Congenital Cytomegalovirus: a "Now" Problem-No Really, Now.
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ABSTRACT:
SUBMITTER: Bernstein DI
PROVIDER: S-EPMC5216425 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Publications
Congenital Cytomegalovirus: a "Now" Problem-No Really, Now.
Clinical and vaccine immunology : CVI 20170105 1
Despite the clear need, progress toward a vaccine for congenital cytomegalovirus (CMV) has been slow. However, recent events have provided new interest, and several vaccine candidates are either in clinical trials or the trials are close to starting. In this issue of Clinical and Vaccine Immunology, Schleiss and colleagues show that a nonreplicating lymphocytic choriomeningitis virus (rLCMV)-vectored vaccine expressing CMV glycoprotein B (gB) and/or pp65 induces B and T cells and improves pup su ...[more]
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Project description:Background: Congenital cytomegalovirus (cCMV) is the leading cause of nongenetic congenital hearing loss in much of the world and a leading cause of neurodevelopmental disabilities. Infected babies can be born to women who are seropositive and seronegative prior to pregnancy, and the incidence is approximately 0.6%-0.7% in the United States. Symptoms vary from mild to severe, and hearing loss can be delayed in onset and progressive. Methods: We reviewed the literature to summarize the epidemiology, clinical manifestations, diagnosis, treatment, and future directions of cCMV. Results: The best way to diagnose the infection is with polymerase chain reaction of urine or saliva within 3 weeks after birth, followed by a repeat confirmatory test if positive. Moderately to severely symptomatic neonates should be treated for 6 months with valganciclovir, and some practitioners also choose to treat infants who have isolated hearing loss only. Treatment is not recommended for asymptomatic infants. All infected infants should be screened for hearing loss and neurodevelopmental sequelae. Universal and targeted screening may be cost effective. Currently, no vaccine is commercially available, although multiple candidates are under study. Conclusion: Congenitally acquired cytomegalovirus is found in all communities around the world with a disease burden that is greater than many other well-known diseases. Advances are being made in prevention and treatment; however, improved awareness of the disease among clinicians and patients is needed.
| S-EPMC6584201 | biostudies-other
Project description:Congenital cytomegalovirus (CMV) is the most common cause of congenital infection worldwide, the most common nongenetic cause of sensorineural hearing loss in children, and a cause of neurodevelopmental disorders in the brain. Infants with symptomatic congenital CMV infection may benefit from hearing and neurodevelopmental outcomes, particularly if antiviral treatment is initiated within the first month of life. Infants with life-threatening symptoms are recommended to receive 2-6 weeks of intravenous ganciclovir and then switch to oral valganciclovir, and those without life-threatening symptoms are recommended to use oral valganciclovir during the entire 6-month period. During antiviral drug treatment, absolute neutrophil count, platelet count, blood urea nitrogen, creatinine, and liver function tests were performed to identify neutropenia, thrombocytopenia, renal failure, and liver failure. This review investigated the evidence to date of treating congenital CMV infection.
| S-EPMC10475861 | biostudies-literature
Project description:Longer lives and fertility far below the replacement level of 2.1 births per woman are leading to rapid population aging in many countries. Many observers are concerned that aging will adversely affect public finances and standards of living. Analysis of newly available National Transfer Accounts data for 40 countries shows that fertility well above replacement would typically be most beneficial for government budgets. However, fertility near replacement would be most beneficial for standards of living when the analysis includes the effects of age structure on families as well as governments. And fertility below replacement would maximize per capita consumption when the cost of providing capital for a growing labor force is taken into account. Although low fertility will indeed challenge government programs and very low fertility undermines living standards, we find that moderately low fertility and population decline favor the broader material standard of living.
| S-EPMC4545628 | biostudies-literature
Project description:BACKGROUND:Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. METHODS:cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time polymerase chain reaction. RESULTS:Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: < 200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (P < 0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intrapartum HIV infection (P < 0.0001). Rates of cCMV among HIV-infected infants were 4-fold greater (adjusted OR, 4.4; 95% CI: 2.3-8.2) and 6-fold greater among HIV in utero-infected infants (adjusted OR, 6; 95% CI: 3-12.1) compared with HIV-exposed, uninfected infants. cCMV was not associated with mode of delivery, gestational age, Apgar scores, 6-month infant mortality, maternal age, race/ethnicity, HIV viral load or CD4 count. Primary cCMV risk factors included infant HIV-infection, particularly in utero infection. CONCLUSION:High rates of cCMV with high urinary CMV VL were observed in HIV-exposed infants. In utero HIV infection appears to be a major risk factor for cCMV in infants whose mothers have not received combination antiretroviral therapy in pregnancy.
| S-EPMC6129438 | biostudies-literature
Project description:BackgroundThe treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time.MethodsWe conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline.ResultsA total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64).ConclusionsTreating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).
| S-EPMC4401811 | biostudies-literature
Project description:Purpose of the reviewCongenital cytomegalovirus infection (cCMV) is the most frequent congenital infection and a leading nongenetic cause of sensorineural hearing loss (SNHL) and brain disease. The purpose of this review is to highlight recent developments in the diagnosis and management of children with cCMV.Recent findingsProgress is being made in the efforts to identify more infants with cCMV, especially those with asymptomatic infection. Largely due to efforts by various advocacy/parent groups, a number of states in the United States and many hospital systems have implemented hearing targeted CMV screening and mandated education of pregnant women about CMV.SummarycCMV is an important cause of SNHL and neurologic morbidity worldwide. Early identification of infected children is critical to improve outcomes by providing timely interventions and guidance for long-term follow up. The fact that most infants with cCMV have no abnormal clinical findings, and the need to obtain samples for diagnosis within the first 2-3 weeks of life, makes it challenging to identify a majority of infants with cCMV without universal newborn CMV screening.
| S-EPMC10494910 | biostudies-literature
Project description:Human cytomegalovirus (CMV) is an ubiquitous pathogen, with a high worldwide seroprevalence. When acquired in the prenatal period, congenital CMV (cCMV) is a major cause of neurodevelopmental sequelae and hearing loss. cCMV remains an underdiagnosed condition, with no systematic screening implemented in pregnancy or in the postnatal period. Therefore, imaging takes a prominent role in prenatal diagnosis of cCMV. With the prospect of new viable therapies, accurate and timely diagnosis becomes paramount, as well as identification of fetuses at risk for neurodevelopmental sequelae. Fetal magnetic resonance imaging (MRI) provides a complementary method to ultrasound (US) in fetal brain and body imaging. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to US in their detection. Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. However, when seen in combination these should raise the suspicion of fetal infection, highlighting the need for a full fetal assessment. Still, some fetuses deemed normal on prenatal imaging are symptomatic at birth or develop delayed cCMV-associated symptoms, leaving room for improvement of diagnostic tools. Advanced MR sequences may help in this field and in determining prognosis, but further studies are needed.
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Project description:Human cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections. However, reliable estimates of prevalence and outcome from developing countries are not available. This is largely due to the dogma that maternal preexisting seroimmunity virtually eliminates the risk for sequelae. However, recent data demonstrating similar rates of sequelae, especially hearing loss, following primary and nonprimary maternal infection have underscored the importance of congenital CMV infection in resource-poor settings. Although a significant proportion of congenital CMV infections are attributable to maternal primary infection in well-resourced settings, the absence of specific interventions for seronegative mothers and uncertainty about fetal prognosis have discouraged routine maternal antibody screening. Despite these challenges, encouraging results from prototype vaccines have been reported, and the first randomized phase III trials of prenatal interventions and prolonged postnatal antiviral therapy are under way. Successful implementation of strategies to prevent or reduce the burden of congenital CMV infection will require heightened global awareness among clinicians and the general population. In this review, we highlight the global epidemiology of congenital CMV and the implications of growing knowledge in areas of prevention, diagnosis, prognosis, and management for both low (50 to 70%)- and high (>70%)-seroprevalence settings.
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Project description:Congenital cytomegalovirus (CMV) infection is an important cause of hearing impairment, mental retardation, and cerebral palsy. Principal sources of infection during pregnancy are young children and intimate contacts. Prevention of maternal and congenital CMV infection depends on counseling women regarding the sources of infection and hygienic measures that might prevent infection. There is currently insufficient evidence to support use of antiviral treatment or passive immunization for postexposure prophylaxis of pregnant women or as a maternal treatment aimed at preventing fetal infection. Vaccines for CMV are under development but it will be a number of years before one is licensed.
| S-EPMC3347968 | biostudies-literature
Project description:The human cytomegalovirus (HCMV) UL144 gene is a tumor necrosis factor-like receptor with the potential to affect HCMV virulence. HCMV strains display genetic variability in the UL144 region, and the analysis of a potential link between UL144 gene polymorphisms and disease severity has scarcely been studied. However, a correlation between the UL144 genotype and congenital-disease outcome has been reported in one previous study, with the observation that all asymptomatic infants had a single UL144 genotype. In order to confirm or refute this finding, we determined the UL144 polymorphisms of HCMV strains recovered from the amniotic fluids of 38 infected fetuses and compared them to HCMV strains obtained from 30 viremic adult controls. The UL144 sequences were distributed among five genotypes (A, B, C, AC, and AB), as previously described. We observed similar percentages of the three major genotypes A (37%), B (33%), and C (27%) in our population. The UL144 genotype distributions were similar among the group of infected adults and the group of infected fetuses and among symptomatic and asymptomatic fetuses (P < 0.05). In our series, all five UL144 genotypes could be vertically transmitted from mothers to fetuses, and all could cause symptomatic congenital infection. We concluded that determination of UL144 polymorphisms in cases of congenital infection is not relevant, since it is unlikely to help predict the outcome of the infection.
| S-EPMC540124 | biostudies-literature