Detection of Cytomegalovirus (CMV) DNA by Polymerase Chain Reaction Is Associated with Hearing Loss in Newborns with Symptomatic Congenital CMV Infection Involving the Central Nervous System

Bradford, Russell D.; Cloud, Gretchen A.; Lakeman, Alfred D.; Boppana, Suresh B.; Kimberlin, David W.; Jacobs, Richard F.; Demmler, Gail J.; Sánchez, Pablo J.; Britt, William J.; Soong, Seng Jaw; Whitley, Richard J.

doi:10.1086/426456

Cited by 111 publications

(83 citation statements)

References 16 publications

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“…In agreement with Bradford et al, 28 treatment decisions currently cannot be based solely on the presence of high CMV blood viral load at birth. However, this finding could identify the population in greatest need of antiviral therapy, whereas a low viral load may save the clinician from administering unnecessary treatments.…”

Section: Figuresupporting

confidence: 76%

“…However, we failed to find a correlation between viremia and symptoms from the reticuloendothelial system, including isolated elevated levels of ALT and thrombocytopenia or hyperechogenic lenticolo-striatal vessels deemed a nonspecific sign. 28 Considering only newborns with clinical evidence of CMV infection, the differences in viral blood load between newborns with and without symptoms became statistically significant.…”

Section: Figurementioning

confidence: 94%

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Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Lanari¹,

Lazzarotto

Venturi³

et al. 2006

Pediatrics

242

163

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OBJECTIVE. Human cytomegalovirus (CMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection in developed countries leading to psychomotor impairment and deafness. Diagnostic techniques for CMV detection have greatly improved during recent years with the advent of sophisticated serological and virological methods. The aim of the present study was to assess the diagnostic and prognostic value of detection and quantification of virus in neonatal blood samples of symptomatic and asymptomatic newborns with CMV congenital infection.METHODS. Between January 1997 and December 2003, we studied 99 newborns who were born to women with primary, recurrent, and undefined CMV infection during pregnancy. CMV congenital infection was identified by isolation of the virus in urine within the second week of life. Fifty-eight of 99 infants were infected and were assessed clinically for disease in the newborn period and classified as having symptomatic or asymptomatic infection on the basis of physical, instrumental, and laboratory findings. The infants were followed up from birth according to a protocol of the tertiary NICU at the University of Bologna in a prospective study of long-term sequelae of congenital infection. Forty-seven blood samples were obtained from 47 infants in the neonatal period: 34 were examined for pp65 antigenemia test and 44 for qualitative and quantitative polymerase chain reaction (PCR and qPCR). Sequelae at 12 months were evaluated in a group of 50 infants.RESULTS. Antigenemia was positive in only 10 of 34 samples of infected newborns (29.4% sensitivity). PCR was performed in 44 samples of infected newborns and was positive in all (100% sensitivity). qPCR showed a finding of Ն100 copies per 10 5 of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 10 5 PMNLs was Ͻ100. Between symptomatic and asymptomatic newborns, the mean values of viral blood load determined by qPCR turned out to be significantly higher in symptomatic newborns. Mean values of neonatal blood viral load were statistically higher in newborns who developed sequelae than in those who did not. Of 20 children with a neonatal viral blood load of Ͻ1000 copies per 10 5 PMNLs, 19 did not develop sequelae (negative predictive value: 95%), whereas 2 of 3 with a viral blood load of Ͼ10 000 copies did develop sequelae.CONCLUSIONS. Different viremia value ranges are correlated to a different risk of sequelae: ϳ70% sequelae were found in newborns with a qPCR higher than 10 000 copies per 10 5 PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia Ͻ1000 copies per 10 5 PMNLs has a negative predictive value of 95%. As an independent predictive factor of outcome, neonatal viremia is another useful element for neonatal counseling and therapeutic choices in symptomatic and asymptomatic newborns.H UMAN CYTOMEGALOVIRUS (CMV) is a ubiquitous human-specific DNA virus that belongs to t...

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Section: Figuresupporting

confidence: 76%

Section: Figurementioning

confidence: 94%

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Lanari¹,

Lazzarotto

Venturi³

et al. 2006

Pediatrics

242

163

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“…98,101,102 It is possible that viremia had not yet occurred at the time of sampling. 103 Moreover, as mentioned earlier, length of storage of the DBS might decrease the apparent viral load. 104 These factors might lead to underestimation of the role of cCMV.…”

Section: Discussionmentioning

confidence: 86%

Hearing Loss and Congenital CMV Infection: A Systematic Review

Goderis¹,

Leenheer²,

et al. 2014

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BACKGROUND AND OBJECTIVE: Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. Today cCMV is the most common cause of nonhereditary sensorineural hearing loss in childhood. Our objective was to provide an overview of the prevalence of cCMV-related hearing loss, to better define the nature of cCMV-associated hearing loss, and to investigate the importance of cCMV infection in hearing-impaired children. METHODS:Two reviewers independently used Medline and manual searches of references from eligible studies and review articles to select cohort studies on children with cCMV infection with audiological follow-up and extracted data on population characteristics and hearing outcomes. RESULTS:Thirty-seven studies were included: 10 population-based natural history studies, 14 longitudinal cohort studies, and 13 retrospective studies. The prevalence of cCMV in developed countries is 0.58% (95% confidence interval, 0.41-0.79). Among these newborns 12.6% (95% confidence interval, 10.2-16.5) will experience hearing loss: 1 out of 3 symptomatic children and 1 out of 10 asymptomatic children. Among symptomatic children, the majority have bilateral loss; among asymptomatic children, unilateral loss predominates. In both groups the hearing loss is mainly severe to profound. Hearing loss can have a delayed onset, and it is unstable, with fluctuations and progression. Among hearing-impaired children, cCMV is the causative agent in 10% to 20%. Despite strict selection criteria, some heterogeneity was found between selected studies.CONCLUSIONS: This systematic review underscores the importance of cCMV as a cause of sensorineural hearing loss in childhood. Pediatrics 2014;134:972-982

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“…In preliminary trials, we found the sensitivity of gB primers to detect CMV DNA to be greater than for either E1 and IE1 (data not shown). Although CMV detection methodology has yet to be universally standardized, gB is routinely used to measure viral levels, which are significantly reduced in latent infection (7,32). Thus, the levels of gB DNA obtained using real-time PCR are representative of measurement of the total viral genome.…”

Section: Resultsmentioning

confidence: 99%

CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

Reuter¹,

Wilson²,

Idoko³

et al. 2005

J Virol

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Cytomegalovirus (CMV) infection is the most common opportunistic infection of the central nervous systemin patients with human immunodeficiency virus or AIDS or on immunosuppressive drug therapy. Despite medical management, infection may be refractory to treatment and continues to cause significant morbidity and mortality. We investigated adoptive transfer as an approach to treat and prevent neurotropic CMV infection in an adult immunodeficient mouse model. SCID mice were challenged with intracranial murine CMV (MCMV) and reconstituted with MCMV-or vesicular stomatitis virus (VSV)-sensitized splenocytes, T cells, or T-cell subsets. T cells labeled with vital dye or that constitutively generated green fluorescent protein (GFP) were identified in the brain as early as 3 days following peripheral transfer. Regardless of specificity, activated T cells localized to regions of the brain containing CMV, however, only those specific for CMV were effective at clearing virus. Reconstitution with unsorted MCMV-immune splenocytes, enriched T-cell fractions, or CD4؉ cells significantly reduced virus levels in the brain within 7 days and also prevented clinical disease, in significant contrast with mice given VSV-immune unsorted splenocytes, MCMV-immune CD8 ؉ T cells, and SCID control mice. Results suggest CMV-immune T cells (particularly CD4 ؉ ) rapidly cross the blood-brain barrier, congregate at sites of specific CMV infection, and functionally eliminate acute CMV within the brain. In addition, when CMV-immune splenocytes were administered prior to a peripheral CMV challenge, CMV entry into the immunocompromised brain was prevented. Systemic adoptive transfer may be a rapid and effective approach to preventing CMV entrance into the brain and for reducing neurotropic infection.

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Detection of Cytomegalovirus (CMV) DNA by Polymerase Chain Reaction Is Associated with Hearing Loss in Newborns with Symptomatic Congenital CMV Infection Involving the Central Nervous System

Abstract: In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease.

Cited by 111 publications

References 16 publications

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Hearing Loss and Congenital CMV Infection: A Systematic Review

CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

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Detection of Cytomegalovirus (CMV) DNA by Polymerase Chain Reaction Is Associated with Hearing Loss in Newborns with Symptomatic Congenital CMV Infection Involving the Central Nervous System

Abstract: In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease.

Cited by 111 publications

References 16 publications

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Hearing Loss and Congenital CMV Infection: A Systematic Review

CD4+T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

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Product

Resources

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CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain