Minor resp 7&8

Question 1

What parts of respiratory tract have commensal flora and which are essentially sterile

Answer 1

The upper tract - nasal cavity pharynx larynx have commensal flora

The lower tract - trachea , bronchi and lungs are essentially sterile

Question 2

Why is the respiratory tract the most common site for infection

Answer 2

It has direct contact with the physical environment

Exposed to many potential pathogens

15000 litres of air breathed every 24 hours

Question 3

What are common characteristics of URT infections

Answer 3

URT infections are usually
benign, transitory and self-
limiting and the majority are caused by viruses

Question 4

What are common characteristics of LRT infections

Answer 4

LRTs esp. Pneumonia can be
severe.
* Bacteria are main
pathogens in LRTIs

Question 5

How does the respiratory tract resist infection and what happens if this is disrupted

Answer 5

Respiratory tract possesses a variety of defence
mechanisms
* Generally providing very effective resistance to infection.
* Lowering of resistance usually necessary for infection.
e.g. Viral infection often precedes bacterial infection.

Question 6

How do viruses infect a cell and how does this lead to tropism

Answer 6

Animal viruses bind to specific receptors on
the host cell surface.
* Variation in the display of receptors in
different cell-types leads to tropism
of different viruses.
– Tissue tropism (Tissues the virus has a preference for)
– Host range (which species the virus can infect)

Question 7

Describe the process of viral replication

Answer 7

1) Virus binds to specific receptors on surface of a host cell

2) The virus delivers its genome to the host cell via uncoating (3 methods uncoating at cell membrane - measles uncoating at endosmome- hep c uncooating at nuclear membrane - adenovirus

3) Replication occurs in which the virus synthesises mRNA. 7 classes of viral genomes determines replication pathway (RNA virus replication occurs in cytoplasm DNA virus occurs in nucleus)

4) Protein synthesis- viral genes encode proteins and use the host vells ribosomes to do this.

5) Viruses leave cell by budding (enveloped) or cell lysis (non enveloped)

Question 8

What is the pharmacological strategy of antivirals

Answer 8

Antiviral agents do NOT ‘kill’ viruses, they inhibit replication
and/or spread.

Question 9

How do viral specific agents work

Answer 9

interact with viral proteins or nucleic acids involved
in viral entry, transcription, replication of the viral genome, assembly, and
release of infectious viral particles.

Question 10

How do host directed antivirals work

Answer 10

modulate the activity of host factors and pathways
involved in the synthesis, processing, and transport of viral building
blocks, as well as in the development of antiviral and inflammatory
responses.

Question 11

What is the Adenovirus

Answer 11

Extremely hardy; can survive long periods
outside the host.
* A dsDNA virus with an icosahedral capsid.

Question 12

Describe what the adenovirus causes and how its transmitted

Answer 12

Usually cause acute respiratory disease.
– More common in young than adults.
– Persistent infection may occur in tonsils.
* Infection usually via droplet transmission.
* Outbreaks most common in winter, spring and
early summer, especially in crowded institutions.
* Multiple human serotypes

Question 13

How does adenovirus present

Answer 13

• Typically types 1-7 responsible for c10% acute
  febrile URT infections.
• Fever, rhinorrhea, cough, and sore throat (3-7
  days).
• Adenoviral lower RTI’s may mimic RSV infection
  or influenza.
  – Conjunctivitis in the presence of bronchitis suggests
  adenoviral infection.

Question 14

How is Adenovirus treated

Answer 14

Disease usually mild and self-limiting; supportive/
symptomatic only.
* Some antivirals used (e.g. Ribavarin and
Ganciclovir) to treat serious infection in the
immunocompromised.
– Vaccine developed for serotypes 4 and 7.

Question 15

What is coronavirus and how is it transmitted and treated ?

Answer 15

Most coronaviruses cause acute, mild upper
respiratory infection (i.e. a cold!): mostly in
winter/early spring.
– Responsible for approx 10–15% of colds.
* Transmission is usually via airborne droplets to
the nasal mucosa.
– Virus replicates locally in cells of the ciliated
epithelium.
* Treatment is symptomatic; hygiene measures
may reduce transmission rate.

Question 16

How is influenza transmitted and how does the body response

Answer 16

• Transmitted in aerosols of respiratory secretions.
  – Virus multiplies in the respiratory mucosa.
  – most contagious in the first 3-4 days of illness.
• Influenza symptoms overlap those of many other viral
  URTIs.
  – A number of other viruses may initially cause influenza-like
  illness.
  – May cause Lower respiratory tract infection.
• Cell-mediated- and antibody response develop post-
  infection.
  – Antibody provides long-lasting immunity against the infecting
  strain.

Question 17

What is croup

Answer 17

• Acute infection of the lining of larynx,
  trachea and bronchi.
• Usually viral (parainfluenza
  virus in 80% cases).
• May also affect epiglottis (epiglottitis).
• Particularly problematic in
  young children and babies.
• Infection can lead to swelling and
  constriction of the airways (steroid
  treatment).
• 60% cases resolve in 48 hrs.

Question 18

What is HPV how is it transmitted and what are the 4 main types

Answer 18

• A Paramyxovirus (enveloped ssRNA virus).
  − related to influenza viruses.
• Transmission is by droplets or direct contact.
• Cause mild or severe upper and lower
  respiratory tract infections.
  – Responsible for 30-40% of childhood colds, croup, bronchitis
  and pneumonia.
• 4 main types:
  – Types 1 & 2: Major cause of croup in children under 5.
  – Type 3: Bronchopneumonia <1 year (second only to RSV as
  cause of pneumonia and bronchiolitis).
  – Type 4: Mild upper respiratory infections.

Question 19

What isa rhinovirus

Answer 19

ssRNA virus: Probably most common infectious agent in
humans.
* Over 100 different serotypes.
– Vaccine production almost
impossible.
– Most use the Intercellular adhesion
molecule-1 (ICAM-1) as the major
cellular receptor.
* Mostly restricted to URT.
– May cause otitis media and sinusitis.
– May also exacerbate asthma, cystic fibrosis, chronic
bronchitis, and serious LRT illness. e.g. In coinfections
with RSV.

Question 20

What is the pathophysiology of a cold

Answer 20

Some virus specificity:
– e.g. Human RV infection alters
expression of genes associated
with immune response (incl.
chemokines). These inflammatory
mediators then produce the
symptoms.

Question 21

What is RSV

Answer 21

• A Paramyxovirus (Enveloped ssRNA
  virus).
• Two major antigenic subgroups, A & B.
• Two surface glycoproteins; G and F:
  – G: Major attachment protein
  – F: Fusion protein
  – F-glycoprotein only on viral surface
  membrane and highly conserved
  Across both subgroups.

Question 22

What are the characteristics of RSV

Answer 22

• Common cause of colds AND the most frequent cause of serious
  respiratory disease in infants and young children.
• RSV initially replicates in the nose and throat before spreading
  to the LRT.
• Usually self-limiting (10–14 days) but may require
  hospitalisation.
  – c30,000 <5 year-olds hospitalised in the UK per year.
  – 33 deaths per year in children under the age of five.
• Can cause severe disease in adults.
  – 8,000 deaths/year in 65+.

Question 23

How is RSV transmitted

Answer 23

Reservoir of RSV is in older children.
* Transmission is primarily by large droplets or hand-to-hand contact.
* Outbreaks occur in autumn, winter and early spring.
* Nosocomial outbreaks (paediatric wards & nurseries) major
problem

Question 24

What is the pathology of RSV

Answer 24

Replicates in ciliated epithelial cells (middle/lower respiratory tract)

Causes:

Enzyme release → inflammation

Necrosis, mucus, fibrin → plugs airways

Otitis media common in infants

Question 25

What is ribavarin

Answer 25

Ribavirin is a synthetic guanosine analogue. * The active form is the triphophate (phosphorylated in vivo). * Used for treatment of severe RSV infection. – Ribavirin is also the only known treatment for some viral haemorrhagic fevers. – 1990’s use vs. HCV. * Mechanism of action uncertain

Question 26

What are humanised monoclonal antibodies like palivizumab and niresevimab

Answer 26

What are they? Antibodies made of 95% human + 5% mouse antibody sequences. What do they do? They prevent serious RSV disease in high-risk children (not for treatment). How do they work? They target the F-glycoprotein (Fusion protein) on the surface of RSV, which helps the virus fuse with human cells. Differences: Palivizumab Older drug Requires multiple doses Nirsevimab Newer drug Has a 3-amino acid change in Fc region → lasts longer Single intramuscular dose covers full RSV season Gives ~10x higher antibody levels than palivizumab ⚠️ Key clinical points: No benefit in active RSV infection (only prevention). Recommended for high-risk infants: Premature babies Babies with congenital heart disease Not used for healthy children.

Question 27

What is hMPV what does it cause and how is it treated

Answer 27

Human Metapneumovirus (hMPV) is a Paramyxovirus, first identified in 2001. It is an enveloped single-stranded RNA virus, closely related to RSV. hMPV has two major groups (A and B) and four subgroups identified so far. It is the second most common cause (after RSV) of paediatric lower respiratory tract infections, responsible for about 10% of hospitalisations. hMPV also causes upper respiratory tract infections in people of all ages. There is no specific antiviral treatment; management is supportive care only.

Question 28

How can viral infections and stress lead bacterial infections

Answer 28

Viral infections damage respiratory epithelium, making it easier for bacteria to stick and infect. Viruses can also suppress the immune system or increase receptor expression through inflammation, promoting more infection. Additionally, stress can change surface protein levels on cells (e.g. increases fibronectin), further helping bacteria attach.

Question 29

What is pharyngitis

Answer 29

Pharyngitis/tonsillitis is acute inflammation of the throat (pharynx) or tonsils. Most cases are viral (self-limiting). If bacterial, it’s usually Streptococcus pyogenes (Group A Strep, GAS). Complications (rare) include: Scarlet fever Rheumatic fever Toxic shock syndrome Quinsy (peritonsillar abscess)

Question 30

What is streptococcus pyrogens and how is it treated

Answer 30

Main cause of scarlet fever. Still mostly sensitive to beta-lactam antibiotics. Has many virulence factors: Carbohydrate capsule stops neutrophil phagocytosis. Capsule + cell wall proteins help it attach to host tissues.

Question 31

What is scarlet fever

Answer 31

Scarlet fever is most common in children aged 2–8 years and is a notifiable disease. It presents with a widespread red-pink rash, red sore throat, fever, and swollen neck glands. The condition is usually mild, but the number of cases in England is currently at its highest level in 50 years.

Question 32

What is epiglottitis

Answer 32

Epiglottitis is a potential medical emergency caused by profound swelling of the upper airways. It is rare and usually caused by Streptococcus species or Haemophilus influenzae type B, but can also involve Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella catarrhalis. After widespread HIB vaccination, affected children’s age shifted from 3 years to 6–12 years. It typically starts with a high fever and sore throat. In adults, it usually occurs in those with some degree of immunocompromise.

Question 33

What is haemophilus infuenzae

Answer 33

Haemophilus influenzae is a gram-negative bacillus. Only 5% are encapsulated, and it is divided into 6 serotypes (A–F). Type B (Hib) is the most virulent, causing pneumonia, septicaemia, meningitis, and epiglottitis in children under 5 years old. In adults, most infections are caused by non-encapsulated strains (NTHi).

Question 34

What is moraxella spp

Answer 34

Moraxella spp. are gram-negative, pleiomorphic, short, non-motile diplobacilli. They belong to the neisseriaceae family. The species Moraxella catarrhalis is the most significant for respiratory disease. These bacteria can be isolated from many body sites, especially the nasopharynx.

Question 35

What is acute otis media

Answer 35

Acute otitis media is inflammation of the middle ear, most common in young children. It is usually viral and self-limiting, but bacteria can cause it too, mainly Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Treatment involves amoxicillin, or erythromycin/clarithromycin if there’s no improvement after 72–96 hours. Antibiotics are given sooner if symptoms worsen or complications arise. Studies confirming these bacteria as the most frequent causes, with S. pneumoniae being most common, followed by H. influenzae and M. catarrhalis

Question 36

What is sinusitis

Answer 36

Otitis media with effusion usually follows a previous upper respiratory tract (URT) infection and is typically viral. If bacterial, the causes are the same as acute otitis media (S. pneumoniae, H. influenzae, M. catarrhalis). Antibiotics are only used for persistent or severe cases. Decongestants can help drainage, and surgery is considered in extreme cases.

Question 37

What is whooping cough

Answer 37

Whooping cough is caused by Bordetella pertussis, a gram-negative cocco-bacillus, an exclusive human pathogen that affects all ages. The disease has three stages: Non-specific (rhinitis, cough) Paroxysmal phase (severe coughing fits, multiple times per hour for weeks, often followed by vomiting) Recovery It is primarily a toxin-mediated disease, peaking every 3–5 years. Bacteria attach to ciliated epithelial cells using adhesins, and produce two key toxins: Pertussis toxin (PT) → multi-subunit exotoxin Adenylate cyclase toxin (ACT) New evidence suggests bacteria may also survive in alveolar macrophages. Pertussis is serious at age extremes, with a 2% infant death rate accounting for 96% of all pertussis deaths. The final slide shows resurgence in countries switching to acellular vaccines (ACV) (e.g., DTaP). Causes include shorter-lasting immunity, protection against disease but not colonisation, and possibly other factors.