Estimating the Seroprevalence of Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) and the Risk of Transfusion-Transmitted and Community-Acquired CMV Infection in Solid Organ Transplant Donors and Recipients

• Author / Creator

  Mabilangan, Curtis

• Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are ubiquitous herpesviruses that establish lifelong, often asymptomatic, infections in healthy people, but are responsible for significant morbidity and mortality in certain hosts. CMV is the most common congenital infection worldwide, causing sensorineural hearing loss, neurodevelopmental delays, and other significant sequelae. CMV seronegative women of childbearing age who experience primary CMV infection during pregnancy are at greatest risk of maternal-fetal CMV transmission. Immunocompromised individuals, such as solid organ transplant (SOT) recipients, are also at serious risk of harm from these viruses. In SOT recipients, CMV infection is known to have “direct” effects including CMV syndrome and tissue-invasive disease as well as “indirect” effects including organ rejection, organ dysfunction and increased risk of opportunistic infections. EBV infection is a major risk factor for EBV-associated cancers in SOT recipients, especially post-transplant lymphoproliferative disorders (PTLD) such as non-Hodgkin lymphoma, Hodgkin and Burkitt lymphoma, T/NK lymphomas and smooth muscle tumors. There is a paucity of data regarding the prevalence of these viruses in Canada; such data would be valuable to assess disease burden as well as to inform public health interventions including vaccine development and vaccine deployment strategies.
  Community-acquired CMV (CA-CMV) is generally transmitted from person to person via contact with infected secretions (including saliva, urine, respiratory and genital secretions); in SOT recipients, CMV can also be acquired from infected donor organs and cellular blood products. CMV seronegative recipients who receive CMV seronegative donor organs are not considered at risk of donor-transmitted (DT)-CMV infections, thus infections occurring in the post-transplant period are either due to CA-CMV or transfusion-transmitted (TT)-CMV. Two main strategies are used to reduce risk of TT-CMV: leukoreduction of blood products and screening for CMV-seronegative blood. Presently, Canadian Blood Services (CBS) uses leukoreduction as the main strategy for preventing TT-CMV, but there is no consensus as to whether additional screening for seronegative blood further reduces risk. The risk of TT-CMV infection in SOT has not yet been evaluated in the current era of universal leukoreduction, and this risk must be assessed while accounting for the risk of CA-CMV.
  Our first objective of the research program was to estimate the age and sex-specific seroprevalence of CMV and EBV in Canada using available data from first time Canadian blood donors who donated blood between 2005 - 2014 and SOT donors and recipients who were transplanted at the University of Alberta/Stollery Children’s Hospitals between 1984 – 2013. Our results show that the age and sex-specific prevalence trends for CMV and EBV in our study populations are similar to those of other western developed countries.
  Our second objective was to estimate the risk of TT-CMV and CA-CMV infection in D-/R- SOT recipients transplanted at our center during the current era of universal leukoreduction. Patients transplanted between 2000 – 2011 were evaluated for receipt of blood products and incidence of CMV infection during follow-up. Our results show that after the implementation of universal leukoreduction, we did not observe any confirmed cases of TT-CMV in our cohort and that the risk of CA-CMV exceeds the risk of TT-CMV.
  Together, our studies give insight into the seroprevalence of CMV and EBV in the Canadian population, and the incidence of CMV infections in our SOT population. Notably, the prevalence of CMV was much lower in blood donors (42%) than in adult SOT recipients (62%) and the prevalence of the general adult Canadian population is likely in between these two values. Our results also show that EBV prevalence rises rapidly early in life among our SOT recipients which supports the targeting of infants in potential future EBV immunization programs. Lastly, the negligible risk of TT-CMV observed in our D-/R- SOT population supports current CBS policy of using universal leukoreduction as the primary strategy to prevent TT-CMV. The risk of CA-CMV is thus a more important consideration than TT-CMV in the follow-up of D-/R- SOT recipients.

• Subjects / Keywords

  • Prevalence
  • Epstein-Barr Virus
  • Transfusion
  • EBV
  • Cytomegalovirus
  • Transplant
  • Incidence
  • Infection
  • CMV
  • Epidemiology

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-5gn0-zp66

• License

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