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1.
Nat Commun ; 11(1): 3548, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669541

RESUMO

Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.


Assuntos
Infecções por Citomegalovirus/sangue , Citomegalovirus/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Perda Auditiva Neurossensorial/epidemiologia , Infecções Assintomáticas , Biomarcadores/sangue , Estudos de Casos e Controles , Pré-Escolar , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Feminino , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Neurossensorial/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Transcriptoma/genética
2.
Int J Infect Dis ; 98: 150-152, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32615325

RESUMO

Ganciclovir and its prodrug valganciclovir are elective treatments for cCMV. Neonates with important symptoms undergo 6 months of therapy to ameliorate/prevent symptoms and late sequelae, but evidence of resistance is emerging. Over the last 5 years, we took care of 59 cCMV infants and experienced two cases of resistance among nine cCMV infants receiving long-term valganciclovir therapy. In the first case, valganciclovir therapy was prolonged beyond 6 months due to severity of symptoms, control of viral load, and absence of adverse events. Resistance was detected in the 8th month of therapy. In the second case, after a significant reduction following valganciclovir administration and no adverse events, CMV viral load suddenly increased in the 6th month of therapy due to resistance. Both events were associated with UL97 gene mutation. The cCMV infants, affected by severe symptoms, remained in a steady state during treatment, and their later neurological development was coherent with initial seriousness of diagnosis. Prolonged therapeutic exposure may therefore be a risk for resistance, suggesting that constant dosage/weight adjustments, monthly surveillance of viral load, and therapeutic drug monitoring could be proposed to monitor resistance onset and optimize the therapy regime. The risk-benefit ratio for long-term therapy, including the possibility of resistance onset, alongside SNHL and neurodevelopmental improvement, should also be evaluated.


Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Doenças do Recém-Nascido/tratamento farmacológico , Valganciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Citomegalovirus/genética , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Farmacorresistência Viral , Feminino , Ganciclovir/uso terapêutico , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/virologia , Masculino , Mutação , Carga Viral/efeitos dos fármacos
3.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32591436

RESUMO

Congenital cytomegalovirus (cCMV) is the most common congenital infection and is associated with sensorineural hearing loss, developmental delays, and visual impairment. The clinical presentation of cCMV is variable, and the majority (80%-90%) of newborns will never manifest any clinical symptoms. Given the clinical heterogeneity of cCMV infection, it is challenging to identify which newborns may benefit from testing. Recently, certain states have implemented a targeted screening program in which newborns who fail the newborn hearing screen are tested for cCMV. Clinicians and legislative bodies have been propelled into debates about the ethical and moral permissibility of a targeted cCMV screening approach. Those who oppose this screening approach describe undue burden on patients, families, and the health care system because the majority of newborns who fail the newborn hearing screen and have cCMV will not go on to have any sequelae related to cCMV, including hearing loss. However, those who support this screening approach cite the importance of early detection and ongoing surveillance for hearing loss and developmental delays in this high-risk group of newborns. This debate will be considered by experts in the field.


Assuntos
Infecções por Citomegalovirus/congênito , Diagnóstico Precoce , Perda Auditiva Neurossensorial/diagnóstico , Triagem Neonatal/métodos , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Testes Auditivos/métodos , Humanos , Recém-Nascido
4.
Int J Pediatr Otorhinolaryngol ; 134: 110055, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361556

RESUMO

Since 2013, after Utah became the first state to implement hearing targeted early CMV screening, a national debate has been percolating about whether this approach should be introduced nationally. Currently Utah, Iowa, Connecticut, and New York have passed legislation mandating early CMV screening, and over 100 birth hospitals across the United States have voluntarily implemented early CMV screening programs as part of their standard of care. We reviewed the evidence related to this approach and used the Wilson and Jungner (1968) criteria to evaluate this method of screening. Based on these criteria, there is substantial rationale and evidence to support a hearing targeted approach to screen for congenital CMV. Given this evidence, we currently recommend that infants who fail newborn hearing screen should undergo CMV screening.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Perda Auditiva Neurossensorial/virologia , Triagem Neonatal , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Perda Auditiva Neurossensorial/diagnóstico , Testes Auditivos , Humanos , Lactente , Recém-Nascido
5.
Trop Doct ; 50(3): 282-284, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437297

RESUMO

We retrospectively analysed the records of nine infants with polymerase chain reaction proven congenital cytomegalovirus (CMV) infection, of which 66% were born preterm. Microcephaly was a universal finding, followed by hepatosplenomegaly in 89%, while chorioretinitis was seen in only 44% cases. The mean age at diagnosis was 3.5 months. Neuroimaging was abnormal in 78%, with ventriculomegaly being the most common finding followed by T2/FLAIR white matter abnormalities, periventricular cysts and intracranial haemorrhage.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/patologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Estudos Retrospectivos , Centros de Atenção Terciária
6.
Int J Pediatr Otorhinolaryngol ; 134: 110043, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305661

RESUMO

INTRODUCTION: Congenital sensorineural hearing loss is a heterogeneous disorder; its etiological profile varies between populations. Pathogenic variants of GJB2 gene are the major cause of non-syndromic hearing loss. Congenital cytomegalovirus infection (cCMV) is the most important prenatal etiological factor causing hearing loss and other disorders. Perinatal events, syndromes, postnatal infections or traumas are less common. Causes of the remaining one third of hearing loss cases are unknown. OBJECTIVES: To determine the etiological profile of hearing loss in pediatric cochlear implant users in Lithuanian population. METHODS: The data of 122 children (70 male/52 female; aged 7.6 ± 3.3 years) cochlear implant users were analysed. Medical records of all children recruited in Santaros Clinics (Vilnius, Lithuania) were analysed to identify prenatal, perinatal, or postnatal risk factors based on the adapted list proposed by the Joint Committee of Infant Hearing. Genetic counselling and testing according to the scheme were performed to 101 children. DNA of 117 children was extracted from the DBS on Guthrie cards and CMV DNA detected using real time PCR. RESULTS: Non-syndromic hearing loss was diagnosed in 65 cases (53.3%), 58 of which were GJB2 gene-associated; syndromic hearing loss was diagnosed to 8 children (6.6%). Perinatal (prematurity, low birth weight, hypoxia, hyperbilirubinemia, sepsis, ototoxicity, and meningitis) and postnatal (meningitis) risk factors were associated with hearing loss in 16 (13.1%) and 4 (3.3%) study participants respectively. CMV DNA was detected in 12 samples (9.8%). The cause of hearing loss remained unknown only for 17 (13.9%) children. CONCLUSIONS: The major cause of HL in the current study was GJB2 gene alterations. Only 14% of the cohort had congenital hearing loss of unknown origin.


Assuntos
Implante Coclear , Conexinas/genética , Infecções por Citomegalovirus/complicações , Surdez/etiologia , Perda Auditiva Neurossensorial/etiologia , Adolescente , Criança , Pré-Escolar , Implantes Cocleares , Estudos de Coortes , Infecções por Citomegalovirus/congênito , Surdez/genética , Surdez/reabilitação , Feminino , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/reabilitação , Humanos , Hiperbilirrubinemia Neonatal/complicações , Hipóxia/complicações , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Lituânia , Masculino , Meningite/complicações , Sepse Neonatal/complicações
7.
J Infect Chemother ; 26(8): 790-794, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32273174

RESUMO

OBJECTIVES: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae. METHODS: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age. RESULTS: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment. CONCLUSIONS: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/urina , Citomegalovirus/isolamento & purificação , Triagem Neonatal/métodos , Antivirais/administração & dosagem , Estudos de Coortes , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/tratamento farmacológico , DNA Viral/urina , Humanos , Recém-Nascido , Estudos Prospectivos , Resultado do Tratamento , Urina/virologia , Valganciclovir/administração & dosagem
8.
Int J Pediatr Otorhinolaryngol ; 133: 110007, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32208178

RESUMO

OBJECTIVE: To determine whether a community engagement approach can provide feedback for implementation of valuable measures to improve the outcome of a clinical trial. METHODS: Review of the results from a Community Engagement Studio (CE Studio) for the ValEAR trial: an NIH-funded, multi-institutional study designed to research the efficacy of valganciclovir in the treatment of congenital cytomegalovirus (cCMV)-induced hearing loss. Participants were given information about the trial then asked a series of questions to assess their input on the merits or weaknesses affecting their participation in the trial. RESULTS: Thirteen parents whose children have congenital CMV infection were recruited for the CE Studio. The overall theme from the responses was a desire to advance the field but a need to clearly understand the risks and benefits of participation. Many requested more educational resources, more printed materials, or greater access to researchers if questions arose. Many welcomed having patient stories and information displayed in a dedicated website or through social media. CONCLUSION: This community engagement approach provided useful feedback from families similar to those expected to be potential enrollees in the CMV ValEAR trial. In response to parental comments, two educational videos were created: one on the general topic of cCMV and the other specific to the CMV ValEAR trial. Researchers who wish to optimize their clinical trial's success should consider incorporating a CE Studio into their study design.


Assuntos
Participação do Paciente , Seleção de Pacientes , Antivirais/uso terapêutico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/tratamento farmacológico , Retroalimentação , Feminino , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/virologia , Humanos , Masculino , Estudos Multicêntricos como Assunto , Pais , Educação de Pacientes como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Participação dos Interessados , Valganciclovir/uso terapêutico
9.
Infection ; 48(3): 463-469, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32125680

RESUMO

Treatment of congenital cytomegalovirus infection is mandatory in cases with severe systemic and/or neurological involvement. However, some patients are paucisymptomatic, with very subtle systemic manifestations and/or minimal brain alterations. Current international guidelines do not clearly state whether these children should be treated, and this decision is not straightforward for clinicians. Of a small series of six infants with congenital cytomegalovirus infection admitted to our neonatal unit between 2015 and 2019, half showed paucisymptomatic neurological manifestations. In these cases, the determination of ß2-microglobulin in cerebrospinal fluid and magnetic resonance imaging aided in the decision-making concerning the therapeutic approach to follow.


Assuntos
Encéfalo/diagnóstico por imagem , Infecções por Citomegalovirus/diagnóstico , Microglobulina beta-2/líquido cefalorraquidiano , Antivirais/uso terapêutico , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico por imagem , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Espanha , Valganciclovir/uso terapêutico
10.
Medicine (Baltimore) ; 99(10): e19419, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150093

RESUMO

Although early detection and intervention may improve the outcome of the congenital cytomegalovirus (cCMV) infection, few studies assessed the real-world clinical practice for cCMV patients. We analyzed medical claims data to assess the patterns of diagnoses and medical care for cCMV patients.We used a subset of medical claims database (JMDC Claims Database) in Japan, covering 207,547 newborns between April 2010 and March 2017 and observed for at least 6 months. The diagnosis of cCMV and related symptoms and sequelae and medical care, including essential examinations and antiviral treatment, were identified using standardized codes.Overall, we identified 53 (25.5 per 100,000 newborns) cCMV patients diagnosed within 6 months after birth; of these, 83% were diagnosed within 1 month and 68% had at least 1 cCMV-related symptom at birth. Objective hearing tests and fundus examinations were performed within 6 months in 60% and 30% of patients, respectively. Antivirals were prescribed in 26% of patients. During the observation period (median = 33 months), sensorineural hearing loss (49%) and developmental problems (28%) were commonly identified as cCMV-related sequelae. The proportions of the patients continuously followed up with objective hearing tests up to 36 months were 30% in total and 56% in antiviral-treated patients, respectively.The cCMV patients did not necessarily receive a timely diagnosis nor continuous follow-ups in usual clinical practice. Although the universal screening for cCMV may, if implemented, facilitate early diagnosis, it should be accompanied by strategic follow-up plans to support timely interventions.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Triagem Neonatal , Antivirais/uso terapêutico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/tratamento farmacológico , Bases de Dados Factuais , Diagnóstico Precoce , Feminino , Perda Auditiva Neurossensorial/complicações , Humanos , Recém-Nascido , Revisão da Utilização de Seguros/estatística & dados numéricos , Japão , Masculino
12.
Am J Obstet Gynecol ; 223(3): 330-349, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32105678

RESUMO

Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. Congenital cytomegalovirus can follow maternal primary infection or nonprimary infection. Sensorineurological morbidity is confined to the first trimester with up to 40-50% of infected neonates developing sequelae after first-trimester primary infection. Serological testing before 14 weeks is critical to identify primary infection within 3 months around conception but is not informative in women already immune before pregnancy. In Europe and the United States, primary infection in the first trimester are mainly seen in young parous women with a previous child younger than 3 years. Congenital cytomegalovirus should be evoked on prenatal ultrasound when the fetus is small for gestation and shows echogenic bowel, effusions, or any cerebral anomaly. Although the sensitivity of routine ultrasound in predicting neonatal symptoms is around 25%, serial targeted ultrasound and magnetic resonance imaging of known infected fetuses show greater than 95% sensitivity for brain anomalies. Fetal diagnosis is done by amniocentesis from 17 weeks. Prevention consists of both parents avoiding contact with body fluids from infected individuals, especially toddlers, from before conception until 14 weeks. Candidate vaccines failed to provide more than 75% protection for >2 years in preventing cytomegalovirus infection. Medical therapies such as cytomegalovirus hyperimmune globulins aim to reduce the risk of vertical transmission but 2 randomized controlled trials have not found any benefit. Valaciclovir given from the diagnosis of primary infection up to amniocentesis decreased vertical transmission rates from 29.8% to 11.1% in the treatment group in a randomized controlled trial of 90 pregnant women. In a phase II open-label trial, oral valaciclovir (8 g/d) given to pregnant women with a mildly symptomatic fetus was associated with a higher chance of delivering an asymptomatic neonate (82%), compared with an untreated historical cohort (43%). Valganciclovir given to symptomatic neonates is likely to improve hearing and neurological symptoms, the extent of which and the duration of treatment are still debated. In conclusion, congenital cytomegalovirus infection is a public health challenge. In view of recent knowledge on diagnosis and pre- and postnatal management, health care providers should reevaluate screening programs in early pregnancy and at birth.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/transmissão , Complicações Infecciosas na Gravidez/virologia , Infecções por Citomegalovirus/complicações , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/epidemiologia , Doenças Fetais/virologia , Perda Auditiva Neurossensorial/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Imagem por Ressonância Magnética , Doenças do Sistema Nervoso/virologia , Cuidado Pré-Concepcional , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Testes Sorológicos , Ultrassonografia Pré-Natal , Valaciclovir/administração & dosagem
13.
Mikrobiyol Bul ; 54(1): 171-190, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050888

RESUMO

Human cytomegalovirus (CMV) infections are common in all populations and CMV seroprevalence in women of childbearing age is in the range of 45-100% worldwide. CMV is the most common cause of congenital infections and is associated with fetal development defects and hearing loss. The risk of congenital infection is directly related to maternal immunity and is between 30-40% and 1-2% range in primary and non-primary infections, respectively. Only 5-10% of newborns with congenital infection are symptomatic at birth. Nearly 4% of these babies can die early in life, while 40-60% have to live with permanent sequelae such as sensorineural hearing loss, cognitive deficit and visual impairment. Asymptomatic newborns including those born from mothers with non-primary infections are also at risk for long-term sequelae. These sequelae often develop in the first 1-2 years of life and may extend up to 5-7 years, but the severity of damage reduces in time. CMV seroprevalence in women of childbearing age and pregnant women in Turkey is between 96% and 99.8%. Until recently, our knowledge about the frequency of congenital CMV infections in Turkey was derived from the studies based on the maternal screening tests. These studies, which were far from reflecting the true prevalence of congenital CMV infections, have begun to be replaced by newborn-based systematic screening studies. CMV DNA positivity was found to be 1.6-1.9% in saliva samples, while both saliva and urine and/or blood samples positivity was found to be 0.2-1.4% in the newborn screening studies carried out in Turkey. Glycoprotein B-1 (gB1) was the most frequently detected genotype (38.4-83.3%) in newborns in Turkey. Standard measures and preventive public health practices such as education of the mother, reducing the contact of pregnant women with virus-spreading children and the hand hygiene come into prominence in the prevention of maternal and congenital infections as a result of the absence of an approved vaccine or low protection of existing vaccines. Advanced measures, such as screening blood products especially for the people with immunodeficiency and serological screening of the in-vitro fertilization applications are also being considered. Monitoring of infected newborns and their mothers during pregnancy, postnatal diagnosis and providing counseling for the parents are also critical. Hearing loss can be detected at an early stage using screening tests that become a routine practice for all newborns. Thus, cognitive and psychosocial development of children affected by infection is supported by speech therapy, the use of hearing aids and other practices. However, it should be noted that hearing functions in infected newborns may be normal at birth, but these newborns are at risk for progressive sensorineural hearing loss. For early diagnosis of asymptomatic newborns, it is important to adopt CMV tests as a part of newborn screening programs. Another preventive approach is to treat the mother and the baby with antiviral drugs and preparations that directly target the virus. Passive immunization of the pregnant and the treatment of the symptomatic newborns with valganciclovir have yielded positive results. In this review article, maternal, fetal and newborn based current approaches used in the diagnosis and follow-up of congenital CMV infections have been discussed.


Assuntos
Infecções por Citomegalovirus , Criança , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/terapia , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/epidemiologia , Humanos , Recém-Nascido , Triagem Neonatal , Gravidez , Estudos Soroepidemiológicos , Turquia/epidemiologia
14.
Rev Med Suisse ; 16(682): 361-364, 2020 Feb 19.
Artigo em Francês | MEDLINE | ID: mdl-32073771

RESUMO

Epidemiological trends in congenital toxoplasmosis and CMV are extremely divergent. While there were only 39 cases of congenital toxoplasmosis in Switzerland between 1982 and 2015, there was an equivalent number of cases of congenital CMV, 38 in total, in 2017 alone. Serological screening for toxoplasmosis was logically abandoned in Switzerland in 2008. Regarding CMV, there is no recommendation for serological screening or neonatal screening in Switzerland, whereas early diagnosis can improve prognosis through the rapid initiation of antiviral treatment. The epidemiological data generated by sentinel surveillance of congenital CMV infections in Switzerland may or may not justify such a measure in our country in the future.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/epidemiologia , Toxoplasmose Congênita/epidemiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Diagnóstico Precoce , Humanos , Recém-Nascido , Triagem Neonatal , Suíça/epidemiologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/tratamento farmacológico
15.
Ital J Pediatr ; 46(1): 3, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906974

RESUMO

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth. Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection. METHODS: We retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral "pass" otoacustic emissions (OAE). None of them underwent antiviral therapy. Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold. RESULTS: In our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5-60 months). CONCLUSION: A delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.


Assuntos
Infecções por Citomegalovirus/congênito , Perda Auditiva Central/virologia , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva Neurossensorial/virologia , Testes Auditivos , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Triagem Neonatal , Estudos Retrospectivos
16.
J Pediatr ; 218: 151-156.e2, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31952844

RESUMO

OBJECTIVES: To understand caregiver knowledge of and attitudes toward congenital cytomegalovirus (cCMV) testing in Utah. STUDY DESIGN: We surveyed 365 caregivers whose children were being seen in an otolaryngology clinic at a tertiary pediatric hospital about their knowledge of and attitudes toward cCMV and cCMV screening. Descriptive statistics and cluster analysis were used to examine their responses. RESULTS: The majority of caregivers were unsure how cCMV was spread, the symptoms of cCMV, and why cCMV screening of infants was important. Most caregivers did not know that cCMV screening was required by law in Utah if an infant is referred after newborn hearing screening. A majority wanted to know if their child had cCMV even if asymptomatic and were willing to pay $20 for cCMV screening. Caregivers of children who had been tested for cCMV were significantly more likely to be strongly in favor of cCMV screening than expected by chance. Caregivers in the highly knowledgeable cluster were more likely to be strongly in favor of cCMV screening. CONCLUSIONS: Caregivers frequently were unaware of cCMV and its implications. Attitudes toward cCMV screening generally were positive. Education on epidemiology and impact of cCMV may benefit both prevention of infection and attitudes toward screening.


Assuntos
Cuidadores , Infecções por Citomegalovirus/congênito , Conhecimentos, Atitudes e Prática em Saúde , Perda Auditiva Neurossensorial/diagnóstico , Triagem Neonatal , Pais , Atitude Frente a Saúde , Criança , Pré-Escolar , Estudos Transversais , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/transmissão , Feminino , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/etiologia , Testes Auditivos , Hospitais Pediátricos , Humanos , Recém-Nascido , Masculino , Educação de Pacientes como Assunto/métodos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Centros de Atenção Terciária , Utah
17.
Otolaryngol Head Neck Surg ; 162(1): 114-120, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593522

RESUMO

OBJECTIVE: To describe the progression of sensorineural hearing loss (SNHL) in the better- and poorer-hearing ears in children with asymptomatic congenital cytomegalovirus (CMV) infection with isolated SNHL. STUDY DESIGN: Longitudinal prospective cohort study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: We analyzed hearing thresholds of the better- and poorer-hearing ears of 16 CMV-infected patients with isolated congenital/early-onset or delayed-onset SNHL identified through hospital-based CMV screening of >30,000 newborns from 1982 to 1992. RESULTS: By 12 months of age, 4 of 7 patients with congenital/early-onset SNHL developed worsening thresholds in the poorer-hearing ear, and 1 had an improvement in the better-hearing ear. By 18 years of age, all 7 patients had worsening thresholds in the poorer-hearing ear and 3 patients had worsening thresholds in the better-hearing ear. Hearing loss first worsened at a mean age of 2 and 6 years in the poorer- and better-hearing ears, respectively. Nine patients were diagnosed with delayed-onset SNHL (mean age of 9 years vs 12 years for the poorer- and better-hearing ears), 6 of whom had worsening thresholds in the poorer-hearing ear and 1 in both ears. CONCLUSION: In most children with congenital CMV infection and isolated SNHL, the poorer-hearing ear worsened earlier and more precipitously than the better-hearing ear. This study suggests that monitoring individual hearing thresholds in both ears is important for appropriate interventions and future evaluation of efficacy of antiviral treatment.


Assuntos
Doenças Assintomáticas , Infecções por Citomegalovirus/congênito , Progressão da Doença , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/etiologia , Fatores Etários , Idade de Início , Limiar Auditivo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Perda Auditiva Neurossensorial/fisiopatologia , Testes Auditivos , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Monitorização Fisiológica/métodos , Triagem Neonatal/métodos , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Estados Unidos
18.
Br Med Bull ; 131(1): 5-17, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31580403

RESUMO

BACKGROUND: Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances. SOURCES OF DATA: Sources of data are recently published research papers and reviews about HCMV treatments. AREAS OF AGREEMENT: Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved by the FDA and EMA. AREAS OF CONTROVERSY: Should we screen newborns for HCMV, and use antivirals to treat sensorineural hearing loss after congenital HCMV infection? GROWING POINTS: Growing points are developing drugs against latently infected cells. In addition to small molecule inhibitors, a chemokine-based fusion toxin protein, F49A-FTP, has shown promise in killing both lytically and latently infected cells. AREAS TIMELY FOR DEVELOPING RESEARCH: We need to understand what immune responses are required to control HCMV, and how best to raise these immune responses with a vaccine.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Antivirais/farmacologia , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/imunologia , Vacinas contra Citomegalovirus , Desenvolvimento de Medicamentos , Diagnóstico Precoce , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunidade Celular/fisiologia , Imunoglobulinas/uso terapêutico , Imunossupressão/efeitos adversos , Recém-Nascido , Transplante de Órgãos/efeitos adversos , Assistência Perinatal , Latência Viral/efeitos dos fármacos
20.
Gac Med Mex ; 155(4): 336-342, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31486792

RESUMO

Introduction: Human cytomegalovirus (HCMV) is recognized as the most common cause of congenital viral infection, which can occur as a result of primary infection, reinfection or infection reactivation in the pregnant woman and be the cause of delay in neuronal development and sensorineural hearing loss in the neonate. Objective: To identify CMVH infection in newborns by real-time polymerase chain reaction (RT-PCR) and cell culture. Method: Observational, cross-sectional, retrospective study with oral swab samples from 362 neonates born within a 10-month period in a public hospital of Mérida, Yucatán. RT-PCR was carried out for the detection of HCMV. Fibroblast primary cell culture was obtained from human foreskin tissue to isolate the virus. Only positive cases were followed. Results: A prevalence of HCMV infection of 0.86 % was found by RT-PCR. No virus was isolated with cell culture. In the follow-up visits, sensory health and neurodevelopment were adequate. Conclusion: The prevalence of HCMV infection is similar to that of worldwide reports, and only was detected by RT-PCR. Asymptomatic infection detected 12-14 h after birth had no long-term health consequences.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/isolamento & purificação , Doenças do Recém-Nascido/epidemiologia , Estudos Transversais , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Feminino , Hospitais Públicos , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Masculino , México , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos
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