because of the emergence of antiviral resistance or other reasons [6]. Furthermore, few of these pharmaceutical measures can be applied at pandemic scale. Only non-pharmaceutical interventions [7–12] including use of face masks, improved hand hygiene, cough etiquette, social distancing measures, and travel restrictions would be available to the majority of the world’s population. Interpan- demic influenza is associated with thousands of deaths every year in Hong Kong [13] and likely hundreds of thousands worldwide every year [14,15], therefore simple personal protective measures could be beneficial during annual epidemics if found to be effective in reducing transmission, and as an adjunct to influenza vaccination. We implemented a prospective cluster-randomized trial [16] to test whether two such non-pharmaceutical interventions can reduce transmission of interpandemic influenza in households. Methods The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Protocol S1 and Checklist S1. Recruitment and follow-up of participants From 30 first-contact outpatient clinics in both the private and public sectors across Hong Kong, we enrolled 944 Hong Kong residents aged at least 2 years, reporting at least two symptoms of influenza-like-illness (ILI) (such as fever $38uC, cough, sore throat, coryza, headache, malaise, chills, fatigue, etc.), and living in a household with at least two other individuals none of whom had reported ILI symptoms in the preceding 14 days. These index subjects provided nasal and throat swab (NTS) specimens which were combined and tested with the QuickVue Influenza A+B rapid diagnostic test (Quidel Corp, San Diego, CA) and those subjects with a positive result for influenza A or B were randomized and further followed up. For participants enrolled after June 1, 2007, those index subjects with a negative QuickVue result but a fever $38uC were also randomized and further followed up. Data on clinical signs and symptoms were collected for all subjects, and an additional NTS was collected for later confirmation of influenza infection by viral culture. Following randomization a home visit was scheduled (to take place within 36 hours) to implement the intervention, collect baseline demographic data and NTS from all household members aged $2 years, and to provide and describe proper use of a free tympanic thermometer and the daily symptom record sheets. During the 9 days following the initial home visit, all household members were asked to keep symptom diaries, and three further home visits were scheduled at 3, 6 and 9 days after the baseline household visit to monitor adherence to interventions and to collect further NTS from all household members aged $2 years. At the final (day 9) home visit, the study nurse collected the symptom diaries and evaluated adherence to interventions by interview and by counting the number of surgical masks remaining or weighing the amount of soap and alcohol left in bottles and dispensers. Ethics All subjects aged 18 years and older gave written informed consent. Proxy written consent from parents or legal guardians was obtained for subjects aged 17 years and younger, with additional written assent from those aged 8 to 17 years. The study protocol was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster and was conducted in compliance with the Declaration of Helsinki [17]. Effectiveness of NPIs for Flu Interventions Our study compared three interventions. In the control arm, households received education about the importance of a healthy diet and lifestyle, both in terms of illness prevention (for household contacts) and symptom alleviation (for the index). Households in the face mask arm received the control intervention plus education about the potential efficacy of masks in reducing disease spread to household contacts if all parties wear masks, distribution of a box of 50 surgical masks (Tecnol – The Lite One, Kimberly Clark, Roswell, GA) for each household member (or a box of 75 paediatric masks for children aged 3–7 years), and demonstration of proper face-mask wearing and hygienic disposal. Index subjects and all household contacts were taught to wear masks as often as possible at home (except when eating or sleeping) and also when the index was with the household members outside of the household. Households in the hand hygiene group received the control intervention plus education about the potential efficacy of proper hand hygiene in reducing transmission, distribution of an automatic alcohol hand sanitizer (WHO recommended formula- tion II, liquid content with 75% isopropyl alcohol, Vickmans Labs Ltd., Hong Kong), liquid hand soap (Avalon organics glycerin hand soap, Petaluma, CA), individual small (125 ml) bottles of alcohol hand gel (Gellygen gel with 70% ethyl alcohol, Brymore SA, Italy), and demonstration of proper hand washing and hand antisepsis [18]. All household members including the index subject were taught to use the liquid soap in place of their regular soap after every washroom visit and in general when their hands were soiled or after sneezing or coughing, while they should use the alcohol hand sanitizer or hand rub when first returning home and immediately after touching any potentially contaminated surfaces. At the final home visit, households were reimbursed for their participation time with a supermarket voucher worth approxi- mately US$20. Objectives The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Outcomes The primary outcome measure was the secondary attack ratio (SAR) at the individual level i.e. the proportion of household contacts of an index case who subsequently became ill with influenza. We evaluated the SAR using a laboratory definition (at least one follow-up NTS positive for influenza by viral culture or PCR) as the primary analysis, and three different clinical definitions of influenza as secondary analyses. The first definition of clinical influenza was fever $38uC or at least two of the following symptoms: headache, coryza, sore throat, aches or pains in muscles or joints, cough, or fatigue. The second definition was at least two of the following signs and symptoms: fever $37.8uC, cough, headache, sore throat, aches or pains in muscles or joints [19]. The third definition was the standard WHO/CDC influenza-like illness definition: fever $37.8uC plus cough or sore throat [20]. A secondary outcome measure was the secondary attack rate (SAR) at the household (cluster) level i.e. the proportion of households with one or more secondary case. PLoS ONE | www.plosone.org 2 May 2008 | Volume 3 | Issue 5 | e2101