CMV Flashcards
Incidence of congenital CMV?
Occurs in 1 out of every 100-200 live births in UK and 1 in 71 in developing nations
Diagnosing CMV in mum with symptoms?
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
When can you do amniocentesis to look for CMV infection?
What is the sensitivity?
What action do you take following the amnio?
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
Indications for valaciclovir to treat CMV in pregnancy?
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)
Presentation of cCMV?
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
Management of cCMV in the neonate?
Ganciclovir 6mg/kg BD or Valgan 16mg/kg - to continue for 6 months
Followup of a neonate with symptomatic cCMV
If treated ID followup for 2 years
Hearing test followup to 6 years
Ophthalmology if symptomatic for 5 years
Sensitivity of Guthrie card for cCMV?
Sensitivity of NAAT performed from a dried blood spot (Guthrie card) has been reported to be between 70-80%
Amniocenteis NPV for symptomatic cCMV?
Negative predictive values of between 92.7% and 95.7% are reported for CMV NAAT assays of amniotic fluid.
CMV disease in immunocompromised. Clinical presentation?
fever, bone marrow suppression, and tissue invasive (pneumonitis, hepatitis, colitis, nephritis and retinitis).
Highest risk SOT for CMV disease?
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)
Duration of CMV prophylaxis in SOT and dose?
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
Define EC50
The concentration of a drug required to inhibit viral replication by 50%
Define low, medium and high levels of EC50 in CMV resistance.
What is the relevance of this for treatment?
- 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)
UL regions for resistance in CMV?
UL54 (10%) - Pol (GCV/FOS/CDV)
UL97 (90%- Kinase - GCV and marabivir)
UL56 - terminase (letermovir)
UL 27 (low level marabivir)
Stopping rules for CMV treatment with gan/valgan?
“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
Prophylaxis in SCT with CMV D-R+
Marabivir 100 days. Can be extended to 200 if high risk of CMV disease
Secondary prophylaxis in CMV
Not recommended in SOT
Can be considered with letermovir in SCT if high risk of reactivation or didn’t recieve primary prohylaxis first time
Can letermovir be used in CMV prophylaxis in SOT?
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
Why is ganciclovir not used as prophylaxis in SCT patients?
“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.
Monitoring of SOT CMV whilst on prophylaxis and preemptive?
Prophylaxis - None
Pre-emptive - at least monthly (guidelines disagree - Kotton suggests weekly)
Marabivir can’t be used in conjunction with ??
Ganciclovir - both act on kinase and marabivir antagonises action of GCV
Which SCT patients should receive letermovir prophylaxis and for how long?
All R+ patients regardless of donor status. For min 100 days but can be extended to 200
What significant drug/drug interaction occurs with letermovir?
Ciclosporin - letermovir requires drug adjustment.
