic Mucocutaneous Candidiasis

A
  • Due to mutation in STAT or AIRE
  • Defective Th17 signaling
  • Severity of presentation varies
  • Treat the endocrine or autoimmune manifestations
45
Q

Mold

A
  • Includes Hyphae and Mycelium (mass of hyphae)
  • Filamentous, cylindrical cels
  • Septae or non-septae
  • sexual reproduciton
46
Q

Fungal cell wall composition

A

Chitin, Glucan, Mannan

47
Q

Chromoblastomycosis (black molds)

Transmission, risk factors, clinical presentation, treatment, diagnosis

A
  • Common in warmer climates
  • Transmitted through thorny plant or splinter
  • Agrucultural laborers who work barefoot at risk
  • Presents with cutaneous and subcutaneous mycosis with chronic granulomas on feet and legs
  • Treat with surgery; deep lesions are treated with itraconazole
  • Pigmented cells on H&E, Gray “mouse fur” mold on culture
48
Q

Testing Antifungal Sensitivity

A

MIC - Minimum Inhibitory Concentration

MIC is the lowest concentration of antifungal that allows visible growth

80% of growth inhibition is commonly used

49
Q

How do fungi disseminate and infect?

A

Fungi form spores, which allow them to disperse in water and air

50
Q

Characteristics that separate fungi from other Domains and Kingdoms

A
  1. Eukaryotic (separates from bacteria)
  2. Heterophilic (separates from plants and algae)
  3. Rigid cell walls (separates from animals)
51
Q

Opportunistic Fungal Infections (species)

A
  • Candida albicans
  • Aspergillus fumigatus
  • Cryptococcus neoformans
  • Mucor and Rhizopus
52
Q

Coccidiomycosis

A
  • Endemic to Southwestern US and California
  • Histology shows spherule filled with endospores (much larger than RBC)
  • Those at risk include retirees, archeologists, farmers, and military
  • Disseminates to skin and bone
  • Erythema nodusum (desert bumps) or mulitforme arthralgias (desert rheumatism)
  • Can cause meningitis
53
Q

General virulance factors of fungi

A

Similar to Bacteria:

  • Adhesins –> Biofilm formation
  • Capsule formation
  • Evasion of host response
  • Modulation of host immune response (dysregulation of cytokines)
  • Aquisition of nutrients from host cells
  • Mycotoxins (Aflatoxin)

Unique:

  • Ability to switch cell type - dimorphism
  • Cell wall barriers
54
Q

Polymorphic

A

fungi that have multiple growth forms but these do not correlate to a distinct stage in their life cycle (hyphal, pseudohyphal, yeast)

55
Q

Cryptococcosis

diagnosis and treatment

A
  • India Ink stain - capsule excludes ink
  • Mucicarmine Stain - red staining is diagnostic
  • Latex agglutination test (for polysaccharide capsule)
  • Grown on Niger Seed Agar

Treatment

  • Amphotericin B and 5-Fluorocytesine
  • Long term Fluconazole for AIDS patients
56
Q

Systemic Mycoses

Characteristics, Organisms

A
  • Involve deep viscera and disseminate widely; often fatal
  • Require aggressive treatment - Azoles for local infection, Amphotericin B for systemic
  • All are dimorphic - mold in cold, yeast in heat
  • Usually diagnosed based on geography
  • Include: Histoplasma, Blastomyces, Coccidioides, and Paracoccidioides
57
Q

5-Flucytosine

A
  • Converted to 5-fluorouracil by Cytosine Deaminase
  • Interferes with fungal DNA Synthesis
  • Our cells do not take up this drug
  • Fungistatic - but rapid acquisition of resistance; must be used in synergy with another class of drug (usually Amphotericin to reduce its side effects)
58
Q

Dimorphic

A

Fungi that grow as mold or yeasts during specific stages of their life cycle

59
Q

Oral Candidiasis

A

Pharyngeal or esophageal thrush - creamy white plaques

At risk:

  • HIV Patients with CD 4 < 200
  • Infants (T cell immunity not developed)
60
Q

Primary pathogen vs Opportunistic pathogen

A

Primary pathogen can cause disease in immunocompetent host

Opportunistic pathogen is restricted to an immunocompromised host

61
Q

Dermatophytes

Pathogenesis, risk factors, clinical presentation, diagnosis, treatment

A
  • Contains keratinases that break down keratin in skin, nails, and hair
  • Acquired from direct contact with infected host
  • Risk factors include: elementary school, contact sports, humid areas, tight shoes, sweating, public showers, and locker rooms
  • Presents with itchy red circular rash (ringworm)
  • Branching Septae visible on KOH prep skin scrapings
  • Treat skin ringworm with non-prescription Azole
  • Treat scalp ringworm with prescription oral anti-fungal
62
Q

Candida morphology

A

Polymorphic

Yeast, pseudohypha, and true hyphae (for invasion)

Ability to form germ tubes is diagnostic feature

63
Q

Dermatophytes species

A

Microsporum, Trichophyton, Epidermophyton

64
Q

Pityriasis Versicolor

A

Disease caused by Malassezia

Liver spots

Foundations of Disease and Therapy (12 decks)

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