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.