Respiratory Infections 4 Flashcards
Bordetella pertussis : Biology
Gram –ve coccobacillus
• Fastidious, requires special media
What agar does Bordetella pertussis use
Regan Lowe, Bordet-Genou agar
• Charcoal blood agar + cephalosporin
• Samples acquired from ciliated nasal epithelium
How to prevent B. pertussis
Acellular Pertussis “aP” component of the DTaP/Tdap vaccine
• Pertussis Toxin (PT), Filamentous hemagglutinin (FHA), Pertactin
• Recommended for infants
• Tdap booster strongly recommended for pregnant woman to prevent
transmission from mom to neonate
B. pertussis: Pathogenesis part 1
- Infectious aerosol droplets are inhaled
- Filamentous Hemagglutinin (FHA), Pertactin, fimbriae facilitate tight binding to ciliated epithelium of nose, trachea, bronchi
B. pertussis: Pathogenesis part 2
Virulence Activation
Colonization impairs ciliary function
Bacteria secrete Tracheal Cytotoxin (direct damage) and Pertussis/Adenylyl Cyclase Toxin (alters GCPR signaling pathways)
B. pertussis: Pathogenesis part 3
Contribution of Host Immune response
• Cilia damage contributes to necrosis
• Leukocytes fail to migrate to infected tissue (leukocytosis)
• Excessive mucus production contribute to cough severity
Which toxin from b pertussis is an
• A-B type Exotoxin
• Inactivates α-subunit GCPR via ADP ribosylation
• Inhibits immune signaling and chemotaxis
Pertussis Toxin
What does Adenylyl Cyclase Toxin do
• Increases cAMP levels of respiratory epithelium
• Contributes to immune cell dysregulation and
increased mucus production
Whooping Cough aka Tracheobronchitis has three stages
Stage 1: catarrhal (1-2weeks)
Stage 2: paroxysmal (1-6weeks)
Stage 3: convalescence (2-3 weeks; susceptible to other respiratory infections)
Clinical Presentation:
Whooping Cough aka Tracheobronchitis stages
Stage 1 Catarrhal • Common cold/Rhino- pharyngitis Stage 2 Paroxysmal • Sore throat • Intense coughing episodes, followed by a “whoop” • Productive clear sputum • Vomiting • Hypoxia/Cyanosis • Lab Finding: Predominant lymphocytosis Stage 3 Convalescence • Residual cough
Which pathogen causes croup
Parainfluenza PIV
Paramyxoviridae Family Biology
• Enveloped ss(-)RNA genome in helical nucleocapsid • Includes: Parainfluenza Virus PIV Respiratory Syncytia Virus RSV Human Metapnemovirus (HMV) Measles Virus Mumps Virus
Paramyxoviridae pathogenic features
Attachment
PIV = HN (Hemagglutinin-Neuraminidase)
RSV, HMV = G-protein
Entry-Penetration
PIV, RSV, HMV = F protein
Genome Synthesis
PIV, RSV, HMV = L protein “Large” RNA- Dependent RNA Polymerase
Parainfluenza PIV Epidemiology
- Very common respiratory pathogen esp. pediatric population
- 4 Serotypes: PIV-1, PIV-2, PIV-3, PIV-4
- Croup is most common in children < 5 years old
- Adults can be asymptomatic carriers
Predisposing factors of PIV
- Asthma
- Vitamin A deficiency
- Lack of breastfeeding
- Environmental smoke or toxins
Transmission of PIV
Respiratory droplets or via directs person-to-person contact with infected secretions or fomites
Type of PIV or HPIV seen In croup
Croup (Laryngeotracheobronchitis)
HPIV-1, HPIV-2, HPIV-3
Most common cause of bronchiolitis
Respiratory Syncytia Virus RSV
- followed by rhinovirus
Parainfluenza PIV Pathogenesis
- HN on virion acts as VAP; binding to host receptor sialic acid on respiratory epithelial cells
- Fusion F-protein has a hydrophobic fusion peptide which is exposed after VAP attaches.
- F-protein inserts into host membrane, triggering fusion of virion and target cell lipid bilayer membranes.
Viral replication leads to surface expression of F-protein, leading to fusion to new cells aka syncytium formation.
Viral replication, syncytia and host response trigger inflammation for lining larynx, trachea and bronchi.
Clinical Presentation of Croup Laryngo-tracheo-bronchitis
Subglottic narrowing of trachea: steeple sign
Onset 3-7 days
Resolution 10 days
- Preceded by non- specific URTI
- Fever (<38°C)
- Sore throat
- Inspiratory stridor
- Barking Cough
- Hoarseness
- Occasionally vomiting
Leading cause of LRTIs in infants and young children
Respiratory Syncytia Virus RSV
When does HPIV peak ?
Fall
When does RSV peak
Winter
RSV: Pathogenesis
- G-protein mediate attachment; F-protein mediates fusion
- Virions directly invade the respiratory epithelium, leading to syncytia formation, which is followed by immunologically-mediated cell injury.
- Necrosis of the bronchi and bronchioles leads to the formation of “plugs” of mucus, fibrin, and necrotic material within smaller airways.
