Epidemiology Flashcards
What is the basic reproductive number (R0)?
the number of secondary infections resulting from introduction of a single infected individual
the outcome of an epidemic depends on R0
–> R0 < 1 = epidemic dies out
–> R0 > 1 = epidemic grows
What are 3 categories of people taken into account when modelling an epidemic?
- susceptible
- infected
- recovered
What are the different types of mutations a pathogen can obtain?
- mutations in nucleotide only
- mutations that change amino acid
- insertions and deletions
- recombination & gene transfer
What is molecular phylogenetics?
the use of molecular data to construct phylogenies
- a phylogeny is a diagram representing the ancestral relationships among characters or genetic sequences
- phylogenetics looks for homology as evidence for common ancestry
- diagrams = trees
–> these are constructed to be able to look at the rates of evolution
What are the differences in evolutionary rates of different pathogens?
RNA viruses
–> fast rate of replication, error prone
DNA viruses
–> slower rate of replication, more conserved
bacteria
–> v slow , but evolution originates mostly from HGT, not from point mutations
parasite
–> v slow
fungi
–> can become resistant to anti-fungals very quickly
What is the structure of a phylogenetic tree?
root
–> origin
internal node
–> hypothetical ancestor
terminal node (leaf)
–> most recent species/strain
clade
–> a group of organisms that includes an ancestral species and all of its descendants, representing a single branch or lineage in the evolutionary history of the organisms being studied
What are rooted trees?
- have a single node that represents a point in time that is earlier than any other node
- have directionality (nodes can be ordered in terms of earlier or later)
- distance between two nodes is represented along the x-axis only (y is meaningless, purely for presentation)
- virus trees can be presented and measure in substitutions per site
What are unrooted trees?
- no directionality
–> do not know if a node is earlier or later than another node - distance along branches directly represents node distance
–> eg genetic distance
What is needed to build a rooted phylogenetic tree?
- sequence data (nucleotide or amino acids)
- a substitution model (also influences branch lengths)
- ability to determine branching order
1 & 2 can be used to build an unrooted tree
What is a substitution model?
- substitution mutations occur between sequences
- some types of substitutions might be more common than others (eg A-G transition)
- therefore, there are different models to reflect this, these specify:
–> the base frequencies
–> the rate of transitions (eg A-G) and transversion (eg G-C)
–> whether there is site to site rate variation eg the proportion of sites which are totally conserved (no changes) or hyper variable
Give an example of a substitution model.
General Time Reversible Model (GTR)
a complex model which states there is unequal base frequencies and all substitution types occur at different rates
What are clustering algorithms?
- the algorithms are v simple and fast
- progressively joins the two closest sequences (or ancestral sequences)
–> eg neighbour joining algorithm
What are optimisation algorithms?
- define an explicit score or goodness of each tree
- try to find the (one) tree which optimises this criterion by swapping parts
–> eg maximum likelihood
How is a time scale added to a phylogenetic tree?
adding a molecular clock
by defining the rate of mutation, a time scale can be added
eg 1 mutation per month
How can it be known who infected who?
next generation sequencing (NGS) can give an idea of who infected whom, but evidence is not generally strong or conclusive
can analyse collections of links between individuals
–> genetic clusters: sequences from samples are genetically similar
similar sequences have recent time to most recent common ancestor (TMRCA)
What is a degree?
how many links an individual has by working it out from clusters
the degree distribution describes how connected individuals are in the network
this also affects R0 because it is about the number of contacts
Apart from time, what is another parameter that can be added to a phylogenetic tree?
locations
-> known as phylogeography
eg the H3N2 tree shows that China and South-east Asia are a backbone for the origin of H3N2
What is a limitation of the R number?
does not tell you how fast an infection is occurring, just in terms of generation
eg the large difference in time between COVID and HIV
A single R number isn’t only indicative of the pathogen…
also takes into account the population it is spreading in
What is the equation for the probability of a major pandemic?
P = 1-(1/R0)
*if a single index case is introduced into the population
What is I-final?
the fraction of a population infected during an outbreak
gives the upper limit, quite a basic indicator
What is the sigma period of infection?
the fraction of infectiousness in absence of symptoms
a small sigma = quarantine and isolation is a simple way of reducing infection as symptoms appear early so reduced no of others infected
a pathogen w a large sigma (eg coronavirus or HIV) means that infection is spread more easily as those infected do not know that they are
What is the herd immunity threshold?
the minimum fraction that must be immunologically protected (by natural exposure or vaccination to reduce R0 below 1
fv = 1 - (1/R0)
For example, if the R0 of a disease is 2 (i.e., each infected person will, on average, infect 2 others), the fv required to achieve herd immunity would be 1 - (1/2) or 50% of the population
R0 is a good indicator of how hard you have to work to control an infection
What is the SLIR model?
Susceptible (S):
- Individuals who are susceptible to infection and have not yet been infected with the disease.
Latent (L):
- Individuals who have been exposed to the infectious agent but are not yet infectious or symptomatic (i.e., incubating period).
- These individuals have been infected but are not yet able to transmit the disease to others.
Infectious (I):
- Individuals who are infectious and can transmit the disease to susceptible individuals.
- These individuals can spread the infection through contact with others.
Recovered (R):
- Individuals who have recovered from the disease and have developed immunity, either naturally or through vaccination.
- These individuals are no longer susceptible to reinfection and do not contribute to disease transmission
the model can be written out as a complex mathematical equation
What is the pathogen pyramid?
pathogens can be categorised into different levels depending on their R0
- exposure
- infection (R0 = 0)
- transmission (0 < R0 < 1)
- epidemic spread (R0 > 1)
only zoonoses are in level 2 (eg rabies) as any human to human infection is level 3
but some zoonotic infection that can go onto human-human transmission can be classed high (eg ebola)
What is Disease X?
the concept of the knowledge that a serious international epidemic could be caused by a pathogen currently known to cause human disease
vets are well versed in animal pathogens, so may have a good idea of which ones have potential to infect humans
What are drivers of pathogen emergence?
- HIV and disease
- Hospitals
- international travel
- land use and agriculture
- climate change
- food and water
- international trade
- failure of control
- pathogen evolution
mainly due to us, not the pathogen itself
where pathogens are likely to pop up can now be accurately determined eg it was known that Wuhan, China was a high risk area
Climate change is a driver for pathogen emergence. Expand.
Habitat Alteration: Climate change can lead to changes in ecosystems, habitats, and biodiversity, affecting the distribution, abundance, and behaviour of wildlife, vectors, and reservoir hosts involved in disease transmission cycles.
Vector-Borne Diseases: Rising temperatures and altered precipitation patterns can expand the geographical range and seasonal activity of vectors (e.g., mosquitoes, ticks) responsible for transmitting diseases such as malaria, dengue fever, Zika virus, Lyme disease, and West Nile virus.
Waterborne Diseases: Changes in rainfall patterns and hydrological cycles can impact water quality, increase the risk of waterborne diseases (e.g., cholera, cryptosporidiosis), and facilitate the transmission of pathogens through contaminated water sources
