Serum specimens were collected from study subjects at baseline immediately before vaccination (November–December 2008), 1 month after vaccination, after the winter influenza season (“mid‐season”; April 2009) and at the end of the follow‐up period (August–October 2009). Serum specimens were also collected from all household contacts at baseline, at mid‐season, and post‐season.
All subjects and household contacts were instructed to record the presence of any systemic and respiratory symptoms in a symptom diary daily throughout the study. Telephone calls were made monthly outside influenza seasons and fortnightly within season to monitor for any acute respiratory illnesses. Households were also reminded to report any acute respiratory illnesses to the study hotline as soon as possible after illness onset. Home visits were triggered by the presence of any 2 symptoms or signs of fever 37.8°C, chills, headache, sore throat, cough, presence of phlegm, coryza, or myalgia in any household member. During home visits, nasal and throat swab samples were collected from all household members regardless of illness. Home visits were repeated at 3‐day intervals until acute illnesses resolved. Households were compensated with supermarket vouchers (or book tokens for children) worth US$65 for enrolment in the study, plus vouchers of US$13 for each serum specimen provided and US$6.5 for each home visit.
Ethics. All subjects aged 18 years gave written informed consent. Proxy written consent from parents or legal guardians was obtained for subjects aged 17 years of age, with additional written assent from those 8–17 years of age. The study protocol was approved by the Institutional Review Board of the University of Hong Kong.
Outcome measures. The primary outcome measure was influenza virus infection in study subjects and their household contacts indicated by a 4‐fold or greater increase in antibody titer. Secondary outcome measures included (1) reverse‐transcription polymerase chain reaction (RT‐PCR)–confirmed influenza, (2) acute respiratory illness (ARI) as determined by self‐reported symptoms (at least any 2 of temperature 37.8°C, headache, sore throat, cough, presence of phlegm, coryza, and myalgia), and (3) influenza‐like illness (ILI), defined as temperature 37.8°C plus cough or sore throat. Acute reactions were recorded by parents for 4 days after vaccination.
Sample size justification. This study was designed as a pilot study for a larger trial and thus was not powered to detect indirect benefits. The sample size of 120 families was chosen to allow us to estimate attack rates in study subjects of 20% to a precision of ±7%, and to confirm the logistical arrangements and the feasibility and acceptability of the study protocol.