Molecular and Genomic Epidemiology of Infections Flashcards
What does Molecular and Genomic Epidemiology of Infections determine?
Disease distribution in time and place
Disease transmission
Disease manifestation
Disease progression
Where do outbreaks of infections occur?
In institutions.
In communities.
In the past.
In the lab.
What are the 2 risks of infection?
Shifts in virulence- drug resistance, etc
Reservoirs of infection.
How do we identify diversity that’s caused by either mutations or non-mutations?
Target- functional characteristics (classical biochemistry, serology, virulence) or genomic characteristics (DNA- genes (resistance gene), amino acid sequence, base sequence- or RNA- ribosomes or miRNA).
How many targets? Single serotype, etc? Choose multiple targets to increase sensitivity. Genome may be rearranged- look at genome locus position, etc.
How much diversity? Single weighting (presence or absent) or additive weighting (combination of single tests). Culture on selective media, serotyping, PCR and phage typing.
Multiple weighting is factoral (genomic factors- base changes)- functional (type of substitution- non/synonymous, copy number, etc) or temporal (mutation rate- time since last alteration).
What is spoligotyping?
different copy number change as organism transfers from one patient to another. Change in genomic copy number and patter (change in position) showing strain. Result is profile of presence/absence of specific repeats at one locus
What is VNTR?
variable number of tandem repeats. Profile of number of specific repeats at multiple genomic loci.
What are corruptive mutations?
Corruptive mutations- deletions/insertions (disrupting coding frame), creation of STOP codons (truncation), corruption of STOP codons (elongation) and corruption of CONTROL sequences (e.g. promoters).
E.g. 3 mutations can create 6 potential types but 4 amino acid types (synonymous).
What is antigenic drift?
Gradual alteration in sequence.
Some mutations have more influence on Ab binding affinity than others.
Herd immunity after large vaccination programme kills most but also selects for escape mutants that maintain drift.
Antigenic drift is same antigen changing its sequence base by base over time of isolation.
What is temporal diversity
With phylogenetic progression, taking into account average time to mutate into different clusters.
What is the molecular clock?
Accurate predictions in molecular epidemiology thus requires an assumption that evolution is driven by a ‘constant molecular clock’.
Can date historical infections by determining speed of
mutation.
Factors affecting speed- bacterial replication rate,
DNA/RNA polymerase proof-reading fidelity, selection pressure from host/environment/degree of redundancy in genome/transmission rate.
What is antigenic drift?
- High sequence mutation rate may not affect pathogenicity (antigenic drift).
- Hypervariable genes- change more than conserved genes, but conserved genes more likely to associated with phenotype and virulence.
- Not all changes are new, and some may revert back to older profile (convergent evolution).
- Large and rapid changes are rare but often lead to escape from existing herd protection.
- Some genes, thus some antigens, can be replaced entirely- “antigenic shift”- with another antigen that has evolved separately. New types not protected against by previous infection or vaccination, so new epidemic.
What is molecular restriction digest typing?
- Can monitor effectiveness of control measures.
- DNA extracted and cut with same restriction enzymes then pieces separated on gel electrophoresis and visualised.
- Same strain and high similarity in an epidemic. Reduction in similarity after controls put into place shows effectiveness.
- Molecular typing and contact tracing to aide outbreak sourcing from reservoirs of infection (e.g. HIV mutation from single patient to several partners). Also determines introduction events- molecular clock dating pinpoints first case of Ebola and then its spread. Cluster analysis used to determine number of cases from each introduction event.
- Drug resistance polymorphisms to be traced.
