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Foundations of Disease and Therapy > Fungi > Flashcards

Flashcards in Fungi Deck (64):
1

Malessezia 

Pathogenesis, risk factors, clinical presentation, diagnosis, treatment

  • 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 

2

Only drug class that exploits fungal cell wall

Echinocandins

3

Why diagnosing fungi is difficult 

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

4

Vaginal Candidiasis

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

5

Subcutaneous Mycoses

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

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

6

Blastomycosis

  • 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 

7

Candida virulence factors

Adherence to catheters, dentures, etc

Proteolytic Enzymes (nutrient acquisition, penetration)

Biofilm formation 

Mofphogenetic transition (yeast --> hyphal)

Immunomodulatory effects 

8

Cryptococcosis

Virulence Factors

Polysaccharide capsule (antiphagocytic)

Survives in macrophages

Melanin

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

9

Fungal drug resistance (drugs and mechanisms) 

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 

10

Dermatophytes (Tinea) Infections - Cutaneous Mycoses 

 

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 

11

Aflatoxin

Mycotoxin produced by Aspergillis 

Leads to hepatocellular carcinoma 

12

Mucormycosis

Species, risk factors, disease

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 

13

Cryptococcosis

Risk factors and disease 

  • 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 

14

Predisposing factors to Candida diseases

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 

15

Mucormycosis

Pathogenesis, Diagnosis, Treatment 

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

16

Aspergillus 

Diagnosis 

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

17

Yeast

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

18

Name the 4 major fungal drug classes and their targets 

  1. Polyenes --> egosterol
  2. Azoles --> egosterol
  3. Echinocandins --> cell wall
  4. Nucleoside inhibitor --> uracil 

19

Invasive Aspergillosis

INflammatory, granulomatous, necrotizing disease of lungs

Can be systemic and fatal

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

20

Azoles

  • 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 

21

Cutaneous Candidiasis

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

Risk factors: Diabetes, diapers, obesity, alcoholism

Treatment: Itraconazole (oral), topical antifungals 

22

Pneumocystis jirovecii 

Diagnosis and treatment 

Diagnosis:

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

Treatment:

  • TMP-SMX

23

Superficial mycoses

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

24

Pneumocystis jirovecii 

Risk factors, disease

  • 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 

25

4 Types of Mycotic Diseases

  1. Superficial
  2. Cutaneous
  3. Subcutaneous
  4. Systemic 

26

Fungal Microscopy methods 

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

Explanation for rise of Opportunistic Fungal Infections 

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

28

What characteristic allows a fungi to become a pathogen?

Ability to grow at 37°C

29

Disseminated Candidiasis

  • 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

Fungi that can acheive person-to-person transmission

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

31

Histoplasmosis

  • 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

Paracoccidioidomycosis 

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

33

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

Size of inoculum and host resistance 

34

What are some ways drugs can exploit fungi? 

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

35

Allergic Bronchopulmonary Aspergillosis (ABPA)

Risk to those infected with COPD, cystic fibrosis, emphysema 

Type 1 Hypersensitivity 

36

Diagnosis of Disseminated Candidiasis 

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

37

Non-invasive Aspergillosis

Colonization of preexisting cavities in lung (TB)

Pulmonary aspergilloma (fungus balls) 

38

Mycetismus

Ingestion of preformed fungal toxin (mushroom poisioning) 

39

Sporotrichosis

  • 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

Important immune players against fungi

  • PRR's
  • Neutrophils
  • T Cells 

41

Echinocandins

  • 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

How do we know if an infection is fungal?

  • Antibiotics don't work
  • Duration - Viral infection would have been cleared already 

43

Amphotericin B

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

44

Chronic Mucocutaneous Candidiasis

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

45

Mold

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

46

Fungal cell wall composition

Chitin, Glucan, Mannan 

47

Chromoblastomycosis (black molds)

Transmission, risk factors, clinical presentation, treatment, diagnosis 

 

  • 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

Testing Antifungal Sensitivity 

MIC - Minimum Inhibitory Concentration

MIC is the lowest concentration of antifungal that allows visible growth 

80% of growth inhibition is commonly used 

49

How do fungi disseminate and infect?

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

50

Characteristics that separate fungi from other Domains and Kingdoms

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

51

Opportunistic Fungal Infections (species)

  • Candida albicans
  • Aspergillus fumigatus
  • Cryptococcus neoformans
  • Mucor and Rhizopus 

52

Coccidiomycosis

  • 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

General virulance factors of fungi 

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

Polymorphic

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

55

Cryptococcosis

diagnosis and treatment

  • 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

Systemic Mycoses

Characteristics, Organisms

  • 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

5-Flucytosine

  • 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

Dimorphic

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

59

Oral Candidiasis 

Pharyngeal or esophageal thrush - creamy white plaques

At risk: 

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

60

Primary pathogen vs Opportunistic pathogen 

Primary pathogen can cause disease in immunocompetent host

Opportunistic pathogen is restricted to an immunocompromised host 

61

Dermatophytes 

Pathogenesis, risk factors, clinical presentation, diagnosis, treatment

  • 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

Candida morphology 

Polymorphic 

Yeast, pseudohypha, and true hyphae (for invasion)

Ability to form germ tubes is diagnostic feature 

63

Dermatophytes species

Microsporum, Trichophyton, Epidermophyton 

64

Pityriasis Versicolor

Disease caused by Malassezia

Liver spots