Smadar Eventov-Friedman1, Hili Manor2, Benjamin Bar-Oz1, Diana Averbuch3, Orit Caplan2, Aliza Lifshitz2, Tali Bdolah-Abram4, Dana G Wolf2,4,5. 1. Department of Neonatology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 2. Clinical Virology Unit, Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 3. Pediatric Infectious Diseases, Pediatric Division, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 4. Hebrew University Faculty of Medicine, Jerusalem, Israel. 5. Lautenberg Center for General and Tumor Immunology, Jerusalem, Israel.
Abstract
BACKGROUND: Saliva real-time polymerase chain reaction (PCR) was shown to be sensitive and specific for the detection of congenital cytomegalovirus (cCMV) in universal screening studies. In the current study, we assessed the performance of saliva real-time PCR in newborns undergoing targeted cCMV screening. METHODS: Saliva real-time PCR results were prospectively correlated with reference-standard urine detection in newborns undergoing targeted cCMV screening over a 3-year period, in successive validation (concurrent testing of all saliva and urine specimens) and routine-screening (confirmatory urine testing of positive saliva results) implementation phases. RESULTS: The sensitivity, specificity, and positive and negative predictive values of saliva real-time PCR were 98.3% (95% confidence interval, 90.8%-99.9%), 91.5% (89.3%-93.3%), 45.6% (36.7%-54.7%), and 99.9% (99.2%-99.9%), respectively, in 856 concurrently tested newborns. True-positive saliva real-time PCR detection (defined in relation to urine detection) was associated with earlier saliva sampling (P = .002) and a higher saliva viral load (P < .001). We further identified a saliva viral load cutoff value that reliably distinguished between true-positive and false-positive saliva results. CONCLUSIONS: In newborns undergoing targeted screening for cCMV, saliva real-time PCR is highly sensitive yet has a low positive predictive value, necessitating confirmatory testing. Early sampling and application of a validated viral load cutoff could improve the assay performance and support its large-scale implementation in this growing clinical setting.
BACKGROUND: Saliva real-time polymerase chain reaction (PCR) was shown to be sensitive and specific for the detection of congenital cytomegalovirus (cCMV) in universal screening studies. In the current study, we assessed the performance of saliva real-time PCR in newborns undergoing targeted cCMV screening. METHODS: Saliva real-time PCR results were prospectively correlated with reference-standard urine detection in newborns undergoing targeted cCMV screening over a 3-year period, in successive validation (concurrent testing of all saliva and urine specimens) and routine-screening (confirmatory urine testing of positive saliva results) implementation phases. RESULTS: The sensitivity, specificity, and positive and negative predictive values of saliva real-time PCR were 98.3% (95% confidence interval, 90.8%-99.9%), 91.5% (89.3%-93.3%), 45.6% (36.7%-54.7%), and 99.9% (99.2%-99.9%), respectively, in 856 concurrently tested newborns. True-positive saliva real-time PCR detection (defined in relation to urine detection) was associated with earlier saliva sampling (P = .002) and a higher saliva viral load (P < .001). We further identified a saliva viral load cutoff value that reliably distinguished between true-positive and false-positive saliva results. CONCLUSIONS: In newborns undergoing targeted screening for cCMV, saliva real-time PCR is highly sensitive yet has a low positive predictive value, necessitating confirmatory testing. Early sampling and application of a validated viral load cutoff could improve the assay performance and support its large-scale implementation in this growing clinical setting.
Authors: Ladawna L Gievers; Alison Volpe Holmes; Jaspreet Loyal; Ilse A Larson; Carlos R Oliveira; Erik H Waldman; Sheevaun Khaki Journal: Pediatrics Date: 2020-07 Impact factor: 7.124
Authors: Angela Nagel; Emmanouela Dimitrakopoulou; Norbert Teig; Peter Kern; Thomas Lücke; Dariusz Michna; Klaus Korn; Philipp Steininger; Khalid Shahada; Katrin Neumann; Klaus Überla Journal: PLoS One Date: 2020-01-09 Impact factor: 3.240