Although antiviral prophylaxis has reduced cytomegalovirus (CMV) DNAemia and disease in seronegative solid organ transplant (SOT) recipients (R‐) receiving seropositive donor organs (D+), its impact on CMV transmission is uncertain. Transmission, defined as CMV antigenemia/CMV DNAemia and/or seroconversion by year 2, and associated demographic risk factors were studied retrospectively in 428 D+/R‐ and 429 D‐/R‐ patients receiving a SOT at our center. The cumulative transmission incidence was higher for lung (90.5%) and liver recipients (85.1%) than heart (72.7%), kidney (63.9%), and pancreas (56.2%) recipients (p < .001) and was significantly lower in living (50.1%) versus deceased donor (77.4%, p < .001) kidney recipients despite identical antiviral prophylaxis. In multivariate analysis, only allograft type predicted transmission risk (HR [CI] lung 1.609 [1.159, 2.234] and liver 1.644 [1.209, 2.234] vs kidney). For 53 D+ donating to >1 R‐ with adequate follow‐up, 43 transmitted to all, three transmitted to none, and seven transmitted inconsistently with lungs and livers always transmitting but donor‐matched heart, kidney or kidney‐pancreas allografts sometimes not. Kidney pairs transmitted concordantly. CMV transmission risk is allograft‐specific and unchanged despite antiviral prophylaxis. Tracking transmission and defining donor factors associated with transmission escape may provide novel opportunities for more targeted CMV prevention and improve outcome analysis in antiviral and vaccine trials.
Background: Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) infections are common, causing significant morbidity in pregnancy (congenital CMV) and transplant recipients (CMV, EBV). Canadian prevalence data are needed to model disease burden and develop strategies for future vaccines. We estimated prevalence using screening data from blood donors and solid organ transplant (SOT) donors and recipients. Methods: We retrospectively analyzed CMV and EBV serology from Alberta SOT donors ( n = 3,016) and recipients ( n = 4,614) (1984–2013) and Canadian Blood Services blood donors ( n = 1,253,350) (2005–2014), studying associations with age, sex, organ, year, and geographic region. Results: CMV seroprevalence rises gradually with age. By age 70, CMV seropositivity ranged from 67% (blood donors) to 73% (SOT recipients). Significant proportions of women of child-bearing age were CMV-seronegative (organ donors, 44%; SOT recipients, 43%; blood donors, 61%). Blood donor CMV seroprevalence decreased from 48% in Western Canada to 30% in Eastern Canada. Women were more likely to be CMV-seropositive (ORs = 1.58, 1.45, and 1.11 for organ donors, SOT recipients, and blood donors, respectively) and EBV-seropositive (ORs = 1.87 and 1.46 for organ donors and SOT recipients, respectively). EBV prevalence rises rapidly, and by age 17–29 years, 81% of SOT recipients and 90% of organ donors were seropositive. Conclusions: Canada has relatively low and perhaps decreasing age-specific EBV and CMV prevalence, making Canadians vulnerable to primary infection-associated morbidity and suggesting benefit from future vaccines. Collection and analysis of routine serology screening data are useful for observing trends.
Solid organ transplant (SOT) recipients who are cytomegalovirus (CMV) seronegative (R−) and receive seronegative donor (D−) organs have a small but currently unquantified risk of both transfusion-transmitted CMV (TT-CMV) and community-acquired CMV (CA-CMV). We retrospectively studied the incidence and clinical symptoms of TT-CMV (infection <1 year posttransplant) and CA-CMV (infection >1 year posttransplant) in a cohort of D−/R− adult and pediatric SOT recipients receiving leukoreduced blood products not screened for CMV seronegativity transplanted at our center between 2000 and 2011. CMV infection was defined as IgG seroconversion or detectable CMV antigenemia/DNAemia. Among 536 consecutive D−/R− recipients, 398 (81.8%) had adequate follow-up, and 231 (58%) received cellular blood products (total: 1626 red blood cell units, 470 platelet units) 30 days pretransplant to 90 days posttransplant. We observed no confirmed TT-CMV cases, but 14 CA-CMV cases (64% symptomatic) were seen. The estimated incidence rate of CA-CMV was higher in children (3.0/100 patient years) than adults (0.46/100 patient years, incident rate ratio of 6.52). The absence of TT-CMV over 11 years suggests neither seronegative blood products nor CMV DNA blood donor screening would provide significant incremental safety when blood is already leukoreduced. D−/R− SOT recipients, particularly children, have a significantly higher and ongoing risk of CA-CMV.
Assignment of CMV infection status in infants awaiting SOT is challenging as passive maternal antibody can lead to false-positive serology. Since 2000, our protocol has recommended sending throat and urine samples for CMV viral detection, culture, or NAAT, for CMV-seropositive infants <18 months awaiting SOT. We reviewed pretransplant CMV serology for 152 infants and, for CMV seropositives, examined relationships between CMV IgG OD values, age, and CMV viral detection to explore time to clearance of maternal CMV IgG and evaluate viral detection in assignment of pretransplant CMV infection status. The proportion of CMV-seropositive infants decreased from 52% in infants 0-6 months of age to 28% in those 12-18 months. Among CMV-seropositive infants, median OD was significantly higher in the 6- to 12- and 12- to 18-month groups compared to the 0- to 6-month group. Distribution of OD by age group suggested that maternal antibody cleared before 12 months. Of 59 eligible CMV-seropositive infants, 49 (83%) had CMV viral detection studies and 18 of 49 (36.7%) had detectable CMV: 9 of 30 (30.0%) infants 0-6 months, 7 of 15 (46.7%) infants 6-12 months, and 2 of 4 (50.0%) infants 12-18 months. CMV viral detection studies are useful to confirm positive CMV infection status in CMV-seropositive infants awaiting SOT. Maternal CMV IgG likely clears before 12 months.
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