Case of Vaccine Refuser Flashcards
Different in active and passive vaccine?
active- cause organism to mount an immune response- as if real infection had taken place
passive- prefabricated immune response (an antibody concentrate)
immunisation for diptheria?
horses injected with cornyebacterium diphteriae toxin- then horse serum collected and the antitoxin us used for human use
horse serum problems?
horse protein will induce anti-antibodies in patient resulting in formation of complexes… secondary immune complex disease
horse igG is 5 days and human is 20 days, rapidly eliminated. Repeat administration can lead to anaphylactic shock. may soon be replaced by human igG produced in bio-reactors
who should not get live vaccines?
compromised immune system people, may not be able to contain that infection,
examples of life vaccine?
shingles, BCG, MMR nasal spray influenza and rubeola, produce stronger immune responses
what does inactivated vaccines require?
repeat doses, booster
examples influenza, pertussis, poliomyleitis, typhoid
what is unique about polysaccharide vaccines?
combined to a carrier to increase imunogenicity
subunit vaccine example
hepatitis b
virus like particle vaccine example
HPV
Subunit conjugate vaccine example
haemophilus influenza B
toxoid vaccine for
tetanus, diphteria
DNA/RNA vaccines for?
COVID- vector based AstraZeneca
liposomal vaccine- Pfizer/ moderna
what do adjuvants do?
increase local immunity to vaccine and attract other immune cells
routine vaccinations start at?
8 weeks
post exposure prophylaxis?
hepatitis B, tetanus and rabies, anti venoms and antitoxins
what should be given to baby whose mother develops varicella 1 week before or after delivery?
VZV hyperimmune globulin
where does SARS Cov2 protein bind?
ACE-2 and Nrp1 (neuropilin1)
what is the issue if one antibody or competing antibodies are given?
novel spike mutation
RNA vaccine does not ?
interfere with host cells genes
mRNA needs to be stable enough to be translated so hence requires?
- A specially modified nucleotide positioned at the 5’ cap
- a poly A tail length
- the composition and structure of the 3’ untranslated region
advantages of mRNA vaccine?
safety- no pathogen particles, RNA strand is degraded when protein is made, not integrated in host genome
efficacy- reliable immune response, well-tolerated and few side effects
production- rapid, standardised, scaled to meet needs of pandemic
can be effective for cancer vaccines
herd immunity?
infection is no longer effectively transmitted across population because too many individuals are immune
herd immunity level?
r naught, in covid 19, 5-6
this would cause hundred thousands of death
original antigenic sin?
antigen exposure causes recruitment of b cells- make antibodies and t cells . second times- t cells and igG peak at 5-10 days
but with slightly changed virus- existing memory response is ineffective, with antibodies not neutralising the changed virus
if similar enough, same antobodies can bind to an extent and the existing memory b cells may expand further but no new immune response is made
narcolepsy is
severe sleep disruption, loss of concentration, social difficulties and complete loss of muscle control
narcolepsy was attributed to?
AS03- adjuvant in GSK vaccine
1/55,000
narcolepsy was attributed to?
AS03- adjuvant in GSK vaccine
1/55,000
adjuvants?
mineral salt: aluminium hydroxide
micro-fluidised detergent, emulsions and saponins- MF59, AS03
TLR agonist- CpG and flagellin
EFFICACY?
works in lab like conditions
how do RCTs protect against confounding?
temporal precedence
higher risk of bias in?
case reports, whereas RCT has the lowest risk of bias
clinical equipoise
genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
what makes a good RCT?
internal validity- is the exposure causing the outcome in the study
external validity- are the findings generalised to others
bias?
partiality that prevents objective consideration of an issue or situation
bias is independent of?
sample size and statistical significance
bias is concerned with?
systematic error
selection bias?
- not adequately capturing relevant population
- systematic difference in comparison groups at outset
performance bias?
introducing differences between groups in care provided/ exposures encountered
attrition bias?
difference between groups in drop outs
observer, detection bias?
not adequately capturing the outcome of interest
systematic differences in the way information is collection for the groups being studied
how to minimise selection bias?
inclusion/exclusion criteria and sampling strategies
randomisation and allocation procedures
how to minimise performance, attrition, observer, detection bias?
blinding/ masking
open RCT?
everyone involved in trial knows
Intention to treat?
analyse outcome for everyone randomised irrespective of whether they have/adhere to interventions allocated
per protocol?
analyse outcomes for only those who received dose of intervention as specified in protocol
Type I error?
there is no true difference but an observed difference
accepted at 5%
Type II error?
There is a true difference but no observed difference accepted at 10/20%
what is p value?
probability that the difference observed could have occurred by chance if the groups were really alike
confidence interval?
range of values within a given probability (95%) that the true value of a variable is contained within that range
RCT advatanges?
safety, efficacy
best single study for causal association
temporal precedence
deals with confounding
RCT disadvantages?
time consuming, laborious
expensive
internal validity issues
issues with external validity