Molecular and Genomic Epidemology of Infections

Question 1

Define molecular epidemiology.

Answer 1

It is a resolved measure (diversity) of differences (variables) that determines:

• disease distribution in time and place
• disease transmission
• disease manifestation
• disease progression

Question 2

What kinds of questions can molecular epidemiology answer?

Answer 2

It can help with CONFIRMING OUTBREAKS and IDENTIFYING DISEASE RISKS.

Confirming outbreaks:

• inside institutions
• in the community
• in the past
• in the lab

Identifying disease risks:

• shifts in virulence
• reservoirs of infection

Question 3

Which targets do we consider?

Answer 3

FUNCTIONAL CHARACTERISTICS:

• Classical (biochemistry)
• Serology (antigens, etc.)
• Virulence (toxins, etc.)

GENOMIC CHARACTERISTIC:

• DNA (gene, amino acid sequence, base sequence)
• RNA (ribosomes, miRNA)

Question 4

For each of the targets listed, how many do we consider?

Answer 4

With functional characteristics, we would only look at a single target.

However, for genomic characteristics, we could look at multiple characteristics at a time. This could be to increase the sensitivity in the testing.

Question 5

How do we determine how diverse the targets are?

Answer 5

With single weighting, we are looking for either the presence of absence of the factor.

For additive weighting, we could use a combination of single tests.

For multiple weighting, we would look at genomic factors, which could be:
- FACTORAL: presence or absence of a gene/base/s change
in genome/gene relative to location in the genome
- FUNCTIONAL: type of substitution (synonymous/ non-synonymous)
- TEMPORAL: mutation rate (time since the last alteration)

Question 6

What is the constant molecular clock, and what is it’s use?

Answer 6

It is the constant time in which there is a possibility that a mutation will occur.

Accurate predictions in molecular epidemiology thus require an assumption that evolution is driven by a ‘constant molecular clock’.

Question 7

List some factors affecting the speed of the ‘molecular clock’.

Answer 7

BACTERIAL REPLICATION RATE:
- a high division rate provides a higher mutation rate

DNA/RNA POLYMERASE PROOF READING FIDELITY:
- some species (eg HIV) have low fidelity promoting high mutation rate

SELECTION PRESSURE FROM HOST/ ENVIRONMENT:

• high selection pressure removes ‘weak’ mutants and emphasises clusters
• loss of selection pressure allows deletions

DEGREE OF REDUNDANCY IN GENOME:

• multiple copies of a single gene in the genome allow for mutations in one copy without compromising overall functionality
• movement or recombination within genome may not effect phenotype

TRANSMISSION RATE:
- high transmission rates relative to the mutation rate results in dissemination and single strain outbreaks

Question 8

Which genes change the most in genetic/antigenic drift?

Answer 8

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

Not all changes are new. Some may be the pathogen reverting BACK to an older profile (convergent evolution).

Large and rapid changes are rare but often lead to escape from existing herd protection.

Question 9

List some epidemiological associations.

Answer 9

TRANSMISSION:
- hospital acquired infection

RESERVOIRS OF INFECTION:

• contact tracing
• determining introduction events

SPREAD OR EMERGENCE OF RESISTANCE