Jackson: Upper Respiratory Tract Infections Flashcards
Variety of organisms colonize oropharynx and upper respiratory tract:
Many commensals colonize upper respiratory tract
Respiratory tract is a continuum from sinuses to alveoli
Professional Invaders:
Professional Invaders: uniquely adapted to the upper respiratory tract; infect HEALTHY respiratory tract
Professional Invaders
Mechanisms:
- Adhesion to mucosal surfaces
- Interfere with cilia
- Resist alveolar macrophages
- Damage local tissues
.
Secondary Pathogens:
Secondary Pathogens: cause infection following initial insult; infect when host defenses impaired
Secondary Pathogens
Mechanisms: (5)
- Primary viral infection
- Impaired local defenses (ie. cystic fibrosis)
- Chronic bronchitis due to tumor
- Depressed immunity (AIDS)
- Decreased resistance (age, alcoholism)
Oral Anaerobes
- Virulence Factors (Relevant to Oral Infection): (2)
- Lymphocyte Activators: produces by oral bacteria; induce inflammatory response
- Activate Complement/Release of PMN Contents: exacerbate tissue damage
Oral Anaerobes
Etiology:
o Autoinfections caused by normal flora
o Usually polymicrobic
o Anaerobes typically form localized absecesses
Oral Anaerobes
Chronic Marginal Gingivitis
Location:
Inflammatory Infiltrate:
Bacteria do NOT invade:
Timeline:
Chronic Marginal Gingivitis: between teeth and gums
Inflammatory Infiltrate: PMNs and lymphocytes enter CT attached to tooth
Bacteria do NOT invade: remain part of the plaque outside host defenses
Timeline: can occur in 2 weeks without proper tooth care
Oral Anaerobes
Periodontitis
Results from:
Bacterial invasion may occur:
Periodontitis: teeth and supporting tissue
- Results from progressive gingivitis: resorption of bone around the neck of the tooth, loss of periodontal ligament and the entire tooth itself
- Bacterial invasion may occur: although anaerobes still also found in dental plaque next to gingival tissues
Oral Anaerobes
Acute Necrotizing Ulcerative Gingivitis (Trench Mouth):
- Ulceration of the gingiva: can lead to bone resorption and tooth loss
• Bacterial invasion of oral epithelium occurs
Oral Anaerobes
Clinical ID
Diagnosis:
Mixed anaerobic infection not differentiated:
Abscesses may be sampled:
o Diagnosis: via symptoms
o Mixed anaerobic infection not differentiated: no specific designation of Gram reaction or morphology
o Abscesses may be sampled: must be cultured in anaerobic conditions; mostly G(-) rods and PMNs
Actinomyces israelii
Etiology:
Colonizes:
Endogenous infection only occurs upon :
Normal flora anaerobe:
• Colonizes mucosal surfaces (oropharynx to lower intestine)
• Endogenous infection only occurs upon penetration of epithelial barrier (low O2 tension)
Actinomyces israelii
Pathogenesis (Cervicofacial Area)
Follows:
Progression rate:
Inflammatory sinuses fill with:
Sinus extension or aspiration can lead to:
Follows mouth trauma (ie. tooth extraction):
• Slowly progressing disease
• Inflammatory sinuses fill with pus and bacteria from initial site of infection
• Sinus extension or aspiration can lead to thoracic actinomycosis
Actinomyces israelii
Staining/Culture of Pus
G+/-?
_________ diagnostic:
Poly vs monomicrobic:
- G(+) filamentaous rod (looks like fungi)
- Sulfur granules diagnostic (yellow granules composed of Actinomyces elements and tissue exudates)
- Polymicrobic infection (also G(-) rods in the sinuses)
Actinomyces israelii
Culture Conditions
Aerobic?
Growth Rate:
o Culture Conditions:
• Anaerobic or microaerophilic conditions
• Slow growth (contaminating bacteria may overwhelm it)
Viridans Streptococci Virulence Factors (Relevant to Oral Infection):
Glucans: complex polysaccharides that permit attachment to teeth
Viridans Streptococci
Normal flora:
Normal flora: of oral and nasopharyngeal cavity (S. mutans associated with dental cavities)
Viridans Streptococci
May Cause:
Tooth extraction lead to:
o May Cause Subacute Bacterial Endocarditis:
• Tooth extraction lead to transient bacteremia and colonization of damaged heart valves
Viridans Streptococci
Shape/Stain:
Cat +/-?
Lancefield Group:
o Shape/Stain: G(+) cocci
o Biochemical:
• Catalase (-)
• No Lancefield group
Candida albicans Virulence Factors (Relevant to Oral Infection)
Adhesion:
Invasion:
Adhesion: mannoprotein binds fibronectin receptors
Invasion:
• Invasive hyphae (bind fibronectin, collagen and laminin)
• Proteases and elastases may also play a role
Candida albicans
Predisposing Factors to Candidiasis: (4)
- Antimicrobial therapy (depresses competing bacterial flora)
- Compromised immune system (leucopenia, corticosteroids, AIDS)
- Disruption of mucosa (indwelling devices or cancer chemotherapy)
- Diabetes (increased glucose and increased surface receptors)
If recurrent candidiasis consider:
If recurrent candidiasis: consider a T cell deficiency
Candida albicans
Stomatitis:
Oral Thrush:
Stomatitis: inflammation of the oral cavity
• Oral Thrush: multiple white cheesy plaques that are loosely adherent to the tongue or palate
• Inflammatory patches on esophagus
Candida albicans
Specimen Collection:
o Specimen Collection: scrapings of infected mucosa
• KOH or Gram stains (budding round yeast with hyphae)
• Germ tube formation speciates C.albicans
BACTERIA CAUSING EAR AND SINUS INFECTIONS: (2)
- Streptococcus pneumoniae
* Haemophilus Influenzae
Streptococcus pneumoniae Virulence Factors (Relevant to Ear and Sinus Infection): (2)
Polysaccharide capsule
Cell Wall Techoic Acid and Peptidoglycan
Streptococcus pneumoniae
Polysaccharide capsule:
Anti-________ and prevents:
Anti-_____ Abs confer immunity
Polysaccharide capsule: primary virulence factor
• Anti-phagocytic and prevents complement deposition
• Anti-capsule Abs confer immunity
Streptococcus pneumoniae
Cell Wall Techoic Acid and Peptidoglycan:
Cell Wall Techoic Acid and Peptidoglycan: contribute to inflammation
Streptococcus pneumoniae
Predisposition for URTIs. Why?
Predisposition for URTIs: high nasopharynx carriage rate
Streptococcus pneumoniae
Predisposition for Acute Otitis Media with S.pneumo:
Viral infection or allergies; common in infants due to short/pliant Eustachian tubes (most common cause after 3 months old)
Streptococcus pneumoniae
Predisposition for Sinus Infection with S.pneumo:
Viral infection, allergies, or anatomical blockage
Streptococcus pneumoniae
Acute Otitis Media:
Acute Otitis Media: middle ear infection
• Eustachian tube inflammation due to bacteria entering middle ear from nasopharynx
Streptococcus pneumoniae
Sinus infection:
Sinus infection: a cause of both acute and chronic sinusitis in all ages
Streptococcus pneumoniae
Diagnosis:
Diagnosis: generally based on clinical exam
• Otitis media: swollen tympanic membrane (due to pus formation)
• Sinusitis: symptoms and radiography
Streptococcus pneumoniae
Needle Aspiration:
Needle Aspiration:
• Otitis media: pus behind tympanic membrane may be collected in difficult cases
• Sinusitis: sinus wall puncture or catheterization
Streptococcus pneumoniae
Staining:
Biochemical:
Staining:
• G(+) lancet shaped diplococcic
Biochemical:
• No Lancefield grouping
• Optochin (P disk) sensitive
Haemophilus Influenzae Virulence Factors (Relevant to Ear and Sinus Infection):
Polysaccharide capsule
IgA protease
Non-pilus adhesins: direct tissue tropism (to mucosal surfaces)
Haemophilus Influenzae
Polysaccharide capsule: (3)
What serotype is most virulent?
Polysaccharide capsule: most important VF
• Antiphagocytic
• Undergoes antigenic variation
• Polyribitol phosphate (PRP) capsule with 6 (a-f); serotype b (Hib) is most virulent
Haemophilus Influenzae
IgA protease:
IgA protease: facilitates colonization
Haemophilus Influenzae
Non-pilus adhesins:
Non-pilus adhesins: direct tissue tropism (to mucosal surfaces)
Haemophilus Influenzae
Normal flora where?
Most normal flora have:
Most causes of:
o Normal flora: high carriage rate in upper respiratory tract
• Most normal flora have no capsule (non-typable)
• Most causes of otitis media non-typable (not influenced by Hib vaccine)
Haemophilus Influenzae
Predisposing Factors:
Predisposing Factors: viral infection, displacement of flora into sterile sits
Haemophilus Influenzae
Otitis media/Sinusitis
Age:
If caused by Hib, can lead to:
- Common cause in kids under 5
* If caused by Hib, can lead to meningitis
Haemophilus Influenzae
Diagnosis:
Needle aspirate:
Staining/Shape:
Culture:
o Diagnosis: based on clinical exam
o Needle aspirate: in difficult/refractory cases
o Staining/Shape: G(-) coccobacillus
o Culture: fastidious; requires Hematin (X factor) and NAD (V factor) for growth
o Capsule serotyping
Streptococcus pyogenes Virulence Factors (Relevant to Infections of the Pharynx):
o Extracellular factors facilitating immune invasion
o Factors facilitating colonization
o Exotoxins
Streptococcus pyogenes
Extracellular factors facilitating immune invasion
M protein:
Protein G/IgG Binding Protein:
Hyaluronic Acid Capsule:
M protein: anti-phagocytic and anti-opsonic
- 80 different serotypes of exposed amino terminus
- Re-infection possible due to antigenic variation
- Cross reactive M protein Abs can cause rheumatic heart disease
Protein G/IgG Binding Protein: binds Fc portion of Abs
Hyaluronic Acid Capsule: antiphagocytic
Streptococcus pyogenes
Factors facilitating colonization
Protein F:
M Protein:
Protein F: binds nasopharyngeal epithelium (regulated by O2 levels)
M Protein: binding epidermis (impetigo)
Streptococcus pyogenes
Exotoxins: (2)
SLO/SLS
Spe A-C
Streptococcus pyogenes
Spe A-C:
SpeA:
Superantigens:
Spe A-C: Erythrogenic/Scarlet Fever Toxins
- SpeA: only produced by a few lysogenized GAS
- Superantigens: with sequence homology to Staph exotoxins
Streptococcus pyogenes
Spe A-C
Induce cytokine release:
Toxic Shock Like Syndrome:
- Induce cytokine release: fever and rash (Scarlet Fever), T cell stimulation and B cell depression, enhanced sensitivity to endotoxic shock
- Toxic Shock Like Syndrome: in GAS bacteremia
Streptococcus pyogenes
SLO/SLS:
_____-hemolysis on BAP:
SLO/SLS: oxygen labile and oxygen stable, respectively
- B-hemolysis on BAP; form large pores in cell membranes (lysis of leukocytes)
Streptococcus pyogenes
Pharyngitis
Basics:
Transmission:
Basics: GAS most common bacterial cause (but usually caused by viruses)
Transmission: droplet spread person to person
Streptococcus pyogenes
Pharyngitis
Treatment:
Treatment: prompt antimicrobial therapy required to prevent postreptococcal sequelae caused by natural development of type-specific immunity (cross reactive Abs)
Streptococcus pyogenes
Scarlet Fever:
Cause:
Presentation:
Scarlet Fever: can occur simultaneously with pharyngitis
• Cause: pyrogenic exotoxins (Spe)
• Presentation: rash spreads from mouth and face to trunk and extremities; strawberry tongue
Rheumatic Heart Disease (Poststreptococcal Sequelae)
Course:
Course: begins ~3 weeks after pharyngitis (does not follow skin infection)
Rheumatic Heart Disease (Poststreptococcal Sequelae)
Symptoms
Systemic Sx:
Cardiac Sx:
Systemic Sx: fever, subcutaneous nodules, chorea (neurologic), migratory polyarthritis
Cardiac Sx: carditis, cardiac enlargement, murmurs, heart failure)
Rheumatic Heart Disease (Poststreptococcal Sequelae)
Symptoms
Rheumatic Carditis:
Subacute bacterial endocarditis:
Rheumatic Carditis: Aschoff body present due to cell mediated response (lesion of lymphocytes and macrophages aggregated around fibrinoid deposits)
Subacute bacterial endocarditis: damage to heart valves due to formation of vegetations, which provide site for colonization during transient bacteremia
Rheumatic Heart Disease (Poststreptococcal Sequelae)
Cause of Heart Damage:
Abs to:
Epitopes shared with:
Progressive heart damage can result from:
Cause of Heart Damage: anti-streptococcal Abs that cross react with cardiac tissue; SLO, Spe and streptokinase (toxins) may also contribute directly to cardiac damage
- Abs to cell wall, cell membrane and M protein
- Epitopes shared with cardiac sarcolemma membranes, smooth muscle cells, and valves
- Progressive heart damage can result from recurrent attacks with new M types
Acute Glomerulonephritis (Poststreptococcal Sequelae)
Course:
Symptoms:
Course: follows respiratory or skin infection (more commonly) with GAS (10 day latent period following infection
Symptoms: edema, HTN, proliferative lesion of glomeruli
Acute Glomerulonephritis (Poststreptococcal Sequelae)
Cause:
Anti-M protein Abs react with:
What also contribute?
• Cause: Ab cross-reactivity and inflammatory response
➢ Anti-M protein Abs react with glomerular proteins (associated with a few M types found in nephrogenic strains)
➢ Deposition of Ag-Ab and complement complexes in glomeruli also contribute
Streptococcus pyogenes
Throat swab of tonsils and pharynx
Culture:
Agglutination test:
- Culture: on BAP for B-hemolysis (CO2 incubation)
* Agglutination test: identify Lancefield Group A (rapid)
Streptococcus pyogenes
Other Contaminants:
Biochemical Tests:
• Other Contaminants: S.pneumo, S.aureus, N.meningitidis, H.influenzae
• Biochemical Tests:
- Catalase (-)
- Bacitracin sensitive
Streptococcus pyogenes
What is seen in patients with rheumatic fever?
High titers of anti-SLO Abs: seen in patients with rheumatic fever
Corynebacterium diphtheriae Virulence Factors (Relevant to Infections of the Pharynx):
o Diphtheria Toxin: only VF
Corynebacterium diphtheriae
Diphtheria Toxin
Structure:
B subunit binds:
Holotoxin uptake by:
Reduction in vesicle releases:
Structure: AB toxin (single polypeptide with nicked chain between A and B subunits)
- B subunit binds epidermal growth factor precursor on cell membrane
- Holotoxin uptake by receptor mediated endocytosis
- Reduction in vesicle releases A subunit (enzymatic)
Corynebacterium diphtheriae
Diphtheria Toxin
Mechanism:
What is needed for translocation of ribosome along mRNA?
Mechanism: A subunit ADP-ribosylates elongation factor 2 of any eukaryotic cell
➢ EF2 is needed for translocation of ribosome along mRNA (halts translation)
Corynebacterium diphtheriae
Diphtheria Toxin
Genetics of Toxin Synthesis
Tox gene is carried by:
Synthesis of the gene is negatively regulated by:
Tox gene is carried by bacterophages (β and ω)
Synthesis of the gene is negatively regulated by iron (free iron levels are low in human host → signals bacteria to turn on toxin production)
Corynebacterium diphtheriae
Prevalence in US:
Only _______ strains produce DT
What can occur in vivo?
Very rare in the US: transients, migrant workers, those who refuse immunization
Only lysogenized strains produce DT: DT required for pathogenesis
• In vivo lysogenization can also occur to convert strain to toxin-producing form
Corynebacterium diphtheriae
Transmission:
What can also transmit?
o Transmission: droplet spread or contact with cutaneous infection or fomite
• Asymptomatic carriers of toxinogenic strains can also transmit disease
Corynebacterium diphtheriae
Bacterial Toxinosis with NO Invasion:
Manifestations due to DT-Mediated Cytotoxicity: (2)
o Bacterial Toxinosis with NO Invasion: DT is solely responsible for ALL pathogenesis
Manifestations due to DT-Mediated Cytotoxicity:
• Pseudomembrane formation: from oropharynx down to trachea (can cause suffocation)
• Systemic manifestations: can cause organ damage (DT attack of heart and CNS)
Corynebacterium diphtheriae
Diagnosis:
Throat swab is difficult:
G+/-?
After division:
Diagnosis: based mostly on clinical symptoms
Throat swab is difficult: normal resident flora of many individuals
• G(+) club shaped rods
• Cells remain attached after division (“Chinese letters”)
• Culture of organism producing toxin
Bordetella pertussis (Whooping Cough) Virulence Factors (Relevant to Respiratory Tract Infections): (4)
o Filamentous Hemagglutinin (FHA) and Pili
o Pertussis Toxin (Ptx)
o Invasive Adenylate Cyclase
o Regulation of Virulence Factors
Bordetella pertussis (Whooping Cough)
Filamentous Hemagglutinin (FHA) and Pili:
Directs organism to:
Can agglutinate:
o Filamentous Hemagglutinin (FHA) and Pili: adhesin for binding to ciliated mucosal epithelial cells
• Directs organism to macrophages
• Can agglutinate RBCs
Bordetella pertussis (Whooping Cough) Pertussis Toxin (Ptx)
Structure:
o Pertussis Toxin (Ptx) major virulence factors
• Structure: AB with 5 non-identical B subunits (binding) and 1 A subunit (enzymatic)
Bordetella pertussis (Whooping Cough) Pertussis Toxin (Ptx)
Mechanism:
Cells unable to:
Increase in __________ leads to increase in ______
• Mechanism: ADP-ribosylates Gi protein (therefore Gs is never turned off)
➢ Cells unable to stop production of adenylate cyclase
➢ Increase in adenylate cyclase leads to increase in cAMP
Bordetella pertussis (Whooping Cough) Pertussis Toxin (Ptx)
Increase in cAMP causes: (4)
o Histamine sensitization
o Promotion of lymphocytosis
o Insulin secretion
o Diminished oxidative killing by macrophages
Bordetella pertussis (Whooping Cough)
Invasive Adenylate Cyclase:
Requires:
Net effect:
o Invasive Adenylate Cyclase: enters cells directly to stimulate cAMP production (also increases cAMP)
• Requires calmodulin (Ca binding protein) for activation
• Net effect: interference with chemotaxis and superoxide production by PMNs
Bordetella pertussis (Whooping Cough) Regulation of Virulence Factors:
Regulation of Virulence Factors: occurs through a 2 component signal transduction system
• BvgS
• BvgA
Bordetella pertussis (Whooping Cough)
Regulation of Virulence Factors
BvgS:
BvgS: transmembrane histidine kinase; body temperature or ion changes cause BvgS to phosphorylate BvgA
Bordetella pertussis (Whooping Cough)
Regulation of Virulence Factors
BvgA:
• BvgA: cytoplasmic response regulator; transcriptional activator of over 20 unlinked genes
Bordetella pertussis (Whooping Cough) Temporal (Timed) Control of VF Expression:
Pili and FHA turned on first (adherence to ciliated epithelium)
Ptx and Invasive AC turned on later (cytotoxicity)
Bordetella pertussis (Whooping Cough)
Disease often seen in:
Only infects:
- Disease often seen in infants and preschoolers
* Only infects human respiratory tract
Bordetella pertussis (Whooping Cough) Transmission:
Transmission: HIGHLY contagious (droplet spread)
• Even immunized patients may have mild symptoms
• Adult pertussis epidemics occur often (adults develop long-term dry cough for up to 3 mo)
• Adult carriers can be a source of infection for unvaccinated newborns
Bordetella pertussis (Whooping Cough)
Whooping Cough:
May also cause:
o Whooping Cough: an acute bronchitis (prolonged disease with paroxysmal/violent cough)
• May also cause edema and hemorrhages in the brain
Bordetella pertussis (Whooping Cough) Mechanism of Disease
PHA directs organism to:
Toxins kill:
Systemic effects are due to:
What leads to cough?
- PHA directs organism to adhere to bronchial epithelium
- Toxins kill ciliated cells and interfere with phagocytosis
- Systemic effects are due to toxin, NOT bacteria
- Local inflammatory response to bacteria in bronchi leads to cough
Bordetella pertussis (Whooping Cough) Deep nasopharyngeal cultures:
- Needs to be cultured immediately (does not survived well)
- Grown on charcoal blood agar + cephalosporins (to inhibit G positives)
- Slow growth (3-7 days)
Bordetella pertussis (Whooping Cough)
Stain/Shape:
Direct fluorescent Ab detection:
G(-) coccobacillus (resembles Haemophilus)
Direct fluorescent Ab detection: should still also be confirmed by culture
