The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

Cardoso, Emanuelle Santos de Carvalho; Jesus, Bruna Laís Santos de; Gomes, Luciano Gama da Silva; Sousa, Sandra Maria Zákia Lian; Gadelha, Sandra Rocha; Marin, Lauro Juliano

doi:10.1590/0037-8682-0200-2014

Cited by 25 publications

(21 citation statements)

References 8 publications

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“…The higher content of CMV DNA and much easier collection and handling suggest that buccal swabs are preferable to urine and EDTA blood samples in neonatal CMV screening programs. In particular, the use of saliva samples improved the inclusion rate in screening programs since many newborns had to be excluded due to unsuccessful sampling of urine [6]. Viral load levels in EDTA blood were more than 10 4 -fold lower than in buccal swabs (Fig 3, S3 Table), consistent with the reduced sensitivity reported for assays based on dried blood spots [22,[25][26][27][28].…”

Section: Discussionsupporting

confidence: 66%

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Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

et al. 2020

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The majority of congenital cytomegalovirus (cCMV) infections are asymptomatic at birth and therefore not diagnosed. Approximately 10-15% of these infants develop late-onset hearing loss and other developmental disorders. Implementation of a universal screening approach at birth may allow early initiation of symptomatic interventions due to a closer follow-up of infants at risk and offers the opportunity to consider treatment of late-onset disease. Realtime PCR assays for the detection of CMV DNA in buccal swab samples demonstrated feasibility and good clinical sensitivity in comparison to a rapid culture screening assay. Because most cCMV infections remain asymptomatic, a universal screening assay that stratifies CMV infected infants according to low and high risk of late-onset cCMV disease could limit the parental anxiety and reduce follow-up costs. We therefore developed and characterized a screening algorithm based on a highly-sensitive quantitative real-time PCR assay that is compatible with centralized testing of samples from universal screening and allows to determine CMV DNA load of saliva samples either as International Units (IU)/ml saliva or IU/10 5 cell equivalents. 18 of 34 saliva samples of newborns that tested positively by the screening algorithm were confirmed by detection of CMV DNA in blood and/or urine samples obtained during the first weeks of life. All screening samples that could not be confirmed had viral loads of <2.3x10 5 IU/ml saliva (median: 6.8x10 3) or 1.3x10 5 IU/10 5 cell equivalents (median: 4.0x10 2). The viral load of screening samples with confirmed cCMV infection ranged from 7.5x10 2 to 8.2x10 9 IU/ml saliva (median: 9.3x10 7) or 1.5x10 2 to 5.6x10 10 IU/10 5 cell equivalents (median: 3.5x10 6). Clinical follow-up of these newborns with confirmed cCMV infection should reveal whether the risk of late-onset cCMV disease correlates with CMV DNA load in early life saliva samples and whether a cutoff can

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Section: Discussionsupporting

confidence: 66%

“…Polymerase chain reaction (PCR) analyses of saliva samples obtained by buccal swabs have been proposed as a universal screening approach for cCMV infections by different studies (e.g. [5][6][7][8][9]). As part of the CHIMES study, 34,989 infants have been investigated for the occurrence of cCMV infection [7].…”

Section: Introductionmentioning

confidence: 99%

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

et al. 2020

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“…The optimal approach to diagnosing in utero congenital infection of CMV is to detect CMV DNA in urine samples of newborns within 3 weeks after birth [23,24]. However, due to the difficulty in collecting urines from newborns, saliva samples are usually used to detect CMV DNA [25][26][27][28]. In the present study, we found that the infants who were delivered virginally and/or breastfed had higher CMV infection rate than those who were delivered by caesarean section and/or formula-fed, indicating that saliva samples from the neonates can be contaminated with maternal CMV.…”

Section: Discussionmentioning

confidence: 99%

Minimal adverse outcomes of postnatal cytomegalovirus infection in term or late preterm infants

J¹,

Zhou²,

Chen³

et al. 2019

Preprint

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Background: To investigate at what extent breastfeeding and vaginal delivery can increase mother-to-child transmission of cytomegalovirus (CMV) and to observe the clinical outcomes of postnatal CMV infection in infants. Methods: In this secondary study of prospectively collected clinical data and serum samples, April 2012 through March 2015, 380 pregnant women with CMV IgG positive/CMV IgM negative and their 384 infants (4 twin pairs) with gestational age ≥32 weeks were included. CMV IgG and IgM were measured with enzyme-linked immunosorbent assay. Results: Of 384 infants followed up at 10.2 ± 2.3 months age, 177 (46.1%) were defined with CMV infection based on the presence of higher CMV IgG levels than in their mothers. The infection rate in 190 breastfed infants was higher than in 194 formula-fed infants (62.6% vs 29.9%, P < 0.001). Vaginally delivered infants (172) had higher CMV infection rate than 212 infants delivered by caesarean section (55.2% vs. 38.7%, P = 0.001). Compared with formula feeding and caesarean section, breastfeeding and vaginal delivery increased postnatal CMV infection respectively (OR = 3.801, 95% CI 2.474‒5.840, P < 0.001; OR = 1.818, 95% CI 1.182‒2.796, P = 0.007). Nevertheless, CMV-infected infants normally developed and did not show adverse clinical outcomes compared to uninfected infants. Conclusions: Breastfeeding and vaginal delivery can increase postnatal CMV infection; however, the infection does not cause adverse events in term or late preterm infants. Detection of CMV DNA in breastmilk should not be routinely performed, and breastfeeding should be encouraged in these infants.

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“…Detection of congenital CMV infection in the neonate needs to be undertaken within three weeks of birth due to the possibility of postnatal infection; for instance, from breast milk [49], and to facilitate prompt interventions [50]. The most suitable diagnostic methodology is real-time polymerase chain reaction using saliva specimens [51][52][53]. Saliva [54] or dried blood spot PCRs [55] have been used in support of newborn hearing loss screening programmes as they offer the capacity to target asymptomatic neonates "at risk" of developing hearing loss and who may benefit from antiviral treatment or other intervention measures [56][57][58].…”

Section: Congenital Cytomegalovirus Infection and Hearing Lossmentioning

confidence: 99%

Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

Maple

2020

Vaccines

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Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein–Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required.

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The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

Cited by 25 publications

References 8 publications

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

Minimal adverse outcomes of postnatal cytomegalovirus infection in term or late preterm infants

Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

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