Molecular and genomic epidemiology of infections Flashcards

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1
Q

What is molecular epidemiology of infections?

A

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
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2
Q

What is the reason for molecular epidemiology?

A
  • confirming outbreaks
  • identifying disease risks
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3
Q

What are the different targets for epidemiology?

A

Functional characterisitcs:

  • classical
  • serology
  • virulence

Genomic:

  • DNA
  • RNA
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4
Q

How can you measure diversity?

A
  1. single weighting
  2. additive weighting
  3. multiple weighting
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5
Q

What is single weighting?

A
  • presence or absence
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6
Q

What is addtive weighting?

A

combination of single tests including:

  • Culture on selective media
  • Serotyping using antibody on blue latex beads
  • PCR of DNA
  • Phage typing
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7
Q

What are the different types of multiple weighting?

A
  • 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
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8
Q

What is the constant molecular clock?

A

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
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9
Q

What is antigenic shift?

A

= 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
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10
Q

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

A

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

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11
Q

What are the epidemiology associations?

A
  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
  1. Spread or emergence of resistance
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12
Q

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

A
  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
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