A Prospective Study of Respiratory Syncytial Virus Infection Among Children Attending Daycare

Abstract

Background: RSV is the most important cause of serious respiratory disease in young children, but transmission among children is not well-characterized. Molecular sequencing of the hypervariable glycoprotein (G) coding portion of the RSV genome allows for description of transmission dynamics. Methods: We prospectively followed children enrolled in full-time childcare during 3 winter seasons. We collected nasopharyngeal (NP) swabs at enrollment and with illness episodes. The child's caregiver completed a symptom diary. Samples were tested for 12 respiratory viruses by reverse transcriptase polymerase chain reaction (PCR) techniques. We developed a heminested PCR assay to amplify and sequence a region of the RSV G protein. Data were analyzed using GEEs and univariate linear regression models. Phylogenetic analysis was performed using the maximum likelihood method. Results: RSV was detected in 62 (12%) of 523 illness episodes. Compared to RSV-negative illness episodes, RSV-positive illness episodes were associated with longer symptom duration, more childcare and work days missed, and increased frequency of health care visits. The median log10 viral copies/mL was 7.50 (2.6-10.0). In 42 (68%) of RSV-positive swabs, another respiratory virus was detected. There was no correlation between RSV viral load and age at illness onset or presence of other respiratory viruses. We observed three RSV outbreaks with a predominance of subtype B in season 1 (21/27) and subtype A in seasons 2 (7/8) and 3 (20/27). In two rooms, 50% of the children had RSV detected within 6 days of the first case, and 75% within 10 days. Sequencing was performed for 27 (44%) of RSV illness episodes. Seven identical strains were isolated in season 1, and 9 identical strains were isolated in season 3. These clusters were distinct from reference sequences, as well as viruses isolated during separate time periods in the childcare facility. Conclusions: Our study examined the impact and spread of RSV in a multiyear community-based prospective childcare study using molecular techniques. These data demonstrate that RSV is readily transmitted within enclosed settings, and that it is the most important respiratory viral cause of symptoms and health care utilization among children in the community.