Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Part 2 Revision > CMV > Flashcards

CMV Flashcards

1
Q

Incidence of congenital CMV?

A

Occurs in 1 out of every 100-200 live births in UK and 1 in 71 in developing nations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Diagnosing CMV in mum with symptoms?

A

Test IgM/G. If only M pos then repeat sample looking for g seroconversion

If M and G pos test earlier sample looking for seroconversion. If both reactive then avidity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

When can you do amniocentesis to look for CMV infection?

What is the sensitivity?

What action do you take following the amnio?

A

This is dependent on foetal urine excretion which starts at 17 weeks (Euro consensus guideline says amnio from 17 weeks, SMI says 21)

This shouldn’t be done until 6 weeks after primary infection in the mother as earlier testing may result in false negative

Around 85-95% sensitive

When fetal CMV infection has been confirmed by amnio-centesis
- Serial ultrasound examination of the fetus should be offered every 2–3 weeks until birth.
- Foetal MRI brain at 28 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Indications for valaciclovir to treat CMV in pregnancy?

A

In cases of maternal primary infection in the periconceptional period or in the first trimester, oral valaciclovir at a dose of 8 g/day should be administered as early as possible after the diagnosis and until the amniocentesis.

From - Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Presentation of cCMV?

A

90% of infants with infection will be asymptomatic at birth
- Around 15% will go on to develop SNHL

10% of cCMV will be symptomatic at birth

Most common
- Petechiae (blueberry muffin rash)
- Hepatosplenomegaly +- hepatitis
- Thrombocytopenia
- CNS involvment
- SNHL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Management of cCMV in the neonate?

A

Ganciclovir 6mg/kg BD or Valgan 16mg/kg - to continue for 6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Followup of a neonate with symptomatic cCMV

A

If treated ID followup for 2 years

Hearing test followup to 6 years

Ophthalmology if symptomatic for 5 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Sensitivity of Guthrie card for cCMV?

A

Sensitivity of NAAT performed from a dried blood spot (Guthrie card) has been reported to be between 70-80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Amniocenteis NPV for symptomatic cCMV?

A

Negative predictive values of between 92.7% and 95.7% are reported for CMV NAAT assays of amniotic fluid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

CMV disease in immunocompromised. Clinical presentation?

A

fever, bone marrow suppression, and tissue invasive (pneumonitis, hepatitis, colitis, nephritis and retinitis).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Highest risk SOT for CMV disease?

A

D+R- - Kidney, liver, pancreas, heart, lung, intestine, face/hand

D- R+ or D+/R+ - higher risk if Campath (alemtuzumab) or ATG (t lymphocyte depletion therapy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Duration of CMV prophylaxis in SOT and dose?

A

Valganciclovir 900mg OD adjusted for renal clearance

Varying recommendations with differences between UK SOT guideline and consensus guideline. Generally
D+r+ kidney and liver at least 3 months (6 in consensus)
“Consider” at least 3 months in heart/lung

D- R+ or D+/R+ - higher risk if Campath (alemtuzumab) or ATG (t lymphocyte depletion therapy) - can consider 3/12 prophylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Define EC50

A

The concentration of a drug required to inhibit viral replication by 50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Define low, medium and high levels of EC50 in CMV resistance.

What is the relevance of this for treatment?

A
  • Insignificant<2x
  • Low >2-5
  • <Mod>5

    </Mod>

Consensus guidelines suggest that if <5x then you can use higher dose GCV (10mg/KG BD instead of 5mg/kg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

UL regions for resistance in CMV?

A

UL54 (10%) - Pol (GCV/FOS/CDV)
UL97 (90%- Kinase - GCV and marabivir)
UL56 - terminase (letermovir)
UL 27 (low level marabivir)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Stopping rules for CMV treatment with gan/valgan?

A

“treatment doses of (val)ganciclovir are recommended until
eradication of CMV DNAemia below a specific threshold
and resolution of all clinical signs of CMV disease. Eradication of CMV DNAemia is defined as below LLOQ on 1
highly sensitive assay (LLOQ < 200 IU/mL; see Diagnostic
section), or lack of detection on 2 consecutive less sensitive
assays.” From SOT consensus guidelines Kotton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Prophylaxis in SCT with CMV D-R+

A

Letermovir 100 days. Can be extended to 200 if high risk of CMV disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Secondary prophylaxis in CMV

A

Not recommended in SOT
Can be considered with letermovir in SCT if high risk of reactivation or didn’t recieve primary prohylaxis first time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Can letermovir be used in CMV prophylaxis in SOT?

A

Not yet recommended by guidelines but growing evidence basis.

“Among adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication’’

Limaye AP, Budde K, Humar A, et al. Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA. 2023;330(1):33–42. doi:10.1001/jama.2023.9106

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why is ganciclovir not used as prophylaxis in SCT patients?

A

“it did not result in improved overall survival because of severe neutropenia and secondary bacterial and fungal infections’’

Einsele H, Ljungman P, Boeckh M. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation. Blood. 2020 May 7;135(19):1619-1629. doi: 10.1182/blood.2019000956. PMID: 32202631; PMCID: PMC7484743.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Monitoring of SOT CMV whilst on prophylaxis and preemptive?

A

Prophylaxis - None
Pre-emptive - at least monthly (guidelines disagree - Kotton suggests weekly)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Marabivir can’t be used in conjunction with ??

A

Ganciclovir - both act on kinase and marabivir antagonises action of GCV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which SCT patients should receive letermovir prophylaxis and for how long?

A

All R+ patients regardless of donor status. For min 100 days but can be extended to 200

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What significant drug/drug interaction occurs with letermovir?

A

Ciclosporin - letermovir requires drug adjustment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
26
What test is the gold standard for diagnosing CMV retinitis? What is observed?
Fundoscopy Characteristic retinal haemorrhage with a fluffy white granular appearance to the retina Confirmatory diagnosis can be using PCR on vitreal fluid
27
What was the most common CMV presentation pre-ART? What is the treatment?
Retinitis IV GCV 2-4 weeks plus intravitreal GCV/FOS In AIDS continue 900 mg valgan OD until CD4 > 100 Be aware of IRIS (start ART 2 weeks after treatment)
28
Patient on biological immunosuppression presents with dysphagia, pain on swelling and ulceration. Possibly diagnosis? How is this diagnosed? What is the treatment?
CMV oesophagitis Histology - 'owl's eye' inclusions and IHC Blood DNA not useful as poor NPV, and not related to end organ disease Reduction of immunosuppression and IV/oral GCV
29
Lab investigation of patient with ?CMV colitis in IBD
CMV IgG - if negative rule out If non-responder to steroids/immunosuppression Blood VL AND biopsy for H&E and IHC Only if high VL and high inclusions would you treat If IHC negative but high suspicion of CMV then PCR on tissue
30
Overview of CMV encephalitis
Generalised cognitive decline, focal neurological signs and cranial nerve palsies are uncommon Rare and only in context of profound immunosuppression (case reports in immunocompetent) Rapid progression can help differentiate from HIV encephalitis/PML PCR on CSF 62-100% sens, 89-100% spec
31
Which patients are at risk of CMV pneumonitis? Symptoms? Diagnosis? What is seen on CT? Treatment
AIDS and HSCT (up to 30%) - high mortality Nonspecific, dry cough, dysponea, breathlessness, fever PCR in blood and BAL - blood PCR may be negative. Lung biopsy is gold standard Diffuse interstitial infiltrates, ground glass or nodular pattern IV GCV for 21 days and CMV IgG
32
What % of neonates have cCMV?
0.2-2.2%
33
How many neonates with cCMV will be symptomatic at birth? How many will develop symptoms later in childhood?
10-15% Another 10-15%
34
What are the chance of primary CMV in pregnancy? What is the chance of foetal infection? What is the chance of a symptomatic neonate? What is the chance this neonate with be affected? What is the chance of having an asympomatic neonate? What is the chance this neonate will be affected?
Primary CMV 1-4% 30-50% risk of foetal infection 10-15% risk of symptomatic neonate, 90% will be affected 85-90% of asymptomatic neonate, 5-15% will be affected
35
What are the chance of CMV reinfection/reactivation in pregnancy? What is the chance of foetal infection? What is the chance of a symptomatic neonate? What is the chance this neonate with be affected? What is the chance of having an asympomatic neonate? What is the chance this neonate will be affected?
1-14% 0.2-2% risk of fetral infection 1% risk of symptomatic neonate, 90% will be affected 99% of asymptomatic neonate, 5-10% will be affected
36
Risk of CMV transmission in: 2-8 weeks pre-conception Peri-conception 1st trimester 2nd trimester 3rd trimester
5.5% 21% 30-40% 30-40% 40-70%
37
Risk of cCMV in: 1st trimester 2nd trimester 3rd trimester
23% 0.1% 0%
38
When should amniocentesis for CMV be performed?
>20 weeks gestation (when feotal urine is well established) and 6-8 weeks after primary maternal infection
39
If amniocentesis is CMV DNA positive what additional testing should be advised on the foetus?
Serial ultrasound and MRI
40
What cells does CMV become latent in?
CD34 myeloid progenator cells
41
How would you treat a pregnant women with primary CMV at 7 weeks gestation?
Valaciclovir 8g per day asap until amniocentesis
42
When should prenatal valaciclovir be considered in pregnancy? What is the evidence?
In confirmed primary maternal CMV in first trimester, treat until amniocentesis (or 18 weeks if no amnio) CYMEVAL study showed reduction (82% to 43%) of affected foetuses (trial of treatment in mild-moderately affected foetuses with confirmed CMV) Reduces vertical transmission by 70%?
43
Should CMV hyperimmune globulin be used to reduce risk of cCMV?
No, initial results looked good but no benefit in Phase 2 clinical trials
44
Symptoms of cCMV
Blueberry muffin rash Petechiae Hepatosplenomegaly Jaundice/transaminitis Chorioretinitis Cataracts IUGR Microcephaly Colitis Pneumonitis Sepsis like syndrome Intracranial calcifications/ventriculomegaly Seizures SNHL
45
Sensitivity of guthrie card for CMV?
65-100%
46
What tests should be performed on a baby with confirmed cCMV?
FBC/creatinine/U&Es/LFTs CMV DNA in plasma Cranial ultrasound Ophthalmic and audiometry assessment
47
When would treatment be offered for cCMV?
Babies born at >32 weeks >1800 g birthweight Acutely unwell infants or well infants with evidence of CNS infection (incl SNHL) Treatment must start in the first 4 weeks of life
48
What is the treatment for cCMV?
Ganciclovir 6mg/kg BD Can change to valgan (16 mg/kg BD) when on ~50% enteral feeds 6 months duration
49
How often is CMV DNA monitored in infants being treated for cCMV?
For acutely unwell infants: day 3 and then weekly for the first 6 weeks, then montly For well infants: Fortnightly for 3 months and then monthly
50
What are the side effects of GCV in cCMV treatment? What is the most common symptom and when does this occur?
Neutropenia, thrombocytopaeniam hepatotoxicity, anaemia Neutropenia is most common and occurs most often in first 6 weeks, may require cessation of therapy
51
What follow up is required in cCMV?
Follow up at 1-2 years of life Audiology assessment every 3-6 m then less frequently until 6 years Opthalmic assessment up to age 5
52
Investigation of SNHL in: <1 years >1 years
2x urine and 2x saliva for PCR CMV IgG +/- urine Alternatively negative CMV IgG in mum
53
Risk factors and presentation of postnatal CMV
Risk factors = <32 weeks, <1500 g, exposure to CMV pos breastmilk Sepsis like syndrome Respiratory distress Thrombocytopaenia Hepato/splenomegaly Jaundice Neutropaenia Usually occurs at 4-6 weeks of age
54
Treatment for postnatal CMV
Treatment only in severe disease in very preterm babies Treat with ganciclovir in 2 week blocks, until virally suppressed/asymptomatic Aim to suppress viraemia and prevent end organ damage Monitor DNA and FBC weekly
55
What is the most common risk of post-natal CMV transmission?
Breastmilk
56
How is donor breastmilk treated in the UK to reduce the risk of CMV?
Frozen, pasteurised and frozen again which greatly reduces CMV transmission greatly
57
Which organ recipients are at greatest risk of CMV disease?
All D+/R- recipients R+ on T cell depleting agents (ATG/alemtuzumab) or treated for acute rejection
58
Which SOT recipients should receive CMV prophylaxis, for how long and with what antiviral?
All D+/R- recipients R+ on T cell depleting agents (ATG/alemtuzumab) or treated for acute rejection 900 mg OD valganciclovir for at least 3 months As per guidelines "offer" for kidney and liver and "consider" in others
59
What CMV monitoring in SOT: a) D-/R- b) D* /R* on prophylaxis c) D+/R* and D*/R+ and not on prophylaxis What increase in VL is considered significant
a) None b) None c) VL at least monthly for at least 3 months 0.5 log
60
Regarding ganciclovir prophylaxis in SOT: Dosing if eGFR <60 ml/min? Monitoring for side effects?
Dose reduction required Monitor FBC every 2 weeks, if myelosuppression switch to monitoring and pre-emotive therapy
61
What is first line for treatment of CMV in SOT? What monitoring? When to stop treatment?
Reduction of immunosuppression if possible Valganciclovir unless worries about adherence/absorption Monitor VL at 2 weeks and then weekly Stop at resolution of symtoms and 2x negative VL 1 week apart
62
What is second line treatment for CMV in SOT if there is suspected ganciclovir resistance?
Maribavir If confirmed resistance (and not resistant to FOS) then foscarnet is an alternative 3rd/4th line = Foscarnet/cidofovir
63
Dose of maribavir for CMV treatment in SOT?
400 mg BD for 8 weeks (oral)
64
Dose of foscarnet for CMV treatment in SOT?
60 mg/kg TDS for 3 weeks (IV)
65
What should be optimised in CMV disease in SOT?
Reduction of immunosuppression if possible Especially MMF/azathioprine if leucopaenia
66
When does CMV disease usually occur in SOT? What are the symptoms?
Primary CMV in D+/R- usually in first 4-6 weeks Late onset CMV can occur in up to 30% after prophylaxis finished (mostly D+/R-) high mortality rate and often results in graft rejection Fevers, fatigue, sweats, myalgia, gastritis is common. Pneumonia, neutropenia, hepatitis. Retinitis is rare but pathognomonic
67
When is CMV disease most likely to occur in HSCT? What are the two most important disease entities?
First 100 days Pneumonitis and gastroenteritis
68
What CMV testing is performed pre-HSCT?
CMV IgG status determined prior to any blood products and then again just before HSCT Pre-HSCT PCR recommended
69
Which HSCT patients receive CMV prophylaxis? What antiviral is used? And for how long?
All R+ patients regardless of D status Letermovir for 100 days, extend to 200 days in high risk groups
70
What alternatives to letermovir are there for CMV prophylaxis?
Valaciclovir Monitoring of CMV and pre-emptive treatment
71
Which HSCT patients are monitored for CMV? And how?
Allo-HSCT in: D+/R+ D+/R- D-/R+ Monitoring via quant CMV DNA weekly in all patients on prophylaxis as failure can occur 10-30% Monitoring should be extended for at least another 3 months in high risk patient
72
What risk factors are associated with high risk of CMV in HSCT?
CMV mismatch Cord blood Patients on steroids Ongoing GvHD Patients with prior of CMV DNAemia
73
When should secondary CMV prophylaxis be considered in: HSCT SOT
Consider letermovir after successful treatment of CMV reactivation in patients at high risk of CMV disease, or post treatment in those who did not receive primary prophylaxis Controversial - not routinely used
74
What impacts the decision for pre-emptive treatment for CMV in HSCT?
Treatment depends on CMV status, times since transplant, viral load, symptoms, level of immunosuppression
75
In which situations would you treat a HSCT patient as soon as CMV DNA positive during monitoring? In other situations what would follow up be?
In cord blood transplant In first 30 days of transplant In D+/R- Repeat test and assess for symptoms
76
What is first line for treatment of CMV in HSCT? Second line? Third line?
Ganciclovir (IV in severe GI GvHD), valganciclovir (add IVIG in pneumonitis) Foscarnet or maribavir if neutropaenia or renal function impairment Cidofovir or GCV/FOS combo
77
What is the treatment threshold value for CMV in HSCT?
No stated level, this is based on local protocol due to sample type and lab test In GGC if low level <4 log and not high risk then can just monitor If strongly positive, rapidly rising DNA or unwell then treat
78
Define refractory vs resistant CMV in HSCT
Refractory = VL increase >1 log after 2 weeks of appropriate treatment Probably refractory when viral load persists but does not increase >1 log after 2 weeks Resistant = CMV disease symptoms worsen after at least 2 weeks of appropriate treatment
79
How can you treat refractory CMV in HSCT?
Maribavir can be considered for resistant/refractory CMV and is linked to lower side effects (not for CNS/eye) Foscarnet is alternative = good for CNS/eye disease but significant toxicity Cidofovir is an option for CMV retinitis CTLs are an option if available Leflunomide or artesunate can be considered in patients resistant or refractory to other second-line and third line antiviral drugs
80
Three actions you would do if you had suspected ganciclovir resistant CMV in HSCT?
Reduce immunosuppression if possible Switch drug class Send for resistance testing
81
Options for CMV infection in HSCT in strain with low level (2-5 fold increase in IC50) ganciclovir resistance?
High dose ganciclovir (7.5-10 mg/kg BD) +/- half dose FOS Alternatively maribavir or foscarnet
82
Which UL97 mutations give: Low level ganciclovir resistance High level ganciclovir resistance
M460I - C592G - L595W M460V - H520Q - A594V - L595S - C603W - L595F
83
What is CMV T cell activity monitoring?
Sequential monitoring of IFN-?-producing CMV-specific T cells The use of commercially-available CMV IGRA are preferable over laboratory-developed flow cytometry-based immunoassays Main applications of these assays: Extending or shortening the duration of prophylaxis Withholding therapy for low level viral loads Identify patients that may benefit from secondary prophylaxis
84
How is transfusion transmitted CMV reduced in D-/R- HSCT?
Transfusion of leukocyte-reduced blood products (i.e., <1 to 5�נ106 residual leukocytes per unit) Transfusion of blood components from CMV- seronegative donors
85
Incubation period of CMV?
3-12 weeks
86
In which situations is maribavir not recocommended in CMV disease?
Neurologocal or eye disease as penetration into CNS is poor
87
Can maribavir be used in conjunction with ganciclovir? And why?
Cannot be used in combination with ganciclovir as MBV inhibits UL97 so impairs phosphylation of GCV
88
How does leflonamide work in CMV infection?
Inhibits protein kinase and interferes with CMV viral assembly Can be used as adjunct therapy in difficult to treat HSCT patients
89
What are the risks for ganciclovir resistance in SOT? What is the rate of resistance?
Prolonged prophylaxis, sub therapeutic dose, T cell depleting therapy, D+/R-, lung tx 3%
90
In ?GCV resistance in SOT, what should you check prior to changing treatment strategy? What is the next step?
Correct dose. Adherence. Absorption Stop val(ganciclovir) Switch to maribavir if suspected resistance Switch to maribavir or foscarnet in confirmed resistance
91
Which genes are related to ganciclovir resistance in CMV and what % are caused by each?
UL97 viral kinase mutation - 90% UL54 DNA pol - 10% (often evolve later)
92
What vaccines are in development for CMV?
Any vaccine needs to stimulate both humoral and cellular compartments Some types in development: VLP, live attenuated, mRNA, vaccinia, chimeric Targets are gB and pp65 Current phase 3 trial 'CMVictory trial' of mRNA based vaccine (Moderna). Based on 6 mRNA sequences encoding 2 CMV antigens gB and pentameric glycoprotein in lipid nanoparticles
93
What is the NPV of CMV PCR in BAL for CMV pneumonitis?
100% - a negative PCR pretty much excludes CMV pneumonia

Part 2 Revision (57 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions