Human Rhinovirus Clades in Infant Bronchiolitis

RATIONALE: The burden of human rhinovirus (HRV) - associated bronchiolitis and the role of the novel clade HRV-C in bronchiolitis are unknown. METHODS: Utilizing the Tennessee Children's Respiratory Initiative (TCRI), we studied term previously healthy infants (≤12 months age) with bronchiolitis or upper respiratory infections (URI) who required hospitalization, emergency department or acute clinic visits at Vanderbilt Children's Hospital from Fall-Spring 2004-2006. Demographic/clinical data were collected; nasopharyngeal swabs were tested by real-time RT-PCR for HRV, RSV, human coronaviruses, human metapneumovirus, influenza A/B, and parainfluenza 1-3. To determine the HRV clade, we sequenced the VP4/VP2 gene from HRV-positive specimens. RESULTS: Of 352 infants enrolled and tested, 273 (77%) had a study virus detected. Of those with detectable study virus, 39.2% had HRV, 32.6% RSV, and 28.2% other virus. Children with HRV were older than those with RSV (median age 22.0 weeks [IQR 8.2,41.8] vs 10.5 weeks [IQR 5.2,20.2], p < 0.001). There was substantial genetic diversity amongst the HRV detected. HRV-C was more common among outpatients than inpatients (78% vs. 50% HRV-A, p = 0.018). Mothers of infants with HRVC were less likely to smoke than mothers of children with HRVA (88% vs 61% did not smoke, p = 0.014). There was seasonal variation in the proportion of each clade over the study seasons. CONCLUSIONS: Human rhinoviruses were detected more frequently than all other study viruses, including RSV, among term previously healthy infants with bronchiolitis or URI. A large proportion of HRV-associated respiratory illness was attributable to the novel clade HRV-C, and there was variation in respiratory illness severity by clade.