We demonstrated a high rate of respiratory virus detection using sensitive molecular-based assays among a large sample of children evaluated for bronchiolitis in a hospital setting. We detected at least one virus in 93% of children with clinical a diagnosis of bronchiolitis. RSV was the most common pathogen but was detected in only 77% of children. A virus other than RSV was detected in 35% of children, and co-infections occurred in 23% of children.
The development of sensitive molecular diagnostic assays has increased the number of viruses detected in comparison to conventional methods. A previous study analysing the viral detection capacities of culture, direct immunofluorescence, and multiplex PCR in children with acute respiratory illness found PCR to be the most sensitive method with 91.5% of children having a virus detected in their nasal samples (7
). Another study in infants with acute lower respiratory tract infections performed PCR on nasopharyngeal aspirates and detected viruses in 77% of patients (8
). These studies found RSV to be the first (43.6%) or second (28%) most commonly detected virus, with rhinovirus (RV) being the second (31.8%) or first (32%) most frequent virus, respectively (7
). Our study demonstrated a similarly high frequency of RSV, followed by adenovirus and hMPV, but we did not test for RV.
The use of molecular techniques for viral detection has increased the identification of multiple viruses in a single sample (13
). The prevalence of co-infections in other studies has ranged from 19–35% in young children with diverse types of respiratory tract infections seen in the hospital or emergency department (7
). Of the published studies that use molecular diagnostics to report co-infections in children with bronchiolitis, few analyse children diagnosed during an entire respiratory season. A study by Ong et al. of 50 infants with RSV bronchiolitis hospitalized during a one-month period identified dual infection in 5 (10%) patients (9
). A study by Greensill et al. of 30 infants with bronchiolitis requiring mechanical ventilation reported a 70% co-infection rate among hMPV and RSV (16
). A co-infection rate of 9% was reported by Mansbach et al. in a multicentre study that sampled children with bronchiolitis for two to three-week periods (10
). Only one previous study was population-based, representing a full viral respiratory season. This study, set in Greece, included 119 infants less than 1 year of age with bronchiolitis. Co-infections were detected in 19.5% of children, 69% of which were dual infections between RSV and RV (11
). In our study, we identified co-infections in 41 (23%) children with bronchiolitis despite not testing for RV. In contrast to the studies by Ong and Greensill, our study population was larger, encompassed an entire respiratory season, and comprised patients discharged from the emergency department or admitted to a general pediatric floor or the intensive care unit.
The AAP Guidelines recommend limiting laboratory tests for disease diagnosis but state that virological testing may be beneficial if patient cohorting is feasible (3
). Many facilities use FA testing to direct cohorting, and Hall and Lieberthal emphasize that the rapid tests available are typically limited to RSV and influenza and perform with variable reliability (17
). Using more sensitive assays, we found that of the 139 children with RSV detected, 34 (24%) were infected with another pathogen and most of these pathogens are not detected well or at all with current FA assays. Interpreting copathogen data with organisms such as coronavirus or adenovirus is problematic due to the difficulty in differentiating acute disease from long-term shedding and the extent that bronchiolitis may be caused or exacerbated by these other viruses has not been definitively established. Our results suggest that the issue of viral testing merits further investigation as it has the potential to impact patient cohorting and management algorithms (18
Limitations of our study include the retrospective design and the use of residual clinical samples. In addition, we did not extend the study into the summer months, potentially decreasing the detection of parainfluenza virus infections. Although we tested for a wide spectrum of viruses, viral detection of bocavirus and picornaviruses, such as rhinovirus, were not included in this study due to limitations of specimen volume. Despite this limitation, we identified one or more viruses in 93% of samples.
Results of our study not only confirm previous observations that RSV is the most frequently detected virus in patients with bronchiolitis, but also highlight the potential significance of other viral pathogens such as hMPV and adenovirus in this clinical setting. Given the substantial presence of viral co-infections in RSV bronchiolitis, providers need to recognize the potential limitations of rapid RSV testing alone for cohorting purposes. Our data underscore that further study is warranted to determine the clinical impact of viruses other than RSV for children with bronchiolitis.