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The "silent" global burden of congenital cytomegalovirus.

ABSTRACT: 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.

SUBMITTER: Manicklal S

PROVIDER: S-EPMC3553672 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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The "silent" global burden of congenital cytomegalovirus.

Manicklal Sheetal S Emery Vincent C VC Lazzarotto Tiziana T Boppana Suresh B SB Gupta Ravindra K RK

Clinical microbiology reviews 20130101 1

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 es ...[more]

PMID: 23297260

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Project description:BackgroundPrevious congenital heart disease estimates came from few data sources, were geographically narrow, and did not evaluate congenital heart disease throughout the life course. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, this study aimed to provide comprehensive estimates of congenital heart disease mortality, prevalence, and disability by age for 195 countries and territories from 1990 to 2017.MethodsMortality estimates were generated for aggregate congenital heart disease and non-fatal estimates for five subcategories (single ventricle and single ventricle pathway congenital heart anomalies; severe congenital heart anomalies excluding single ventricle heart defects; critical malformations of great vessels, congenital valvular heart disease, and patent ductus arteriosus; ventricular septal defect and atrial septal defect; and other congenital heart anomalies), for 1990 through to 2017. All available global data were systematically analysed to generate congenital heart disease mortality estimates (using Cause of Death Ensemble modelling) and prevalence estimates (DisMod-MR 2·1). Systematic literature reviews of all types of congenital anomalies to capture information on prevalence, associated mortality, and long-term health outcomes on congenital heart disease informed subsequent disability estimates.FindingsCongenital heart disease caused 261 247 deaths (95% uncertainty interval 216 567-308 159) globally in 2017, a 34·5% decline from 1990, with 180 624 deaths (146 825-214 178) being among infants (aged <1 years). Congenital heart disease mortality rates declined with increasing Socio-demographic Index (SDI); most deaths occurred in countries in the low and low-middle SDI quintiles. The prevalence rates of congenital heart disease at birth changed little temporally or by SDI, resulting in 11 998 283 (10 958 658-13 123 888) people living with congenital heart disease globally, an 18·7% increase from 1990 to 2017, and causing a total of 589 479 (287 200-973 359) years lived with disability.InterpretationCongenital heart disease is a large, rapidly emerging global problem in child health. Without the ability to substantially alter the prevalence of congenital heart disease, interventions and resources must be used to improve survival and quality of life. Our findings highlight the large global inequities in congenital heart disease and can serve as a starting point for policy changes to improve screening, treatment, and data collection.FundingBill & Melinda Gates Foundation.

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.).

Project description:ImportanceCongenital cytomegalovirus (cCMV) infection is the most common congenital infection and the leading acquired cause of developmental disabilities and sensorineural deafness, yet a reliable assessment of the infection burden is lacking.ObjectivesTo estimate the birth prevalence of cCMV in low- and middle-income countries (LMICs) and high-income countries (HICs), characterize the rate by screening methods, and delineate associated risk factors of the infection.Data sourcesMEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases were searched from January 1, 1960, to March 1, 2021, and a total of 1322 studies were identified.Study selectionStudies that provided data on the prevalence of cCMV derived from universal screening of infants younger than 3 weeks were included. Targeted screening studies were excluded.Data extraction and synthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Extraction was performed independently by 3 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Random-effects meta-analysis was undertaken. Metaregression was conducted to evaluate the association of sociodemographic characteristics, maternal seroprevalence, population-level HIV prevalence, and screening methods with the prevalence of cCMV.Main outcomes and measuresBirth prevalence of cCMV ascertained through universal screening of infants younger than 3 weeks for CMV from urine, saliva, or blood samples.ResultsSeventy-seven studies comprising 515 646 infants met the inclusion criteria from countries representative of each World Bank income level. The estimated pooled overall prevalence of cCMV was 0.67% (95% CI, 0.54%-0.83%). The pooled birth prevalence of cCMV was 3-fold greater in LMICs (1.42%; 95% CI, 0.97%-2.08%; n = 23 studies) than in HICs (0.48%; 95% CI, 0.40%-0.59%, n = 54 studies). Screening methods with blood samples demonstrated lower rates of cCMV than urine or saliva samples (odds ratio [OR], 0.38; 95% CI, 0.23-0.66). Higher maternal CMV seroprevalence (OR, 1.19; 95% CI, 1.11-1.28), higher population-level HIV prevalence (OR, 1.22; 95% CI, 1.05-1.40), lower socioeconomic status (OR, 3.03; 95% CI, 2.05-4.47), and younger mean maternal age (OR, 0.85; 95% CI, 0.78-0.92, older age was associated with lower rates) were associated with higher rates of cCMV.Conclusions and relevanceIn this meta-analysis, LMICs appeared to incur the most significant infection burden. Lower rates of cCMV were reported by studies using only blood or serum as a screening method.

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The "silent" global burden of congenital cytomegalovirus.

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The "silent" global burden of congenital cytomegalovirus.

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