Saliva Polymerase-Chain-Reaction Assay for Cytomegalovirus Screening in Newborns

Abstract

BACKGROUND Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives — real-time polymerase-chain-reaction (PCR)–based testing of a liquid-saliva or dried-saliva specimen obtained at birth — have been developed. METHODS In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. CONCLUSIONS Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.)

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

“…Therefore, saliva samples procurement as an alternative to urine can dramatically (up to 100%) improve the inclusion index in neonatal screening for CMV. It was previously demonstrated that analysis of properly collected saliva samples can yield a sensitivity of >97% and a specifi city of 99.9% for the detection of congenital CMV infection with molecular techniques (3) . Our results are in line with these published values (specifi city of 100% for both samples).…”

Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity

“…However, a reasonable estimate of the overall birth prevalence of congenital HCMV infection is about 4 to 5/1,000 live births based on recent findings from a large, multicenter study performed in the United States (7,8). When the prevalence of congenital HCMV infections is compared to those of other causes of disease and disability in infants, such as congenital heart malformations (10/1,000) and cystic fibrosis (0.3/1,000), or those of chromosomal abnormalities, such as trisomy 21 (1.2/ 1,000), the significance of congenital HCMV infection as a cause of disease in infants and children can be appreciated.…”

Congenital cytomegalovirus infection: Diagnosis, treatment, and prevention

“…Предпочтительнее буккальный соскоб или моча, так как они содержат большую концентрацию вируса, исследования яв-ляются высокочувствительными и неинвазивными [1,5,8,15,[32][33][34]. Для буккального соскоба определена чувствительность >97% и специфичность 99,9% [35].…”

“…Вирусовыделение при врожденной цитомегалови-русной инфекции может персистировать до 5-6 лет [15,18,35]. Итальянские авторы, изучавшие пер-систенцию цитомегаловируса при бессимптомной врожденной цитомегаловирусной инфекции, также показали длительное выделение вируса: у 50% детей виремия обнаруживалась более 3 мес, а вирусурия -более 36 мес [40].…”