title: 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.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01995851.
authors.affiliation: Public Health Ontario, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Institute for Clinical Evaluative Sciences, Toronto, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, Canada; University Health Network, Toronto, Canada. Electronic address: jeff.kwong@utoronto.ca.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Kwong
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pereira
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Quach
authors.affiliation: Peterborough County-City Health Unit, Peterborough, Canada.
authors.forename: Rosana
authors.initials: R
authors.lastname: Pellizzari
authors.affiliation: Peterborough County-City Health Unit, Peterborough, Canada.
authors.forename: Edwina
authors.initials: E
authors.lastname: Dusome
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Russell
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
authors.forename: Jemila S
authors.initials: JS
authors.lastname: Hamid
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Yael
authors.initials: Y
authors.lastname: Feinberg
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Anne-Luise
authors.initials: AL
authors.lastname: Winter
authors.affiliation: Public Health Ontario, Toronto, Canada; Department of Laboratory Medicine and Pathobiology and Department of Paediatrics, University of Toronto, Toronto, Canada.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Gubbay
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Brittany
authors.initials: B
authors.lastname: Sirtonski
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Deanna
authors.initials: D
authors.lastname: Moher
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: Doug
authors.initials: D
authors.lastname: Sider
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Toronto Public Health, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Finkelstein
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Loeb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D062665:Epidemiological Monitoring; D005191:Family Characteristics; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D012574:Schools; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated
keywords: Canada; Influenza; Influenza vaccines; Live vaccines; Ontario