Respiratory Pathogens, Influenza and Corona Viruses

Question 1

How does airborne transmission occur (aerosols)

Answer 1

• Give rise to large (ground / surfaces) and moderate to small (micro droplets in air) droplets
• Effectively transmitted only over short distances
• Sneezing and coughing

Question 2

Describe streptococcus pyogenes disease

Answer 2

• Group A streptococci
• Upper respiratory tract of healthy individuals, can cause pus-forming wounds
• Causative agent of strep throat
• Strains carry lysogenic bacteriophage (exotoxins causing TSS / scarlet fever)
• Untreated can lead to rheumatic fever

Question 3

What is acute rheumatic fever

Answer 3

• Caused by mimicry between M protein / host tissue of streptococcus pyogenes
• Major issues for indigenous
• Long term prophylactic antibiotic regime (poor compliance)
• No vaccine

Question 4

What is diphtheria

Answer 4

• Severe respiratory disease
• Caused by Corynebacterium diphtheriae (irregular rods during growth)
• Preventable and treatable (resistance via previous infection / immunisation)
• Spreads via airborne droplets
• Pathogenic strains lysogenised by bacteriophage β, produce exotoxin causing tissue death (prevent protein synthesis in throat)

Question 5

What is pertusis

Answer 5

• Whooping cough
• Infectious respiratory disease
• Caused by Bordetella pertusis
• Observed in school age children
• High risk are those inadequately immunised
• Consistent and upwards trend of infection since 1980’s

Question 6

Generally describe respiratory viral infections

Answer 6

• Less easily controlled by chemotherapeutic methods
• Most prevalent human infections
• Most viral diseases are acute, self-limiting infections
• Few serious diseased have been effectively controlled by vaccines (small pox / rabies)

Question 7

What is measles

Answer 7

• Caused by paramyxovirus
• Acute, highly infectious, often epidemic
• -ve strang RNA virus
• Virus enters nose / throat via airborne transmission
• Isolated outbreaks due to worldwide immunisation program (1960’s)
• Still over 600,000 deaths per year worldwide
• Decline in vaccination causes global spread

Question 8

What is mumps

Answer 8

• Caused by paramyxovirus
• -ve strand RNA enveloped virus
• Highly infectious, occasional outbreaks
• Airborne droplets / saliva
• ## Inflammation of salivary glands

Question 9

What is rubella

Answer 9

• +ve strand RNA enveloped virus of toga group
• Symptoms resemble measles
• Milder and less contagious
• Routine childhood immunisation

Question 10

What is varicella-zoster

Answer 10

• Papular rash (chicken pox)
• dsRNA enveloped varicella-zoster virus
• Transmitted by infectious droplets
• Lifelong latent infection in nerve cells
• Virus occasionally migrates to kin causing shingles

Question 11

What is the common cold

Answer 11

• Caused by rhinoviruses
• ssRNA +ve enveloped virus
• Nearly 115 strains identified
• 15% colds due to coronaviruses, 10% due to other viruses
• Antiviral drugs are ineffective
• Large number of pathogens precludes complete protective immunity / vaccines

Question 12

What is influenza

Answer 12

• RNA virus orthomyxovirus, enveloped
• Subgroups due to allelic expression of haemagglutinin (HA) and neuraminidase (NA) proteins
• 14kb genome (10 genes)
• 8 ssRNA -ve segments (A/B)
• 7 ssRNA -ve segments (A/C)

Question 13

What is influenza A

Answer 13

• Affects wide variety of birds
• Ancestor of influenza strain circulating in swine, horses and humans
• 3 polymerase proteins (PB1-3)
• 2 major surface glycoproteins (HA and NA)
• 3 structural proteins (NP, M1-2)
• 2 non-structural proteins (NS1-2)
• Some strains contain PB1, encodes protein involved in host apoptosis
• Can undergo adaptations to infect humans (shift)

Question 14

What is influenza B and C

Answer 14

• B: Infects humans

- C: Infects humans, haemagglutinin esterase (HE) assumes function of HA / NA

Question 15

What is antigenic shift

Answer 15

• Major change in virus antigen due to gene reassortment (not the same as recombination)
• Replacement of HA and or NA alleles
• When 2 virtues infect the same cell, viral gene segments randomly mix giving rise to a new virus
• Avoid immune detection, high rate of infection, significant morbidity / mortality
• Give rise to pandemic
• Pigs act as mixing vessel for bid and human influenza virus (can then reinfect humans)

Question 16

What is antigenic drift

Answer 16

• Minor changes in virus antigens due to gene mutation
• Small changes to the HA and NA proteins
• Caused by plasticity of virus genome (influenza)
• RNA polymerases of RNA viruses lack a proof reading mechanism, mutations accumulate
• Leads to annual outbreaks and limited vaccine efficacy

Question 17

What are characteristics of human influenza and epidemics / pandemics

Answer 17

• Occur periodically
• Epidemic when incidence of influenza rises above the seasonal baseline
• Winter outbreaks occur in north / south hemispheres
• 1 type / subtype of influenza can circulate during an influenza season

Question 18

Who is at high risk for influenza

Answer 18

• Young children and infants
• Immunocompromised individuals
• Elderly / ageing population
• Un-immunised people

Question 19

What is host specificity in relation to Influenza A (birds vs humans)

Answer 19

• Preferential binding of avian viruses to sialic acid receptors, have galactose linked via a2,3-glycosidic bonds
• Molecules are found on intestinal epithelia in birds
• Human sialic acid receptors have a2,6 linked glycosidic bonds
• Limits spread of bird viruses to humans
• Highlights importance of adhesion / specific receptors to allow infection

Question 20

What is genetic reassortment

Answer 20

• Reassortment of viral RNA segments
• Expression of new surface proteins (HA or NA)
• Immune system has no existing immunity to Ag
• Random association of 8 different genetic segments in pigs
• If new virus can replicate / transmit from pig to other hosts, pandemic may spread

Question 21

What molecular technique did scientists use to study virulence and pathogenicity of 1918 Spanish flu

Answer 21

• Reverse genetics
• Non-pathogenic human viruses showed enhanced virulence when carrying 1918 HA protein
• Recombinant viruses containing 1918 HA / NA proteins were highly lethal in mice
• NS1 protein affects virulence by blocking interferon response

Question 22

What are the innate immune mechanisms important for control of influenza virus

Answer 22

• Release of type 1 IFNs
• Produce Abs to recognise HA / NA
• Abs block viral binding to target cells / subsequent cell entry
• Abs not essential for protection (prevent reinfection)
• Increased memory leads to decreased viral load
• Importance of having an effective vaccine

Question 23

How do pigs aid transmission from birds to animals (influenza)

Answer 23

• Due to host receptor specificity, direct transmission of bird flu viruses to humans is uncommon
• Pigs express both types of sialic acid receptors
• Pigs can be infected by human and bird flu
• Allows mixing vessel where genetic reassortment and selection of novel viruses may occur
• Last swine flu virus caused pandemic in 2009

Question 24

What are the clinical symptoms / complications of influenza

Answer 24

Symptoms
- Fever and chills, sore throat, headache, retro-orbital pain
- Severe myalgia (muscle aches), fatigue, prostration, and general malaise
- Nausea, vomiting and diarrhoea
Complications:
- Infection with bacteria, especially, Staph. aureus, Haemophilus influenzae, Strep. pneumoniae or Strep. pyogenes resulting in pneumonia
- Encephalitis with confusion, delirium and coma may occur as well as myocarditis

Question 25

What was the Spanish flu of 1918

Answer 25

• H1N1 influenza A
• 50 million deaths worldwide
• Low transmissibility but high per-case mortality rate
• High death rate for young adults (14-34)
• Wide dissemination, high and rapid replication
• Aberrant and persistent activation of cytokines
• 2.5% case fatality