Positive CMV-DNA Research Articles

P1356 Comparison of different diagnostic test for detection of CMV colitis in hospitalized patients with ulcerative colitis: an interim analysis

Abstract Background Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC) as an independent risk factor for hospitalization and surgery. European guidelines indicate that immunohistochemistry [IHC], tissue polymerase chain reaction [PCR], or possibly both, are essential for confirming active CMV colitis in IBD and should be considered as standard tests. The aim of our study is to evaluate the diagnostic performance of different tests used for diagnosis of CMV infection in comparison with the gold standard in hospitalized patients for UC flare. Methods We prospectively included consecutive UC patients hospitalized for a UC flare since March 2024. UC activity was assessed according to the Truelove&Witts score together with CMV-DNA PCR on blood, stool, tissue and IHC on colonic biopsies were all performed within 5 days from admission. Demographic data, history of medications, lab test at admission were collected for every patient. Patients were treated for UC according to guidelines; in case of CMV positivity on IHC or tissue CMV PCR > 250 cp/mg (qPCR) they received either ganciclovir or vanganciclovir if useful according to investigators. We registered clinical remission and need of surgery within 30-days from hospitalization. Results In this interim analysis we collected data on 51 patients. Of these, 70.6% were admitted with severe UC according to the Truelove&Witts score, with a median endoscopic Mayo score of 3, and 49% of the patients were steroid-refractory at hospital admission. 63% of patients achieved clinical remission 30 days after admission, whereas 37% did not show signs of response, including 4 patients who needed surgery within this time frame. In our cohort 16/51patients (31.4%) were diagnosed with CMV colitis according to IHC or qPCR > 250 cp/mg, while only 3/51 patients (5.8%) confirmed the diagnosis according to IHC criteria. Only 8 patients received antiviral treatment; in the remaining 8 cases antiviral treatment was not indicated due to lack of presumed clinical benefit. Blood positive CMV-DNA was found in 8 patients; among them 5 were confirmed with CMV colitis. Only 3 patients tested positive for stool CMV-DNA, however all of them received a subsequent confirmation of CMV colitis. Conclusion Concordance between diagnostic criteria (qPCR vs IHC criteria) was low confirming the unreliability of currently accepted diagnostic test. Preliminary data about alternative sources of CMV DNA testing looks promising and more reliable. Further data are needed to attain definite conclusions.

Congenital cytomegalovirus infection cases and follow-up findings in Antalya, Turkey

Objective: To investigate the presence of cCMV infection and the CMV-DNA virus in the newborns who applied for newborn hearing
 screening test (NHST) and CMV-DNA viruria with physical, mental-motor development and hearing status of cCMV cases in the
 second year of age.
 Patients and Methods: CMV-DNA was investigated in 1150 newborns’ oral swabs (0-21 days) by polymerase chain reaction kit and
 urine of patients with positive CMV-DNA in saliva. Transient Evoked Otoacoustic Emission test was performed for NHST.
 Results: CMV-DNA was posititve in saliva of 38 (3.3%) newborns and urine of 10 out of 37 newborns. The prevalence of cCMV
 was 0.87% (95% CI=0.697-1.042). All newborns passed the NHST. In newborns with cCMV:jaundice in 60% (6/10), low birthweight
 in 40% (4/10), small for gestational age in 50% (5/10) of them. Jaundice was the most significant variable (P

Cytomegalovirus cell tropism and clinicopathological characteristics in gastrointestinal tract of patients with HIV/AIDS

BackgroundCytomegalovirus (CMV) has been recognized as one of the frequently occurring opportunistic infections (OIs) reported in the patients having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In addition, it has been identified as the factor leading to gastrointestinal (GI) tract disorder among HIV/AIDS population. CMV exhibits broad cell tropism in different organs. This study evaluated the CMV cell tropism and clinicopathological characteristics of CMV infection in the different GI regions in HIV/AIDS cases.MethodsUsing nucleic acid in situ hybridization (ISH), CMV was detected in the gastrointestinal mucosal biopsy samples. The paraffin-embedded samples were stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC), respectively.ResultsA total of 32 HIV/AIDS patients were enrolled in this study. Fourteen of these patients underwent gastroscopy, while the remaining eighteen received colonoscopy. CMV-infected cells were observed at 46 GI sites. Among them, the colon was the region with the highest susceptibility to GI CMV infection (n = 12, 26.1%). The CMV giant cell inclusion bodies were detected in epithelial cells and mesenchymal cells, including histiocytes, smooth muscle cells, fibroblasts, and endothelial cells. In the duodenum, there were markedly more positive epithelial cells than mesenchymal cells (p = 0.033). In contrast, in the esophagus (p = 0.030), cardia (p = 0.003), rectum (p = 0.019), colon (p < 0.001), and cecum (p < 0.001), there were notably less positive epithelial cells than mesenchymal cells. The expression levels of PDGFRα and Nrp2 in the mesenchymal cells were higher than the epithelial cells in cardia, cecum, colon, sigmoid, and rectum, especially in the areas with ulcers. However, Nrp2 in the epithelial cells was higher than that in the duodenum. Moreover, the positive CMV DNA in peripheral blood was related to the CMV-positive cell count, as well as the ulceration in GI tract (p = 0.035 and 0.036, respectively).ConclusionsThe colon has been identified as the GI site with the highest susceptibility to CMV infection. There are different CMV-infected cells in the different sites of the GI that relate to the expression level of PDGFRα and Nrp2. CMV DNA positive in the blood is related to the positive CMV cell count, as well as ulceration in the GI tract.

Pooled saliva CMV DNA detection: A viable laboratory technique for universal CMV screening of healthy newborns.

Most infants with congenital cytomegalovirus (cCMV) have no overt manifestations at birth, yet may later develop CMV-related sensorineural hearing loss (SNHL). With targeted screening, many asymptomatic neonates are missed and lose the opportunity for timely anti-viral treatment to ameliorate SNHL. Saliva is the preferred screening specimen given its ease of collection. Assess a pooled saliva CMV DNA detection technique for cCMV screening of healthy full-term neonates. We conducted a prospective laboratory CMV PCR screening study in a secondary hospital from March-June 2019. Saliva specimens were obtained from 1000 newborns two-four hours after birth. Specimens were analyzed for CMV DNA with a real-time PCR platform (Altona) in pools of 10 and individually (40 μL and 400 μL, respectively). Neonates with positive saliva CMV DNA detection required urine CMV PCR testing to confirm cCMV diagnosis. From the 1000 saliva samples, there were 6 urine-confirmed cCMV cases, yielding a prevalence rate of 0.6 %. The specificity was high for both pooled and individual saliva sampling (99.9 % and 98.1 %, respectively). The positive predictive value of the pooled sample was 85.7 %, compared to 24.0 % for a single saliva sample. Pooling saliva of healthy newborns appears to be a reliable method to identify asymptomatic cCMV infection when positive results are confirmed by urine CMV DNA. Pooling in sizes appropriate to the cCMV prevalence rate may improve the laboratory workflow and decrease costs. Further studies should evaluate the clinical implications of this widespread cCMV pooled screening technique.

2334. Saliva Screening for Congenital Cytomegalovirus Infection in the Neonatal Intensive Care Unit: Beware!

BackgroundCongenital cytomegalovirus (cCMV) infection is the most common cause of non-genetic sensorineural hearing loss in infancy. Screening of newborns for cCMV infection has been performed utilizing saliva due to ease of collection and high sensitivity. Positive saliva screens for CMV DNA by polymerase chain reaction (PCR) testing has been reported to occur secondary to breast milk feeding without signifying congenital infection. The NICUs of Nationwide Children’s Hospital recently began universal saliva screening of all admissions. We report 3 neonates whose saliva CMV screen was positive yet the urine CMV PCR test was negative in order to inform CMV screening strategies.MethodsRetrospective review of the electronic health records of neonates admitted to the neonatal intensive unit (NICU) at Nationwide Children’s Hospital, Columbus, OH who had CMV detected by PCR from saliva specimens but not from urine. Pertinent demographic and clinical data were obtained.ResultsThree female neonates had a positive saliva CMV DNA PCR test but urine CMV PCR was negative. The first infant (gestational age [GA] 34 weeks, birth weight [BW]1790 Grams) was a monochorionic diamionic twin gestation and born vaginally with unknown duration of rupture of membranes (ROM). At 16 days of age, the infant had a positive saliva CMV PCR but a negative urine CMV PCR test. The infant received maternal milk. The twin’s CMV PCR tests of saliva and urine were negative. The second infant (GA 38 weeks, BW 2952 grams) was born vaginally after 9 hours of ROM. On the first day of age, the infant had a positive saliva CMV PCR test that was followed by a negative urine CMV PCR on the third day of age. The infant had not been breastfed. The third infant (GA 33 weeks, BW 1762 grams) was born by C-section delivery with ROM at delivery. Saliva CMV PCR screen was positive on the second day of age but urine PCR was negative twice (days 5 and 7). All 3 infants had no signs/symptoms of cCMV infection and passed the newborn hearing screen.ConclusionTesting of saliva for CMV DNA by PCR is not always confirmatory for cCMV infection as contamination of saliva specimens with CMV could result from exposure to maternal milk and possibly vaginal secretions. Definitive diagnosis of cCMV infection requires additional confirmatory testing preferably with urine.Disclosures All authors: No reported disclosures.

A Case Report of 1p36 Deletion Syndrome and Suspected Cytomegalovirus Infection

\n 1p36 Deletion Syndrome is a rare disease characterized by a partial deletion in the short arm of chromosome 1. The first reports of cases with microdeletion of chromosome 1p36 were published in 1980s, beginning with a report by Hain et al. The first pure case of 1p36 Deletion Syndrome was identified in the 1987 by Magenis et al. Its incidence is presumed as 1:5000 to 1:10000 and prevalence among men/women is 1/2. Characteristic signs are dysmorphic facial features, developmental delay, feeding difficulties, central nervous system anomalies, seizures, microcephaly, intellectual disability, vision problems, sensorineural deafness, congenital heart defects, skeletal and renal anomalies. Congenital Cytomegalovirus infection is an intrauterine disease with persistent effects on the fetus with no specific treatment. Common clinical findings are petechiae, jaundice at birth, hepatosplenomegaly, microcephaly, hypotonia, poor suck, sensorineural hearing loss, vision abnormalities, seizures, developmental cerebral anomalies, intrauterine development delay, prematurity and stillbirth. This case has been reported due to being a unique case having both such a rare disease like 1p36 Deletion Syndrome and a corresponding clinical picture to congenital Cytomegalovirus infection which she has firstly been determined with a positive CMV-DNA level when she was 7 months old.\n

Cytomegalovirus Infection in IBD: Single Center Experience

Introduction: In patients with Inflammatory Bowel Diseases (IBD) there is an increased risk of Cytomegolovirus (CMV) infection possibly due to malnutrition and immunosuppressive medication. There are other risk factors such as advanced age and disease duration more than 5 years. Moreover, there is evidence that CMV infection increases colectomy rates. Anti-viral treatment in CMV infection in IBD patients is controversial. In this study, we aimed to define the CMV infection effect on IBD course. Methods: Patients with IBD who had positive serum CMV-DNA (> 42 copies/ml) between 2013 and 2016 were identified in Ankara University IBD cohort. Patient charts were reviewed retrospectively. We identified 75 patients with positive serum CMV-DNA. Patient demographics, colectomy rates, medication types, mortality rates were abstracted from database retrospectively. Results: Out of 78 patients, 66 patients had Ulcerative Colitis (UC) (88%). Mean age of patients was 39.4 years. 54 % of UC patients had either extensive disease or pancolitis. There was no correlation between age, gender, leucocyte count, crp levels, hemoglobin levels and either mortality or colectomy. CMV viremia did not lead to colectomy. However, in patients who had clinical events (colectomy or mortality), median serum CMV-DNA level was 1038 copies/ml whereas in patients who had spontaneous remission, median serum CMV-DNA level was 182 copies/ml (p value: 0.006). There were higher mortality and colectomy rates in patients with serum CMV DNA levels > 1000 copies/ml (p value: 0.032). Trombosis was found to be an independent risk factor for mortality and colectomy (%95 CI: 19.3 (1.9-188);P:0.011). Steroid use was found to be in 82% of the patients. There was no correlation between steroid use and mortality or colectomy rates. Conclusion: Serum CMV-DNA levels more than 1000 copies/ml increases the colectomy rates in IBD patients. Steroid use seems not to be a factor increases colectomy rate in this cohort. Thrombosis is an independent risk factor for colectomy and mortality in IBD patients with CMV infection.

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome.

To compare the clinical manifestation of cytomegalovirus (CMV) retinitis and microvascular retinopathy (MVR) in patients with acquired immunodeficiency syndrome (AIDS) in China. A total of 93 consecutive patients with AIDS, including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed. Highly active antiretroviral therapy (HAART) status was recorded. HIV and CMV immunoassay were also tested. CD4+ T-lymphocyte count and blood CMV-DNA test were performed in all patients. Aqueous humor CMV-DNA test was completed in 39 patients. Ophthalmological examinations including best corrected visual acuity (BCVA, by International Standard Vision Chart), intraocular pressure (IOP), slit-lamp biomicroscopy, indirect ophthalmoscopy were performed. In MVR group, the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13. Blood CMV-DNA was 0 (0, 269 000) and 42 patients (80.77%) did not receive HAART. In CMV retinitis group, 13 patients (31.71%) had anterior segment abnormality. The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470 (0, 1 450 000). Nineteen patients (46.34%) had not received HAART. MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%, respectively. Two patients with MVR progressed to CMV retinitis during the follow-up period. In comparison of CMV, patients with MVR have relatively mild visual function impairment. Careful ophthalmological examination and close follow-up are mandatory, especially for patients who have systemic complications, positive CMV-DNA test and without received HAART.

A rare case of cytomegalovirus papillitis in patient with immunodeficiency

A 26-year-old male diagnosed with AIDS came with sudden blurred vision and central sco-toma in left eye since 2 weeks before admission. His visual acuity was counting finger at 5 meters with normal IOP and anterior segment. The posterior segment revealed edematous optic nerve covered by exudates and hemorrhages. Due to low CD4+ count and serological test result, we considered a HIV-related opportunistic ocular infection, specifically HSV infection. As visual acuity worsened during treatment with acyclovir, we performed PCR ex-amination from aqueous tap which revealed positive CMV DNA. Unfortunately, the visual acuity had worsened to no light perception before he received any specific anti-CMV agent. CMV papillitis is an unusual presentation of CMV retinitis. PCR examination from aqueous or vitreous tap should be performed while waiting for serological test result, especially in doubtful cases. Therefore, appropriate diagnosis and management can be established early to prevent irreversible visual loss.

Cytomegalovirus transmission in pediatric renal transplant recipients during the window period

We report two CMV naïve children who received deceased donor renal transplants from a CMV IgG-negative single donor. CMV IgG in both recipients and the donor were negative immediately prior to transplant. Both recipients had early recurrences of their original disease in their transplants, requiring multiple sessions of plasmapheresis. All blood products used were leukoreduced or CMV seronegative. A few days post-transplant, both recipients developed significant positive CMV viremia. Both required initiation of oral valganciclovir. Case 1 responded to oral valganciclovir only while the case 2 had a delayed response to it and hence required intravenous ganciclovir with good response. When checked retrospectively, CMV IgM in the donor was positive along with positive CMV DNA PCR from the white cells. Here we describe a very unusual scenario of CMV transmission in two pediatric renal transplant recipients from a single donor during the CMV window period.

Cytomegalovirus infection and atherosclerosis in candidate of coronary artery bypass graft.

Background:Although there is enough evidence that infectious agents such as Chlamydia pneumonia and Helicobacter pylori may play a pathogenic role in atherosclerosis, this role for cytomegalovirus (CMV) is yet controversial.Objectives:The aim of the present study was to detect CMV-DNA in atherosclerotic plaques in patients who underwent coronary artery bypass graft (CABG).Patients and Methods:In this case-control study, candidates for CABG (cases) and patients with valvular or congenital malformation but without atherosclerotic plaques (controls) were studied from 2012 to 2013 at Golestan hospital, Ahvaz, IR Iran. Demographic and laboratory data were collected. Atherosclerotic and histological samples were obtained from visible plaques and from aorta by the surgeon. All the samples were examined for the presence of CMV-DNA by polymerase chain reaction (PCR) method using a commercial kit (SinaClon, Tehran, IR Iran).Results:The mean ages in case and control groups were 60.8 ± 6.8 and 57.5 ± 11.5 years, respectively, with no significant difference (P = 0.09). Thirty patients (54.5%) in case and 32 (58.2%) in control groups were male with no significant difference (P = 0.7). CMV-DNA was present in 8 (14.5%) of the cases and 2 (4%) of the controls. CMV-DNA was associated with higher risk of atherosclerosis (OR: 7.7, 95% CI = 1.1-51.4, P = 0.03). Of the total normal aortic samples (55 in cases and 55 in controls), there was no individual with simultaneous positive CMV-DNA among aortic atherosclerotic and normal tissue samples.Conclusions:The presence of CMV-DNA in aortic plaques is associated with increased risk of atherosclerosis. CMV infection may be considered as an independent risk factor for this event.

Risk factors analysis of cytomegalovirus infection after nonmyeloablative allogeneic peripheral blood stem cell transplantation

The aim of this study was to analyze the risk factors of cytomegalovirus (CMV) infection and CMV disease after nonmyeloablative allogeneic hematopoietic stem cell transplantation(NST) and develop a rational strategy for the diagnosis, monitoring and preemptive treatment of CMV infection. The Clinical data of 80 patients undergoing NST from November 2009 to November 2012 in the hospital 307 were retrospectively analyzed. The cytomegalovirus load in peripheral blood of patients was detected by using RT-PCR. The results indicated that the incidence of CMV infection was 77.5% (62/80), and the median time for the positive CMV-DNA firstly detected by RT-PCR was day 35 (17-133) after NST. The total of 100-day cumulative incidence of CMV disease was 11.3%(9/80) after early preemptive therapy. Both univariate and multivariate analysis showed thymoglobulin (ATG) used in preconditioning regimen, other herpesvirus infection and fungal infection in medical history before NST were the risk factors of CMV infection after NST.Univariate analysis revealed that CMV viremia and ATG used in preconditioning regimen were the risk factors for CMV disease, while the same result was not found in the multivariate analysis.The incidence of CMV infection in patients with II-IV grade of aGVHD was 91.3%,while the incidence of CMV infection in patients with 0-1 grade of aGVHD was 71.9% (P = 0.06), it seems that II-IV grade of aGVHD was not the risk factor of CMV infection for NST. It is concluded that the ATG used in preconditioning regimen may increase the incidence of both CMV infection and CMV disease after NST. CMV infection easily accompanies by other herpesvirus infection and fungal infection.Therefore other herpesvirus infection and fungal infection should be attentively monitored and prevented after trans-plantation.

Saliva sample for screening of congenital cytomegalovirus

Objective To investigate the feasibility of congenital cytomegalovirus (CMV)infection screening by saliva polymerase chain reaction.Methods From November 1,2010 to February 29,2012,6733 newborns born in Changzhou Maternal and Child Health Care Hospital were enrolled.Saliva samples (0.2 ml) were collected within 3 days after birth,CMV-DNA was detected by real time-polymerase chain reaction and hearing screening was done with EroScan transient-evoked otoacoustic emissions at the same time.The positive rate of congenital CMV infection screening was calculated and clinical manifestations were analyzed.Chi square test was applied to statistical analysis.Results Totally 6733 newborns were screened and 107 of them were found to be positive with CMV DNA,the positive rate was 1.59％ (107/6733),among which 88 were asymptomatic (82.2％) and 19 were symptomatic (17.8 ％).The major clinical manifestations of the neonates with positive CMVDNA were pathological jaundice (13 cases),hepatomegaly (5 cases),granulocytopenia,thrombocytopenic purpura,anemia and small for gestational age (two cases each).Fourteen newborns had only one major clinical manifestation,three newborns had two major clinical manifestations and two newborns had three major clinical manifestations.There was no statistical difference between newborns with positive and negative CMV DNA on hearing screening [hearing loss in one ear:8.4％ (9/107) vs 5.8％ (382/6626); hearing loss in two ears:3.7 ％ (4/107) vs 2.4 ％ (159/6626),x2 =2.776,P=0.241].Conclusion It is feasible to screen congenital CMV infection with saliva sample. Key words: Cytomegalovirus infections ; Saliva ; Specimen handling ; Screening

Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

Cytomegalovirus (CMV) infection is common in humans. The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression. The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease (CD) and ulcerative colitis (UC). CMV does not interfere in the clinical course of CD. However, CMV reactivation is frequent in severe or steroid-resistant UC. It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease. Different methods are used to diagnose CMV colitis. Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry, other tests on blood or tissue samples are currently being investigated. Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease; further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa. Specific endoscopic features have not been described in active UC and CMV infection. CMV colitis is usually treated with ganciclovir for several weeks, there are different opinions about whether or not to stop immunosuppressive therapy. Other antiviral drugs may be used. Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

Maternal IgM antibody status in confirmed fetal cytomegalovirus infection detected by sonographic signs

To evaluate the value of maternal IgM to cytomegalovirus (CMV) as a predictive factor of fetal infection in fetuses with sonographic markers. Observational study (2006-2011) including a consecutive series of 19 fetuses with sonographic markers of fetal infection and confirmed infection by positive CMV-DNA in amniotic fluid or fetal blood. We evaluated the status of maternal CMV IgM at the time of sonographic suspicion. During this 6-year study period, CMV infection was diagnosed in 19 fetuses from 18 pregnancies, including 16 singletons, both twins of a monochorionic diamniotic pregnancy and one twin of a dichorionic pregnancy. Sonographic suspicion was established on the basis of one or more of the following: brain abnormalities (14), fetal hydrops (4), hyperechogenic bowel (4), pericardial effusion (1), cardiomegaly (1), oligoanhydramnios (4), and placentomegaly (2). Maternal IgG antibodies were positive in all cases but maternal IgM antibodies were negative in 56% of pregnancies. Five of the 10 pregnancies with negative maternal IgM were diagnosed in the second trimester and five in the third trimester. In around half of fetuses with confirmed CMV infection ascertained by sonographic markers, maternal IgM antibodies are negative and should therefore not be used as a diagnostic parameter.

Congenital Cytomegalovirus Infection as a Cause of Sensorineural Hearing Loss in a Highly Immune Population

The burden of congenital cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) in populations with CMV seroprevalence approaching 100% is unknown. The purpose of this study was to assess the rate, associated factors, and predictors of SNHL in CMV-infected infants identified by newborn screening in a highly seropositive maternal population. Newborns with positive saliva CMV-DNA that was confirmed by virus isolation in the first 2 weeks of life were enrolled in a prospective follow-up study to monitor hearing outcome. Of 12,195 infants screened, 121 (1%) were infected with CMV and 12 (10%) had symptomatic infection at birth. Hearing function could be assessed in 102/121 children who underwent at least one auditory brainstem evoked response testing at a median age of 12 months. SNHL was observed in 10/102 (9.8%; 95% confidence interval: 5.1-16.7) children. Median age at the latest hearing evaluation was 47 months (12-84 months). Profound loss (>90 dB) was found in 4/5 children with bilateral SNHL while all 5 children with unilateral loss had moderate to severe deficit. The presence of symptomatic infection at birth (odds ratio, 38.1; 95% confidence interval: 1.6-916.7) was independently associated with SNHL after adjusting for intrauterine growth restriction, gestational age, gravidity, and maternal age. Among 10 infants with SNHL, 6 (60%) were born to mothers with nonprimary CMV infection. Even in populations with near universal immunity to CMV, congenital CMV infection is a significant cause of SNHL demonstrating the importance of CMV as a major cause of SNHL in children worldwide. As in other populations, SNHL is more frequently observed in symptomatic CMV infection.

Cytomegalovirus infection is associated with venous thromboembolism of immunocompetent adults—a case–control study

Cytomegalovirus (CMV) seems to contribute to the development of venous thromboembolism (VTE) in immunocompromised patients whereas literature data on the role in immunocompetent individuals are mainly limited to case reports. This study aimed to investigate if cytomegalovirus infection contributes to the development of VTE in immunocompetent individuals. CMV-IgG and CMV-IgM antibody titres, CMV-IgG avidity and CMV-DNA were identified in samples from 166 VTE patients and from 166 healthy blood donors matched for gender and age. CMV-IgG antibodies were found more frequently in VTE patients compared to controls [57.8% vs. 44.0%; adjusted OR 1.75 (95% CI 1.13-2.70); p = 0.016]. Accordingly, median CMV-IgG titres were significantly higher in the case group (89.4 vs. 1.8 AU/ml; p = 0.002). Although the overall rate was low, CMV-IgM antibodies were detected more often among cases than controls. The difference was significant in patients with an unprovoked VTE event [7.4% vs. 0.6%; adjusted OR 5.26 (95% CI 1.35-20.8); p = 0.017]. CMV-IgG antibodies of almost all VTE patients (98.9%) and controls (98.6%) were found to be of high avidity. The rate of positive CMV-DNA samples was low and not different between cases and controls. With the exception of age, no association was found between CMV seropositivity and established VTE risk factors within the VTE group. CMV infection seems to play a role in the development of VTE in immunocompetent patients. Recurrent infection might be more important than acute CMV infection.

Diagnosis and treatment of congenital cytomegalovirus infection in neonates

Obiective To summarize the main clinical features, diagnosis and treatment of congenital cytomegalovirus (CMV) infected neonates. Methods Serum CMV antibodies were tested by enzyme-linked immunosorbent assay, and urine CMV-DNA was detected by fluorescent real-time quantitative polymerase chain reaction. From Jan. 2007 to Dec. 2008,145 neonates were diagnosed as congenital CMV infection. Effects and side effects were observed in 56 of 101 symptomatic patients treated with ganciclovir. Results The main clinical manifestations and abnormal laboratory items in symptomatic infection included pathologic jaundice, hepatosplenomegaly, interstitial pneumonitis, petechiae, poor suck, thrombocytopenia, elevated glutamic-pyruvic transaminase. There were 87 patients(60.0%) had positive urine CMV-DNA, 43(29.7%) had positive CMV-IgM, 21(14.5%) had 4 times increase of CMV-IgG titers within 2 weeks after birth, 13 patients showed positive CMV-DNA in urine or CMV-IgM in serum and their serum CMV IgG levels were more than doubled compared to their mothers. There was significant improvement in clinical and laboratory findings after ganciclovir treatment with minimal side effects including lightly decreasing of granulocyte and platelet, but without damage of liver and kidney function. Conclnsions Neonatal congenital CMV infection might lead to multiple organs damage and had various clinical features. Urine CMV-DNA test might have higher positive rate in infected neonates. The other evidence for the diagnosis is positive CMV-IgM and 4 times increasing of CMV-IgG titers. Over two times of the CMV-IgG level in the neonates than in the mothers is one of the laboratory findings also. Ganciclovir is effective in the treatment of symptomatic CMV infection. Key words: Cytomegalovirus infections; Infant, newborn; Ganciclovir

Cytomegalovirus Reactivation and Relapse Following Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen.

Background: Recent studies have reported CMV reactivation rates of 42% to 65% in patients treated with allogeneic stem cell transplantation using reduced intensity conditioning regimens (RIT). However, published data on RIT patients who experience CMV reactivation, are treated successfully with antiviral therapy to eliminate detection, and who subsequently develop CMV relapse, is sparse.Methods: We performed a retrospective cohort analysis of 106 patients who underwent RIT at Tufts-New England Medical Center using a preparative regimen of pentostatin, extracorporeal photophoresis, and reduced total body irradiation, from 1997–2003. All patients received identical graft-versus-host disease (GVHD) prophylaxis, which consisted of IV cyclosporine and PO methotrexate. CMV serostatus was determined on all patients prior to transplant. All patients were screened weekly by CMV antigen capture assay after day +14. Patients did not receive CMV prophylaxis. CMV reactivation was defined as 2 consecutive positive (>2.1 pg/mL) CMV DNA measurements. CMV reactivation was treated with either Ganciclovir 5mg/kg IV daily or Valganciclovir 450mg PO BID until whole blood CMV DNA levels were no longer detectable. Patients were treated with antiviral therapy until a documented negative CMV DNA assay. Those found to have detectable CMV DNA after adequate therapy were then defined as having CMV relapse. Patients were also assessed for incidence of GVHD and mortality. Attributable mortality was defined as mortality in patients who had CMV relapse compared to those who had CMV reactivation without relapse. Fisher's exact test was used to compare proportions, Kruskal-Wallis was used to compare means, and survival and time to reactivation and relapse were analyzed by Kaplan-MeierResults: Of 106 patients, 49 (46.2%) were CMV seropositive prior to transplant. Twenty -five (51%) of forty-nine CMV positive patients developed CMV reactivation at a median of 43 days (range 26 – 312 days) after receiving stem cells. Among patients with CMV reactivation, 36 were MRD and 13 were MUD. Nine (36%) of 25 patients with CMV reactivation developed CMV relapse. CMV relapse occurred at a median of 16 days (range 4 – 77 days) after CMV reactivation. CMV reactivation occurred earlier among those who relapsed (median 34 days, range 26 – 70 days) compared to those who did not relapse (median 55.5 days, 27 – 312 days, p=.03). Peak viral load was significantly higher in CMV relapsers (median 55.3 pg/mL, range 14.5 to 486.8) compared to non–relapse patients (median 4.4 pg/mL, range 2.1 – 58.2, p=. 0007). There was no difference in acute GVHD in the groups (100% vs. 75%, p=.26). However, those who did relapse had a higher incidence of chronic GVHD than those who did not (89% vs. 38%, p=.03). There was no difference in median survival between non-relapse and relapse patients (13 months vs. 16 months, p=. 99). The attributable mortality rate due to CMV relapse was 23%.Conclusions: Our results suggest there is a subgroup of patients who are at high risk for CMV relapse in the post RIT setting. Risks for CMV relapse include early reactivation and higher peak CMV viral loads. In addition, there was a higher risk of chronic GVHD in CMV relapse patients. We have identified a high- risk subset of patients who reactivate CMV for whom additional therapeutic strategies may be warranted.