Mycology III - Opportunistic Flashcards
What are “Opportunists”?
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
Defects that lead to increased susceptibility
Compromised anatomic and physical barriers
Inherited immunodeficiency
Cancer (esp. lymphohematologic malignancies)
Chemotherapy and Radiation Therapy
Hospitalization
Extremes of Age
Other Infections
Specific drugs in chemotherapy that increase susceptibility
Cytotoic drugs and radiation targeting proliferating cells (such as lymphocytes and neutrophils)
Steroids (suppress macrophage activity)
Cyclosporin (transplant patients, suppress T-cell activation)
Specific infections that increase susceptibility
Herpes based: Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV)
HIV (Destruction and suppression of CD4+ lymphocytes)
Candida - Morphology
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
Candida - Environmental Niche
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
Candida - Epidemiology
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
Candida - Virulence determinants
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
Biofilms (Definition, What increases risk for them, Immunological repercussions)
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
Candida - Infection
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
Candida - Clinical Syndromes
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
3 Main Risk factors for invasive candidiasis/candidemia
Central venous catheter
Broad spectrum antibiotics
Surgery (especially if transects gut wall)
Candida - Clinical challenges
Differentiating candida pseudohyphae (no speta) from Aspergillus and other true hyphae in tissue
Azole resistance, esp. non-albicans
Oral candidiasis in asthmatics
Cryptococcus - Morphology
Uninucleate budding yeast with poly saccharide capsule
Monomorphic
Cryptopcoccus - Geographic distribution and niches
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
Cryptococcus - Variants and strains
C. neoformans var. grubii - serotype A
C. neoformans var. neoformans - serotype D
C. gattii - serotype B, C
Does cryptococcus have outbreaks?
Not C. neoformans
C. gattii does, example in Pacific NW
Cryptococcus - Epidemiology
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
Cryptococcus - Virulence
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
Cryptococcus - Infection
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
Cryptococcus - Clinical syndromes
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
Aspergillus - Morphology
Mold - septate (crosswalls) hyphae (mycelia) + conidia
No yeast form
Aspergillus - Geography and environmental niches
Ubiquitous in environment, decomposing vegetation, household dust, building materials
Airborne exposure common
Aspergillus - Strains that cause infection
***Only a few of the 100+ species A. fumigatus: 60-70% A. flavus: 10-20% A. terreus: 3-12% A. niger: 0-5%
Aspergillus - Outbreaks
Construction projects and materials in several hospitals
Aspergillus - Virulence
Hydrolytic enzymes (proteases) for tissue destruction Allergens inducing host response
Aspergillus - Infection
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
Aspergillus - Clinical Syndromes
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
Main Challenge for Aspergillosis
Quick diagnosis
Zygomycosis - Overview
Includes Rhizopus, Mucor, Fusarium
Recently emerged as significant causes of morbidity and mortality in immunocompromised patients
Zygomycosis - Morphology
Molds in environment and in host
Fusarium are septate, others are not
Zygomycosis - Geographic distribution and environmental niches
Ubiquitous, commonly soil, fruit, plants, insects, bread
Zygomycosis - Epidemiology
Worldwide, no biases
Spread in hospitals via AC systems
Zygomycosis - Virulence Determinants
None known
Zygomycosis - Infection
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
Zygomycosis - Special challenges
Discriminating zygomycosis from common bacterial and fungi infections
Correcting underlying conditions like ketoacidosis
