DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands

Korver, Anna M.H.; Vries, Jutte J.C. de; Konings, Saskia; Jong, Jan Willem de; Dekker, Friedo W.; Vossen, Ann C.T.M.; Frijns, Johan H. M.; Oudesluys‐Murphy, Anne Marie

doi:10.1016/j.jcv.2009.09.007

Cited by 47 publications

(29 citation statements)

References 29 publications

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“…These children had permanent bilateral hearing impairment at the age of 3 to 5 years, since that was an inclusion criterion for participation in the DECIBEL study from which they were recruited (22). A genotype could be assigned to 7 of the 9 (78%) DBS from children with hearing impairment.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 41 DBS from newborns with congenital CMV infection were obtained from earlier studies (median CMV DNA load of 5,000 copies/ml whole blood; range, Ͻ1,000 to 800,000 copies/ml). Nine of the 41 newborns participated in the previously described DECIBEL study, which included infants with permanent bilateral hearing impairment (Ն40 dB in the better ear) at the age of 3 to 5 years (median CMV DNA load of 32,000 copies/ml whole blood) (22). Clinical data included symptoms at birth, developmental score, and severity of hearing loss.…”

Section: Plasma Samples Of Immunocompromised Patientsmentioning

confidence: 99%

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Rapid Genotyping of Cytomegalovirus in Dried Blood Spots by Multiplex Real-Time PCR Assays Targeting the Envelope Glycoprotein gB and gH Genes

et al. 2012

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Genotyping of cytomegalovirus (CMV) is useful to examine potential differences in the pathogenicity of strains and to demonstrate coinfection with multiple strains involved in CMV disease in adults and congenitally infected newborns. Studies on genotyping of CMV in dried blood spots (DBS) are rare and have been hampered by the small amount of dried blood available. In this study, two multiplex real-time PCR assays for rapid gB and gH genotyping of CMV in DBS were developed. Validation of the assays with 39 CMV-positive plasma samples of transplant recipients and 21 urine specimens of congenitally infected newborns was successful in genotyping 100% of the samples, with gB1 and gB3 being the most prevalent genotypes. Multiple gB and gH genotypes were detected in 36% and 33% of the plasma samples, respectively. One urine sample from a newborn with symptomatic congenital CMV was positive for gB1 and gB2. DBS of congenitally infected newborns (n ‫؍‬ 41) were tested using 9 l of dried blood, and genotypes were detected in 81% (gB) and 73% (gH) of the samples, with gB3 being the most prevalent genotype. No clear association of specific genotypes with clinical outcome was observed. In conclusion, the CMV gB and gH PCR assays were found to be rapid, sensitive for detecting mixed infections, and suitable for direct usage on DBS. These assays are efficient tools for genotyping of CMV in DBS of congenitally infected newborns. C ytomegalovirus (CMV) is the most common cause of congenital infection worldwide and an important viral pathogen affecting immunocompromised patients (13, 21). Both in congenitally infected newborns and in immunocompromised patients, genotyping of CMV has been used to study potential differences in pathogenicity of specific strains. However, few authors describe a correlation between specific CMV genotypes and severity of disease (29,32,34,40). More important, genotyping of CMV has enabled the discrimination of reactivation of latent virus from reinfection with new CMV strains in transplant patients, allowing a better definition of donor-to-recipient transmission patterns (24). Congenital CMV infections mainly result from recurrent infections among pregnant women (37), comprising both reactivation and reinfection. The discrimination of reactivation from reinfection may give insight into the mother-to-fetus transmission pattern and the possible associations with the outcome of congenital CMV infections.Genotyping of CMV has mainly focused on envelope glycoproteins gB (UL55) and gH (UL75), which play a role in virus entry and are major targets for neutralizing antibody response. The most frequently used methods for genotyping of CMV are nucleotide sequence analysis (27) and restriction fragment length polymorphism of PCR products (25, 28). Recently, real-time PCR-based assays have been used for rapid detection and quantification of CMV gB and gH genotypes (12,15,24,26). However, they have mainly been applied to plasma or other high-volume samples. Also, deep-sequencing-based methods, sensitive in the de...

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Section: Resultsmentioning

confidence: 99%

Section: Plasma Samples Of Immunocompromised Patientsmentioning

confidence: 99%

Rapid Genotyping of Cytomegalovirus in Dried Blood Spots by Multiplex Real-Time PCR Assays Targeting the Envelope Glycoprotein gB and gH Genes

et al. 2012

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“…23 Special attention should be paid to the habilitation of these children. Further insight into the developmental consequences of the various causes of hearing impairment will only be achieved if future studies take etiology into account.…”

Section: Commentmentioning

confidence: 99%

Newborn Hearing Screening vs Later Hearing Screening and Developmental Outcomes in Children With Permanent Childhood Hearing Impairment

Korver

Konings²,

Dekker³

et al. 2010

JAMA

188

141

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“…HCMV is also the leading cause of sensorineural hearing loss in newborns, accounting for up to 25% of all childhood deafness (5)(6)(7). In recognition of the major impact of congenital HCMV infection on pediatric health, the development of a protective maternal HCMV vaccine has remained a "top priority" of the National Academy of Medicine for the past 15 years (8)(9)(10).…”

mentioning

confidence: 99%

Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission

Fan

Nelson

Bialas

et al. 2017

Clin Vaccine Immunol

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Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4 ϩ T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant. Compared to the CD4 ϩ T cell-depleted dam that experienced fetal loss, the immunocompetent, nontransmitting dam had a more rapid and robust plasmablast response that produced a high proportion of RhCMVreactive antibodies, including the first identified monoclonal antibody specific for soluble and membrane-associated RhCMV envelope glycoprotein B (gB). Additionally, we noted that plasmablast RhCMV-specific antibodies had variable gene usage and maturation similar to those observed in a monkey chronically coinfected with simian immunodeficiency virus (SIV) and RhCMV. This study reveals characteristics of the early maternal RhCMV-specific humoral immune responses to primary RhCMV infection in rhesus monkeys and may contribute to a future understanding of what antibody responses should be targeted by a vaccine to eliminate congenital HCMV transmission. Furthermore, the identification of an RhCMV gB-specific monoclonal antibody underscores the possibility of modeling future HCMV vaccine strategies in this nonhuman primate model.

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DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands

Cited by 47 publications

References 29 publications

Rapid Genotyping of Cytomegalovirus in Dried Blood Spots by Multiplex Real-Time PCR Assays Targeting the Envelope Glycoprotein gB and gH Genes

Rapid Genotyping of Cytomegalovirus in Dried Blood Spots by Multiplex Real-Time PCR Assays Targeting the Envelope Glycoprotein gB and gH Genes

Newborn Hearing Screening vs Later Hearing Screening and Developmental Outcomes in Children With Permanent Childhood Hearing Impairment

Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission

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