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Improving the Assignment of Cytomegalovirus Infection Status in Adults and Children Awaiting Solid Organ Transplant

  • Author / Creator
    Burton, Catherine EC
  • Cytomegalovirus (CMV), a herpes-virus, is widespread in the human population as a lifelong and largely asymptomatic infection in immunocompetent people, but it is a major cause of morbidity in solid organ transplant (SOT) recipients. Knowledge of pre-transplant CMV infection status, generally determined using serology to detect IgG antibodies to CMV, is critical in stratifying the risk of CMV disease post-transplant and affects decisions regarding the use of anti-viral prophylaxis and enhanced surveillance including additional laboratory testing for CMV disease post-transplant. Unfortunately, serology-based determination of CMV infection status has limitations in situations where passive antibodies may lead to falsely positive CMV serology, such as in young infants who may have maternal antibody and in individuals who have received a recent transfusion of plasma-containing blood products. While guidelines suggest that CMV serology may be unreliable in infants less than 12 or 18 months of age, the time to clearance of passive maternal CMV IgG is not well established. Our first objective with this program of research was to gain insight into the age of clearance of passive maternal CMV IgG in infants to aid in identification of the group of infants in whom CMV serology may be unreliable due to passive maternal antibody. This was accomplished with a retrospective review of pre-transplant CMV serology and viral detection studies for all infants <18 months of age awaiting solid organ transplant at the Stollery Children’s Hospital over a 20 year period. The results suggested that maternal CMV IgG was cleared before 12 months of age, thus supporting that 12 months, as opposed to 18 months, may be a more appropriate cut-off for considering CMV serology potentially unreliable due to passive maternal antibody. Our second objective was to evaluate the use of novel assays, not affected by potential passive antibody, to more accurately assign CMV infection status in adults and children awaiting SOT, especially in those whose true CMV infection status may be obscured by potential passive antibody. In our first study, we evaluated our experience with the use of CMV culture and nucleic acid amplification tests (NAAT) to detect CMV shedding, a marker of true CMV infection, in young infants with potential passive antibody awaiting SOT. In our second study, we prospectively evaluated the use of CMV NAAT as well as the detection of CMV-specific CD4+ T cells by flow-cytometry, and the CD27-CD28- CD4+T cell phenotype as adjuncts to CMV serology in the assignment of CMV infection status in adults and children awaiting solid organ transplant. Our results clearly highlight that CMV NAAT, from urine and saliva or throat samples, is a useful adjunct to CMV serology in CMV seropositive infants with potential passive antibody as it confirms true positive CMV infection status in a significant number of infants. Detection of CMV-specific CD4+ T cells showed promise as an adjunct to CMV serology in pre-transplant CMV risk stratification in children >12 months of age and in adults but lacked sensitivity in identifying true positive CMV infection status in young infants (<12 months). T cell phenotype analysis for CD27-CD28- CD4+T cells is unlikely to be a valuable tool in establishing true CMV infection status in children but may have a role in clarifying true pre-transplant CMV infection status in adults with unreliable CMV serology. Taken together our studies support that CMV NAAT, of urine and saliva or throat swab, should be implemented for routine pre-transplant screening of CMV seropositive infants less than 12 months of age and could be considered in older children who have been transfused and have no pre-transfusion sample available. Detection of CMV-specific CD4+ T cells showed promise as an adjunct to CMV serology in determining true CMV infection status in adults and children >12 months of age with potential passive antibody but further evaluation, with larger numbers of pre-SOT subjects, is needed. However, detection of CMV-specific CD4+ T cells should not be used in isolation to determine CMV infection status in CMV seropositive infants < 12 months with potential passive antibody.

  • Subjects / Keywords
  • Graduation date
    2017-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R31J97Q5T
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.