Late-onset cytomegalovirus (CMV) disease commonly occurs after discontinuation of antiviral prophylaxis. We determined the utility of testing CD8+ T-cell response against CMV as a predictor of late-onset CMV disease after a standard course of antiviral prophylaxis. Transplant patients at high-risk for CMV disease were enrolled. CD8+ T-cell-mediated immunity (CMI) was tested using the QuantiFERON-CMV assay at baseline, 1, 2 and 3 months posttransplant by measurement of interferon-c response to whole blood stimulation with a 21-peptide pool. The primary outcome was the ability of CMI testing to predict CMV disease in the first 6 months posttransplant. There were 108 evaluable patients (D+/R+ n = 39; D-/R+ n = 34; D+/R-n = 35) of whom 18 (16.7%) developed symptomatic CMV disease. At the end of prophylaxis, CMI was detectable in 38/108 (35.2%) patients (cutoff 0.1 IU/mL interferonc ). CMV disease occurred in 2/38 (5.3%) patients with a detectable interferon-c response versus 16/70 (22.9%) patients with a negative response; p = 0.038. In the subgroup of D+/R-patients, CMV disease occurred in 1/10 (10.0%) patients with a detectable interferon-c response (cutoff 0.1 IU/mL) versus 10/25 (40.0%) patients with a negative CMI, p = 0.12. Monitoring of CMI may be useful for predicting late-onset CMV disease.
Community-acquired RVIs are frequently detected in BAL samples from lung transplant patients. In a significant percentage of patients, symptomatic or asymptomatic viral infection is a trigger for acute rejection and obliterative bronchiolitis/BOS.
Little is known about adenovirus infections in adult organ transplant recipients. We prospectively assessed adenovirus infection in 263 transplant recipients using polymerase chain reaction (PCR) on plasma samples at regular intervals post-transplant. Adenovirus DNA was detected in 19 of 263 patients (7.2%). Viremia by transplant type was: liver (n = 10 of 121 [8.3%]), kidney (n = 6 of 92 [6.5%]) and heart (n = 3 of 45 [6.7%]). Time to viremia onset was within 10 days post-transplant (n = 4), on day 28 (n = 1), on day 100 (n = 7) and between months 6 and 12 (n = 7). At the time of viremia, 11 of 19 (58%) patients had no symptoms, 2 of 19 (10.5%) had gastrointestinal (GI) symptoms, 2 of 19 (10.5%) had respiratory symptoms and 4 patients (21%) had vague/non-specific symptoms. All patients recovered spontaneously. Only 1 of 19 (5%) patients had subsequent acute rejection. Adenovirus viremia is relatively common in adult liver, kidney and heart transplant recipients and most infections are asymptomatic, transient and self-limited. No serious clinical sequelae or effects on subsequent acute rejection were observed.
HHV-6 reactivation after transplant is common and is associated with the development of opportunistic infections and CMV disease and possibly with a subgroup of acute rejection episodes. HHV-6 infection likely has a significant impact in transplant recipients through indirect effects of viral replication.
Late-onset cytomegalovirus (CMV) disease is a significant problem in D+/R− solid organ transplant (SOT)patients who receive antiviral prophylaxis. We assessed the clinical utility of CMV IgG and IgM serology testing for predicting late-onset CMV disease. We evaluated 352 D+/R− transplant recipients who participated in a trial comparing 100 days of ganciclovir versus valganciclovir prophylaxis. CMV serology was assessed on day 28, 56, 100, and 6 and 12 months post-transplant. IgG seroconversion occurred in 26.9% of patients by day 100, and in 63.4% and 75.3% by 6 and 12 months, respectively. IgM seroconversion occurred in 8.3%, 41.8% and 54.9% by day 100, month 6 and month 12, respectively. Seroconversion by day 100 (end of prophylaxis) was not predictive of subsequent CMV disease (CMV disease 13.3% if seropositive vs. 17.8% if seronegative; p = NS). However, at 6 months post-transplant, IgG serostatus was predictive of subsequent CMV disease between month 6 and 12 (CMV disease 1.3% if seropositive vs. 10.0% if seronegative; p = 0.002). In D+/R− patients, CMV serology testing is for the most part not clinically useful for predicting subsequent disease. However, seroconversion by 6 months may be useful for identifying patients at risk of late-onset CMV disease.
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