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Cytomegalovirus (CMV) excretion in urine is frequently observed in clinical practice. However, the specific circumstances and pathophysiological mechanisms underlying this shedding remain largely unknown. Here, we address some of the key questions regarding urinary CMV excretion, focusing on new hypotheses raised by recent advances in the field. Cellular origins of CMV shedding, clinical contexts of occurrence, systemic spread of the virus versus compartmentalization in the urinary tract, and clinical impact are successively discussed., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: The value of the widely applied maternal cytomegalovirus (CMV) serological testing approach in predicting intrauterine transmission in highly seroprevalent regions remains unknown., Methods: A nested case-control study was conducted based on a maternal-child cohort study. Newborns with congenital CMV (cCMV) infection were included, and each of them was matched to 3 newborns without cCMV infection. Retrospective samples were tested for immunoglobulin G (IgG) avidity and immunoglobulin M (IgM) antibodies in maternal serum and CMV DNA in maternal blood and urine to analyze their associations with cCMV infection., Results: Forty-eight newborns with cCMV infection and 144 matched newborns without infection were included in the study. Maternal IgM antibodies and IgG avidity during pregnancy were not statistically associated with intrauterine transmission. The presence of CMV DNAemia indicated a higher risk of cCMV infection, with odds ratio values of 5.7, 6.5, and 13.0 in early, middle, and late pregnancy, respectively. However, the difference in CMV shedding rates in transmitters and nontransmitters was not significant in urine., Conclusions: The value of current maternal CMV serological testing in regions with high seropositivity rates is very limited and should be reconsidered. The detection of DNAemia would be helpful in assessing the risk of intrauterine transmission., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An early diagnosis and intervention for congenital cytomegalovirus infection can reduce long-term disability; however, the introduction of universal neonatal screening has been controversial worldwide. The present study clarified the outcome of a targeted screening protocol for detecting congenital cytomegalovirus infection based on suggestive perinatal conditions. In addition, the positive rate was compared to those from the reported studies and the validity of the targeted screening criteria was discussed. A total of 2121 newborn infants were admitted to our hospital between October 2018 and October 2021. Cytomegalovirus DNA was examined by the isothermal nucleic acid amplification method for urine samples from newborns with any of the following: microcephaly, abnormal ultrasound findings in the brain and visceral organs, repeated failure in neonatal hearing screening, suspicious maternal cytomegalovirus infection during pregnancy, and other abnormal findings suggestive of congenital cytomegalovirus infection. Among 2121 newborns, 102 (4.8%) were subject to the urine cytomegalovirus DNA test based on the abovementioned criteria. Of them, three were cytomegalovirus DNA-positive. According to the protocol, the cytomegalovirus DNA-positive rates were 0.14% among the total enrollment of 2121 newborns and 2.9% (3/102) among the targeted newborns. This protocol may overlook congenital cytomegalovirus infection that is asymptomatic or exhibits inapparent clinical manifestations only at birth; however, it is feasible and helps lead to the diagnosis of congenital cytomegalovirus infection that may otherwise be overlooked., (© 2023 Japanese Teratology Society.)

Background: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection., Methods: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion., Results: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48)., Conclusion: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection., (© 2021. The Author(s).)

We assessed maternal and infant cytomegalovirus (CMV) infection in Colombia. Maternal serum was tested for CMV immunoglobulin G antibodies at a median of 10 (interquartile range: 8-12) weeks gestation (n = 1501). CMV DNA polymerase chain reaction was performed on infant urine to diagnose congenital (≤21 days of life) and postnatal (>21 days) infection. Maternal CMV seroprevalence was 98.1% (95% confidence interval [CI]: 97.5%-98.8%). Congenital CMV prevalence was 8.4 (95% CI: 3.9%-18.3%; 6/711) per 1000 live births. Among 472 infants without confirmed congenital CMV infection subsequently tested at age 6 months, 258 (54.7%, 95% CI: 50.2%-59.1%) had postnatal infection., (© 2021 Wiley Periodicals LLC.)

Congenital cytomegalovirus infection (cCMVi) is an important cause of sensorineural hearing loss in newborns. Detection of human cytomegalovirus (HCMV) DNA in urine has been used to screen for cCMVi in newborns. However, the matrix effect of urine on HCMV DNA detection is unclear. To evaluate the matrix effect of urine on HCMV DNA detection and optimize the sample process strategy to eliminate or minimize the impact of urine on HCMV DNA detection, DNA in spiked samples was extracted using different DNA extraction methods, and urine samples that could inhibit HCMV DNA detection were mixed to evaluate the inhibitory substances, inhibitory mechanism, and elimination of the inhibitory effect. The optimal urine sample process strategy was evaluated using 42 adult female urine samples and 42 newborn urine samples spiked with HCMV. Some urine samples were found to inhibit HCMV DNA detection due to DNA degradation. The addition of ≥5 mM EDTA to the urine before extraction eliminated the inhibitory effect of urine and did not affect the detection results of urine exhibiting no inhibition. Of the 42 adult female and 42 newborn urine samples, four and two samples, respectively, could inhibit HCMV DNA detection. However, the inhibitory effects of these six urine samples were eliminated after the addition of EDTA. The collective results indicate that the addition of EDTA can completely eliminate the impact of inhibitors present in urine on HCMV DNA extraction and improve the detection of HCMV in urine., (© 2021 Wiley Periodicals LLC.)

Background: Immunosuppression in solid organ transplantation is associated with frequent infections. Renal allograft recipients are susceptible to opportunistic infections and can acquire human cytomegalovirus (HCMV) infections even within the allograft. There, HCMV can be found in both the glomerulus and tubular cells, but is mostly restricted to specific and circumscribed sites. Therefore, not all organ infections are identifiable by immunohistology for HCMV proteins in fine needle core biopsies. Thus, we performed a urinalysis study to search for HCMV-specific RNA transcripts in the urine sediment of patients with acute kidney injury., Methods: Urinary sediment of 90 patients with acute kidney injury (AKI), including 48 renal transplant recipients (RTX) and 42 non-transplant recipients (nRTX), was collected from morning urine for RNA extraction and reverse transcription. The copy number of HCMV transcripts was evaluated using a UL132 HCMV-specific probe set and by real-time quantitative polymerase chain reaction (RT-qPCR)., Results: Of the 48 RTX patients, ten showed HCMV copies in their urine sediment cells. Within this group, three recipients had negative HCMV serology and received an allograft from an HCMV-seropositive donor. In addition, all three RTX patients on a belatacept-based immunosuppressive regimen had HCMV transcripts in their urine. Of the 42 nRTX patients, only two had detectable HCMV transcripts in urine sediment cells and both were under immunosuppression., Conclusions: Ten immunosuppressed renal allograft recipients and two immunosuppressed non-transplant patients with AKI showed HCMV copies in urine sediment. Thus, HCMV positivity in urinary sediment appears to be associated with immunosuppression. This study describes a novel noninvasive method for detection of HCMV in urinary sediment. Whether all HCMV infections can be detected or only those with viral replication warrants further investigation.

Background: Congenital cytomegalovirus disease (cCMV) is common and can be fatal or cause severe sequelae. Circulating strains of cytomegalovirus carry a high number of variable or disrupted genes. One of these is UL146, a highly diverse gene with 14 distinct genotypes encoding a CXC-chemokine involved in viral dissemination. UL146 genotypes 5 and 6 lack the conserved ELR motif, potentially affecting strain virulence. Here, we investigate whether UL146 genotypes 5 and 6 were associated with congenital CMV infection., Methods: Viral DNA was extracted and UL146 sequenced from 116 neonatal dried blood spots (DBS) stored in the Danish National Biobank since 1982 and linked to registered cCMV cases through a personal identifier. These sequences were compared to UL146 control sequences obtained from CMV DNA extracted from 83 urine samples from children with suspected bacterial urinary tract infections., Results: Three non-ELR UL146 genotypes (5 and 6) were observed among the cases (2.6%) and two were observed among the controls (2.4%; P > 0.99). Additionally, no significant association with cCMV was found for the other 12 genotypes in a post-hoc analysis, although genotype 8 showed a tendency to be more frequent among cases with 12 observations against three (P = 0.10). All fourteen genotypes were found to have little intra-genotype variation. Viral load, gender, and sample age were not found to be associated with any particular UL146 genotype., Conclusions: No particular UL146 genotype was associated with cCMV in this nationwide retrospective case-control study. Associations between CMV disease and disrupted or polymorph CMV genes among immunosuppressed people living with HIV/AIDS and transplant recipients should be investigated in future studies.

Objectives: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae., Methods: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age., Results: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment., Conclusions: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries., Competing Interests: Declaration of Competing Interest All authors report no potential conflicts of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

To evaluate the potential of dried blood spots (DBS) as a congenital cytomegalovirus (cCMV) testing specimen, the laboratory diagnostic accuracy of polymerase chain reaction (PCR) on DBS was compared to viral urine cultures from neonates suspected for cCMV. Two different extraction methods (EasyMAG, bioMérieux versus Qiagen) and 2 real-time PCR protocols (in-house versus Argene) were compared. We were able to collect both DBS and urine samples in 6 Belgian neonatal units from 276 neonates suspected for cCMV registered in CMVREG (an online neonatal registry system). Forty-eight neonates (17.4%) were positive by viral culture in urine. Laboratory diagnostic accuracy parameters of DBS-PCR were both extraction method and PCR protocol dependent. Not all DBS-CMV-PCR methods successfully detected urine-culture-positive neonates born after first-trimester seroconversions. Interestingly, however, all urine-culture-positive neonates having clinical signs of cCMV did consistently score positive., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this six-year study, there were 1118 newborn genetic testing; there were 162 genetic testing for symmetrically growth retarded infants. Out of this, only six infants had positive results yielding a low odds ratio of 0.21 for having any significant chromosome results. Urine CMV testing was positive only in one infant out of 118 tested., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Children with congenital CMV infection (cCMV) shed virus in urine and saliva for prolonged periods of time. Outcome of cCMV varies from asymptomatic infection with no sequelae in most cases, to severe longterm morbidity. The factors associated with asymptomatic cCMV are not well defined. We evaluated the viral shedding in a cohort of infants with cCMV identified on newborn screening. In addition, we describe the distribution of viral genotypes in our cohort of asymptomatic infants and previous cohorts of cCMV children in the literature., Methods: Study population consisted of 40 children with cCMV identified in screening of 19,868 infants, a prevalence of 2/1000. The viral shedding was evaluated at 3 and 18 months of age by real-time CMV-PCR of saliva and plasma, and CMV culture of urine. CMV positive saliva samples were analyzed for genotypes for CMV envelope glycoproteins gB (UL55), and gH (UL75) by genotype specific real-time PCR, and gN (UL73) by cloning and sequencing RESULTS: At 3 months age 40/40 saliva and urine samples, and 19/40 plasma samples were positive for CMV. At 18 months age all urine samples tested (33/33), 9/37 of saliva samples, and 2/34 plasma samples were positive for CMV. The genotype distribution did not differ from the published data CONCLUSIONS: The urinary virus shedding is more persistent than salivary shedding in children with cCMV. The genotype distribution was similar to previous literature and does not explain the low disease burden of cCMV in our population., Competing Interests: Declaration of Competing Interest S. Boppana has been consultant in CMV Vaccine Advisory Committee, Merck, Inc. Other authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Our objective was to evaluate the prevalence and different diagnostic methods of breastmilk (BM)-acquired cytomegalovirus (CMV) infection in a pathologically jaundiced cohort., Methods: A total of 400 infants confirmed with pathological jaundice at The People's Hospital of Qingyang City were screened for BM-acquired CMV infection between February 2018 and February 2019. A total of 300 infants were finally enrolled in our study. CMV infection was confirmed by detecting both CMV-DNA in various samples using FQ-PCR and CMV-IgM with chemiluminescence. Clinical and other laboratory data were collected from these infants during their hospitalization or regular visits., Results: Ninety-eight (32.67%) subjects were confirmed to be BM CMV-DNA-positive, and 18 (18.37%) were diagnosed with a BM-acquired CMV infection. All 18 (100%) infants with a BM-acquired CMV infection were CMV-DNA-positive in urine, while 5 (27.78%) cases and 11 (61.11%) cases were confirmed in plasma and peripheral blood mononuclear cells (PBMCs), respectively. Only 6 (33.33%) infants were CMV-IgM-positive. Birthweight, direct bilirubin, aspartate aminotransferase, and the viral load in BM of the BM-acquired CMV group were higher than those in the non-infected group (P < .05). Low birthweight and viral load in BM were risk factors for BM-acquired CMV infection. Detecting CMV-DNA in urine samples exhibited better performance than the other methods for screening BM-acquired CMV infections., Conclusions: Our study found a high prevalence of BM-acquired CMV infection in jaundiced infants, and detecting CMV-DNA in a urine sample was the most sensitive method for disease screening., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: There is a paucity of data on the burden of congenital cytomegalovirus (cCMV) infections in low- and middle-income countries, including their association with maternal human immunodeficiency virus (HIV) infections. We investigated the prevalence of cCMV in a patient population with a high rate of HIV and antiretroviral therapy (ART) use during pregnancy in Soweto, Johannesburg., Methods: Saliva from neonates were screened for cytomegalovirus (CMV) infection by polymerase chain reaction (PCR) at birth. Additional saliva and urine samples were tested within 3 weeks of birth to confirm positive saliva results. HIV PCR testing was done on the whole blood of HIV-exposed neonates. Maternal and neonatal data were extracted from clinical records., Results: Of 2685 neonates screened for cCMV, 828 (31%) were born to HIV-infected women, 95% of whom (790/828) were on ART at delivery. The overall prevalence of cCMV was 2.5% (95% confidence interval [CI] 1.9-3.2), with significantly higher cCMV prevalence in HIV-exposed neonates (5.2%, 95% CI 3.8-6.9) than HIV-unexposed neonates (1.4%, 95% CI 0.9-2.0). The risk of in utero HIV infection was 20-fold greater (odds ratio 20.1, 95% CI 6.09-66.46) in HIV-exposed, cCMV-infected neonates, and this increased risk was not associated with the maternal CD4+ T-cell count or the maternal duration of ART., Conclusions: The prevalence of cCMV in our setting is substantially higher than the global estimate of 0.64%, partly due to the increased susceptibility for cCMV in HIV-exposed neonates. The significantly increased risk of in utero HIV infection in neonates with cCMV indicates that CMV coinfection plays a major role in the residual burden of in utero HIV transmission, even in the era of ART., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Due to its ease of collection saliva was recently recommended as the preferred specimen, not only for screening, but also for diagnosis of congenital cytomegalovirus (CMV) infection., Objective: To compare the diagnostic performance of saliva PCR to urine PCR in infants born to mothers with primary CMV infection during pregnancy., Study Design: We retrospectively analyzed available data of infants tested for CMV DNA in urine and saliva at birth. PCR was performed with RealStar® CMV-PCR Kit 1.0 (altona Diagnostics). Infectious virus was detected in urine by rapid culture., Results: A total of 133 newborns were eligible for final analysis. Saliva swabs and urine were collected at birth with a time interval of 0-8 days (median 0; IQR 0-1). In 55% of newborns, cord blood was also tested. The overall concordance of saliva and urine PCR was 91% (27 positive, 94 negative). In 12 cases with discordant findings the discrepancy was due to false-negative (n = 2) or false-positive (n = 10) PCR results in saliva. Compared to urine, PCR in saliva showed a positive predictive value of 73%. Viral load in saliva was significantly lower (p < 0.0001; Mann-Whitney test) in the 10 false-positive cases than in the 27 cases with concordantly positive results., Conclusions: Positive CMV PCR results in saliva, especially low positive, have to be confirmed by urine testing. In our opinion detection of CMV by PCR in neonatal urine remains the gold standard for diagnosing congenital CMV infection in infants of mothers with primary infection in pregnancy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR)., Study Design: Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth., Results: One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine β-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection., Conclusions: Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A 27-year-old pregnant woman who was positive for anti-cytomegalovirus (CMV) antibodies gave birth to a congenitally CMV-infected neonate at 40 weeks of gestation. According to strain-specific serological analysis, which is able to determine the two types of CMV glycoprotein H (gH), the mother possessed anti-gH(To) antibodies only, but the neonate possessed anti-gH(AD) and anti-gH(To) antibodies at 4 weeks after birth. As the anti-gH(To) IgG was decreased in the neonate at 8 months post-delivery, these antibodies are thought to have been transferred from the mother as maternal antibodies. The anti-gH(AD) IgG level was maintained in the child even after 8 months post-delivery. Congenital infection with a CMV gH(AD) type strain was confirmed by strain-specific real-time PCR using a urine specimen from the child. On the other hand, anti-gH(AD) IgG was not detected even after 8 months post-delivery in a maternal specimen. The mother only produced antibodies against the CMV strain identified as the primary infection, which is characteristic of original antigenic sin., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The indirect effects of cytomegalovirus (CMV) viremia can be related to chronic changes in renal allograft structure, but its real impact in early and late graft function remains speculative. A total of 159 patients undergoing renal transplantation using a preemptive therapeutic strategy to prevent CMV disease were included in the present study. The patients were prospectively followed, with serial measurements of urinary retinol-binding protein (uRBP), a marker of proximal tubule injury. uRBP levels and their dynamic performance were compared according to CMV viremia and the 5-year estimated glomerular filtration rate (eGFR), as measured with the modification of diet in renal disease (MDRD) equation. CMV viremia was detected in 79.9% of the patients, with high uRBP levels being detected in 76.0% of these patients (compared with 40.7% in CMV-, P =0.005). High uRBP was associated with male recipients ( P =0.02), the number of mismatches ( P =0.02) and CMV infection ( P =0.001). Five-year eGFR was worse in patients with high uRBP levels (50.3 ± 25.8 compared with 59.8 ± 26.4 ml/min, P =0.04). In a multivariate model, eGFR <60 ml/min was associated with donor age ( P <0.001), the number of mismatches ( P =0.04), thymoglobulin dose ( P =0.02), the presence of and time with delayed graft function (DGF) ( P =0.005 and P =0.04), 1-month tacrolimus levels ( P =0.03), and uRBP levels after CMV treatment ( P =0.01). Patients with CMV viremia in whom uRBP levels were normalized up to 3 months after treatment showed significantly better 5-year eGFR than those in whom uRBP remained high: 61.0 ± 24.2 compared with 42.3 ± 23.9 ml/min, P <0.001. CMV viremia was associated with high uRBP levels, which represent a profile of proximal tubule injury, and the dynamic performance of uRBP after treatment was associated with long-term kidney graft function., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: There are no data on the prevalence of cytomegalovirus (CMV) shedding from a representative sample of the US population. This information is critical for understanding and preventing CMV., Methods: We tested urine specimens from CMV immunoglobulin (Ig) G-positive participants aged 6-49 years in 3 racial/ethnic groups from the National Health and Nutrition Examination Surveys 1999-2004 for the presence of CMV DNA using real-time polymerase chain reaction assay. We examined the association of sociodemographic characteristics with shedding prevalence and viral loads., Results: Among 6828 CMV IgG-positive participants tested, 537 had CMV DNA detected in urine-a shedding prevalence of 9.70%. Among persons aged 6-49 years, shedding prevalence was 3.83%. The prevalence of urinary shedding was inversely associated with increasing age (26.60%, 6.50%, and 3.45% in CMV IgG-positive participants aged 6-11, 12-19, and 20-49 years, respectively; P < .001 for trend test and pairwise comparisons). Urinary viral load also decreased significantly with age (mean, 2.97, 2.69, and 2.43 log10 copies/mL in those age groups, respectively; P < .001 for trend test and pairwise comparisons)., Conclusions: Urinary CMV shedding and viral loads decreased dramatically with age, likely reflecting higher rates of primary CMV infection and longer duration of shedding in younger individuals. The findings demonstrate that children aged 6-11 years continue to shed CMV at higher rates and viral loads than adolescents and adults and thus may still be an important source for CMV transmission.

Human cytomegalovirus (HCMV) is a herpes virus that can cause severe infections. Still, the available methods for its diagnostic have the main disadvantage of requiring long time to be performed. In this work, a simple magnetic particle-based enzyme immunoassay (mpEIA) for the quantification of glycoprotein B of Human cytomegalovirus (gB-HCMV) in urine samples is proposed. The immunosensor scheme is based on the analyte protein gB-HCMV sandwiched between a primary monoclonal antibody, (MBs-PrG-mAb1), and a secondary anti-gB-HCMV antibody labelled with Horseradish peroxidase (Ab2-HRP) to allow spectrophotometric detection. The mpEIA analytical performance was tested in urine samples, showing a linear dependence between gB-HCMV concentration and the absorbance signal at 450 nm in a range of concentrations from 90 to 700 pg mL -1 . The calculated detection limits for gB-HCMV were 90 ± 2 pg mL -1 and the RSD was about 6.7% in urine samples. The immunosensor showed good selectivity against other viruses from Herpesviridae family, namely varicella zoster and Epstein Barr viruses. The recoveries of spiked human urine samples at 0.30-0.50 ng mL -1 concentration levels of gB-HCMV ranged between 91 to 105%. The proposed mpEIA method was validated following the guidelines of the European Medicines Agency (EMEA-2014), and allows rapid, successful and easy quantification of gB-HCMV in urine samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV)., Methods: A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens., Results: Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV., Conclusion: In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants., Clinical Trials Registration Number: NCT00099359., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

BACKGROUND The aim of this study was to investigate the involvement of CMV infection in wheezing infants and the association between CMV-DNA and immunoglobulins (Igs). MATERIAL AND METHODS A total of 243 wheezing infants and 3,000 parturients were enrolled in this study. The infants were randomly grouped to receive blood HCMV-DNA tests (n=46) or urine HCMV-DNA tests (n=197). Furthermore, all participants had serum CMV-specific IgM and IgG testing. Afterwards, 10 HCMV-IgG positive infants were randomly selected for simultaneous blood and urine HCMV-DNA tests, and 25 HCMV-IgG positive puerperants were randomly selected for urine HCMV-DNA tests. RESULTS The detection rate of urine HCMV-DNA was significantly higher than that of blood HCMV-DNA (67.5% vs. 13.0%, p<0.001). Fifteen (6.2%) and 190 (80.0%) infants showed positive CMV-specific IgM and IgG results (p<0.001), respectively. Among the 10 HCMV-IgG positive infants tested further, only two infants had positive HCMV-DNA blood tests, while all of the 10 infants had positive HCMV-DNA urine tests. However, HCMV-DNA was not detected in the urine of the 25 randomly selected parturients positive for HCMV-IgG. CONCLUSIONS CMV infection may be one of the causes of wheezing in infants; CMV infection can be detected by urine-HCMV-DNA and serum HCMV-IgG testing. Infants were more susceptible to CMV infection than parturients.

Background: Congenital cytomegalovirus (CMV) is reported to affect up to 1% of all live births in the United States. T-cell immunity may be important for controlling CMV replication in congenital CMV-infected infants. We describe the natural history of CMV-specific T-cell evolution and CMV replication in infants with congenital CMV infection., Methods: Cytomegalovirus viral load, CMV urine culture, and CMV-specific CD4 and CD8 T-cell responses were assessed in a prospective longitudinal cohort of 51 infants with congenital CMV infection who were observed from birth to 3 years of age., Results: We found a kinetic pattern of decreasing urinary CMV replication and increasing CMV-specific CD4 and CD8 T-cell responses during the first 3 years of life. We also found higher CMV-specific CD8 T-cell responses were associated with subsequent reduction of urine CMV viral load., Conclusion: For infants with congenital CMV infection, our data suggest an age-related maturation of both CMV-specific CD4 and CD8 T-cell immunity that is associated with an age-related decline in urinary CMV replication., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Congenital cytomegalovirus (CMV) infection is the leading cause of sensoneurinal disability due to infectious congenital disease. The diagnosis of congenital CMV infection is based on the search of CMV in the urine within the first two weeks of life. Viral culture of urine is the gold standard. However, the PCR is highly sensitive and faster. It is becoming an alternative choice. The objective of this study is the validation of real-time PCR by Abbott RealTime CMV with m2000 for the detection of cytomegalovirus in urine. Repeatability, reproducibility, detection limit and inter-sample contamination were evaluated. Urine samples from patients (n=141) were collected and analyzed simultaneously in culture and PCR in order to assess the correlation of these two methods. The sensitivity and specificity of PCR were also calculated. The Abbott RealTime CMV PCR in urine is an automated and sensitive method (detection limit 200 UI/mL). Fidelity is very good (standard deviation of repeatability: 0.08 to 0.15 LogUI/mL and reproducibility 0.18 LogUI/mL). We can note a good correlation between culture and Abbott RealTime CMV PCR (kappa 96%). When considering rapid culture as reference, real-time PCR was highly sensitive (100%) and specific (98.2%). The real-time PCR by Abbott RealTime CMV with m2000 is optimal for CMV detection in urine.

Background: Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment., Subjects/methods: Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae., Results: Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%)., Conclusions: This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

A TaqMan real-time quantitative PCR (qPCR), based on amplification of HCMV UL54 gene specific sequence, was developed and compared with shell vial viral culture assay, the gold standard technique for the diagnosis of congenital HCMV infection, using urine samples collected from 110 newborns. The results indicate that this qPCR is slightly more sensitive than shell vial assay suggesting that qPCR may be considered a useful alternative for diagnosing congenital HCMV infection., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Urine is an important source for the detection of infections caused by CMV in stem cell transplant patients. Currently, there is no agreement about the type of urine specimen. In order to investigate which is the better specimen type for quantitative detection of CMV, we compared the results from urine supernatant and sediment from the same patients., Methods: Seventy urine specimens were collected from patients with hematological disorders or solid tumors. After performing shell vial culture, residual urine specimens were centrifuged. Then, 10 mL of each urine supernatant and sediment were taken and immediately frozen at -70 degrees C. Afterwards, archived urine specimens were thawed at room temperature and CMV-quantitative PCR was performed on both the supernatant and sediment fraction of urine. The results from each patient were reviewed for CMV antigenemia, blood shell vial culture, CMV-IgM or IgG, and clinical symptoms., Results: CMV-qPCR results for the urine sediment fraction revealed a significant difference (p = 0.012) between the active CMV infection group and the latent CMV infection group. In addition, receiver operating characteristic curves for active CMV infection revealed that CMV-qPCR using urine sediment produced more accurate results than urine supernatant., Conclusions: These findings suggest that the sediment fraction of urine is a more suitable specimen in CMV-qPCR testing.