Episodes Of Cytomegalovirus Infection Research Articles

Comparison of prophylaxis and preemptive strategy as cytomegalovirus prevention in liver transplant recipients.

Prophylaxis (P) or pre-emptive strategy (PS) in high-risk liver transplant recipients (LTRs) are either recommended. We compared the results of each strategy. Two groups of LTR transplanted during two consecutive periods were compared. Only cytomegalovirus (CMV)-mismatched LTR (Donor +/ Recipient -) were included. The primary endpoints were: the onset of polymerase chain reaction-based DNAemia and the proportion of patients with CMV disease. A number of episodes of CMV infection, antiviral therapy, ganciclovir resistance, infectious or immunological complications, cost of both strategies, and survival (1, 5, and 10 years) were also compared. Forty-eight and 60 patients were respectively included in the P and PS groups. Eighteen (38%) in the P group and 56 (93%) in the PS group had CMV DNAemia (p <.0001) with a similar CMV disease rate (16.7% and 15%). Duration of curative therapy was longer in the PS group: 91 days versus 16 (p <.0001). Acute rejection was less frequent (p=.04) and more patients experienced a ganciclovir-resistant CMV infection in the PS group (10% vs. 0, p=.03). The drug-associated cost of PS was higher (10 004vs. 4804€) and the median number of rehospitalization days tended to be higher (6vs. 4, p=.06). Survival at any time was similar. We reported more CMV DNAemias and ganciclovir-resistant CMV events with PS. The cost of the PS strategy was higher.

Utility of the Interferon-Gamma Enzyme-Linked Immunosorbent Spot Assay to Predict Risk of Cytomegalovirus Infection in Kidney Transplant Recipients.

Non-specific interferon-gamma (IFN-γ) enzyme-linked immunosorbent (ELISpot) responses after solid organ transplant (SOT) and their relationship with cytomegalovirus (CMV) reactivation have hardly been investigated. Adult kidney transplant (KT) recipients underwent measurement of IFN-γ-producing T cells using the ELISpot assay before and 1 month after transplantation. Data for CMV infection episodes were collected. Risk factors for post-transplant CMV infection, based on IFN-γ responses, were analyzed using a Cox proportional hazards model. A total of 93 KT recipients were enrolled in the study and 84 evaluable participants remained at 1 month post KT. Thirty-three (39%) recipients developed subsequent CMV infection within 6 months post-transplant. At 1-month post-transplant, IFN-γ-producing T cells with <250 spot-forming units (SFUs)/2.5 × 105 peripheral blood mononuclear cells (PBMCs) were significantly associated with CMV infection (HR 3.1, 95% CI 1.4-7.1, p = 0.007). On multivariable analysis, posttransplant IFN-γ-producing T cells with <250 SFUs/2.5 × 105 PBMCs remained independently associated with CMV infection (HR 3.1, 95% CI 1.2-7.8, p = 0.019). Conclusions: KT recipients with low IFN-γ-producing T cells measured by the ELISpot assay are more likely to develop CMV infection after transplantation. Therefore, measurement of nonspecific cell-mediated immunity ELISpot responses could potentially stratify recipients at risk of CMV infection (Thai Clinical Trials Registry, TCTR20210216004).

Significant Increase in Cytomegalovirus (CMV) Infection in Solid Organ Transplants Associated With Increased Use of Thymoglobulin as Induction Therapy?

Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.

Acquisition of Antibody Against Cytomegalovirus After Kidney Transplantation in Seronegative Recipients

Cytomegalovirus (CMV) infection is one of the most important infectious diseases affecting recipients of kidney transplantation (KTx). However, the timing of seroconversion for CMV infection in seronegative recipients remains unclear. We evaluated CMV infections in CMV-seronegative recipients and the time to acquire antibodies against CMV. We conducted a retrospective study of 228 recipients who underwent KTx between March 1988 and February 2018 at the Niigata University Hospital. The anti-CMV IgG antibody profile before and after transplantation was analyzed. Oral acyclovir or valganciclovir was used as prophylactic therapy for at least 6 months after transplantation. Cytomegalovirus infection was defined as CMV viremia detected using the CMV pp65 antigenemia assay. In this study, 50 cases (21.9%) were CMV-seronegative recipients. Over a median follow-up period of 126.7 months, 68% (34/50) of CMV-seronegative recipients experienced CMV viremia or overt disease symptoms as the first episode of CMV infection. The median duration from transplant to CMV infection was 69.0 days (range, 22-7426). All the recipients who experienced CMV infections acquired seroconversion. The median duration from KTx to seroconversion was 7.2 months (range, 2.8-252.3). Almost all CMV-seronegative recipients could acquire anti-CMV IgG antibodies within 2.5 years. In seronegative recipients whose donors were seronegative, no CMV viremia was found, and none developed anti-CMV IgG antibodies. In the clinical practice of CMV-seronegative recipients, we should consider that physicians must closely monitor the occurrence of CMV infection up until 2.5 years after KTx.

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management.

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management.

6 vs 12 Month CMV Prophylaxis in CMV-Mismatched Heart Transplants

<h3>Purpose</h3> Cytomegalovirus (CMV) infection commonly affects heart transplants (HT). Guidelines recommend 3-6 months of prophylaxis (ppx) for primary mismatch (D+/R-) with (val)ganciclovir. We sought to assess the frequency of CMV infection subsequent to our protocol change where ppx was decreased from 12 to 6 months. <h3>Methods</h3> This was a single-center, retrospective study of adults who underwent CMV D+/R- HT from 2009-2020 with a follow up of 18 months (5 patients had shorter follow up but all developed CMV infection and were included for analysis). <h3>Results</h3> Overall, 76 HT recipients met inclusion criteria. Patient characteristics are shown in Table 1. In the 6 and 12 month ppx protocols, there were 23 (71.9%) and 12 (27.3%) CMV infection episodes, respectively. Of these infections, 46.9% and 9.1% of HT were hospitalized. Kaplan-Meier showed a significant difference between the two groups (Fig. 1). Median time to infection from transplant was 246 and 398 days, with most infections occurring after stopping ppx. More patients in the 12 month protocol received induction and CMV immunoglobulin. While nearly all patients were on a calcineurin inhibitor, mycophenolate (MP), and prednisone at 3 months post-HT, fewer were on MP and prednisone at 6 and 12 months in the 6 month ppx cohort and more patients were on sirolimus or everolimus in the same group. <h3>Conclusion</h3> Patients in the 6 month CMV ppx protocol had significantly higher incidence of CMV infection and hospitalization. While a longer ppx protocol may theoretically increase risk of leukopenia and financial burden, our study suggests 12 months of ppx is a better strategy when considering that hospitalization for CMV is no trivial matter.

Primary sclerosing cholangitis as an independent risk factor for cytomegalovirus infection after liver transplant.

Cytomegalovirus (CMV) infection is one of the most common infectious complications after solid organ transplant; it is associated with morbidity and mortality and with many direct and indirect effects. However, monitoring and therapeutic procedures are very heterogeneous across treatment centers. Additionally, factors that place patients at risk of CMV infection are poorly defined. Clinical and demographic data from 833 LT recipients and their donors were retrospectively analyzed. Univariate and multivariate analysis were applied. CMV infection was detected by quantitative nucleic acid testing with a lower limit of detection of 40IU/mL. In total, 192 of 833 patients (23%) experienced at least one episode of CMV infection after LT; CMV infection occurred to a large extent during the first year after transplant (70%). Multivariate analysis demonstrated that CMV donor-recipient risk constellation (OR 2.05, 95% CI) and primary sclerosing cholangitis (PSC) before LT (OR 3.76, 95% CI) are independent risk factors for CMV infection after LT. Patients with high-risk serostatus, PSC, or both should be monitored more thoroughly and should receive prolonged prophylaxis against CMV infection.

1075. Absolute Lymphocyte Count as a Predictor of Cytomegalovirus (CMV) Infection and Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients

BackgroundCytomegalovirus (CMV) is a serious complication following Hematopoietic Stem Cell Transplant (HSCT) and can lead to serious organ disease and mortality. This study aimed to investigate the association between absolute lymphocyte count (ALC) and CMV to determine whether ALC could help to identify those at an increased risk of CMV infection and recurrenceMethodsAdults undergoing HSCT between 2011 and 2016 at Rigshospitalet, Denmark were included. Cox proportional hazards models investigated risk factors, including ALC, for CMV infection in the first year post-transplant and recurrent CMV infection 6 months after clearance and stopping CMV treatment for the first infection. For the primary outcome ALC was investigated as a time-updated risk factor lagged by 7 days, and for recurrent CMV, ALC measured at the time at the time of stopping treatment for the first CMV infection was investigated (+/- 7 days).ResultsOf the 352 HSCT recipients included, 57% were male, 40% received myeloablative conditioning, 42% had high risk (D-R+) CMV IgG serostatus at transplant and the median age was 56 (IQR 43-63). 143 (40.6%) patients had an episode of CMV DNAemia a median of 47 days after transplant (IQR 35-62). A lower current ALC (≤ 0.3 x109/L) was associated with a higher risk of CMV infection in univariate analysis compared to a high current ALC (> 1 x109/L). However, this association was attenuated after adjustment, particularly for acute graft versus host disease (Figure). 102 HSCT recipients were investigated for risk of recurrent CMV of which 41 (40.2%) had a recurrent CMV episode a median of 27 days (IQR 16-50) after stopping CMV treatment for the first infection. A lower ALC (≤ 0.3 x109/L) at the time of stopping CMV treatment was associated with a significantly higher risk of recurrent CMV after adjustment (Figure). A higher peak viral load (> 1500 IU/ml) during the first episode of CMV infection was also associated with an increased risk of recurrent CMV (aHR 2.47, 95%CI 1.00-6.10 compared to < 750 IU/ml).Association between absolute lymphocyte count (ALC) and risk of CMV infection and recurrent CMV within 6 months. **First CMV infection multivariable model also adjusted for sex, CMV serostatus, age, year of transplant, Charlson Comorbidity Index, Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease (time-updated) *Recurrent CMV infection multivariable model also adjusted for conditioning regimen, sex, CMV serostatus, age, year of transplant Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease and peak CMV viral load during the first CMV infectionConclusionA lower ALC at the time of stopping treatment for the first CMV infection was associated with an increased risk of recurrent CMV and could be used to help guide decisions for augmented CMV surveillance and clinical awareness of CMV disease symptoms in these patients. Disclosures All Authors: No reported disclosures

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies.

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7–14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management.

Acute murine cytomegalovirus disrupts established transplantation tolerance and causes recipient allo-sensitization.

We have previously shown that acute cytomegalovirus (CMV) infection disrupts the induction of transplantation tolerance. However, what impact acute CMV infection would have on the maintenance of established tolerance and on subsequent recipient allo-sensitization is a clinically important unanswered question. Here we used an allogeneic murine islet transplantation tolerance model to examine the impact of acute CMV infection on: (a) disruption of established transplantation tolerance during tolerance maintenance; and (b) the possibility of recipient allo-sensitization by CMV-mediated disruption of stable tolerance. We demonstrated that acute CMV infection abrogated transplantation tolerance during the maintenance stage in 50%-60% recipients. We further demonstrated that acute CMV infection-mediated tolerance disruption led to recipient allo-sensitization by reverting the tolerant state of allo-specific T cells and promoting their differentiation to allo-specific memory cells. Consequently, a second same-donor islet allograft was rejected in an accelerated fashion by these recipients. Our study therefore supports close monitoring for allo-sensitization in previously tolerant transplant recipients in whom tolerance maintenance is disrupted by an episode of acute CMV infection.

Monitoring of CMV-specific cell-mediated immunity with a commercial ELISA-based interferon-γ release assay in kidney transplant recipients treated with antithymocyte globulin.

Monitoring for cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA-based interferon (IFN)-γ release assay (QTF-CMV) from posttransplant months 2-5 (362 points) in 120 CMV-seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92days). Forty-seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF-CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF-CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV-CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1-year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P=.244). Specificity and PPV to predict protective CMV-CMI improved by elevating the IFN-γ cutoff value to 1.13IU/mL (65.7% and 71.4%) and 7.0IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF-CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG-treated CMV-seropositive KT recipients. This performance is slightly improved by modifying the IFN-γ positivity threshold.

Cytomegalovirus disease in a retinoblastoma cohort: The role of preemptive screening.

Cytomegalovirus (CMV) disease is underrecognized in children with retinoblastoma. This study investigated rates of CMV infection and disease in this specific population receiving chemotherapy. From a cohort of 164 patients with retinoblastoma diagnosed from 2011 to 2018, 107 patients were evaluated for CMV infection determined by antigenemia assay or real-time PCR. Preemptive CMV screening was implemented in 2013. CMV disease was diagnosed by tissue biopsy, culture, or ophthalmic examination. Thirty-seven and 70 patients before and after the screening strategy, respectively, were included. Before screening, 10/37 (27%) were diagnosed with CMV infection during chemotherapy. Among them, 5 (50%) developed CMV disease (hepatitis, pneumonia, and retinitis) and one patient died of CMV pneumonia. During screening, 18/70 (26%) were documented with 36 episodes of CMV infection and 9 patients received 25 preemptive antiviral therapies. Age at chemotherapy tended to be younger in patients with CMV infection, and fewer were seronegative prior to chemotherapy. Patients who started chemotherapy at <12months of age received preemptive therapies significantly more often than those started at ≥12months. Two (11%) out of 18 patients with CMV infection developed CMV retinitis and colitis, and there were no fatal cases. Preemptive therapy along with active CMV screening significantly reduced the risk of developing CMV disease, from 14% to 2.9% (P=0.047). Children with retinoblastoma can experience significant morbidity and even mortality from CMV infection during chemotherapy in Korea. Preemptive screening and appropriate antiviral therapy can reduce the development of CMV disease and subsequent mortality.

The impact of recurrent cytomegalovirus infection on long-term survival in solid organ transplant recipients.

Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid organ transplantation (SOT). While recurrent infection occurs in up to 30% of patients, its impact on mortality is unclear. The aim of this study was to explore the relationship between recurrent CMV infection and long-term survival in SOT recipients. We performed a retrospective cohort study of SOT recipients who completed treatment for an episode of CMV infection. Patients were followed until death, loss to follow-up or 10years following CMV treatment completion. Univariable and multivariable hazard ratios (HR) were calculated, treating relapse and rejection following CMV as time-varying. About 79 kidney, 52 heart, 34 liver, and 5 liver-kidney transplant recipients were included. About 62/170 died, at a median of 3.8years (IQR 0.8-6.6years). Median follow-up among the 108 survivors was 7.4years (IQR 3.7-10years). Recurrent CMV infection occurred in 49/170 (29%), 67% within 6months of treatment completion. Mortality among those who relapsed was 39% (19/49) vs 36% (43/121) in those who remained relapse-free (unadjusted HR 1.59, 95% CI 0.92-2.75, P=.10). After adjusting for age and transplanted organ, findings were similar (HR 1.68, 95% CI 0.93-3.04, P=.09). Mortality following CMV remains high even in the valganciclovir era. Although our findings suggest a possible increased risk of death among patients with recurrent CMV, these did not reach statistical significance. The complex nature of these patients, multiple potential confounders, and limited statistical power made detection of small effects difficult. Larger prospective studies evaluating the clinical impact of strategies to reduce recurrence are needed.

Cytomegalovirus Infection and Disease in Lung Transplant Recipients

Purpose Cytomegalovirus (CMV) infection causes significant morbidity and mortality in lung transplant recipients (LTR), the most important risk factor for which is the serostatus of donor (D) and recipient (R). Our program employs a CMV prophylaxis strategy. In 2016, our protocol for management of D+ R- changed from 3-6 months of valganciclovir (VGCV) with CMV hyperimmune globulin to 12 months of VGCV with human normal immunoglobulin. Aims: To determine the effect of changing CMV prophylaxis protocol for D+ R- on the incidence of CMV infection/disease in LTR. Methods We retrospectively reviewed laboratory results and clinical notes from all LTR transplanted between 1/01/2014 - 31/12/2017 in the National Heart and Lung Transplant Centre, Ireland. Data were collected for a minimum of ten months post-transplant, with a longer follow-up of those transplanted earlier. Results Data were available on 134 of 137 LTR, Table 1. There were fewer episodes of infection (14 v 30, p = 0.19) and less tissue invasive disease (TID) (0 v 4, p = 0.14) in the D+ R- 2016-17 group. The average time to infection/disease was longer (9 v 7.7 months) in the 2016-17 group. The incidence of CMV infection and disease was 29% in LTR transplanted in 2016-17 and 36% in 2014-15. Conclusion Recent guidelines (1) advocate a minimum of 6 months VGCV prophylaxis in D+ R- LTR. Our data demonstrates there is a trend for less adverse events such as TID with a longer duration. The average time to infection in the 2016-17 group of 9 months suggests some patients are not tolerating prophylaxis and terminating early. In conclusion, following a change in protocol less CMV infection episodes and no invasive CMV disease were reported in our cohort. Reduction in CMV disease and infection will reduce graft loss, morbidity and mortality. Innovations to improve tolerability of VGCV may further delay time to infection.

Viral Infections After Kidney Transplantation in a Cohort of Children: A Retrospective Single-Center Study

BackgroundViral infections are known to be common complications after kidney transplant (KTx), causing significant numbers of mortality and morbidity. ObjectivesWe aimed to highlight the pattern of viral infections after KTx in children and its impact on allograft function. MethodsWe included children who underwent KTx between 2012 and 2017. Baseline demographics, immunosuppressive agents, episodes of viral infections with cytomegalovirus (CMV), BK virus, and Epstein-Barr virus (EBV), and serum creatinine were collected. All children received induction agent followed by maintenance immunosuppression. Oral valganciclovir was given to all high-risk patients for CMV for 180 days as prophylaxis. CMV and EBV polymerase chain reactions were monitored every 2 weeks initially until the ninth month, then monthly until the end of the second year, and then every 3 months. Urine BKV polymerase chain reactions were monitored monthly in the first year and then every 3 months. ResultsA total of 18 children received transplants. There was 1 episode of CMV infection (5.6%), 2 episodes (11.1%) of isolated BK viruria (1 of the 2 with an episode of BK viremia [5.6%] with no associated BK nephropathy [0%]), and no episodes of EBV or lymphoproliferative disease (0%). Allograft functions continued to be stable with mean serum creatinine of 52.2 μmol/L during the study period with 2 episodes (11.1%) of acute cellular rejection and 1 episode (5.6%) of early antibody-mediated rejection. ConclusionProlonged prophylaxis and strict viral monitoring protocol can be effective ways of controlling viral infections after KTx.

Very Early Cytomegalovirus Infection After Renal Transplantation: A Single-Center 20-Year Perspective.

Background:Cytomegalovirus (CMV) infection risk in the first month after transplantation is felt to be minimal; however, the epidemiology has not been specifically investigated, particularly in the modern era of potent immunosuppressive regimens and universal CMV prophylaxis.Objective:The aim of this study was to describe the incidence of and risk factors associated with CMV occurring less than 30 days after transplant and evaluate the effect of very early CMV on outcomes.Methods:Retrospective, single-center study of adult renal transplant (RTX) recipients between January 1, 1994 and December 31, 2014.Results:A total of 5225 patients who received a renal transplant in the study time period were reviewed for the presence of CMV infection occurring less than 30 days after transplant. Of these, only 14 patients demonstrated this finding for an overall incidence of 0.27%. Half of these patients were considered to be at heightened risk due to being a recipient of a non-primary transplant or on chronic immunosuppression. This left seven patients without known risk factors for very early CMV to evaluate. In this group, time from transplant to CMV infection was 13.5 ± 7 days. The majority (57.1%, n = 4) were high-risk serostatus (CMV D+/R−) and occurred in the valganciclovir era (71.4%, n = 5). Lymphocyte-depleting induction predominated (57.1%, n = 4). Average cold ischemic time (CIT) was 19.7 ± 7.7 hours. Three patients had post-operative complications, two required exploratory-laparotomy for hemorrhage. When evaluating outcomes, 43% (n = 3) had subsequent episodes of CMV infection, 28.6% (n = 2) developed rejection, and 28.6% (n = 2) died. Outcomes between patients with CMV infection less than 30 days and those with CMV infection more than 30 days after transplant were not significantly different.Conclusions:In our review of over 5000 kidney transplants, the incidence of CMV infection in the first 30 days after renal transplant is 0.2%. Notable common patient characteristics include hemorrhage requiring re-operation and prolonged CIT. Outcomes were similar to CMV occurring more than 30 days after transplant. This study should provide the clinician with some reassurance; despite potent immunosuppressive therapy, CMV infection in the first 30 days is unlikely.

Going beyond serology for stratifying the risk of CMV infection in transplant recipients.

Knowledge of donor and recipient (D/R) cytomegalovirus (CMV) serostatus is critical for risk stratification of CMV infection and disease in transplant recipients, particularly in the solid organ transplantation (SOT) setting. Despite its broad availability and the success of it use, the risk stratification based on the D/R serostatus is not free of limitations since there are a nondepreciable number of patients that are not accurately categorized by this approach. In fact, up to 20% of seropositive SOT recipients, classically considered at intermediate risk, develop episodes of CMV infection and disease after transplantation. Here, we provide an overview of additional donor and recipient factors that may have utility in identifying patients at risk for post-transplant CMV infection. Specifically, we summarize our current understanding regarding the potential use of use CMV-specific T-cell-mediated immunity, neutralizing antibodies and host genetics that may influence the risk of CMV infection and disease. We provide an overview of the benefits and limitations associated with using these immunological factors in risk stratification and propose specific variables that could be analyzed at the pretransplant evaluation to improve the identification of patients with increased individual susceptibility.

Clinical significance of post-prophylaxis cytomegalovirus infection in lung transplant recipients.

Cytomegalovirus (CMV) disease has been associated with the development of chronic lung allograft dysfunction (CLAD) after transplantation. However, the relevance of CMV replication occurring after the discontinuation of antiviral prophylaxis on the development of CLAD has not been fully established. Patients who underwent lung transplantation during 2004-2014 were included. All patients received antiviral prophylaxis for 3-6months, followed by monitoring of CMV replication during the first year post-transplantation (preemptive therapy). Risk factors for the development of CLAD were assessed by Cox models. A linear regression model with an interaction coefficient between time and CMV infection was used to evaluate the influence of CMV infection on the evolution of FEV1 . Overall, 69 patients were included, 30/69 (43%) patients developed at least 1 episode of significant CMV infection, and 8/69 (11.5%) patients developed CMV disease. After a median follow-up of 3.67years, 25/69 (36%) patients developed CLAD and 14/69 (20%) patients died. In the univariate Cox analysis, significant CMV infection (HR 1.177, P=.698), CMV disease (HR 1.001, P=.998), and duration of CMV replication (HR 1.004, P=.758) were not associated with CLAD. Only bacterial pneumonia tended to be associated with CLAD in the multivariate model (HR 2.579, P=.062). We did not observe a significant interaction between CMV replication and evolution FEV1 (interaction coefficient 0.006, CI 95% [-0.084 to 0.096], P=.890). In this cohort of lung transplant recipients receiving antiviral prophylaxis and monitored by preemptive therapy post-prophylaxis, CMV infection did not have impact on long-term allograft lung function.

Heart Transplantation and Risk of Cardiac Vasculopathy Development: What Factors Are Important?

BackgroundThe aim of this study was to find the main risk factors for development of cardiac allograft vasculopathy (CAV), especially factors identified before the surgical procedure and factors related to the recipient profile and the medical history of the donor.Material/MethodsThere were 147 patients who had heart transplantation (HT) included in this study: mean age was 45.8±15.3 years. All study patients had coronary angiography after HT. Analyzed risk factors were: non-immunologic recipient risk factors (age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT), immunologic recipient risk factors (acute cellular rejection (ACR), acute humoral rejection (AMR), cytomegalovirus (CMV) episodes), and donor-related risk factors (age, sex, catecholamine usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest).ResultsCAV was recognized in 48 patients (CAV group); mean age 53.6±13.6 years. There were 99 patients without CAV (nonCAV group); mean age 48.3±15.5 years. A univariate Cox analysis of the development of coronary disease showed statistical significance (p<0.05) for baseline high-density lipid (HDL), ACR, AMR, CMV, and donor age. Multivariate Cox regression model confirmed that only baseline HDL, episodes of ACR, donor age, and CMV infection are significant for the frequency of CAV after HT.ConclusionsOlder donor age is highly associated with CAV development. Older donor age and low level of HDL in heart recipients with the strongest influence of immunologic risk factors (ACR, CMV infection) were linked with development of CAV.

The impact of virus population diversity on the dynamics of cytomegalovirus DNAemia in allogeneic stem cell transplant recipients.

Mixed cytomegalovirus (CMV) infections are associated with delayed viral clearance in solid organ transplant recipients. We investigated whether this could be extrapolated to allogeneic stem cell transplant (allo-SCT) recipients. A total of 48 plasma specimens, obtained during 29 episodes of active CMV infection in 25 non-consecutive allo-SCT patients, were analysed. Baseline blood specimens, drawn shortly prior to the inception of pre-emptive antiviral therapy (pre-treatment specimen; n=29), as well as follow-up samples obtained either after the initiation of antiviral therapy (post-treatment specimen; n=15) or during recurrent episodes (n=4) were analysed. Plasma CMV DNA loads were quantified by real-time PCR and the CMV genotyping was performed by ultra-deep sequencing of hypervariable regions in the genes coding for glycoproteins N (gN) and O (gO). A trend towards higher CMV DNA peak loads, longer CMV DNAemia episode durations and slower CMV DNAemia decay rates was observed for episodes with mixed CMV genotype populations compared to those caused by single CMV variants, although the differences did not reach statistical significance. The length of the treatment course required to clear DNAemia was significantly longer in these mixed episodes (P=0.002). Significant changes in the number or frequency of CMV gN or gO genetic variants were documented following the initiation of antiviral therapy or in recurrent episodes. CMV diversity may have a major impact on the kinetics of CMV DNAemia clearance during the treatment of active CMV infection episodes in allo-SCT recipients.