Mycology III - Opportunistic

Question 1

What are “Opportunists”?

Answer 1

Microbes/pathogens that only cause disease in host when defenses are disturbed (i.e. immunocompromised) or if they migrate from normal tissue to other tissues

Question 2

Defects that lead to increased susceptibility

Answer 2

Compromised anatomic and physical barriers
Inherited immunodeficiency
Cancer (esp. lymphohematologic malignancies)
Chemotherapy and Radiation Therapy
Hospitalization
Extremes of Age
Other Infections

Question 3

Specific drugs in chemotherapy that increase susceptibility

Answer 3

Cytotoic drugs and radiation targeting proliferating cells (such as lymphocytes and neutrophils)
Steroids (suppress macrophage activity)
Cyclosporin (transplant patients, suppress T-cell activation)

Question 4

Specific infections that increase susceptibility

Answer 4

Herpes based: Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV)
HIV (Destruction and suppression of CD4+ lymphocytes)

Question 5

Candida - Morphology

Answer 5

Both yeast and hyphae seen within human host
Intermediate: pseudohyphae or chains of yeast
Non-encapsulated
Cultivate at room temperature and acidic pH
Pseudohyhal form is tissue invasive and grows in physiological conditions
A variety of the forms can be found in a clinical specimen

Question 6

Candida - Environmental Niche

Answer 6

Commensal part of the normal flora on human skin and mucous membrane
50-80% of normal individuals may have in oropharynx, GI, or vagina w/o disease
Prefers moist skin

Question 7

Candida - Epidemiology

Answer 7

Candidiasis begins from their own commensals, for newborns from mother’s GI or GU tract
Superficial cutaneous and mucosal infections common in normal hosts
75% of women have at least one bout of vulvovaginal candidiasis (uncommon prepuberty)
Most common microbial infection in AIDS, 90% of patients have thrush and 10% have esophagitis

Question 8

Candida - Virulence determinants

Answer 8

Adhesions
- Can mimic integrin CR3, CR4 on host macrophages
- Mannoproteins similar to integrins for binding to ECM components
- Hwp1: Hyphal wall protein helps mediate binding
Invasive pseudohyphae to infect tissue, yeast at the disease site
Hydrolytic enzymes for destroying host tissue and tissue invasion

Question 9

Biofilms (Definition, What increases risk for them, Immunological repercussions)

Answer 9

Structured microbial communities that are attached to a surface or encased in ECM
Devices such as stents, implants, catheters increase biofilm proliferation
Biofilm prevents phagocytosis, reservoir for future infection, increased resistance to antifungal therapy

Question 10

Candida - Infection

Answer 10

Skin, nail and mucosal infection due to compromised local host defenses
Host environmental conditions can favor fungal growth
Sites of surgical procedures, catheters favor candida growth and colonization
Candida spp. are leading cause of neonatal ICU deaths
Severe mucosal infections and invasive and disseminated disease occur in seriously immunocompromised individuals

Question 11

Candida - Clinical Syndromes

Answer 11

Cutaneous - Dermatitis, onychomycosis, otitis external
Mucosal - Vulvovaginal, oropharyngeal (thrush, white patches in mouth), denture-associated stomatitis, esophageal
Chronic mucocutaneous candidiasis - Mixture of these infections, often reduced T-cell response but good or enhanced humoral response
Invasive/disseminated - Pulmonary, fungemia, endocarditis, urinary tract, meningitis

Question 12

3 Main Risk factors for invasive candidiasis/candidemia

Answer 12

Central venous catheter
Broad spectrum antibiotics
Surgery (especially if transects gut wall)

Question 13

Candida - Clinical challenges

Answer 13

Differentiating candida pseudohyphae (no speta) from Aspergillus and other true hyphae in tissue
Azole resistance, esp. non-albicans
Oral candidiasis in asthmatics

Question 14

Cryptococcus - Morphology

Answer 14

Uninucleate budding yeast with poly saccharide capsule

Monomorphic

Question 15

Cryptopcoccus - Geographic distribution and niches

Answer 15

Worldwide, ubiquitous in soil
Associated with bird guano especially pidgeons but do not cause birds to become ill
Not part of normal human microbial flora

Question 16

Cryptococcus - Variants and strains

Answer 16

C. neoformans var. grubii - serotype A
C. neoformans var. neoformans - serotype D
C. gattii - serotype B, C

Question 17

Does cryptococcus have outbreaks?

Answer 17

Not C. neoformans

C. gattii does, example in Pacific NW

Question 18

Cryptococcus - Epidemiology

Answer 18

Global, particularly bad in sub-Saharan africa: 720,000 cases per year, 65% dying within 3 mos of diagnosis
Life-threatening in 6-12% of AIDS patients
High mortality in developing countries with poor drug availability

Question 19

Cryptococcus - Virulence

Answer 19

Growth at 37 C
***Capsule - Protects against phagocytosis by hiding fungal cell wall ligands or making yeast too large
Depletion of complement components
Down-regulates immune response, NO synthase, leukocyte migration
Phenoloxidase activity/melanin production protect against oxidation
Mannitol production to scrub free radicals

Question 20

Cryptococcus - Infection

Answer 20

Exposure - Very common via respiratory and GI
Major route - Desiccated yeast become airborne, inhaled by mammalian host, penetrate small airways
***Location predominately extracellular in host
No necrosis or organ damage till late, little inflammation
Rare in children regardless of HIV

Question 21

Cryptococcus - Clinical syndromes

Answer 21

Pulmonary - Patients may be asymptomatic or present with cough, fever, pneumonia like symptoms
Meningitis - Oftern first indication of cryptococcal infection, most common and most serious (100% mortality w/o treatment, 12% with)
Skin and Prostate also targets of dissemination

Question 22

Aspergillus - Morphology

Answer 22

Mold - septate (crosswalls) hyphae (mycelia) + conidia

No yeast form

Question 23

Aspergillus - Geography and environmental niches

Answer 23

Ubiquitous in environment, decomposing vegetation, household dust, building materials
Airborne exposure common

Question 24

Aspergillus - Strains that cause infection

Answer 24

***Only a few of the 100+ species
A. fumigatus: 60-70%
A. flavus: 10-20%
A. terreus: 3-12%
A. niger: 0-5%

Question 25

Aspergillus - Outbreaks

Answer 25

Construction projects and materials in several hospitals

Question 26

Aspergillus - Virulence

Answer 26

Hydrolytic enzymes (proteases) for tissue destruction
Allergens inducing host response

Question 27

Aspergillus - Infection

Answer 27

DIsease is uncommon unless compromised adaptive or innate immunitiy.
Host defense begins with mucous layer and ciliary action in the airway
Macrophages kill conidia, neutrophils kill hyphae
Neutropenic patients are at high risk for invasive aspergillosis
HIV alone often not enough to cause susceptibility

Question 28

Aspergillus - Clinical Syndromes

Answer 28

Saprophytic colonization of pre-existing body cavities
***Invasive - Inflamation, granulomatous, necrotizing lung diseases. Invade blood vessels and disseminate. Very poor prognosis.
Allergy - Hypersensitivity pneumonitis or Allergic Bronchopulmonary aspergillosis (ABPA). ABPA can lead to fibrotic end-stage lung disease
Mycotoxicosis - Aflatoins are hepatotoxic and carcinogenic

Question 29

Main Challenge for Aspergillosis

Answer 29

Quick diagnosis

Question 30

Zygomycosis - Overview

Answer 30

Includes Rhizopus, Mucor, Fusarium

Recently emerged as significant causes of morbidity and mortality in immunocompromised patients

Question 31

Zygomycosis - Morphology

Answer 31

Molds in environment and in host

Fusarium are septate, others are not

Question 32

Zygomycosis - Geographic distribution and environmental niches

Answer 32

Ubiquitous, commonly soil, fruit, plants, insects, bread

Question 33

Zygomycosis - Epidemiology

Answer 33

Worldwide, no biases

Spread in hospitals via AC systems

Question 34

Zygomycosis - Virulence Determinants

Answer 34

None known

Question 35

Zygomycosis - Infection

Answer 35

Inhalation, ingestion, or contamination by spores
Rarely disease in immunocomptent, but aggressive in immunocompromised (usually fatal)
In particular target acidotic patients, diabetic
Breakthrough infections in bone marrow transplant

Question 36

Zygomycosis - Special challenges

Answer 36

Discriminating zygomycosis from common bacterial and fungi infections
Correcting underlying conditions like ketoacidosis