Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection

OBJECTIVE: To determine the prevalence of cytomegalovirus infection in patients with steroid-refractory ulcerative colitis who required colonic resection, and to assess its possible association with the use of immunosuppressive and steroid treatment and outcome after colectomy. PATIENTS AND METHODS: The study included surgical specimens and related pre-operative endoscopic biopsy specimens of 77 consecutive ulcerative colitis patients (34 females) who underwent colectomy because of intractable steroid-refractory ulcerative colitis (55 patients), toxic megacolon (6 patients), dysplasia or cancer (7 patients) or loss of function of the colon (9 patients). Clinical features and current and past treatments were analysed. Haematoxylin and eosin and specific immunohistochemical staining for cytomegalovirus were used to detect inclusion bodies in all specimens. RESULTS: Cytomegalovirus infection was found in 15 of 55 steroid-refractory ulcerative colitis patients (27.3%) and in 2 of 22 non-refractory patients (9.1%) (p=0.123). Only six patients had positive staining for cytomegalovirus in pre-operative endoscopic biopsy specimens. Detection of cytomegalovirus inclusion in biopsy specimens was not related to the number of biopsies or to time that had elapsed since colonoscopy and index surgery. Cytomegalovirus-positive patients were more likely to be on systemic corticosteroids (p=0.03). In contrast, current use and duration of immunosuppressive treatment, number of steroid cycles since diagnosis and in the last year, as well as chronic use of steroid in the last year were not significantly related to cytomegalovirus infection. Cytomegalovirus-positive patients did not receive antiviral therapy following proctocolectomy but did not show endoscopic or histological cytomegalovirus reactivation in the ileo-anal pouch and in the remaining bowel. CONCLUSIONS: Cytomegalovirus infection is frequently found in surgical specimens of patients with steroid-refractory ulcerative colitis and is more likely in patients on corticosteroid treatment. Cytomegalovirus infection is frequently unrecognised in pre-operative biopsy specimens, thus raising concerns about the accuracy of the available diagnostic tools. Unrecognised and untreated cytomegalovirus infection does not affect the outcome of ulcerative colitis patients following proctocolectomy.     

Impact of cytomegalovirus serostatus on outcome of unrelated cord blood transplantation for adults: a single-institute experience in Japan

Cytomegalovirus (CMV) disease is one of the major infectious complications after allogeneic hematopoietic stem cell transplantation (SCT). Several studies have shown that CMV-seropositive patients have a substantial survival disadvantage after bone marrow transplantation (BMT) or peripheral blood SCT (PBSCT). Between August 1998 and February 2006, 101 adult patients underwent myeloablative cord blood transplantation (CBT) from unrelated donors at our institution. Sixteen and 85 patients were CMV-seronegative and CMV-seropositive, respectively, prior to CBT. Outcomes of CBT were compared between CMV-seronegative and CMV-seropositive patients. The cumulative incidences of neutrophil engraftment at 60 d after CBT did not differ between CMV-seronegative and CMV-seropositive patients (100% and 94%, P = 0.09); however, the cumulative incidence of platelet engraftment at 100 d was higher in CMV-seronegative patients than CMV-seropositive patients (100% vs. 86%, P < 0.005). The cumulative incidence of CMV antigenemia at 100 d was lower in CMV-seronegative patients than CMV-seropositive patients (0% vs. 77%, P < 0.001); however, the cumulative incidences of CMV disease did not differ between CMV-seronegative and CMV-seropositive patients (0% vs. 1%, P = 0.84). The probabilities of disease-free survival at 2 yr also did not differ between CMV-seronegative and CMV-seropositive patients (92% vs. 72%, P = 0.16). The outcomes of CBT for CMV-seropositive patients as well as CMV-seronegative patients in our series were favorable. This might be due to effective antiviral therapy for CMV infection. Large-scale studies are needed to determine the impact of recipient CMV serostatus on the outcome of CBT for adults.     

Rapid increase in the serum Cytomegalovirus IgG avidity index in women with a congenitally infected fetus

BackgroundHuman Cytomegalovirus (CMV) is the virus most frequently responsible for severe diseases of the fetus and newborn. The reported intrauterine transmission rate of CMV following primary maternal infection is approximately 40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV infection.ObjectivesThe aim of this study was to evaluate whether the rapidity of change in the CMV IgG avidity index (AI) is associated with the presence of congenital CMV infection among mothers with suspected primary CMV infection.Study designThe serum CMV IgG AI was repeatedly measured in 17 pregnant women with positive or borderline test results for CMV IgM together with an initial IgG AI value of <40%. Their neonates underwent polymerase chain reaction analyses for the presence of CMV DNA in the urine. The rapidity of change in the IgG AI per 4 weeks was defined as the ΔAI (%). The ΔAI of women with congenital CMV infection was compared with that of women with no infection.ResultsThe ΔAI of nine mothers with congenital CMV infection (median,15.7%; range,7.8–42.8%) was significantly higher than that of eight mothers with no infection (median, 6.5%, range, 2.0–8.8%; p < 0.001). The incidences of congenital CMV infection were 100.0%, 16.7%, and 0.0% among mothers with a ΔAI of >10, 5–10, and <5%, respectively.ConclusionsMeasurement of the ΔAI in pregnant women might be useful for estimating the risk of mother-to-neonate CMV transmission.     

Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients

BackgroundPreemptive antiviral therapy relies on viral load measurements and is the mainstay of cytomegalovirus (CMV) prevention in hematopoietic cell transplant (HCT) recipients. However, optimal CMV levels for the initiation of preemptive therapy have not been defined.ObjectivesThe objectives of our work were to evaluate the relationship between plasma CMV DNA levels at initiation of preemptive therapy with time to resolution of viremia and duration of treatment.Study designRetrospective analysis of HCT recipients undergoing serial CMV PCR testing between June 2011 and June 2014 was performed.Results221 HCT recipients underwent preemptive therapy for 305 episodes of CMV viremia. Median time to resolution was shorter when treatment was initiated at lower CMV levels (15 days at 135–440 international units (IU)/mL, 18 days at 441–1000 IU/mL, and 21 days at >1000 IU/mL, P < .001). Prolonged viremia lasting >30 days occurred less frequently when treatment was initiated at 135–440 IU/mL compared to 441–1000 IU/mL and >1000 IU/mL (1%, 15%, 24%, P < .001). Median treatment duration was also shorter in the lower viral load groups (28, 34, 37 days, P < .001).ConclusionInitiation of preemptive therapy at low CMV levels was associated with shorter episodes of viremia and courses of antiviral therapy. These data support the utility of initiating preemptive CMV therapy at viral loads as low as 135 IU/mL in HCT recipients.     

Influence of major histocompatibility complex class I chain-related gene A polymorphisms on cytomegalovirus disease after allogeneic hematopoietic cell transplantation

Objective/BackgroundCytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT.MethodsWe conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity.ResultsIn multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00–1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83–2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor–recipient mismatch (HR = 1.05; 95% 95% CI, 0.66–1.68; p = .83 and HR = 0.94; 95% CI, 0.51–1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79–1.31; p = .89 and HR = 0.89; 95% CI, 0.65–1.22; p = .47, respectively).ConclusionThese findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT.     

婴儿巨细胞病毒性肝炎抗病毒治疗前后血T细胞亚群和尿CMV DNA变化

目的研究婴儿巨细胞病毒（CMV）肝炎治疗前后血T细胞亚群和尿CMV DNA的变化及临床意义。方法选择CMV肝炎患儿46例,CMV无症状性感染患儿20例,健康查体婴儿20例,比较3组间尿CMV DNA含量和血T细胞亚群的差异。比较46例CMV肝炎患儿治疗前后血T细胞亚群和尿CMV DNA的水平。结果 CMV肝炎患儿组尿CMV DNA含量明显高于CMV无症状性感染组和健康对照组,差异有统计学意义（t=2.375、P〈0.05;t=16.27、P〈0.01）。CMV肝炎患儿组CD4^＋T淋巴细胞的水平和CD4^＋/CD8^＋T淋巴细胞的比值较无症状性感染组和健康对照组均降低,CD8^＋T淋巴细胞水平较其他组升高,差异有统计学意义。CMV肝炎患儿抗病毒治疗后,尿CMV DNA含量明显下降,CD4^＋T淋巴细胞的水平和CD4^＋/CD8^＋T淋巴细胞的比值较治疗前升高,差异有统计学意义,CD8^＋T淋巴细胞水平较治疗前明显下降,差异有统计学意义。结论 CMV肝炎患儿细胞免疫功能受损。抗CMV治疗能有效改善患儿的细胞免疫功能,治疗前后监测血T细胞亚群和尿CMV DNA变化对判断预后和指导临床治疗有重要意义。     

Cost minimization analysis of an in-house molecular test for cytomegalovirus in relation to a commercial molecular system

IntroductionCytomegalovirus may cause severe disease in immunocompromised patients. Nowadays, quantitative polymerase chain reaction is the gold-standard for both diagnosis and monitoring of cytomegalovirus infection. Most of these assays use cytomegalovirus automated molecular kits which are expensive and therefore not an option for small laboratories, particularly in the developing world.ObjectiveThis study aimed to optimize and validate an in-house cytomegalovirus quantitative polymerase chain reaction test calibrated using the World Health Organization Standards, and to perform a cost-minimization analysis, in comparison to a commercial cytomegalovirus quantitative polymerase chain reaction test.Study designThe methodology consisted of determining: optimization, analytical sensitivity, analytical specificity, precision, curve variability analysis, and inter-laboratorial reproducibility. Patients (n = 30) with known results for cytomegalovirus tested with m2000 RealTime System (Abbott Laboratories, BR) were tested with the in-house assay, as well as patients infected with other human herpes virus, in addition to BK virus. A cost-minimization analysis was performed, from a perspective of the laboratory, assuming diagnostic equivalence of the methodologies applied in the study.ResultsThe in-house assay had a limit of detection and quantification of 60.3 IU/mL, with no cross-reactivity with the other viral agents tested. Moreover, the test was precise and had a R² of 0.954 when compared with the m2000 equipment. The cost analysis showed that the assay was economically advantageous costing a median value of 37.8% and 82.2% in comparison to the molecular test in use at the hospital and the m2000 equipment, respectively.ConclusionsThese results demonstrated that in-house quantitative polymerase chain reaction testing is an attractive alternative in comparison to automated molecular platforms, being considerably less expensive and as efficacious as the commercial methods.     

Gastrointestinal complications after kidney transplantation

Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease(IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.