Questions from S Flashcards
You are on clinical review, and authorising a CMV/EBV DNA PCR run. Amongst results is patient with CMV DNA virus load of 10,135 IU/ml in haematology patient who had haematopoeitic stem cell transplant 3 months ago. Last samples was sent two weeks previously with level 1020IU/ml. Serial weekly samples prior to this were not detected.
What would you do next?
Gain further information:
- Check correct patient bled
- Check comparable assay used
- FBC/UE – suppression/ renal disease
- Stem cell transplant – matching CMV donor status
- Conditioning regimen
- Any blood products
You are on clinical review, and authorising a CMV/EBV DNA PCR run. Amongst results is patient with CMV DNA virus load of 10,135 IU/ml in haematology patient who had haematopoeitic stem stell transplant 3 months ago. Last samples was sent two weeks previously with level 1020IU/ml. Serial weekly samples prior to this were not detected.
Further information:
D+R-
6 weeks post-transplant
On Letermovir
No concerns regarding absorption
Why is patient on Letermovir?
What advice would you give?
- Letermorvir is licensed for CMV prophylaxis (not treatment). Less myelosuppressive and better for renal disease than alternatives
Steroids/ immunosuppression from GVHD
- Primary infection
- End organ disease either from CMV, or from GVHD – eyes/ lungs/ GI/ liver
- Consider other infections
- Send for CMV whole genome sequencing/ resistance testing
Why is this patient of Letermovir
- Less myelosuppressive/ nephrotoxic than ganciclovir/ foscarnet
- High risk D+/R-
Advice
- If no disease, consider observing, as undergoing primary infection - is this wrong?
- If no disease, switch to valganciclovir prophylaxis. As rising viral load on letermovir suggests failure, and likely viral load to rise further
- End-organ disease – IV ganciclovir treatment. Less myelosuppression as 3 months – should be engrafted
What are treatment options for CMV?
Valganciclovir
Ganciclovir
Foscarnet
Cidofovir
Brincidofovir
Maribavir
Letermovir only licensed as prophylaxis
What are mechanism of action of drugs for CMV?
Valganciclovir
Ganciclovir
Foscarnet
Cidofovir
Brincidofovir
Letermovir
Ganciclovir/ Valganciclovir - guanosine analogue, inhibits DNA polymerase
Foscarnet - pyrophosphate analogue, non-competitively inhibits DNA polymerase
Cidofovir/Brincidofovir - nucleotide analogue inhibits DNA polymerase
Letermovir- DNA termianse complex inhibitor
Post-stem cell transplant patient being treated for CMV infection.
rising viral load, and concerned about viral resistance.
Which genes are targeted during CMV resistance testing?
Mutations leading to CMV drug resistance have been described in
UL54 - DNA polymerase
UL 56 - viral terminase complex
UL97 - phosphotransferase encoding region
UL54 mutation - Ganciclovir resistance/ Cidofovir/ Foscarnet resistance
UL56 mutation - Letermovir resistance
UL97 mutation - Ganciclovir
Miller-Fisher variant GBS - virology FRCPath2 oral question
What is common presentation?
What auto-antibody is detected in 90% of cases?
What is treatment?
Miller Fisher Syndrome (MFS) is a variant of GBS.
Usually begins with the rapid development, over days, of 3 problems:
- ascending paralysis - leg weakness/ respiratory failure
- weak eye muscles, with double or blurred vision, and often drooping eyelids with facial weakness. Cranial nerve involvement is typical for Miller-Fischer
- loss of deep tendon reflexes, such as the knee and ankle jerk
Possible preceeding viral/ diarrhoeal illness few days before - Campylobacter/ HEV/ Influenza/ EBV/ CMV possible triggers
Associated with antibodies against ganglioside GQ1b - >90% patients
Treatment:
Steroids
IVIG
Plasma exchange
International Committee of Taxonomy of viruses (ICTV)
Explain their role in the classification of viruses
The objectives of the International Committee on Taxonomy of Viruses are
Agrees upon universal name, describe and classift each unique virus
Name must be stable and not confusing
GenBank sequences compiles list of nucleotide sequences which are not currently named.
What is required for PCR?
List all reagents/ equipment
Lysis
Extraction of DNA template
PCR -
Oligonucleotides
Primers
DNA Polymerase/ RT if required
Buffer - magnesium
Fluorescent probe
Thermal cycler
Analysis -
Analyser
What is meant by genetic barrier to resistance?
Number of mutations required to evade neutralisation of by a drug
low barrier -
Lamivudine HIV - M184V
Lamivudine HBV- L180M/ M204I/ M204V
Efavirenz - K103 RT mutation
high barrier - entecavir - requires high number of mutations before becoming ineffective
RTA – orthopod has needlestick during surgery
IVDU is unlikely gain consciousness again
What is the process of consent for HIV testing?
Cannot consent – either await until awake, or have an external party consent in best interests.
When testing a source, make sure to word it in is in the best interests of both the source and the recipient to know the infection status
RTA – orthopod has needlestick during surgery
IVDU is unlikely gain consciousness again
Orthopod doesn’t want to take PEP.
What are the side-effects?
Advise not to stall, as it must be taken within 72 hours, as is more effective the sooner it is taken.
Raltegravir: loss of appetite, headache, difficulty in sleeping, abnormal dreams, depression, dizziness, vertigo, abdominal pain, bloating, flatulence, diarrhoea, nausea, vomiting, indigestion, rash, weakness, fatigue, fever, raised liver or pancreatic enzymes, and raised triglycerides.
emtricitabine/ tenofovir: The most common side-effects were fatigue (37% of PEP users), diarrhoea (25%), nausea (24%), flatulence (24%), abdominal cramps (21%), bloating (16%), headache (15%), vivid dreams (15%), depression (10%) and thirst (10%)
Check does not interact with any other medications
RTA – orthopod has needlestick during surgery
IVDU is unlikely gain consciousness again
What is the testing follow up for HCV, in the recipient?
6 weeks RNA
12 weeks RNA/Ab
24 weeks Ab
HCV incubation period is 2weeks - 6 months
Recipient - can check RNA on weeks 2 and 4 to help detect earlier.
Source - IVDU may be anti-HCV neg, but RNA pos, if had a very recent infection. Consider RNA testing if active IVDU
RTA – orthopod has needlestick during surgery
IVDU is unlikely gain consciousness again
HBV
Had HBV immunisation course previously. But last immunity check was 20iu/ml
What action would you take?
Clarify source infection status - consent issue
Give booster as it has been >12 months since last vaccine
HBV expouse NSI
unsure if been vaccinated before
Level checked >10 iu/ml
Booster given at same time
Does it need follow up testing for immunity?
As level >10 iu/ml - not classified as a non-responder
Therefore just needs booster, with no follow-up
RTA – orthopod has needlestick during surgery
IVDU is unlikely gain consciousness again
Concerned about HLTV
What would you do?
Consent issue - same as HIV.
Time sensitive - PEP occasionally offered if from known HTLV source. would be discussed with national HTLV centre
Clarify local population HTLV prevalence. And whether source is from high risk area -
HTLV 1 - Caribbean, West Africa, Japan
HTLV2 - Americas, and West Africa
Even if low risk, might still consider testing see note below
Testing includes Ab testing, and if positive proviral DNA testing
Incubation period is long - 6 months to years. So test initially, then likely re-test at 6 months.
Check PEP - UKAP suggest raltegravir, zidovudine, lamivudine for 6 weeks, as in vitro shows activity against HTLV1. But has not shown any clinical benefit
UKAP has noted that there is a gap in guidance on the investigation and management of HTLV-1 exposures for both patients and HCWs, and treatment recommendations. It would be beneficial for guidance to be developed by professional bodies in order to standardise clinical practice and improve reporting.
Testing for HTLV-1 infection in the event of a needlestick injury to HCWs may be one way of gathering such evidence for this cohort. Further research is required to better understand the prevalence of HTLV-1 infection in the general population and key risk groups including HCWs and those at risk of other BBVs for example, people who inject drugs or engage in other behaviours that are associated with BBV transmission risk. In particular, longitudinal studies into disease progression should be instigated to establish the risk of long-term morbidity and mortality.
https://www.gov.uk/government/publications/ukap-htlv-1-in-healthcare-workers-and-exposure-prone-procedures/ukap-statement-on-risk-of-htlv-1-transmission-from-healthcare-workers-to-patients-during-exposure-prone-procedures#:~:text=Recommendation%3A%20UKAP%20does%20not%20currently,1%20from%20HCWs%20to%20patients.
