Risk Factors For CMV Infection Research Articles

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan

BackgroundCytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. MethodsThis retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. ResultsThere were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. ConclusionThe study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Epidemiology and Risk Factors for Viral Infections in Pediatric Liver Transplant Recipients and Impact on Outcome.

Infections after liver transplantation (LT) are risk factors for morbidity and mortality. Infections, especially of viral etiologies, still have an impact on the graft function and overall outcome. The aim was to review the epidemiology and risk factors of EBV, CMV and non-EBV non-CMV viral infections and their impacts on outcomes after LT. Demographic, clinical, and laboratory data were retrieved from patients' electronic databases. Over 2 years, 96 patients were transplanted at the Pediatric Liver Centre at Kings College Hospital. The majority of the infections were of viral origin; 73 (76%) patients. The incidence of EBV viremia was 60.4%, CMV infection 35.4%, and other viruses 30%. Older donor age, auxiliary graft, and bacterial infections were risk factors for EBV infection. Younger recipient age, D+R- CMV IgG, and left lateral segment graft were risk factors for CMV infection. More than 70% of patients with non-EBV and CMV viral infections stayed positive post-LT but did not contribute to increased complications. Despite the high prevalence of viral infections, EBV, CMV, and non-EBV non-CMV viral infections were not associated with rejection, morbidity, or mortality. Although some of the risk factors for viral infections are unavoidable, identifying the characteristics and risk pattern will help improve the care for pediatric LT recipients.

Sero-prevalence and risk factors for cytomegalovirus infection among pregnant women in a teaching hospital in Ogun state, Nigeria

Background: Infection with cytomegalo virus is usually asymptomatic however in pregnant women the risk of congenital infection and foetal abnormalities makes antenatal screening for CMV infection necessary. The aim of this study was to determine the sero-prevalence and risk factors for CMV infection among pregnant women in Babcock University Teaching Hospital (BUTH), Ilishan Remo, Ogun State, Nigeria.Methods: The study was a cross-sectional descriptive study conducted between January and May, 2017 on patients attending the antenatal clinic of Babcock University Teaching Hospital. Enzyme Linked Immunosorbent Assay (ELISA) Kits were used to determine IgM and IgG anti CMV antibody titresinvenous blood samples obtained from study participants.Results: A total of 80 patients were recruited into the study. The mean age was 30 years.All (100%) respondents were sero-positive for anti CMV IgG antibodies while 28.75% of respondents were seropositive for anti CMV IgM antibodies.Conclusion: There was a highsero-prevalence rate of CMV infection in the study. Screening of pregnant women for CMV infection is necessary due to the risk of congenital infection and fetal defects.

Risk Factors for Polyomavirus, Cytomegalovirus, and Viruria Co-Infection for Follow-Up of Renal Transplant Patients.

BACKGROUND The interaction of viral infection may be associated with increased morbidity after renal transplantation. This study aimed to identify the incidence and risk factors of viruria infections in renal transplant recipients. MATERIAL AND METHODS In this longitudinal study, 502 episodes recorded in 81 kidney transplant patients from 1/2019 to 12/2021 in a hospital in Vietnam were included. BK, JC polyomaviruses, CMV, EBV, and HSV were detected. Multivariable Cox regression analysis was performed to evaluate risk factors for the viruria infection. RESULTS Fifty-six patients (69.1%) had viruria co-infection. The incidence of JC, CMV, and BK infection was the most common viruria, with 67.9%, 61.7%, and 56.8%, respectively. Cox regression revealed that the risk factors for JC were single infection, dose of MMF (HR 1.002), corticoid (HR 1.02), hypertension (HR 1.65), and hematuria (HR 2.03); risk factors for CMV infection were male sex (HR 1.92) and eGFR (HR 0.98); risk factors for BK single infection were hypertension (HR 1.67), proteinuria (HR 3.80), higher tacrolimus trough level (HR 1.17), and dose of MMF (HR 1.002). Hypertension (HR 1.68), fasting plasma glucose (HR 1.13), proteinuria (HR 6.01), tacrolimus trough level (HR 1.12), and dose of MMF (HR 1.004) were independent risk factors for the viruria co-infection. CONCLUSIONS Kidney function was associated with the incidence of viruria. Higher tacrolimus trough level and dose of MMF were associated with higher risk of BK, JC, and co-infection.

Incidence of Post-Transplant Cytomegalovirus Viremia in Patients Receiving Lungs After Ex Vivo Lung Perfusion

<h3>Purpose</h3> CMV infection following lung transplant (LTx) is associated with increased morbidity and mortality. Inflammation, infection and longer ischemic times are important risk factors for CMV infection. Ex vivo lung perfusion (EVLP) has helped to successfully increase utilization of high-risk donors over the last decade. However, the impact of EVLP on post-transplant CMV infection is unknown. <h3>Methods</h3> Single-center, retrospective analysis of all LTx recipients from 2010 to 2020. The primary endpoint was comparison of CMV viremia in recipients that received EVLP vs. non-EVLP donor lungs. CMV viremia was defined as CMV PCR > 1000 IU/mL within two years post-transplant. Secondary endpoints were time from LTx to CMV viremia, peak CMV PCR and survival. Outcomes were also compared between the different donor (D)-recipient (R) CMV serostatus matching groups. <h3>Results</h3> Included were 862 recipients of non-EVLP lungs and 389 recipients of EVLP lungs. There was no significant difference in the distribution of the CMV serostatus matching groups. 35.8% of patients in the non-EVLP group developed CMV viremia vs. 31.9% in the EVLP group (p=0.18). Median time to CMV viremia was 234 days [IQR, 179-318] in non-EVLP and 249 days [IQR, 186-313] in EVLP group (p=0.5). The mean±SD peak viremia was 4.1±0.8 log₁₀ IU/mL in the non-EVLP group and 4.2±0.8 log₁₀ IU/mL in the EVLP group (p=0.4). There was also no difference in survival of the viremic patients between the groups (log-rank p=0.8). All outcomes were similar when comparing non-EVLP and EVLP patients within each serostatus matching group (Fig.1). <h3>Conclusion</h3> Lung transplant activities have significantly increased with the use of high-risk donor lungs evaluated on EVLP. The practice of utilizing more injured donor organs via EVLP has not affected CMV viremia rates and severity in lung transplant recipients. EVLP could further provide the opportunity to pre-treat donor lungs prior to implantation, perhaps decreasing incidence of post-transplant CMV infection.

933. Incidence and Risk Factors for Cytomegalovirus Infection in Intestinal Transplant Recipients

BackgroundCytomegalovirus (CMV) infection is the most common infection after solid organ transplantation. Data on CMV infection in intestinal transplant recipients is limited. MethodsThis is a single-center retrospective cohort study which includes all consecutive intestinal transplant recipients who were transplanted between 2009 and 2019. We excluded recipients that showed CMV seronegativity of both donor and recipient. We also excluded those patients who did not have more than 3 months of follow-up. Univariate and multivariate analyses were performed to identify the risk factors for CMV infection. Of note, at our center CMV prophylaxis in intestinal transplant recipients is one year of valganciclovir. ResultsA total of 173 recipients were transplanted; 46 recipients were because of CMV serostatus and 32 due to short follow-up. Ninety-five recipients were included finally. The characteristics of our cohort are summarized in Table 1. Of note, the median age was 32 years [range 0-67] and 44 (46.3%) were male. Eighteen (18.9%) recipients needed to stop valganciclovir prophylaxis due to the side effect, especially cytopenia. Twenty-one recipients developed CMV infection including asymptomatic viremia (12/21, 57.1%), CMV syndrome (5/21, 23.8%) and end-organ disease (2 (9.5%) pneumonitis and 2 (9.5%) colitis) at median time of 155 [Interquartile range, IQR 28-254] days from transplant. The median peak viral load and time to negativity were 16000 [IQR 1500-43892] IU/ml and 56 [IQR 49-109] days, respectively. Younger age (p=0.007, Odds ratio 1.03, 95% confidence interval 1.003-1.055) was the independent factor associated with CMV infection. ConclusionDespite prolonged prophylaxis, 21 (22.1%) of intestinal transplant recipients developed CMV infection around 5 months post-transplant. This may be because they cannot tolerate valganciclovir prophylaxis and early termination was required. Further strategy should be developed to prevent CMV infection in this vulnerable population.Disclosures All Authors: No reported disclosures

The Prognostic Impact of the Donor/Recipient CMV Serostatus in Patients with Different Chronic Hematological Disorders after Allogeneic Hematopoietic Stem Cell Transplantation: A Report from the Infectious Diseases Working Party of EBMT

IntroductionCytomegalovirus (CMV) seropositivity of the recipient and/or the donor is still associated with a major overall survival (OS) decline in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) despite the fact that the incidence of CMV disease has markedly been reduced by preemptive treatment of CMV infection. However, CMV infection after allo-HSCT might also have a favourable effect by reducing the relapse incidence (RI), at least in acute myeloid leukemia. Less is known about the prognostic impact of the CMV serostatus in patients with different chronic hematological disorders undergoing allo-HSCT.MethodsWe analyzed the prognostic impact of the CMV serostatus in a large cohort of 6968 patients who underwent allo-HSCT between the year 2005 and the year 2016 and who were documented in the database of the European Bone Marrow Transplantation Group. Patients with the following diseases were included: Myelodysplastic syndrome (n=2326), multiple myeloma (n=1788), myeloproliferative neoplasm other than Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) (n=979), follicular lymphoma (n=673), Ph+ CML (n=458), mantle cell lymphoma (n=433) and B cell chronic lymphocytic leukemia (n=311). The primary endpoint was 2-year progression-free survival (PFS) of patients with CMV seronegativity of both the donor and the recipient vs the remaining patients.ResultsThe analysis encompassed 2026 patients (29%) with CMV seronegativity of both the donor and the recipient, 2510 patients (36%) with CMV seropositivity of both of them in addition to 815 (12%) and 1617 patients (23%) with CMV seropositivity only of the donor or the recipient, respectively.Patients with CMV seronegativity of both the donor and the recipient had a significantly superior 2-year PFS (52.5%) compared to patients with CMV seropositivity of the donor and/or the recipient (49.5%, p=0.03). In addition, 2-year OS was significantly shorter for patients with CMV seropositivity of the donor and/or the recipient (62.3%) than for those cases with CMV seronegativity of both of them (65.4%, p=0.01). The negative prognostic impact of CMV seropositivity of the donor and/or the recipient remained in a multivariate Cox regression analysis including other important variables (e.g., T cell depletion, donor type) with a significantly reduced PFS (HR 1.09, 95% CI 1.01-1.17, p=0.03) and OS (HR 1.13, 95% CI 1.04-1.23, p=0.003).CMV-seropositive patients allografted from a CMV-seronegative donor showed a particular unfavorable OS compared to patients with CMV seronegativity of both of them (HR 1.21, 95% CI 1.10-1.34) whereas OS was only slightly reduced in patients with CMV seropositivity of only the donor (HR 1.03, 95% CI 0.91-1.17) or of both of them (HR 1.07, 95% CI 0.98-1.17) (p=0.001). Patients with CMV seropositivity of the donor and/or the recipient further showed a significantly increased non-relapse mortality (NRM) in a multivariate Cox regression analysis (HR 1.15, 95% CI 1.03-1.28, p=0.02). CMV-seropositive patients with a CMV-seronegative donor had the highest NRM (HR 1.22, 95% CI 1.07-1.39), followed by CMV-seropositive recipients with CMV-seropositive donors (HR 1.05, 95% CI 0.93-1.19) and finally CMV-seronegative recipients with CMV-seropositive donors (HR 0.99, 95% CI 0.83-1.18) (p=0.01).The donor/recipient CMV serostatus had no significant impact on acute or chronic graft- vs -host disease, donor/recipient hematopoietic chimerism or RI. Interaction analyses revealed that there are not relevant differences on the prognostic impact of the CMV serostatus among different underlying diseases and donor types.ConclusionsOur data show that the CMV serostatus still has a significant prognostic impact in patients with different chronic hematological disorders undergoing allo-HSCT, despite the implementation of sophisticated antiviral strategies in recent years. CMV-seronegative donors should be avoided whenever possible for CMV-seropositive recipients whereas a CMV-seropositive donor might be adequate for a CMV-seronegative recipient. The fact that CMV seropositivity of the donor and/or the recipient - as the most important risk factor for CMV infection - had no significant impact on the RI argues against a clinically relevant 'virus vs malignancy´ effect in these disorders. DisclosuresSocié:Alexion Pharmaceuticals, Inc.: Consultancy. Lamy:Roche: Consultancy, Honoraria.

IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis

BackgroundCytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients.MethodsA total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses.ResultsA total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49–73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05–119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively.ConclusionsHigh-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.

P0428CYTOMEGALOVIRUS INFECTION IN PATIENTS WITH GLOMERÜLER DISEASE TREATED WITH CYCLOPHOSPHAMIDE: A SINGLE-CENTER EXPERIENCE

Abstract Background and Aims Cytomegalovirus (CMV) infection is an important complication in immunocompomised patients. Although approach to CMV infection is well-defined in stem cell and solid organ transplant recipients, less is known about the frequency and risk factors of CMV disease in patients with glomerulonephritis (GN). As few studies have shown that cyclophosphamide (CYC) treatment is a risk factor for CMV infection in GN patients, we aimed to describe the frequency and risk factors of CMV infection in GN patients treated with CYC. Method 268 patients diagnosed GN between January 2017 and November 2019 in Ankara University İbni Sina Hospital, Nephrology Department. We recruited 43 GN patients who were treated with CYC and screened all patients for viral DNA monthly. CMV infection defined by CMV DNA detected &amp;gt;500 copies/µl. Patients developed CMV and no-CMV infection were compared for age, sex, glomerular pathology, renal function and clinical status before and after treatment. Results CMV infection was detected in 10 (23,3%) patients at 2±1 (min:1 max:3) months of CYC treatment (Table-1). 7 patients were treated for CMV infection with parenteral ganciclovir, while the other 3 patients with low CMV DNA level (509, 538 and 540 copies/ml) and no disease symptoms were monitored without antiviral treatment. Patients with CMV infection had higher serum creatinine (4,2±3,2 vs. 1,9±1,8 mg/dl, p=0,006), lower estimated glomerular filtration rate (29±11 vs. 65±8 (ml/min/1.73 m2, p=0.016), lower low-density lipoprotein (144±71 vs. 221±83 mg/dl, p=0,012) at diagnosis compared with no-CMV infection patients (Table-2). Also more patients were diagnosed with rapidly proggressive GN (80,0% vs. 27.3%, p=0,007), and secondary GN was the most common GN diagnosis (80,0% vs. 27.3%, p=0.007) in CMV infection group. Conclusion CMV infection is a common complication in GN patients treated with CYC. Routine monitoring and prophylaxis should be considered for the patients who have risk factors for CMV infection.

Incidence, risk factors and prognostic impact of cytomegalovirus infection after heart transplantation

Introduction and objectivesTo assess the risk factors of CMV infection after heart transplant (HT) and its influence on long-term prognosis. MethodsWe conducted a retrospective single-centre study of 222 H T recipients. Risk factors for CMV infection were identified by means of multivariable Cox´s regression. Kaplan-Meier analysis and Cox´s regression were used to assess the long-term prognostic impact of CMV infection during the first post-transplant year. ResultsDonor-recipient CMV serologic matching (hazard ratio [HR] 1.92, 95% confidence interval [95% CI] 1.2–3.09, p = .007), recipient age (HR 1.02, 95% CI 1.00–1.1, p = .02), diabetes mellitus (HR 1.86, 95% CI 1.4–3.05, p = .01), pre- transplant circulatory support (HR 1.59, 95% CI 1.06–2.38, p = .03) and the use of tacrolimus (HR 1.64, 95% CI 1.13–2.36, p = .009) were independently associated with increased risk of CMV infection. CMV infection during the first year post-HT was not associated with worse transplant outcomes in terms of mortality, incidence of heart failure, cardiac allograft vasculopathy or acute rejection. ConclusionsCMV infection was not associated with impaired long-term prognosis after HT.

1750. Epidemiology of Cytomegalovirus DNAemia in Pediatric Solid-Organ Transplant Patients

BackgroundDespite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR is limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR.MethodsA retrospective cohort study of patients <22 yr of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2014 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). Primary outcome was CMV DNAemia (plasma level ≥ 1,000 IU/mL). Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots.ResultsAmong 465 SOTR, 57 (12%) had CMV DNAemia ≥ 1,000 IU/mL; this included 9/52 (17%) lung, 22/155 (14%) liver, 16/125 (13%) heart, 1/9 (11%) multi-organ, and 9/124 (7%) kidney recipients. 6 (10%) SOTR had early-onset CMV reactivation while on antiviral prophylaxis. Post-prophylaxis, 48 (85%) SOTR had CMV reactivation and 3 (5%) had primary infection. Median time to DNAemia > 1,000 IU/mL was 366 days post-transplant for lung, 115 for liver, 185 for heart, and 290 for kidney (P = 0.04), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R- for heart, liver, kidney and D+ and/or R+ for lung) was associated with CMV DNAemia (P < 0.01, Figure 2). DNAemia was not associated with age at transplantation, type of organ, or induction immunosuppression. There was no difference in survival during the study follow-up period (1 – 5 years) for SOTR with vs. without DNAemia. Overall, 18/465 (4%) SOTR had CMV disease: 2 (4%) lung, 3 (2%) liver, 5 (4%) heart, 1 (11%) multi-organ, and 7 (6%) kidney recipients. 16 had CMV syndrome and 2 had tissue-invasive disease. Median (range) maximum viral loads were 35,768 IU/mL (3,239–4,807,992) for SOTR with vs. 2,605 IU/mL (1,000–112,000) for SOTR without CMV disease (P < 0.01)ConclusionThis large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted. DisclosuresFlor M. Munoz, MD, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

Risk factors for cytomegalovirus infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

AimsCytomegalovirus (CMV) infection under immunosuppression sometimes causes death. This study aimed to elucidate risk factors for CMV infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).MethodsPatients with AAV who underwent remission induction treatment at Okayama University Hospital between 2006 and 2016 were retrospectively analyzed. The primary outcome was the development of CMV infection within 3 months.ResultsOf the 111 patients, 13 (11.7%) patients developed CMV infection. Patients with CMV infection were older (p = 0.030) and had a higher body mass index (p = 0.029) in comparison to those without CMV infection. A higher proportion had a severe form (p = 0.001) and granulomatosis with polyangiitis (GPA) (p = 0.001), as well as a higher Birmingham Vasculitis Activity Score (p = 0.018) and C-reactive protein (p = 0.018) levels at baseline. Using logistic regression analysis, severe form and GPA were independent risk factors (odds ratio [OR] = 9.68, 95% confidence interval [CI] = 1.92–60.23, and OR = 7.46, 95% CI = 1.46–47.60, respectively). In addition, patients with CMV infection were more likely than those without infection to be glucocorticoid-related diabetes mellitus (p = 0.025).ConclusionOur study highlights disease severity and subgroups of AAV as risk factors for CMV infection.

The risk of cytomegalovirus infection after treatment of acute rejection in renal transplant recipients.

The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P<0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P<0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P<0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28-2.96, P<0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31-3.58, P<0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65-5.09, P<0.01) and mortality (HR 1.82, 95% CI: 1.12-4.24, P=0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.

Cause of End-Stage Renal Disease Is Not a Risk Factor for Cytomegalovirus Infection After Kidney Transplant

BackgroundCytomegalovirus infection (CMV) after kidney transplantation leads to increased morbidity and mortality. Whether the cause of end-stage renal disease (ESRD) influences the risk of CMV infection post-transplant is not known. MethodsWe analyzed data from 2741 adult kidney transplant recipients from January 1993 through December 2014. The causes of ESRD included diabetes mellitus (n = 947), hypertension (n = 442), polycystic kidney disease (n = 549), and glomerulonephritis (GN) (n = 803). The primary outcome was incidence of CMV infection, defined as the first episode of detectable CMV DNA in the blood following transplant. ResultsThree hundred and thirty patients developed a CMV infection over a median follow-up of 4.5 years. Patients with diabetes mellitus (DM) as the cause of ESRD had a higher incidence of CMV infection post-transplant compared to patients with GN (2.37 vs 1.58/100 person-years, P < .005) whereas hypertension (HTN) and autosomal dominant polycystic kidney disease (PKD) were similar (2.17 and 2.07/100 person-years). DM was associated with a 35% higher risk of CMV infection compared to GN in unadjusted analyses [hazard ratio=1.35 [95% confidence interval 1.02–1.78], P = .04). However, after adjustment for age, the risk of CMV infection was similar in all groups (DM: age-adjusted hazard ratio 1.02 [0.78–1.39]; HTN: 0.96 (0.67–1.36); PKD: 1.08 [0.78–1.48]; compared to GN). The risk of CMV infection increased with age (adjusted hazard ratio=1.32 [1.18–1.47] for every decade of life, P < .001). ConclusionsOur study demonstrates that the cause of ESRD is not a significant risk factor for CMV infection in kidney transplant recipients once adjusted for age. Future studies are needed to identify risk factors for CMV infection to define patient-centered monitoring and prevention.

Cytomegalovirus infection in pediatric patients with hepatoblastoma after liver transplantation.

No studies have examined CMV infection in pediatric patients with HB receiving LT. Here, we retrospectively analyzed the incidence of and risk factors for CMV infection in 24 pediatric patients with HB who underwent LT between 1997 and 2015. CMV infection was monitored by measuring expression of pp65 CMV antigen for up to 4months post-LT. CMV infection, defined as detection of at least one pp65-positive leukocyte, was detected in nine (37.5%) patients who did not develop CMV disease. Nine (47.4%) of nineteen patients who received post-LT chemotherapy experienced CMV infection; however, no CMV infection was observed in the five patients who did not receive post-LT chemotherapy (P=0.012). There were no significant differences in the incidence of CMV infection between patients with ACR (60.0%) and those without (21.4%, P=0.092), or between CMV seropositive (55.6%) and seronegative patients (33.3%, P=0.675). All nine patients with CMV infection did not experience CMV disease due to the use of preemptive antiviral therapy. Close monitoring of CMV infection is recommended for patients with HB, particularly those receiving post-LT chemotherapy. Preemptive antiviral therapy is feasible for prophylaxis of CMV disease.

Influence of MHC Class I Chain-Related Gene Α (MICA) Polymorphisms on Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation

BackgroundCytomegalovirus (CMV) is a common infectious complication after allogeneic hematopoietic cell transplantation (alloHCT). Efforts to enhance immune reconstitution post-transplant have been pursued to help facilitate clearance of such infections. Assessment of natural killer (NK) cell allo-reactivity with investigation of killer cell immunoglobulin-like receptors has been reported to be associated with protection from CMV infection after alloHCT (Davis ZB et al, BBMT 2015). In addition, the activating NKG2D receptor controls immune responses by regulating NK cells, NKT cells and γδ-T cells. MHC class I chain-related gene A (MICA) is a polymorphic ligand of the NKG2D receptor on these immune effector cells. Given the potential benefit of NK cell allo-reactivity for protection from CMV infection after alloHCT we hypothesized that MICA polymorphisms may influence CMV infection rates after such transplants.MethodsWe conducted a single center, retrospective analysis of allogeneic HCTs for adults with hematologic malignancies in which MICA data were available for donors and recipients. Analysis was restricted to patients with T-cell replete HLA-8/8 matched related or unrelated donor. Fine and Gray regression was used to identify risk factors for CMV infection. The first episode of graft-versus-host-disease (GVHD) was analyzed relative to CMV as a time-dependent covariate. An analysis was performed examining dimorphisms at the MICA-129 position, which previously has been categorized as weaker (valine/valine: V/V), heterozygous (methionine/valine: M/V), or stronger (methionine/methionine: M/M) receptor binding affinity.ResultsFrom 2000-2016, 423 alloHCT patients were identified who had MICA data. Diagnoses included 197 AML, 82 MDS, 34 ALL, 34 NHL, 22 CML, 12 CMML, 9 CLL, 9 myelofibrosis, 9 plasma cell myeloma, 9 other leukemias, and 6 Hodgkin lymphoma. High, intermediate, and low co-morbidity index was seen in 42%, 33%, and 25% of patients, respectively. Median age at transplant was 52 years (range, 18-76), with 95% Caucasian. A myeloablative transplant was performed in 80% of patients and 52% had a bone marrow graft source. CMV infection occurred in 141 (33%) of patients at a median time of 46 days post-transplant (range, 0-609 days) with 29 (21%) occurring within 30 days, 108 (77%) within 100 days and 33 (23%) after day 100. Thirty-three (8%) patients were MICA mismatched with their donor. Donor MICA-129 dimorphisms included 203 (48%) V/V, 190 (45%) M/V and 30 (7%) M/M. Baseline donor(d)/recipient(r) CMV serostatus for V/V vs. M/V + M/M cohorts were 25% vs. 28% for d+/r+, 11% vs 9% for d+/r-, 39% vs. 37% for d-/r+, and 25% vs. 26% for d-/r- (P=0.75). In univariate analysis, MICA mismatch was associated with a higher risk of CMV (HR 1.64, CI 1.00-2.69, P=0.049), and V/V donor MICA-129 dimorphism with a marginally higher risk of CMV (HR 1.32, CI 0.85-1.83, P=0.10). In multivariable analysis, MICA mismatch was not associated with CMV infection (HR 1.38, CI 0.83-2.29, P=0.22) while V/V donor MICA-129 dimorphism was associated (HR 1.40, CI 1.00-1.96, P=0.05) (Figure 1). Other significant variables in multivariable analysis were year of transplant (HR 0.95, CI 0.92-0.99 P=0.01), non-Caucasian race (HR 2.15, CI 1.18-3.91, P=0.01), high-risk disease (HR 1.62, CI 1.13-2.32 P=0.008), baseline CMV serostatus (HR 7.51, CI 3.76-15.0, P<0.001 for d+/r+, HR 7.73, CI 3.90-15.3, P<0.001 for d-/r+, both relative to d-/r-), and development of GVHD prior to CMV (HR 2.02, CI 1.37-2.96, P<0.001). There was no association of MICA mismatch with acute (HR 1.05, CI 0.66-1.68, P=0.83) or chronic (HR 0.94, CI 0.51-1.76, P=0.85) GVHD. As compared to the V/M+M/M cohort, patients with V/V donors had a longer interval from diagnosis to transplant (median 8.2 vs 6.2 months, P=0.036) and more often received myeloablative conditioning (P=0.030).ConclusionWe conclude that the donor MICA-129 V/V dimorphism with weak NKG2D receptor binding affinity is associated with increased risk of CMV infection after alloHCT. The presence of at least one M residue encoding allele may confer enhanced NK cell anti-viral reactivity. These observations potentially may have implications in optimizing donor selection. Further investigation of MICA may also help better predict which patients are at higher risk of CMV infection in order to consider intervening sooner with CMV specific therapy or more rapid tapering of immunosuppression. [Display omitted] DisclosuresGerds:CTI BioPharma: Consultancy; Incyte: Consultancy. Majhail:Sanofi: Honoraria; Anthem, Inc.: Consultancy.

リンパ系腫瘍は同種造血幹細胞移植後早期のサイトメガロウィルス感染の危険因子となる

リンパ系腫瘍は同種造血幹細胞移植後早期のサイトメガロウィルス感染の危険因子となる

Cytomegalovirus infection in the Netherlands: Seroprevalence, risk factors, and implications

BackgroundCytomegalovirus (CMV) infections occur worldwide and are usually asymptomatic in healthy individuals. In fetuses and immunocompromised persons, they can cause severe disease and disabilities. ObjectiveTo determine the CMV seroprevalence and risk factors for CMV infection in the Netherlands. Study designIn a cross-sectional population-based study (PIENTER-2, 2006–2007), sera and questionnaire data were collected from 6386 individuals. Sera were tested for CMV-specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA). ResultsThe CMV seroprevalence in the general population (6 months–79 years) was 45.6%. Age and country of origin were the most prominent independent risk factors. The seroprevalence was significantly lower in native Dutch and Western individuals (41.5%) than in non-Western individuals (76.7%). Multivariable logistic regression analysis showed that age, lower educational level, first-generation migrancy, and among native Dutch/Western individuals, female gender and having contact with young children, were independently associated with CMV seropositivity. The geometric mean concentrations of antibodies increased with age and were higher in women than in men. ConclusionCMV seroprevalence in the Netherlands is relatively low compared to other countries. This is in line with our finding of a higher seroprevalence among migrants compared to the native population. The higher seroprevalence in women and individuals who have contact with young children is especially important for women of reproductive age. Preventing CMV infection in these women, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections.

Treatment for CMV Infection in IBD Inpatients Does Not Change Clinical Outcomes

Purpose: To assess the frequency of CMV infection on tissue level in IBD inpatients, to compare the clinical outcomes between CMV negative and positive patients, and also between CMV positive patients, with treatment and without, and to assess the risk factors for CMV infection. Methods: A total of 140 patients (96 UC and 44 CD) admitted for active colitis from 2005 to 2013, who had colon biopsy for CMV, were recruited. Positive CMV infection was defined as detection of CMV via immunohistochemistry on pathology. Seventeen demographic data were collected. Six clinical outcomes (length of hospital stay, ICU transfer, requirement for GI surgeries within 30 days and 12 months, rehospitalization, and mortality) were compared between CMV negative and positive patients, and also between CMV-positive patients with treatment and without. Results: Among 140 patients, 33 (23.6%) patients had positive CMV detection on the biopsy. In addition, 28 received treatment, while five did not. Among the demographic variables, older age (OR 1.07 with P<0.001), pre-admission use of mesalamines (OR 12.67 with P<0.001), and extra-intestinal manifestations (OR 6.52 with P=0.007) were found to have strong association with CMV infection (Table 1). CMV-positive patients tend to have longer hospital stay (P=0.035) and more frequent IBD-related rehospitalization (P=0.002) compared to negative ones. However, treatment for CMV-positive patients had no positive impact on the clinical outcomes (Table 2).Table 1: Risk factors for CMV infectionTable 2: Clinical outcomes of CMV infected IBD inpatientsConclusion: 23.6% of IBD inpatients had positive CMV colon infection, based on tissue immunohistochemistry. Older patients with pre-admission use of mesalamines and presence of extra-intestinal manifestations were found to have higher risk for CMV infection. Gancyclovir treatment in 85% positive patients did not improve the clinical outcomes. Our study highly suggests that treatment for CMV may not be critical for management of these patients. The CMV infection status could be a surrogate marker for sicker patients who require closer follow-up and more aggressive therapy.

Cytomegalovirus infection after kidney transplantation, susceptibility to CMV-infection in association with HLA-genotype — Doctoral dissertation summary

Abstract Cytomegalovirus infection is a major infectious complication of transplant recipients, causing significant morbidity and mortality. It is possible to treat this infection effectively only if we know the direct and indirect effects of it, if we take the risk-factors into account, and use sensitive and reliable diagnostic methods for early establishment of diagnosis. In order to avoid severe CMV-infection, it is possible to administer prophylactic therapy. For prophylaxis planning it is important to know the CMV-seroprevalence of Hungarian population and its characteristics. Our results have shown that the seroprevalence of Hungarian population is high: 86%. The primary CMV-infection in Hungary occurs in childhood or in early adulthood, till age of 20 years the seroprevalence is 72%. CMV-seronegative recipients should be transplanted using organs of seronegative donors, however, the chance obtaining the graft from a CMV-seronegative donor was shown to be 2% only. Since such seromatching is rear, we have to know that the constellation of negative recipient and positive donor is the highest risk-factor for developing severe primary CMV-infection. While investigating data of 147 CMV-seronegative recipients from high-risk group it has been established that CMV-infection prophylaxis is essential for high risk patients in the early post-transplant period of 3 months, the administration of any of investigated prophylactic protocols is advantageous in comparing with prophylaxis free management of those patients (P=0.006). The study has also proven that monoprophylaxis with ganciclovir or valganciclovir is the most effective and cost-effective procedure as compared to other protocols (P=0.006). It is important to take into consideration that in prophylactic groups the “late-onset” CMV-infection occurred often (25.4%), and that there were no signs of seroconversion after the primary CMV-infection in 14% of the patients. For the first time it has been found and proven that the female sex is a risk factor for CMV-infection (P=0.0006). Genetic variability influences susceptibility to infectious diseases and HLA-molecules are critical for viral antigen uptaking, processing and presenting. Our data of 129 of high-risk patients suggest that recipients positive for HLA-DQ3 are more susceptible to CMV-infection than a comparable group of patients negative for this HLA-type. This result was not due to rejection and/or treatment for rejection and was not influenced by induction therapy or number of HLA-mismatches. The multivariate Cox Regression analysis has shown that HLA-DQ3 positivity is an independent predictor of primary CMV-infection in CMV-seronegative recipients with seropositive donor grafts (P=0.001). The cognition of HLA-DQ3 is useful in the prediction of acute CMV-infection in high-risk patients, and should influence the planning of the patients' management.