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Introduction: Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing., Materials and Methods: We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count., Results: Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm 3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019)., Conclusions: Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening., Competing Interests: Declaration of competing interest Mitsubishi Tanabe Pharm Corp. provided Valixa™ dry syrup during the study period for treatment, but this company had no role in this clinical trial. None of the authors have any conflict of interest to declare., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate the relationship between herpes simplex virus (HSV) and hearing loss using comprehensive population-based research., Design: This cross-sectional study utilised data from the National Health and Nutrition Examination Survey (NHANES) to examine the relationship between HSV (types 1 and 2) and hearing loss. The final sample comprised 4608 participants aged 20-49 years. Weighted multivariate regression, subgroup and sensitivity analyses were employed for statistical evaluations., Setting: Utilising the NHANES data, this cross-sectional study provides insights into the American population aged 20-49 years., Participants: The study includes 4608 participants from the NHANES 2011-2012 and 2015-2016 cycles, focusing on those with complete data on HSV infection and hearing assessment., Interventions Exposure: The study analyses the association between HSV (types 1 and 2) infection and hearing loss, using weighted multivariate regression for statistical evaluations., Results: We observed an association between HSV-1 infection and an increased likelihood of hearing impairment (OR, 1.4 (95% CI 1.1 to 1.9)). A similar association was noted for those coinfected with HSV-1 and HSV-2 (OR, 1.6 (95% CI 1.1 to 2.3)). Similarly, higher grades of hearing loss and elevated pure-tone averages were more prevalent in these groups. Notably, the association between HSV-1 and hearing impairment was more pronounced in individuals aged 20-34 (OR, 2.1 (95% CI 1.4 to 3.3); P for interaction=0.020) and those with a body mass index (BMI) below 30 (OR, 1.8 (95% CI 1.1 to 2.8); P for interaction=0.028)., Conclusions: Our findings suggest an association between HSV-1 infection or coinfections with HSV-1 and HSV-2 and the presence of hearing impairment. The association appears particularly pronounced among younger individuals and those with a lower BMI. Further prospective research is needed to explore the causal impact of HSV on auditory function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations., Methods: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years., Results: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes., Conclusion: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Objectives: To identify and understand the evidence regarding hearing changes related to acquired Dengue, Chikungunya, and Zika virus infection in adult individuals., Methods: A scoping review was performed according to the recommendations of The Joanna Briggs Institute and guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews in the Embase, PubMed/Medline, ScienceDirect, Scopus, and Web of Science databases without restriction on language and year of publication. Case studies, observational studies, and clinical trials reporting hearing loss in adult subjects (>18-60 years of age) of both sexes with DENV, CHIKV, or ZIKV diagnosed by positive molecular/serological examination by RT-PCR or IgM/IgG by ELISA method were included., Results: Thirteen studies met the inclusion criteria and were selected for review. The occurrence of auditory symptoms caused by arboviroses and the presence of permanent or transient sensorineural hearing loss was variable in adults., Conclusions: Dengue, Chikungunya, and Zika infections in adults are associated with a variety of auditory symptoms. The frequency of permanent or transient sensorineural hearing loss is low but not negligible., (Copyright © 2023 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.)

Backgrounds: SARS-CoV-2 is known to be a neurotrophic virus. However, the effect of this virus on the hearing system is still uncertain., Objectives: We aimed to investigate the possible effect of COVID-19 on hearing., Materials and Methods: Thirty healthcare workers who had COVID-19 after hearing evaluation with pure tone audiometry (PTA) for any reason in the last 1 year were included in the study. PTA and transient evoked otoacoustic emissions (TEOAE) tests were performed in 15 of 30 patients during the active infection period. For all 30 patients, otoscopic examination plus PTA and TEOAE tests were performed at the end of the first month after their treatment., Results: When the PTA results of 30 patients (60 ears) before and after COVID-19 were compared, a significant decrease in hearing level was found only at 1000 Hz ( p  < .05). There were no significant differences at other frequencies. When the PTA and TEAOE test results of 15 patients (30 ears) that were performed during and after COVID-19 were compared, no significant differences were found., Conclusion and Significance: We conclude that COVID-19 may cause hearing loss. However, this result needs to be confirmed with comprehensive studies to be conducted in larger patient groups.

Hearing loss, one of the most prevalent chronic health conditions, affects around half a billion people worldwide, including 34 million children. The World Health Organization estimates that the prevalence of disabling hearing loss will increase to over 900 million people by 2050. Many cases of congenital hearing loss are triggered by viral infections during different stages of pregnancy. However, the molecular mechanisms by which viruses induce hearing loss are not sufficiently explored, especially cases that are of embryonic origins. The present review first describes the cellular and molecular characteristics of the auditory system development at early stages of embryogenesis. These developmental hallmarks, which initiate upon axial specification of the otic placode as the primary root of the inner ear morphogenesis, involve the stage-specific regulation of several molecules and pathways, such as retinoic acid signaling, Sonic hedgehog, and Wnt. Different RNA and DNA viruses contributing to congenital and acquired hearing loss are then discussed in terms of their potential effects on the expression of molecules that control the formation of the auditory and vestibular compartments following otic vesicle differentiation. Among these viruses, cytomegalovirus and herpes simplex virus appear to have the most effect upon initial molecular determinants of inner ear development. Moreover, of the molecules governing the inner ear development at initial stages, SOX2, FGFR3, and CDKN1B are more affected by viruses causing either congenital or acquired hearing loss. Abnormalities in the function or expression of these molecules influence processes like cochlear development and production of inner ear hair and supporting cells. Nevertheless, because most of such virus-host interactions were studied in unrelated tissues, further validations are needed to confirm whether these viruses can mediate the same effects in physiologically relevant models simulating otic vesicle specification and growth.

After following 141 children with likely asymptomatic congenital cytomegalovirus infection in a highly immune population in China, four children (2.8%) were found to have late-onset hearing loss. No maternal or childhood factors, except higher saliva cytomegalovirus viral load at birth (P = 0.03), were associated with increased risk of developing a hearing loss.

Importance: Congenital cytomegalovirus infection (cCMVi) is one of the most common infections associated with childhood hearing loss. Prevention and mitigation of cCMVi-related hearing loss will require an increase in newborn screening, which is not yet available in China., Objective: To estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system., Design, Setting, and Participants: A decision tree for a simulated cohort population of 15 000 000 live births was developed to compare the costs and health effects of 3 mutually exclusive interventions: (1) no screening, (2) targeted screening using CMV polymerase chain reaction assay for newborns who fail a universal hearing screening, and (3) universal screening for CMV among all newborns. Markov diagrams were used to evaluate the lifetime horizon (76 years)., Main Outcomes and Measures: Cost, hearing-related health outcomes, and incremental cost-effectiveness ratios (ICERs) were estimated based on a direct medical costs perspective. Costs and ICERs were reported in 2018 US dollars., Results: Incidence of cCMVi among newborns was reported to be approximately 0.7% in China. Targeted screening was less costly but also less effective than universal screening, identifying 41% of cases needing antiviral treatment and preventing nearly half of less severe or profound hearing loss. To avoid 1 CMV-related severe or profound hearing loss, 13 and 16 newborns need to be treated by targeted and universal screening, respectively. The ICERs of targeted and universal screening vs no screening were $79 and $2087 per quality-adjusted life-year gained, respectively, at the discounted rate of 3.5%. Both screening options were cost-effective for the Chinese health care system based on the willingness-to-pay threshold of 3 × gross domestic product per capita. The sensitivity analysis showed that the prevalence of cCMVi, as well as diagnosis and treatment costs, were key factors that may be associated with decision-making., Conclusions and Relevance: To achieve cost-effectiveness and best health outcomes, universal screening could be considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.

Objective: Lassa fever (LF) a hemorrhagic fever endemic to Western has an incidence of approximately 500,000 cases per year. Here, we evaluate hearing loss and other sequelae following LF., Methods: This case-control study enrolled laboratory confirmed LF survivors, non-LF Febrile controls and Matched Community controls with no history of LF or recent hospitalization for a febrile illness. Study participants completed a symptom questionnaire. Pure-tone audiometry was completed by a subset of participants., Results: One hundred forty-seven subjects were enrolled aged from 3-66 years (mean = 23.3). LF survivors were significantly more likely to report balance difficulties (55% vs 20%, p < 0.001), hair loss (32% vs 7%, p < 0.001), difficulty speaking (19% vs 1%, p < 0.001), social isolation (50% vs 0%, p < 0.001), and hearing loss (17% vs 1%, p = 0.002) in comparison to Matched-Community Controls. Similar trends were noted in comparison to Febrile Controls, although these findings were non-significant. Fifty subjects completed audiometry. Audiometry found that LF survivors had significantly more bilateral hearing loss in comparison to Matched-Community Controls (30% vs 4%, p = 0.029)., Conclusion: This study characterizes the sequelae of LF and highlights the need for increased access to hearing care in West Africa., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Antiretroviral therapy (ART) has had a major impact on life expectancy from HIV as many people now live with it as a chronic disease. Chronic HIV has been associated with a range of comorbid disabilities and health conditions, one of which is hearing loss. Undiagnosed and untreated hearing loss, particularly in children, has been linked to poorer spoken language skills, with subsequent effects on academic performance., Methods: This systematic scoping review aimed to summarize the available peer-reviewed literature on hearing loss in HIV-infected children, specifically to describe its extent and nature. The review followed the framework proposed by Arksey and O'Malley. Key search terms included hearing loss (and synonyms), child (and synonyms), and HIV. Electronic databases (EBSCOhost Research Platform, PubMed, Web of Science and Scopus databases) were searched for any relevant articles published from January 1, 2000 to June 30, 2019. Reference lists of included articles were pearled for additional relevant articles not already identified. Each stage of the selection process was conducted independently by two authors. The results were then collated by a third author who also resolved any discrepancies. Extracted data included sample descriptors, audiologic tests, hearing loss prevalence, hearing loss descripts, and factors associated with hearing loss., Results: Seventeen articles were included; 10 from Africa, four from South America, two from North America and the remaining article from Asia. Although most of the articles reported on pure tone audiometry, the samples as well as the cut-off criteria for normal hearing were heterogenous. Prevalence of hearing loss varied across articles (from 6% to 84%). Conductive hearing loss occurred more frequently than sensorineural or mixed hearing loss. ART use and ear infection were reported as significant in three of five articles that reported on significant associates of HIV-related hearing loss., Conclusion: There was a modest volume of research from a limited number of countries. Heterogeneity in sampling and audiometric methods precluded a clear understanding of potential associations between chronic HIV-related hearing loss and contributing factors., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of hearing loss and neurological disorder in children. Its overall prevalence is approximately 0.5% in Europe. In France, systematic screening during pregnancy is not recommended; screening is performed only if there are maternal or fetal symptoms suggestive of this infection. Approximately 90% of infected newborns are asymptomatic at birth, and among them the risk of neurosensory sequelae is 5-15%. By contrast, the prevalence of neurosensory impairment in symptomatic newborns at birth varies from 17% to 60%. Congenital CMV infection must be confirmed at birth before the 21st day of life by polymerase chain reaction (PCR) on saliva or urine samples. A complete clinical examination, blood tests (blood count, liver function test, CMV PCR), hearing tests, brain ultrasound and eye fundus examination should be performed. Neurological and auditory follow-up must be extended well beyond the neonatal period because the occurrence of neurosensory sequelae may be delayed. Oral valganciclovir is the recommended treatment in moderate or severe congenital CMV infections for a period of 6 weeks to 6 months; such treatment requires regular monitoring because of its possible side effects., (Copyright © 2020. Published by Elsevier Masson SAS.)

Introduction: Possible associations between Zika virus infection and hearing loss were observed during the epidemic in the Americas., Objective: To describe the auditory alterations, pathogenesis and recommendations for follow-up in individuals with prenatal or acquired Zika virus infection., Methods: Bibliographic research conducted in March/2018-April/2019 at the main available databases. Article selection, data extraction and quality evaluation were carried out by two independent reviewers. Studies containing auditory evaluation of patients with congenital or acquired Zika virus infection; and/or hypotheses or evidences on the pathophysiology of auditory impairment associated with Zika virus; and/or recommendations on screening and follow-up of patients with auditory impairment by Zika virus were included., Results: A total of 27 articles were selected. Sensorineural and transient hearing loss were reported in six adults with acquired Zika virus infection. Of the 962 studied children, 482 had microcephaly and 145 had diagnostic confirmation of Zika virus; 515 of the 624 children with auditory evaluation performed only screening tests with otoacoustic emissions testing and/or automated click-stimuli auditory brainstem response testing. Studies in prenatally exposed children were very heterogeneous and great variations in the frequency of altered otoacoustic emissions and automated click-stimuli auditory brainstem response occurred across the studies. Altered otoacoustic emissions varied from 0% to 75%, while altered automated click-stimuli auditory brainstem response varied from 0% to 29.2%. Sensorineural, retrocochlear or central origin impairment could not be ruled out. One study with infected mice found no microscopic damage to cochlear hair cells. Studies on the pathogenesis of auditory changes in humans are limited to hypotheses and recommendations still include points of controversy., Conclusion: The available data are still insufficient to understand the full spectrum of the involvement of the auditory organs by Zika virus, the pathogenesis of this involvement or even to confirm the causal association between auditory involvement and virus infection. The screening and follow-up recommendations still present points of controversy., (Copyright © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

The neglected tropical diseases Zika, Ebola, and Lassa fever (LF) have all been noted to cause some degree of hearing loss (HL). Hearing loss is a chronic disability that can lead to a variety of detrimental effects, including speech and language delays in children, decreased economic productivity in adults, and accelerated cognitive decline in older adults. The objective of this review is to summarize what is known regarding HL secondary to these viruses. Literature for this review was gathered using the PubMed database. Articles were excluded if there were no data of the respective viruses, postinfectious complications, or conditions related to survivorship. A total of 50 articles were included in this review. Fourteen articles discussing Zika virus and subsequent complications were included. Across these studies, 56 (21.2%) of 264 Zika-infected individuals were found to have HL. Twenty-one articles discussing Ebola virus and subsequent complications were included, with 190 (5.7%) of 3,350 Ebola survivors found to have HL. Fifteen additional articles discussing LF and subsequent complications were included. Of 926 individuals with LF, 79 (8.5%) were found to have HL. These results demonstrate a relationship between HL and infection. The true prevalence is likely underestimated, however, because of lack of standardization of reporting and measurement. Future studies of viral sequelae would benefit from including audiometric evaluation. This information is critical to understanding pathophysiology, preventing future cases of this disability, and improving quality of life after survival of infection.

Lassa virus (LASV) is endemic in West Africa, causing an estimated 100000-300000 new infections and up to 5000-10000 deaths yearly. There are no vaccines and therapeutics are extremely limited. Typical case fatality rates are ∼1%, although a recent 2018 Nigerian outbreak featured an unprecedented 25.4% case fatality rate. Survivors of infection suffer a lifetime of sequelae with sudden onset sensorineural hearing loss (SNHL) being the most prevalent. The cause of this hearing loss remains unknown, and there is a critical need for further research on its mechanisms and potential therapeutics. The objective of this review is to outline the only currently available small animal model for LASV-induced hearing loss and to identify potential surrogate models., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Congenital Cytomegalovirus (cCMV) is the most common cause of non-genetic hearing loss in childhood. A newborn hearing screening program (NHSP) is currently running in Italy, but no universal cCMV nor statewide hearing-targeted CMV screening programs have been implemented yet. This observational monocentric study was aimed at estimating the rate of cCMV infections identified by CMV-DNA analysis on Dried Blood Spots (DBS) samples in deaf children identified via NHSP in Northern Italy in the period spanning from 2014 to 2018., Methods: Children with a confirmed diagnosis of deafness and investigated for CMV-DNA by nucleic acid extraction and in-house polymerase-chain reaction (PCR) on stored newborns screening cards (DBS-test) were included in this study. Deafness was defined by a hearing threshold ≥20 decibel (dB HL) by Auditory Brainstem Responses (ABR); all investigated DBS samples were collected within 3 days of life., Results: Overall, 82 children were included (median age: 3.4 months; lower-upper quartiles: 2-5.3 months; males: 60.9%). Most of them (70.7%) presented bilateral hearing loss with a symmetrical pattern in 79.3% of the cases. ABR thresholds were ≥ 70 dB HL (severe/profound deafness) in 46.5% of children. Among all tested children, 6.1% resulted positive for cCMV. The rate of severe/profound deafness was statistically higher in children with cCMV infection., Conclusions: The addition of DBS-test to the NHSP allowed the identification, in their first months of life, of a cCMV infection in 6.1% of children who had failed NHS. The introduction of a targeted CMV screening strategy could help clinicians in the differential diagnosis and in the babies' management. DBS samples can be considered a "universal newborns biobank": their storage site and duration should be the subject of political decision-making.

Importance: Many survivors of Ebola virus infection describe new-onset hearing loss after infection. The prevalence, severity, and pathophysiologic features of hearing loss in this population have not been well characterized., Objective: To perform a systematic review of the current literature to characterize hearing loss in survivors of Ebola virus infection., Evidence Review: This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Searches through PubMed, Embase, and Google Scholar were performed to include publications written in English from January 1, 1965, to October 1, 2018. Relevant vocabulary terms and key terms related to Ebola and hearing loss were used. Two investigators independently screened the eligible studies, extracted data, and assessed quality and risk of bias., Findings: Of 127 publications reviewed, 15 met the criteria for inclusion; 3 were retrospective case-control studies (level of evidence, 3), and 12 were cross-sectional studies or case reports (level of evidence, 4). Studies included 1775 survivors of Ebola virus infection (993 female [55.9%]) and 363 uninfected controls (186 female [51.2%]) from the Democratic Republic of the Congo, Uganda, Guinea, Liberia, and Sierra Leone. The duration of follow-up ranged from 0 to 29 months (median, 5 months). Hearing loss was reported in 147 survivors of Ebola virus infection (8.3%). Among studies that compared survivors with controls, the reported odds ratios for hearing loss in survivors was 7.50 (95% CI, 3.91-14.39; range, 1.4-12.1). Including all studies, the odds ratio of hearing loss in survivors vs controls in countries where Ebola virus infection is endemic was 1.84 (95% CI, 1.10-3.08)., Conclusions and Relevance: Survivors of Ebola virus infection had higher rates of hearing loss than uninfected controls in regions where the infection is endemic. Further research with consistent objective methods and pure-tone audiometry may be needed to better characterize the hearing loss, understand its pathophysiologic features, and develop treatments.

Background: Viral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear., Methods: Post hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy., Results: Higher baseline VL was associated with central nervous system involvement (3.82 log, range 1-5.65 vs 3.32 log, range 1-5.36; P = .001), thrombocytopenia (3.68 log, range 1-5.65 vs 3.43 log, range 1-5.36; P = .03), and transaminitis at presentation (3.73 log, range 1-5.60 vs 3.39 log, range 1-5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing., Conclusions: In infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Congenital cytomegalovirus (CMV) infection is a major cause of sensorineural hearing loss. By law, newborns in Connecticut who fail newborn hearing screening are tested for infection with CMV. This targeted screening is controversial, because most children with congenital CMV infection are asymptomatic, and CMV-related hearing loss can have a delayed onset. Our hospital uses a saliva polymerase chain reaction (PCR) assay (confirmed by a urine PCR assay) to detect CMV. Here, we report the results of the first year of our screening program., Methods: We reviewed the medical records of newborns in the Yale New Haven Health System who failed the newborn hearing screening test between January 1 and December 31, 2016., Results: Of 10964 newborns, 171 failed newborn hearing screening, and 3 of these newborns had positive saliva CMV PCR test results. Of these 3 newborns, 2 had positive results on the confirmatory test (for 1 of them the confirmatory test was not performed until the infant was 10 weeks old), and 1 had a negative result on the confirmatory test. Three additional newborns with congenital CMV infection were tested because of clinical indications (1 for ventriculomegaly on prenatal ultrasound and 2 for CMV infection of the mother). Results of audiology follow-up were available for 149 (87.1%) of the 171 newborns who failed newborn hearing screening; 127 (85.2%) had normal results., Conclusion: Our targeted screening program for congenital CMV infection had a low yield. Consideration should be given to other strategies for identifying children at risk of hearing loss as a result of congenital CMV infection., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: to describe the results of hearing screening performed in children with Congenital Zika Virus Syndrome (CZS) in Fortaleza, Ceará, Brazil., Methods: this was a descriptive cross-sectional study involving children with CZS receiving health care in Fortaleza, 2016; the hearing screening tests performed were immittance audiometry, transient otoacoustic emissions (TOAE), acoustic reflexes, and cochleopalpebral reflex (CPR)., Results: The study included 45 children with an average age of 10 months. 44 of them underwent tympanometric screening, with 16 of these having the right ear within the normal range and 22 having the left ear within the normal range. Among the 43 children evaluated by TOAE, 30 "passed" in both ears, nine "refered" in both ears and four "refered" just in ear; 13/43 "refered" and needed to repeat screening. 43 children evaluated by CPR, 37 showed responses., Conclusion: most of the children evaluated had completed cochlear function and middle ear results refer in compatible with their age range.

Background and Objectives: Australian national surveillance data was used to assess recognition, sequelae, and antiviral therapy for congenital cytomegalovirus (CMV) cases., Study Design: Data from congenital CMV cases reported through the Australian Paediatric Surveillance Unit born January 1999 to December 2016 were described and Chi-square tests used to characterise trends and associations in case reporting, maternal CMV serology testing, and antiviral therapy. Descriptive analyses for hearing loss and developmental delay were reported for cases born ≥2004, following introduction of universal neonatal hearing screening., Results: There were 302 congenital CMV cases (214 symptomatic, 88 asymptomatic). Congenital CMV was suspected in 70.6% by 30 days of age, with no differences across birth cohorts. Maternal CMV serology testing was associated with maternal illness during pregnancy but not birth cohort. There was increasing antiviral use for symptomatic cases, being used in 14% born 1999-2004, 19.6% born 2005-2010, and 44.4% born 2011-2016 (p < 0.001). For those born ≥2004, hearing loss was reported in 42.1% of symptomatic and 26.6% of asymptomatic cases; while developmental delay was reported in 16.9% of symptomatic and 1.3% of asymptomatic cases., Conclusion: There appears to be under-reporting and under-recognition of congenital CMV despite increasing use of antiviral therapy. Universal newborn CMV screening should be considered to facilitate follow-up of affected children and targeted linkage into hearing and developmental services, and to provide population-level infant CMV epidemiology to support research and evaluation of antiviral and adjunctive therapies., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Objective: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection, with the majority of infected newborns having no detectable signs. The aim of this study was to examine the accuracy of our newly developed DBS-based assay as an appropriate mass screening method for cCMV infection., Methods: Between May 2011 and October 2016, newborns delivered at six hospitals in Nagano Prefecture, Japan were enrolled prospectively. We employed dried blood spot (DBS)-based assays with real-time quantitative PCR (qPCR)., Results: Prior to the clinical study, confirmation analysis was carried out using positive and negative controls. The sensitivity and specificity of this DBS-based qPCR assay for the detection of CMV DNA were 83 and 97%, respectively. During the study period, 9675 newborns were enrolled. The total recovery rate of DBS was 99.92% (9,667/9,675). From our analysis of the 9,667 samples, 47 DBS samples were found positive by the qPCR test (0.48%), and 9620 (99.5%) DBS samples were CMV-negative., Conclusions: The risk of neural disorders associated with cCMV infection is thought likely to increase with CMV viral load in the blood. DBS screening for cCMV may be sufficient in a clinical setting, and offers a realistic and feasible option for universal mass screening.

Background: Congenital cytomegalovirus (CMV) is the most common non-genetic cause of sensorineural hearing loss. Currently, there are no universal CMV screening programs for newborns or routine CMV testing of neonates with hearing loss in Australia, or elsewhere., Objectives: This study was undertaken to determine the prevalence of congenital CMV infection in infants with hearing loss identified using routine resources via the Australian universal neonatal hearing screening (UNHS) program., Study Design: Infants who failed UNHS, referred for audiological testing and found to have permanent hearing loss were screened for CMV via PCR of urine and saliva. Congenital CMV was diagnosed if CMV was detected in infants ≤30 days of age, or using retrospective testing on stored new born screening cards, retrospective testing, or using clinical criteria if >30 days of age. The cohort was analyzed for time of testing and prevalence of congenital CMV determined., Results: The Audiology Department reviewed 1669 infants who failed UNHS between 2009 and 2016. Thirty percent (502/1669) had permanent hearing loss confirmed, of whom 336/502 were offered CMV testing. A definite (n = 11) or probable (n = 8) diagnosis of congenital CMV occurred in 19/323 (5.9%), of whom definite diagnoses were made in 4/19 on tests positive prior to 21 days of life, in 5/19 who were positive on neonatal blood screening card (NBSC) testing, in 2/19 who were positive on placental testing. In 8/19 probable diagnoses were made based on positive testing between ages 23-42 days and a consistent clinical syndrome in the absence of another cause for hearing loss after genetic and other testing. CMV testing mirrored the timing of audiological testing, with ∼40% completing audiology and CMV testing by 21 days, and 64% by 30 days., Conclusion: This program, utilizing existing clinical services identified probable congenital CMV in ∼6% of a large cohort failing UNHS with permanent hearing loss, of whom more than half were definite diagnoses. No additional assets were required to those already existing in this tertiary referral pediatric centre, whilst providing useful and timely data for clinical and audiological management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Congenital cytomegalovirus infection (cCMV) is a leading nongenetic cause of permanent congenital or early-onset hearing loss (PCEHL). Although cCMV rates are high despite near-universal seroimmunity, the contribution of cCMV to PCEHL in the developing world is unclear., Methods: Neonates at a rural North Indian hospital were screened for cCMV by saliva polymerase chain reaction and hearing by distortion-product otoacoustic emission testing. Cytomegalovirus (CMV)-positive infants and those not passing newborn hearing screening (NHS) were evaluated by auditory brainstem response to confirm PCEHL. Infants with cCMV and those with PCEHL were tested for mutations within the GJB2 gene., Results: Of the 1720 infants screened, 40 (2.3%) did not pass NHS and 20 (1.2%) were CMV positive. Auditory brainstem evoked response testing confirmed unilateral or bilateral PCEHL in 11 (0.64%) children who either did not pass NHS or CMV positive. PCEHL was 20-fold higher in neonates with cCMV (2/20, 10%) than those without (9/1700, 0.5%; P < 0.01). None of 11 infants with PCEHL had connexin 26 mutations., Conclusion: PCEHL incidence is high in India, with cCMV contributing significantly despite near-universal seroimmunity. Our findings also demonstrate the feasibility and the utility of simultaneous newborn screening for both cCMV and hearing loss in a resource-limited setting.

Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular, inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (the conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision making and guide prevention and (genetic) counselling. Management options include specific antimicrobial therapies, surgical treatment of craniofacial abnormalities and implantable or non-implantable hearing devices. An improved understanding of the pathophysiology and molecular mechanisms that underlie hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

Conclusions: The majority of hearing loss due to mumps presents as unilateral profound sensorineural hearing loss, which is refractory to treatment. In rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is recommended to prevent mumps-associated hearing loss., Objective: The objective of this study is to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes., Subjects and Methods: The clinical parameters were analyzed under a retrospective multi-institutional study design in patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016., Results: Sixty-seven patients with hearing loss due to mumps were enrolled. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three patients presented with unilateral, and 4 with bilateral hearing loss. Profound hearing loss was observed in 65 ears. Only one ear with severe hearing loss showed complete recovery. Four patients with bilateral hearing loss received cochlear implant surgery. Most of the patients with hearing loss due to mumps had no history of vaccination.

Importance: Congenital cytomegalovirus (cCMV) infection is a major cause of childhood deafness. Most cCMV infections are not diagnosed without newborn screening, resulting in missed opportunities for directed care., Objective: To estimate the cost-effectiveness of universal and targeted newborn cCMV screening programs compared with no cCMV screening., Design, Setting, and Participants: Models were constructed using rates and outcomes from prospective cohort studies of newborn cCMV screening in US postpartum care and early hearing programs. Costs of laboratory testing, treatment, and hearing loss were drawn from Medicaid data and published estimates. The benefits of cCMV screening were assumed to come from antiviral therapy for affected newborns to reduce hearing loss and from earlier identification of hearing loss with postnatal onset. Analyses were performed from July 2014 to March 2016., Interventions: Models compared universal or targeted cCMV screening of newborns with a failed hearing screen, with standard care for cCMV infection., Main Outcomes and Measures: The incremental costs of identifying 1 cCMV infection, identifying 1 case of cCMV-related hearing loss, and preventing 1 cochlear implant; the incremental reduction in cases of severe to profound hearing loss; and the differences in costs per infant screened by universal or targeted strategies under different assumptions about the effectiveness of antiviral treatment., Results: Among all infants born in the United States, identification of 1 case of cCMV infection by universal screening was estimated to cost $2000 to $10 000; by targeted screening, $566 to $2832. The cost of identifying 1 case of hearing loss due to cCMV was as little as $27 460 by universal screening or $975 by targeted screening. Assuming a modest benefit of antiviral treatment, screening programs were estimated to reduce severe to profound hearing loss by 4.2% to 13% and result in direct costs of $10.86 per newborn screened. However, savings of up to $37.97 per newborn screened were estimated when costs related to functionality were included., Conclusions and Relevance: Newborn screening for cCMV infection appears to be cost-effective under a wide range of assumptions. Universal screening offers larger net savings and the greatest opportunity to provide directed care. Targeted screening also appears to be cost-effective and requires testing for fewer newborns. These findings suggest that implementation of newborn cCMV screening programs is warranted.

Background: Cytomegalovirus infection is the most common perinatal viral infection that can lead to severe long-term medical conditions. Antenatal identification of maternal cytomegalovirus infections with proven fetal transmission and potential postnatal clinical sequelae remains a major challenge in perinatology. There is a need to improve the prenatal counseling offered to patients and guide future clinical management decisions in cases of proven primary cytomegalovirus infection., Objective: We sought to evaluate the accuracy of fetal ultrasound for predicting sequelae in fetuses infected with congenital cytomegalovirus after maternal primary infection., Study Design: We conducted a prospective observational study from 1996 through 2012 in pregnant women with serological evidence of primary cytomegalovirus infection and proven vertical transmission to the fetus, based on viral load in the amniotic fluid. Fetal ultrasound was performed in all patients. Pregnancy termination was presented as an option for infected fetuses. Hearing and neurological clinical assessments were performed for all neonates with cytomegalovirus-positive urine samples., Results: A total of 67 patients (69 fetuses) with proven vertical transmission were included in this study, including 64 singleton and 3 twin pregnancies. Eight fetuses were lost to follow-up. Of the remaining 61 fetuses, termination of the pregnancy was performed for 26, including 11 with fetal ultrasound anomalies. Autopsy provided histological evidence of fetal cytomegalovirus infection in all cases. In the 15 terminated fetuses without ultrasound anomalies, histological evidence of damage caused by fetal infection was detected in 13 cases. Among the 35 live-born infants, 12 had fetal ultrasound anomalies suggestive of congenital infection. Of these 12 infants, 6 had normal clinical evaluations, whereas 6 presented with either hearing and/or neurological anomalies, classified as severe in 4 cases. Among the 23 live-born infants with normal prenatal ultrasound, 5 developed hearing impairments and 1 showed mild neurological developmental delay., Conclusion: Fetal ultrasound anomalies were detected in 37.7% of pregnant women with primary cytomegalovirus infection acquired in early pregnancy and proven fetal infection, and were confirmed by autopsy or postnatal clinical evaluation in 73.9%. Autopsy or postnatal clinical evaluation also detected cytomegalovirus-related anomalies in 55% of infants with normal fetal ultrasound evaluations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Congenital infection with Zika virus causes microcephaly and other brain abnormalities (1). Hearing loss associated with other congenital viral infections is well described; however, little is known about hearing loss in infants with congenital Zika virus infection. A retrospective assessment of a series of 70 infants aged 0-10 months with microcephaly and laboratory evidence of Zika virus infection was conducted by the Hospital Agamenon Magalhães in Brazil and partners. The infants were enrolled during November 2015-May 2016 and had screening and diagnostic hearing tests. Five (7%) infants had sensorineural hearing loss, all of whom had severe microcephaly; however, one child was tested after receiving treatment with an ototoxic antibiotic. If this child is excluded, the prevalence of sensorineural hearing loss was 5.8% (four of 69), which is similar to that seen in association with other congenital viral infections. Additional information is needed to understand the prevalence and spectrum of hearing loss in children with congenital Zika virus infection; all infants born to women with evidence of Zika virus infection during pregnancy should have their hearing tested, including infants who appear normal at birth.

Background: Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy., Objective: We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection., Study Design: We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination., Results: In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P = .001, and P = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively., Conclusion: Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients with herpes zoster oticus (HZO) may exhibit diverse symptoms regarding cochleovestibular dysfunction. This study investigated the clinical manifestations of HZO by comparing symptoms associated with dysfunctions of the 7th and 8th cranial nerves (CN VII and VIII, respectively). This study is a retrospective case series. Eighty-one patients with HZO who had dysfunction of CN VII or VIII were included in this study. Electroneuronography (ENoG) values were compared among patient groups with facial weakness. Patients with ipsilateral facial weakness (62 of 81) were more common than those without. Among 81 patients, those with facial weakness, hearing loss, and vertigo were most common, and only 1 patient had vertigo without hearing loss or facial weakness. Most patients with vertigo also had hearing loss (28 of 30), and patients without hearing loss did not have vertigo (19 of 21). While patients with vertigo had worse ENoG values than those without vertigo, ENoG values were not significantly different between patients with and without hearing loss. In conclusion, various clinical manifestations of CN VII and VIII dysfunction are possible in patients with HZO. Patients with vertigo had worse ENoG values than those without, which may indicate that vertigo reflects more severe facial nerve degeneration in HZO patients with facial weakness.

Objective: To analyze speech in children with profound hearing loss following congenital cytomegalovirus (cCMV) infection with cochlear implantation (CI) before the age of 3 years., Material and Methods: In a cohort of 15 children with profound hearing loss, speech perception, production and intelligibility were assessed before and 3 years after CI; variables impacting results were explored., Results: Post-CI, median word recognition was 74% on closed-list and 48% on open-list testing; 80% of children acquired speech production; and 60% were intelligible for all listeners or listeners attentive to lip-reading and/or aware of the child's hearing loss. Univariate analysis identified 3 variables (mean post-CI hearing threshold, bilateral vestibular areflexia, and brain abnormality on MRI) with significant negative impact on the development of speech perception, production and intelligibility., Conclusion: CI showed positive impact on hearing and speech in children with post-cCMV profound hearing loss. Our study demonstrated the key role of maximizing post-CI hearing gain. A few children had insufficient progress, especially in case of bilateral vestibular areflexia and/or brain abnormality on MRI. This led us to suggest that balance rehabilitation and speech therapy should be intensified in such cases., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: In this study, we estimate an ex ante cost-benefit analysis of a Utah law directed at improving early cytomegalovirus (CMV) detection., Study Design: We use a differential cost of treatment analysis for publicly insured CMV-infected infants detected by a statewide hearing-directed CMV screening program., Methods: Utah government administrative data and multi-hospital accounting data are used to estimate and compare costs and benefits for the Utah infant population., Results: If antiviral treatment succeeds in mitigating hearing loss for one infant per year, the public savings will offset the public costs incurred by screening and treatment. If antiviral treatment is not successful, the program represents a net cost, but may still have non-monetary benefits such as accelerated achievement of diagnostic milestones., Conclusions: The CMV education and treatment program costs are modest and show potential for significant cost savings., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives/hypothesis: Gene therapy offers the possibility of delivering corrective genetic materials to the cochlea, potentially improving hearing. In animals, the most commonly used surgical methods for viral gene therapy delivery to the cochlea are the round window and the cochleostomy approaches. However, the patterns of viral infection and the effects on hearing have not been directly compared between these two approaches. In this study, we compare the patterns of cochlear infection and effects on hearing between these two surgical approaches using adeno-associated virus serotype 2/8 (AAV8) as the gene delivery vehicle., Study Design: Animal study and basic science research., Methods: One- to two-month-old CBA/J mice were used in this study. AAV8-green fluorescent protein (GFP) was delivered to the cochlea by either the round window or the cochleostomy approach (described below). Auditory brainstem response was used to examine hearing thresholds before and after surgery. Animals were examined at 1, 2, 3, and 4 weeks after surgery for the patterns of cochlear infection and hearing loss., Results: Cochlear gene transfer was successful through both surgical approaches. In both approaches, AAV8-GFP mostly infected the inner hair cells. There was occasional low-level infection of the outer hair cells and supporting cells. The two surgical approaches resulted in comparable viral infection efficiencies. The round window approach resulted in less surgical trauma, as indicated by hearing loss, than the cochleostomy approach., Conclusions: Adeno-associated virus-mediated gene transfer to the cochlea can be accomplished using either the round window or the cochleostomy surgical approach. The round window approach resulted in less hearing loss compared to the cochleostomy approach., Level of Evidence: NA., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Conclusions: Murine congenital cytomegalovirus (CMV) (MCMV) infection of the inner ear cochlea, which caused continuous pathological change, occurred on the third day after intracerebral injection and persisted for a very long time., Objective: Our study used the MCMV-induced hearing loss neonatal mouse model to investigate the pathological changes of the cochlea in different time windows., Methods: Sixty newborn BALB/c mice were randomly and equally divided into the experimental group (MCMV intracerebral injection) and control group (normal saline intracerebral injection). At 1, 3, 5, 7, and 21 days after intracerebral injection, cochleas were extracted and evaluated by MCMV-DNA PCR analysis and histopathological examination., Results: Two mice died before the end of the experiment in the experimental group, while there were no deaths in the control group. In the experimental group, the MCMV-DNA PCR samples did not show positive results in the gel electrophoresis until the 3-21 days after intracerebral injection, while no positive result was found in the control group. Pathological changes including hemorrhage and inflammatory cell infiltration of the scala vestibule and scala tympani began on the third day, spiral ganglion cell gap widening and cell thinning began on the seventh day, and scala tympani fibrosis began on the 14th day.

Congenital human cytomegalovirus (HCMV) occurs in 0.5-1% of live births and approximately 10% of infected infants develop hearing loss. The mechanism(s) of hearing loss remain unknown. We developed a murine model of CMV induced hearing loss in which murine cytomegalovirus (MCMV) infection of newborn mice leads to hematogenous spread of virus to the inner ear, induction of inflammatory responses, and hearing loss. Characteristics of the hearing loss described in infants with congenital HCMV infection were observed including, delayed onset, progressive hearing loss, and unilateral hearing loss in this model and, these characteristics were viral inoculum dependent. Viral antigens were present in the inner ear as were CD(3+) mononuclear cells in the spiral ganglion and stria vascularis. Spiral ganglion neuron density was decreased after infection, thus providing a mechanism for hearing loss. The lack of significant inner ear histopathology and persistence of inflammation in cochlea of mice with hearing loss raised the possibility that inflammation was a major component of the mechanism(s) of hearing loss in MCMV infected mice.

Auricular pruritus coexisted with multiple cranial nerve lesions in Ramsay Hunt syndrome has been rarely reported in the literature especially its treatment. However, auricular pruritus cannot be better improved along with the improvement of multiple cranial nerve lesions. We tried to solve the problem with acupuncture and got experience from it. The following 2 cases of Ramsay Hunt syndrome show a potential modality for the treatment of auricular pruritus with acupuncture.

Aim: Although cytomegalovirus (CMV) is the most common congenital infection, existing research has not provided us with a full picture of how this can affect children in the future. The aim of this case-control study was to evaluate disabilities in a well-defined group of children with congenital cytomegalovirus (CMV) infection, who had been fitted with cochlear implants because of severe hearing impairment., Methods: A multidisciplinary team assessed 26 children with congenital CMV infection for balance difficulties, neurodevelopmental disabilities and language and visual impairment. We also included a control group of 13 children with severe hearing impairment due to connexin 26 mutations., Results: The majority of the children with congenital CMV infection (88%) displayed balance disturbances, including walking at a later age, but there were no cases in the control group. The CMV group also displayed frequent neurodevelopmental disabilities and feeding difficulties., Conclusion: Congenital CMV infection affects the general development of the brain and gives rise to a complex pattern of difficulties. Identifying comorbid conditions is very important, as children with associated difficulties and disabilities need more support than children with just hearing impairment. Congenital CMV infection needs to be considered in children with hearing impairment and/or balance disturbance and/or neurodevelopmental disabilities., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Cytomegalovirus (CMV) is a leading cause of congenital infection and a leading infectious cause of hearing loss in children. The ORF UL75 gene encodes envelope glycoprotein H (gH), which is essential for CMV entry into host cells and the target of the immune response in humans. However, the distribution of gH variants and the relationship between the viral genotype, viral load, and sequelae in children infected with CMV is debated. The UL75 genetic variation of CMV isolates from 42 newborns infected congenitally with CMV and 93 infants with postnatal or unproven congenital CMV infection was analyzed. Genotyping was performed by analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. There were no differences in the distribution of gH genotypes in the children infected congenitally and postnatally. Mixed-genotype infections with both gH1 and gH2 variants were detected in approximately 25% of the examined patients. No relationship between UL75 gene polymorphisms and the symptoms at birth was observed. The results suggest that the infection with gH2 genotype diminishes the risk of hearing loss in children (P = 0.010). In addition, sensorineural hearing loss was associated with CMV gH1 genotype infection in infants (P = 0.032) and a high viral load in urine (P = 0.005). In conclusion, it was found that the gH genotype does not predict clinical sequelae in newborn infants following congenital CMV infection. However, these results suggest that the gH genotype might be associated with hearing loss in children., (© 2014 Wiley Periodicals, Inc.)

A number of viral infections can cause hearing loss. Hearing loss induced by these viruses can be congenital or acquired, unilateral or bilateral. Certain viral infections can directly damage inner ear structures, others can induce inflammatory responses which then cause this damage, and still others can increase susceptibility or bacterial or fungal infection, leading to hearing loss. Typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing losses can be seen following infection with certain viruses. Occasionally, recovery of hearing after these infections can occur spontaneously. Most importantly, some of these viral infections can be prevented or treated. For many of these viruses, guidelines for their treatment or prevention have recently been revised. In this review, we outline many of the viruses that cause hearing loss, their epidemiology, course, prevention, and treatment., (© The Author(s) 2014.)

Objective: Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. This study aims to investigate the pathogenesis CMV-induced hearing loss from the view of integrity of blood-labyrinth-barrier (BLB)., Methods: Newborn BALB/c mice were randomly divided into three groups (n=22, respectively): CMV group, control group and normal group. The CMV group and control group were intracerebrally injected with equal volume (15 μl) of murine CMV (MCMV; 10(4)IU/0.1 ml) and PBS, respectively, and normal group did not receive any treatment. After three weeks, auditory-evoked brainstem response was assessed, and permeability of BLB was evaluated by Evans blue method. Means between groups were compared using t-test., Results: We observed that mice injected with MCMV had a hearing loss and it was connected with the permeability changes of BLB. Besides, using hematoxylin-eosin staining, we noticed hyperaemia in stria vascularis and spiral ligament and bleeding in scala vestibule and scala tympani in CMV group., Conclusion: All these data indicated the possible association between CMV-induced hearing loss and BLB dysfunction with the characteristics of inflammation. Our data provide a possible path to investigate the mechanism of CMV-induced hearing damage., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We sought to elucidate the pathogenesis of hearing loss in newborns due to congenital cytomegalovirus. We used the model of murine cytomegalovirus (MCMV) infection and evaluated concentrations of free calcium, calmodulin levels, and mitochondrial membrane potential in cochlear neurons of infected newborn mice. MCMV infection was established by intracranial inoculation of newborn mice with viral suspension (20 μl of MCMV TCID(50)--10(4) IU/0.1 ml); the mice in control group were injected 0.9 % NaCl. Concentration of intracellular free calcium concentration ([Ca(2+)] i ), mitochondrial membrane potential, and the mRNA level of calmodulin (CaM) in the cochlear neurons were evaluated, when the mice were 1 month old. Compared with control group, intracellular [Ca(2+)] i and CaM mRNA levels significantly (p < 0.05; both comparisons) increased, while the mitochondrial membrane potential significantly (p < 0.05) decreased in the MCMV-infected group. In conclusion, alteration of [Ca(2+)] i and CaM levels and mitochondrial membrane potentials in cochlear neurons may be the pathological basis of sensorineural hearing loss associated with MCMV infection.

Few adult patients with HIV/AIDS are evaluated for communication disorders. A broad inventory of the communication disorders was obtained in a convenience sample of 82 adult HIV/AIDS patients who presented for medical appointments. Each participant underwent a head and neck exam and a communications skills evaluation. Speech, language, and cognition were assessed using a 10-item test battery. A 14-item hearing test battery was conducted in a separate session. The primary outcomes were the presence and degree of communication disorders. Head and neck exams revealed 40% with ear-related issues. Only 2 participants showed normal findings on all 24 communication skills assessments. Four demonstrated normal findings on all speech-language-cognitive assessments, whereas 8 had normal findings on the complete hearing test battery. A relatively high prevalence of cognitive and language deficits and central auditory disturbances were found. Clinicians must recognize the potential for communication deficits even in a relatively healthy patient with HIV.

Objective: To evaluate the audiological outcome of children with congenital cytomegalovirus infection., Methodology: In a prospective study, the hearing of 98 congenitally cytomegalovirus-infected children born between January 2003 and July 2009 was systematically evaluated until the age of six using the Flemish CMV protocol. Symptomatic children with hearing loss at birth were treated with ganciclovir, if parents consented., Results: Seventy children passed initial screening, 28 had unilateral or bilateral hearing loss. In the normal hearing group, one asymptomatic and two symptomatic children developed late-onset hearing loss. Eight children in the group with hearing loss at birth received ganciclovir. Nine symptomatic and 11 asymptomatic children did not receive ganciclovir. In the treated group, 37.5% of the children had stable hearing loss, and 37.5% had progressive and/or fluctuating hearing loss. First progression or fluctuation always occurred after the age of one year. The hearing threshold improved in 25.0%. The improvement took place during or shortly after treatment. Hearing loss remained stable in 33.3% of the untreated symptomatic children, while progression or fluctuation occurred in 55.5%. In the asymptomatic group, hearing loss was most commonly stable (63.6%). The first change in the hearing threshold was almost always detected before the age of one year in both untreated groups., Conclusions: Hearing loss caused by congenital cytomegalovirus infection cannot be defined unequivocally either with respect to the level of hearing loss or its evolution over time. Treating symptomatic children with ganciclovir leads to a better prognosis during the first year of life, after which progression or fluctuation again becomes more likely. However, overall, progression is more common in the untreated symptomatic group. Asymptomatic children with SNHL are more likely to have a stable hearing status.

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Background: Little is known about hearing loss in children with HIV infection (HIV+). We examined the prevalence of hearing loss in perinatally HIV+ and HIV-exposed but uninfected (HEU) children, compared these with the percentage with hearing loss in the general population and evaluated possible risk factors for hearing loss in HIV+ and HEU children., Methods: Audiometric examinations were completed in children who met any prespecified criteria for possible hearing loss. The hearing examination consisted of a tympanogram in each ear and pure-tone air-conduction threshold testing from 500 through 4000 Hz. Hearing loss was defined as the pure-tone average over these frequencies ≥ 20 dB hearing level. The associations of demographic variables, parent/caregiver, HIV disease and HIV treatment with hearing loss were evaluated with univariate and multivariable logistic regression models., Results: Hearing testing was completed in 231 children (145 HIV+ and 86 HEU). Hearing loss occurred in 20.0% of HIV+ children and 10.5% of HEU children. After adjusting for caregiver education level, HIV infection was associated with increased odds of hearing loss (adjusted odds ratio = 2.13, 95% confidence interval: 0.95-4.76, P = 0.07). Among HIV+ children, those with a Centers for Disease Control and Prevention class C diagnosis had over twice the odds of hearing loss (adjusted odds ratio = 2.47, 95% confidence interval: 1.04-5.87, P = 0.04). The prevalence of hearing loss was higher in both HIV+ and HEU children compared with National Health and Nutrition Examination Survey III children., Conclusions: Hearing loss was more common in both HIV+ and HEU children than in children from a US population sample. More advanced HIV illness increased the risk of hearing loss in HIV+ children.

Background: Primary cytomegalovirus (CMV) infection early in gestation causes severe disease., Methods: Case patients were 32 congenitally infected children aged 1-5 years who had either hearing deficit and/or psychomotor retardation and whose mothers had a confirmed or probable primary CMV infection at ≤ 20 weeks' gestation. Control subjects were 32 congenitally infected normal children whose mothers had a confirmed primary infection at ≤ 20 weeks' gestation. Case patients and control subjects were matched by the weeks of maternal gestation (± 1 week) at the mother's infection and by the child's age (± 1 year) at evaluation., Results: For the case patients and control subjects, the mean age was 3.0 years. The mean number of weeks of gestation at maternal infection was 11 weeks. The only risk factor for an affected child was the mother not receiving immunoglobulin (P = .001). Of the 32 case patients, only 4 mothers received CMV immunoglobulin, compared with 27 of the 32 mothers of control infants (adjusted odds ratio, 14 [95% confidence interval, 1.7-110]). The rate of both psychomotor retardation and hearing deficit decreased with immunoglobulin., Conclusions: These results support the efficacy of immunoglobulins for decreasing the severity of disabilities caused by fetal CMV infection after a primary maternal infection during pregnancy.