Vaccinations Flashcards
What are personal and community benefits of vaccinations?
vaccination offers personal protection by preventing you from getting sick, but also offers a public health benefit by decreasing your ability to transmit (beta) removing susceptible hosts from the population (s)
fraction of susceptible individuals determines the predicted size of an outbreak
What are the assumptions about the population in vaccination studies?
- fractional of susceptible individuals is uniform throughout the population
- fraction of susceptible individuals remains below the epidemic therhold
What is the threshold theorem?
- expected attack rate in population is protected by solid herd immunity
-one to one relationship between the attack rate and the fraction of susceptible
-small size of outbreaks means low susceptible
What predicts the size of the outbreaks?
fraction of susceptible individuals determines the predicted size an outbreak
What is the factor that tells you about the probability of a larger outbreak?
probability that an outbreak will be major increases with the fraction of individuals in excess of the threshold
Where does the variability in the size of an outbreak come from?
variability in the size of an outbreak is due to chance event in transmission
When is the variability in the outbreak size the largest?
variability becomes large when the fraction of susceptible individuals is close to the epidemic threshold
What is second threshold theorem?
This variability becomes very large when the fraction of susceptible individuals is close to the epidemic threshold level. When the fraction of susceptible individuals exceeds the threshold level, chance events determine whether a minor or a major outbreak will occur. The probability that the outbreak will be a major one increases with the fraction of susceptible individuals in excess of the threshold In their 1927 paper, Kermack and McKendrick showed that when the proportion of susceptible individuals is only slightly above the threshold level, almost two infections occur per susceptible individual in excess of the threshold level during a major outbreak ; this so-called second threshold theorem has been useful in calculating expected outbreak sizes
Why don’t we get resistance to vaccines?
For most infectious diseases, hours to days elapse between
exposure to a pathogen and symptomatic infection in a host.
Typically, relatively few pathogen virions or cells establish an
infection but then, as replication proceeds, populations balloon
to the vast numbers associated with illness and infectiousness
(e.g. [47–49]). Pathogen replication during this incubation
period creates opportunities for mutations to arise, while
pathogen transmission after this incubation period creates
opportunities for these mutations to spread to new hosts.
- you can’t really detect symptoms before the population is quite large → the treatment doesn’t come in until then either
- with prophylactic treatment such as vaccines ongoing use of an intervention prior to known exposure is the extreme limit of early treatment
- the protective immune responses that vaccines elicit tend to keep pathogen populations from ever achieving large sizes, reducing the accumulation of diversity and opportunities for onward transmissiuon
give an example of drugs used prohylatically
- there are several examples where the prohylactic use of drugs has successfully prevented drug resistancee
- monotherapy with the antiretroviral zidovudine to prevent HIV infection in healthcare workers
- this therapy routinely leads to evolution of resistance when given to HIV-infected patients but when used as postexposure prophylaxis it reduced the infection risk in healthcare workers fivefold
why then does the pathogen evolution regularly undermine drug efficacy but rarely undermine vaccine efficacy?
- A drug often interferes with a specific step in a specific metabolic pathway.
- A vaccine, however, often exposes the host immune system to multiple pathogen proteins (antigens), and multiple potential binding sites (epitopes) on each antigen.
- Example: approximately 100 unique tetanus-toxoid-specific antibodies can be observed in healthy humans after receiving a tetanus-toxoid booster vaccine
- vaccines work on multiple targets
What happened with Bacteria Yersinia ruckericauses vaccines?
- Bacteria Yersinia ruckericauses enteric redmouth disease in farmed salmonids.
- Resistance evolved multiple times but all new biotypes were characterized by its lack of flagella and phospholipase secretion activity
- attributed to single mutational events that differed between the lineages but that acted in the same flagellar secretion pathway.
- The high multiplicity-of-target-sites benefit of vaccination was absent here: a single mutational event was capable of generating resistance to many mechanisms of action simultaneously.
Mark’s disease vaccine
- Marek’s disease- a commercially important disease of chickens caused by Marek’s disease virus
- Two generations of vaccines were undermined by viral evolution
- Vaccines prevented disease, but they did not prevent viral infection, replication, or transmission.
- Marek’s disease virus reached large population sizes even within vaccinated hosts and was able to transmit to new hosts.
- Virus was likely able to generate genetic diversity within vaccinated hosts, and vaccine-induced selection was able to act during transmission between hosts
Describe the HVT bird experiment
- Groups of ten birds were HVT-vaccinated or not and experimentally infected with one of our three most virulent MDV strains, and co-housed with ten unvaccinated sentinel birds.
- What do expect-
- Survival of the birds that experimentally infected and vaccinated
- Infection rates in the sentinel birds
- Mortality in sentinel birds
The vaccinated birds survive longer
A greater proportion of the sentinels test positive when held with the vaccinated birds
Mortality is higher among sentinels held with the unvaccinated birds
