Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (LTRI) in children. With 33 million cases of RSV LRTI occurring worldwide each year, it is crucial to accurately diagnose and estimate RSV incidence for effective preventive interventions. Among various diagnostic methods, reverse transcription polymerase chain reaction (RT-PCR) tests have emerged as the most sensitive in detecting RSV in the pediatric population. In this article, we will explore the findings of a recent systematic review published in The Journal of Infectious Diseases that assessed the diagnostic performance of different testing types and specimens for RSV in children.
The Prevalence of RSV in Children
RSV is the leading cause of acute LRTI in children, affecting millions of young individuals globally. As specific treatments for RSV are currently unavailable, supportive care remains the primary approach. However, accurate estimation of RSV incidence is crucial for implementing preventive interventions in affected patients. The systematic review aimed to quantify the underascertainment of RSV due to varying specimen and testing types while summarizing the accuracy of these methods.
Study Methodology
The systematic review included studies reporting RSV detection in children and adults younger than 18 years using two or more types of specimens or diagnostic tests in the same population. The researchers analyzed the number of RSV cases detected by each testing method or specimen. The study selection process involved searching Embase, MEDLINE (via PubMed), and Web of Science databases from January 1, 2000, to December 27, 2021. The majority of the studies focused on hospitalized children, with lower respiratory tract infection (LRTI) being the most common clinical presentation.
Breakdown of Study Results
The study categorized children younger than 18 years into three subgroups: infants (younger than 12 months), young children (1-5 years), and older children (5-18 years). The index test referred to the test under evaluation, while the reference test served as the comparator. A true positive indicated positive results in both the index and reference tests, whereas a false positive was positive in the index but negative in the reference. A false negative denoted negative results in the index but positive in the reference, and a true negative test was negative in both tests.
The studies collected nasopharyngeal aspirates (NPA) in 54.1% of the cases and swabs (NPS) in 33.8%. RT-PCR multiplex and singleplex tests were evaluated in 54.8% and 31.8% of the studies, respectively. The age distribution of the study population was as follows: 35% for children aged 0 to 5 years, 39.5% for children aged 0 to 18 years, and 3.8% for infants 12 months and younger.
Impact of Testing Methods and Specimens
The review found that using multiple respiratory specimens for testing resulted in a slight overall increase in RSV detection. Additional testing of oropharyngeal swabs to NPS/NPA raised the RSV detection rate by 5% (detection rate ratio [DRR], 1.05; 95% CI, 0.96-1.14). Similarly, testing nasal swabs (NS) alongside NPA/NPS increased the detection rate by 8% (DRR, 1.08; 95% CI, 0.94-1.25). Adding NPS to NPA showed a 1% increase in RSV detection (DRR, 1.01; 95% CI, 0.94-1.08). Moreover, combining serology testing with RT-PCR on NPS demonstrated a 10% increase in RSV detection (DRR, 1.10; 95% CI, 0.95-1.27).
Comparing RT-PCR with Other Tests
When comparing RT-PCR with rapid antigen detection tests (RADT), the pooled sensitivity for children aged 0 to 5 years was 63% (95% CI, 49%-76%), while for children up to 18 years, it was 78% (95% CI, 74%-82%). The overall specificity of RADT was 97% (95% CI, 95%-98%).
In terms of direct fluorescence antibody (DFA) testing against RT-PCR, the pooled sensitivity was 87% (95% CI, 78%-93%). Within each age group, the sensitivity was 82% for children aged 0 to 5 years (95% CI, 76%-87%) and 88% for children aged 0 to 18 years (95% CI, 73%-95%). The pooled specificity of DFA was 99% (95% CI, 97%-100%).
Study Limitations and Recommendations
It is essential to acknowledge certain limitations of the review. Approximately 60% of the included studies had a high or unclear risk of bias, and some studies lacked demographic data and information regarding specimen storage. Additionally, the inclusion of case-control studies might introduce a bias by including both the sickest and healthiest participants, potentially affecting diagnostic accuracy. Furthermore, the review did not stratify studies by retrospective and prospective design, and the true accuracy of RT-PCR remains unknown.
The study emphasized that when exploring the added benefit of combining multiple specimen types, the pediatric population showed a more modest magnitude compared to the adult population. Nevertheless, it is recommended to conduct further research on this topic, considering the combined effects of adding multiple specimen types, which is likely to provide valuable insights.
Conclusion
In conclusion, reverse transcription polymerase chain reaction (RT-PCR) tests have demonstrated superior sensitivity in diagnosing respiratory syncytial virus (RSV) in children. As the most sensitive diagnostic test currently available, RT-PCR plays a crucial role in accurately detecting RSV cases, allowing for timely preventive interventions. However, further studies focusing on combining multiple specimen types are necessary to enhance the understanding of RSV diagnostics and improve overall detection efficiency in pediatric populations.
Reference
Onwuchekwa C, Atwell J, Moreo LM, et al. Pediatric RSV diagnostic testing performance: a systematic review and meta-analysis. J Infect Dis. Published online June 7, 2023. doi:10.1093/infdis/jiad185