Preferred Testing for CMV in Infants
DNA PCR testing of saliva is the preferred initial screening method for cytomegalovirus (CMV) in infants due to its high sensitivity and ease of collection, but positive results should be confirmed with urine PCR testing which remains the gold standard for diagnosis of congenital CMV infection.
Diagnostic Methods for CMV in Infants
Saliva PCR Testing
- Saliva PCR is recommended as the preferred initial screening specimen for CMV detection in infants due to its ease of collection and high sensitivity 1
- Using centrifugation-assisted shell vial culture amplification techniques, CMV can be detected within 16-40 hours of culture inoculation 2
- While convenient for screening purposes, positive saliva PCR results, especially those with low viral loads, should be confirmed with urine testing due to potential false positives 3
Urine PCR Testing
- Urine PCR remains the gold standard for diagnosing congenital CMV infection, particularly in infants of mothers with primary infection during pregnancy 3
- Urine PCR has shown superior performance compared to saliva testing, with studies showing 98.8% positivity in infected infants 1
- Urine testing is particularly important for confirmation of positive saliva results, as saliva has shown a positive predictive value of only 73% compared to urine in some studies 3
Timing of Testing
- Diagnosis of congenital CMV must be performed using specimens collected within the first 21 days of life to distinguish congenital from acquired postnatal infection 2
- After 3 weeks of life, congenital CMV can only be diagnosed using retrospective samples collected during the neonatal period 2
Comparative Performance of Testing Methods
Sensitivity and Specificity
- DNA assays (PCR) are more sensitive than traditional buffy-coat or urine cultures for detecting CMV 2
- In studies comparing methods, saliva PCR has shown a sensitivity of 89.4% and specificity of 99.5% compared to urine PCR 4
- Some studies have found discordant results between saliva and urine testing, with false-negative (n=2) or false-positive (n=10) PCR results in saliva compared to urine 3
Practical Considerations
- Saliva specimens are easier to collect than urine, making them practical for large-scale screening programs 1
- PCR testing offers more rapid turnaround, is less affected by storage and transport conditions, has lower cost, and may be adapted to high-throughput situations 1
- Dried blood spots have also been evaluated but show lower sensitivity (approximately 80%), meaning up to 20% of cases may be missed using this method alone 2, 5
Testing Recommendations for Different Clinical Scenarios
Universal vs. Targeted Screening
- Some pediatric HIV experts recommend testing all infants with HIV infection for CMV with a urine culture during the first months of life 2
- For general population screening, saliva PCR is increasingly used for initial testing, with confirmation by urine PCR for positive results 2, 1
- Currently, 13 states have hearing-targeted screening legislative or public health mandates for CMV 2
Follow-up Testing
- Quantitative DNA PCR can be used as a marker of risk for disease progression and to monitor response to therapy 2
- Annual CMV antibody testing of previously seronegative and culture-negative infants and children, beginning at age 1 year, can identify those who develop occult CMV infections 2
Pitfalls and Caveats
- Antibody testing has limited utility in infants under 12 months due to maternal antibody transfer - a positive CMV antibody assay in an infant aged <12 months indicates maternal infection but not necessarily infection of the infant 2
- A positive CMV culture or PCR indicates infection but not necessarily disease - clinical correlation is essential 2
- False-positive results in saliva can occur, particularly with low viral loads, necessitating confirmation with urine testing 3
- Diagnosis must occur within the first 21 days of life to definitively establish congenital infection 2