Randomized evaluation of live attenuated vs. inactivated influenza vaccines in schools (RELATIVES) cluster randomized trial: Pilot results from a household surveillance study to assess direct and indirect protection from influenza vaccination.

BACKGROUND: Children are key drivers of influenza transmission. Vaccinating school age children decreases influenza in the community. OBJECTIVE: To pilot-test the methods for a future trial to compare the direct and indirect benefits of inactivated influenza vaccine (IIV) vs. live attenuated influenza vaccine (LAIV) in preventing influenza infection. METHODS: During the 2013-14 influenza vaccination campaign, we piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario, Canada. We randomized schools on a 1:1 basis to have students receive IIV or LAIV. We invited a subset of vaccinated students and their households to participate in a surveillance sub-study, which involved completing daily symptom diaries during influenza season and collecting mid-turbinate swabs from symptomatic individuals to detect influenza infection. The main outcome measure was confirmed influenza infection using a real-time reverse transcriptase polymerase chain reaction (PCR) assay. RESULTS: One hundred and nineteen households (166 students and 293 household members) participated. During 15 weeks of surveillance, we detected 22 episodes of PCR-confirmed influenza (21 influenza A/H1N1 and 1 influenza B). The incidence of influenza per 1000 person-days was 1.24 (95% CI, 0.40-2.89) for IIV-vaccinated students, compared to 0.13 (95% CI, 0.003-0.72) for LAIV-vaccinated students; the incidence rate ratio was 0.10 (95% CI, 0.002-0.94). Similarly, the incidence of influenza per 1000 person-days was 1.33 (95% CI, 0.64-2.44) for IIV household members, compared to 0.47 (95% CI, 0.17-1.03) for LAIV household members; the incidence rate ratio was 0.36 (95% CI, 0.11-1.08). The overall incidence rate ratio (combining students and household members) was 0.27 (95% CI, 0.09-0.69). CONCLUSIONS: Household surveillance involving participant monitoring and reporting of symptoms and self-collection of mid-turbinate swabs is feasible. A larger study is required to validate the suggestion that vaccinating children with LAIV might confer more protection against influenza for both children and their household contacts, compared to IIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01995851.

Randomized evaluation of live attenuated vs. inactivated influenza vaccines in schools (RELATIVES) pilot study: a cluster randomized trial.

BACKGROUND: School-based influenza immunization can effectively address accessibility barriers, but injected inactivated influenza vaccines (IIV) may not be acceptable to some children and parents in school settings. OBJECTIVES: To better understand the feasibility of offering intranasal live attenuated influenza vaccines (LAIV) through schools, we assessed uptake, stakeholder acceptability, and cost of school-based delivery of LAIV compared to IIV. METHODS: We piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario during the 2013-2014 influenza vaccination campaign. Schools were randomized to having students receive IIV or LAIV at publicly-funded school-based clinics organized by the local public health department. We measured the percentage of students vaccinated with at least one dose of influenza vaccine at school. Stakeholder acceptability was evaluated through a questionnaire of parents and interviews of public health department personnel and school principals. We compared the costs per dose of vaccine administered, including staff time and costs of vaccines and supplies. RESULTS: Single-dose influenza vaccine uptake was higher for the five schools offering LAIV than for the five offering IIV (19.3% vs. 12.2%, p=0.02). Interviews with nine school principals and five public health department personnel suggested that the clinics ran smoothly with little disruption to school routines, and that LAIV was associated with increased efficiency and calmer children. All interviewees cited unfamiliarity with LAIV and the study recruitment package length as potential reasons for low uptake. The cost per vaccine dose administered was $38.67 for IIV and $43.50 for LAIV. CONCLUSIONS: Use of LAIV in school-based clinics was associated with increased vaccine uptake and the perception among immunizing staff of reduced child anxiety, but also slightly higher vaccine administration costs, compared to IIV. However, uptake was low for both groups. More effective strategies to promote influenza vaccines and to obtain parent consent may improve vaccine uptake. TRIAL REGISTRATION: ClinicalTrials.gov NCT01995851. FUNDING: Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network.