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.
Progression of RSV PATHOGENESIS leads to
Infection can progress to alveolar sacs (atypical interstitial pneumonia) or trigger Bacterial Secondary Super- infections
What does this picture show
Section of Lung with Respiratory Syncytial Virus infection. H&E A &B: Necrosis, inflammation and syncytial giant cell formation (note the eosinophilic para-nuclear inclusions, arrows).
Clinical Presentation:
Bronchiolitis – Interstitial Pneumonia
- Preceded by non- specific URTI
- Onset ~7 days
- Fever (<38°C)
- Respiratory distress (↑ RR, retractions, wheezing, crackles)
- Atelectasis
- Hypoxia, cyanosis
What is seen on chest radiograph of Respiratory Syncytial Virus pneumonia and bronchiolitis.
Bilateral interstitial infiltrates, hyper-expansion of the lung, and right upper lobe atelectasis (arrow) are present.
Human Metapneumovirus HMPV biology
Family: Paramyxoviridae
• Genetically, Epidemiologically similar to RSV
• Clinical Presentations are similar to RSV
• Non-specific febrile disease, Bronchitis, Bronchiolitis, Pneumonia
Confirmatory differential diagnosis For RSV vs HMPV requires
RT-PCR
Bronchitis prognosis
▪ Good outcome, usually self-limiting
▪ 90% Bronchitis is viral and does not require antibiotics
▪ Antibiotics for Whooping cough will shorten the course
▪ Complications include interstitial pneumonia (esp. infants) exacerbation of asthma and COPD, bronchiectasis, rib fracture
Examples of LRTI (corresponds to pathogens in this set)
- Laryngotracheitis
- Bronchitis
- Bronchiolitis
- Pneumonia/Pneumonitis
Examples of URTI
- Rhinitis/Rhinosinusitis
- Sinusitis
- Otitis Media
- Epiglottitis
- Pharyngitis/Tonsillitis
How to prevent bronchitis
▪ TDaP/Tdap vaccines, esp for infants and pregnant women
▪ Post-exposure prophylaxis can be used for contacts of person infected with B. pertussis
▪ Ribavirin antiviral recommended for severe RSV
