1 | P a g e
Supplemental Digital Content, Methods
International Survey of Cytomegalovirus Management in Solid Organ Transplantation following Publication of Consensus Guidelines: Survey Questions (summarised)
1. PERSONAL DETAILS OF RESPONDER
1. Name2. City 3. Country
4. In which transplant field are you working?
5. In which hospital/laboratory are you working?
2. GENERAL
We understand that you as a Transplant Infectious Diseases specialist or Transplant Clinician will treat every patient on an individual basis. The following questions are based on a patient without a history of
Cytomegalovirus (CMV) disease, without a history of CMV resistance and without a history of rejection unless otherwise indicated.
6. In what kind of laboratory are you doing the assays for CMV management?
7. Are you aware of the 'International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation'? (Published in the journal 'Transplantation' in 2010:
http://www.ncbi.nlm.nih.gov/pubmed/20224515)
8. What transplantation type does your institute specialize in?
9. If the protocol for CMV management is different for the different transplantations at your institution, please select one type of transplantation for the purpose of answering this questionnaire.
10. Does your institute use a protocol for CMV management?
11. If you selected more than one option in question 9, is the protocol for CMV management different between the different organs?
12. Do you screen the renal function during prophylaxis, pre-emptive therapy, secondary prophylaxis or therapy (during CMV infection or disease)?
3. PROPHYLAXIS AFTER TRANSPLANTATION
Two major strategies are commonly used for prevention of CMV in the different sero groups: universal prophylaxis and pre-emptive therapy. Within each of these strategies, significant variation in clinical practice exists and some centers use a hybrid approach. Universal prophylaxis involves the administration of antiviral medication to all patients or a subset of "at-risk" patients usually started immediate or very early in the post- transplant period.
13. Do you use universal prophylaxis after transplantation?
2 | P a g e
14. Which serogroups receive universal prophylaxis?
15. What is the best prophylactic dose of Valganciclovir in kidney transplant recipients with standard good graft function?
16. Which antiviral do you use prophylactically, for how long do you give the universal prophylaxis, and which dose do you use for patients with a normal renal function?
17. Do you use an adjuvant CMV immunoglobulin in the different serogroups prophylactically?
4. SECONDARY PROPHYLAXIS
Secondary prophylaxis for CMV is prophylaxis after therapy (where CMV has already developed) to protect the patient against worsening or reinfection with CMV.
18. Do you give secondary prophylaxis after therapy?
19. Which serogroups receive secondary prophylaxis?
20. Which antiviral do you use for secondary prophylaxis, for how long do you give secondary prophylaxis and which dose do you use for patients with a normal renal function?
21. Do you use an adjuvant CMV immunoglobulin in the different serogroups as secondary prophylaxis?
5. PRE-EMPTIVE THERAPY
In pre-emptive therapy, laboratory monitoring is performed at regular intervals to detect early, asymptomatic viral replication. Once viral replication reaches a certain threshold, antiviral therapy is initiated to prevent the progression to clinical disease.
22. Do you use pre-emptive therapy in certain transplant groups?
23. Which serogroups receive pre-emptive therapy?
24. Which drug(s) do you use as pre-emptive therapy in the different serogroups, for how long do you give your pre-emptive therapy and when do you stop with pre-emptive therapy?
25. Do you use an adjuvant CMV immunoglobulin in the different serogroups as part of pre-emptive therapy?
6. CMV TREATMENT
26. Which antiviral do you use for the treatment of CMV infection (CMV replication regardless of symptoms) or disease (CMV infection with clinical symptoms)?
27. Do you use an adjuvant CMV immunoglobulin in the different serogroups as therapy for CMV infection or CMV disease?
7. MONITORING
Laboratory monitoring is performed to prevent the patient for an (re) infection (during or after primary prophylaxis, during or after secondary prophylaxis, before or during pre-emptive therapy) by checking early, asymptomatic viral replication. Monitoring is also used during therapy to check the response on therapy and after therapy. In the guidelines the definition of CMV infection: evidence of CMV replication regardless of symptoms. In the guidelines the definition of CMV disease: evidence of CMV infection with attributable symptoms.
3 | P a g e
28. Do you monitor CMV in your patient after transplant? (During universal prophylaxis, During secondary prophylaxis, After universal or secondary prophylaxis, For pre-emptive therapy, During therapy of CMV infection/disease, After therapy of CMV infection/disease, During increased immunosuppressive treatment) 29. How do you monitor for CMV? At each stage listed above, with options of PCR blood, pp65 antigenemia on blood, PCR bronchoalveolar lavage, PCR specimen specific body site, Culture bronchoalveolar lavage, Culture blood, Culture urine, Culture of other tissue specimens, quantiFERON assay, serology, none of these.
30. How often do you use the assay (or combination of assays) which you chose in question 30 to monitor the patient?
31. For how long do you monitor in the different serogroups (asked for each serogroup)? During universal prophylaxis, During secondary prophylaxis, After universal or secondary prophylaxis, For pre-emptive therapy, During therapy of CMV infection/disease, After therapy of CMV infection/disease, During increased
immunosuppressive treatment
32. If you use the PCR or antigenemia assay, which method are you using to start therapy? Options: PCR with pre-defined threshold, PCR with upgoing trend, Positive qualitative PCR, Depends on patient symptoms, Other 33. Do you use immunohistochemistry ('owl's eye inclusions) or immunocytochemistry (viral antigens) in your decision to start with therapy?
34. Do you use an assay to estimate the risk of developing CMV disease? Options: QuantiFERON CMV assay, ELISPOT assay, or other assay
35. Which PCR do you use for CMV management? Options: Qualitative PCR, Quantitative PCR 36. What kind of blood do you use for your CMV PCR? Options: Whole blood, Plasma, Buffy Coat
8. IMMUNOSUPPRESSION, SIDE EFFECTS MEDICATION & ANTIVIRAL RESISTANCE
37. Do you decrease immunosuppression? For severe CMV disease, recurrent CMV disease, Non responding patients, patients with high viral loads, patient with leukopenia? Options: Yes, when we start antiviral treatment;
Yes, independent of antiviral treatment; Other, No.
38. After CMV infection has been eliminated do you resume previous levels of immunosuppression therapy?
For severe CMV disease, recurrent CMV disease, patients with high viral loads, patient with leukopenia?
Options: Yes, when we start antiviral treatment; Yes, independent of antiviral treatment; Other; No.
39. Which typical agents do you use for induction of immunosuppressive therapy?
40. How do you manage neutropenia associated with antiviral therapy? Options: Change immunosuppression, GCV reduction, GCV cessation, GCSF, Reduce other bone marrow suppressive drugs
41. How do you diagnose CMV antiviral resistance? Options: Clinical, Increasing viral load, Genotyping, Phenotyping, Other, Never seen it, Don't know
If you selected 'Genotyping' above, do you use UL97, UL54 or both for genotyping?
42.Do you use an algorithm to manage CMV resistance?
43.Can you estimate how often you see drug resistance (% patients) in one year?
44.Have you had a patient die due to drug resistance in the last 10 years (how many)?
45. When (val)ganciclovir treatment is failing, which antiviral do you use as a second-line agent? Options:
Foscarnet, Cidofovir, Other