Exam question ideas Flashcards
Describe potential vaccine strategies for CMV
What should be the strategy for RSV prevention in coming season for children(incomplete)
At risk groups include
All neonates and infants- more severe sequelae in those with chronic conditions or prem
Children with chronic conditions
Older adults
Options in children are both passive immunity (unlikely to establish active immunity is baby in time for RSV season)
Options: 1) vaccinate pregnant women, offers neutralising abs to baby. Vaccines trialled in this group prefusion F vaccine:
problems: vaccine data has signalled risk of SGA babies, therefore recommended at 32-36 weeks as a precaution but still a potential issue, also may attenduate pertussis vaccine
2) Nirsevumab, monoclonal ab directed against pre-fusion F. Trials indicate reduction in hospital admissions and severe disease
Better neutralisation capabitilities than paviluzimab, longer half life. one dose lasts ?
Problems: supply and demand issue
In older adults: vaccine shown to reduce hospital admissions. Modelling by JCVI found cost effective for those 75 and over
Describe core principle screening strategies
the condition should be an important health problem
the natural history of the condition should be understood
there should be a recognisable latent or early symptomatic stage
there should be a test that is easy to perform and interpret, acceptable, accurate, reliable, sensitive and specific
there should be an accepted treatment recognised for the disease
treatment should be more effective if started early
there should be a policy on who should be treated
diagnosis and treatment should be cost-effective
case-finding should be a continuous process
https://www.gov.uk/guidance/principles-of-population-screening/principles-of-screening
Hep C in pregnancy screening: why not done in uk
Reasons it should be done (incomplete, see review)
how many pregnant women in the UK have hepatitis C
why some mothers pass the virus to their child and others don’t
Not known: how accurate screening tests are for hepatitis C in pregnant women
how effective treatments for hepatitis C would be for pregnant women and their children
if treatments would prevent unborn babies from catching hepatitis from their mother
Reasons it should be done
-to aid WHO 2030 goal of eliminating HCV
-currently variation in practice, people with past PWID may not be identified: 2/3rds of people with HCV are past injectors or have no current risk factors
-potential to test partners
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683241/
How would you go about setting up HCV screening in in your lab
Discuss management of the recipient of a hhv8 positive organ.
Baseline serology lytic and latent ifats for hhv8 antibodies and DNA testing to guide pathway.
D+/R+: Monthly PCR for 6 months (most are within three years)
D+/R-: DNA monthly for 3 months, 3 monthly then serology at 18 months
Look out for signs of hhv8 related disease (usually apparent by 18 months):
KS
MCD
PEL
one more
Will draft further at work.
If have further immunosupression may need to consider more monitoring
You are bringing in a new assay in to your lab- which statistical analysis can you do to ascertain whether it is adequate in comparison to your current assay
sensitivy,specificity
Bland Altman
Could do ROC curve against gold standard
Pathogenesis of measles
(incomplete)
Fusion protein - fusion of virus and host cell membrane, viral penetration and haemolysis
H protein- bind virus to host cells
Binds to CD46, Nectin-4 on epithelial cells and CD150 on lymphocyte
Primary site of infection is alveolar macrophages or dendritic cells.
After two days spreads via lymphoid tissue, then systematic infection.
following further viral replication in reticuloendothelial system second viraema at 5-7 days. During this phase, infected lymphocyte and dendritic cells migrate and transmit measles to to epithelial cells.
Lymphocyte Cell fusion, syncitia and formation of giant cells Lytic virus
What are the criteria to look for in a new assay
Diagnostic sensitivity and specificity
Analytical sensitivity and specificity
Accuracy
Precision
Reproducibility
Good TAT
?linear ranges
INCOMPLETE
Description of measles outbreaks in UK
Liverpool 2012-2013- large outbreak, in older unvaccinated children, 650 cases (Wakefield cohort), there was a targeted campaign at teenagers
Very few cases in pandemic (travel restrictions)
2023 resurgence: measles coverage is lowest it has ever been over past decade (1st dose 89%, 2nd dose 83%).
80% of cases in west-midlands. Cases peaked mid-january. Most cases in children under 5
London least vaccinated region, lots of regional variation. Inequalities in vaccine uptake by ethnicity, geographical location and deprivation.
Approx 380 cases this outbrek
Steps for measles containment (not complete)
Media involvement
Benefits of multiplex panels
Easier for person organising test (i.e. can request symptom specific panel rather than individual test
Useful for when same symtpom has muliple pathogens
Lower sample volume required
Can reduce other tests needed- i.e culture for bacti, possibly endoscopy for patient
Useful from public health perpesctive- produces data, may identify an outbreak
Aids IPC
Disadvantages of multiplex
User may not appreciate what is not on panel (i.e. measles on a resp panel)
May interpret result as causative agent when it is not the true underlying pathology (eg if someone has a IBD but you detect norovirus)
May find a pathogen of unknown significance
Increased cost
increased targets may come at a cost of sensitivity
More complex assay design
- increased risk of primer mispairing
- increased risk of non-specific amplification
-the enzymes, primers, other reaction components, and temperature cycling for each target may differ, making it difficult to find a single set of conditions (eg anneling temp) that are optimal for all of the targets in the panel
Describe Mpox outbreak
First isolated from research monkeys in 1950, first detected in humans in 1970’s
Endemic is west and central africa
First case outside Africa was in 2003- close contact with prairie dogs
Outbreak in Nigeria in 2017
In UK with travel history to Nigeria in 2019-2021
2022 multiple cases form non-endemic countries with no clear travel history
As of 2022 45,000 cases, of which 390 from endemic regions
(INCOMPLETE- describe clades)
Describe Adeno-asociated virus outbreak
(INCOMPLETE)!
Unexplained hepatitis in children, identified in scotland in 2022
Approx 1000 cases subsequently reported
First step was excluding non-infective causes and other infectious causes (hep A-E), CMV, EBV, HSV
Then undertook metagenomics and target enrichment (TE) next-generation sequencing (NGS) on all available clinical samples from the 9 recruited patients
Did case-control study
Then did a look back
Subsequent wastewater surveillance
