Molecular and genomic epidemiology of infections

Question 1

What is molecular epidemiology of infections?

Answer 1

A resolved measure (diversity) of differences (variables) that determines:

1. Disease distribution in time and place
2. Disease transmission - people and places
3. Disease manifestation - different types, levels of seriousness, chronic/acute
4. Disease progression

Question 2

What is the reason for molecular epidemiology?

Answer 2

• confirming outbreaks
• identifying disease risks

Question 3

What are the different targets for epidemiology?

Answer 3

Functional characterisitcs:

• classical
• serology
• virulence

Genomic:

• DNA
• RNA

Question 4

How can you measure diversity?

Answer 4

1. single weighting
2. additive weighting
3. multiple weighting

Question 5

What is single weighting?

Answer 5

• presence or absence

Question 6

What is addtive weighting?

Answer 6

combination of single tests including:

• Culture on selective media
• Serotyping using antibody on blue latex beads
• PCR of DNA
• Phage typing

Question 7

What are the different types of multiple weighting?

Answer 7

• factoral
  
  • presence or abesnce of a gene/base at location on genome
    
    • spoligotyping - profile of the presnce/abese of specific repeats at one locus - shows relatedness of patten
    • variable number of tandem repeats (VNTR) - profile of the number of specific repeats at multiple genomic loci
• functional
  
  • synonymous/non-synonymous - silent changes will not affect the phenotype of the organism
  • Drift = gradual alteratinon in sequence, same antigen changing its sequence base by base
    
    • herd immunity and vaccination kills most but some can escape and maintain the drift
• temporal
  
  • mutation rate = time since the last alteration
  • to see how fast the organism is changing in the past and for the future
  • involves the constant molecular clock
  • Diversity progresses because random mutations occur at a regular rate

Question 8

What is the constant molecular clock?

Answer 8

Accurate predictions in molecular epidemiology thus requires an assumption that evolution is driven by a constant molecular clock

Factors affecting this:

• bacterial replication rate
  
  • high division rate provides higher mutation rate
• proof reading fidelity
  
  • low fidelity promotes high mutation rate
• selection pressure from the host
  
  • high selection pressure removes weak mutants and emphasises clusters
• degree of redundancy in the genome
  
  • multiple copies of a single gene in the genome allow for mutations in one copy without comprinising overall functionality
• transmission rate
  
  • high transmission rates are relative to the mutation rate resulting in single strain outbreaks

Question 9

What is antigenic shift?

Answer 9

= sudden replacement of an antigen by recombination with another viral type that has evolved separately.

• New types will not be protected against previous infection or vaccination - leading to new epidemics

Question 10

What’s the difference between hyper-variable genes and conserved genes?

Answer 10

Hyper-variable genes change more rapidly than conserved genes but conserved genes are more likely to be associated with phenotype and virulence

Question 11

What are the epidemiology associations?

Answer 11

1. Transmission - hospital acquired
   * Molecular restriction digest typing can monitor effectiveness of control measures pre and post outbreak
2. Reservoirs of infection

• Contact tracing
  
  • Can be aided by molecular typing
• Determining introduction events

3. Spread or emergence of resistance

Question 12

What do you have to know before choosing the most appropirate system to test for molecular epidemiology?

Answer 12

1. KNowing the most appropriate variable
2. quantitating variations and deriving diversity
3. generating identities or clusters
4. applying related date - geopgrpahic location, time of isolatino, incidence, prevalence and transmission rate