Molecular and genomic epidemiology of infections Flashcards
What is molecular epidemiology of infections?
A resolved measure (diversity) of differences (variables) that determines:
- Disease distribution in time and place
- Disease transmission - people and places
- Disease manifestation - different types, levels of seriousness, chronic/acute
- Disease progression
What is the reason for molecular epidemiology?
- confirming outbreaks
- identifying disease risks
What are the different targets for epidemiology?
Functional characterisitcs:
- classical
- serology
- virulence
Genomic:
- DNA
- RNA
How can you measure diversity?
- single weighting
- additive weighting
- multiple weighting
What is single weighting?
- presence or absence
What is addtive weighting?
combination of single tests including:
- Culture on selective media
- Serotyping using antibody on blue latex beads
- PCR of DNA
- Phage typing
What are the different types of multiple weighting?
- 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
- presence or abesnce of a gene/base at location on genome
- 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
What is the constant molecular clock?
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
What is antigenic shift?
= 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
What’s the difference between hyper-variable genes and conserved genes?
Hyper-variable genes change more rapidly than conserved genes but conserved genes are more likely to be associated with phenotype and virulence
What are the epidemiology associations?
- Transmission - hospital acquired
* Molecular restriction digest typing can monitor effectiveness of control measures pre and post outbreak - Reservoirs of infection
- Contact tracing
- Can be aided by molecular typing
- Determining introduction events
- Spread or emergence of resistance
What do you have to know before choosing the most appropirate system to test for molecular epidemiology?
- KNowing the most appropriate variable
- quantitating variations and deriving diversity
- generating identities or clusters
- applying related date - geopgrpahic location, time of isolatino, incidence, prevalence and transmission rate