Preliminary Findings of a Randomized Trial of Non- Pharmaceutical Interventions to Prevent Influenza Transmission in Households Benjamin J. Cowling 1 , Rita O. P. Fung 1 , Calvin K. Y. Cheng 1 , Vicky J. Fang 1 , Kwok Hung Chan2, Wing Hong Seto3, Raymond Yung 4 , Billy Chiu5, Paco Lee6, Timothy M. Uyeki7, Peter M. Houck8, J. S. Malik Peiris2, Gabriel M. Leung 1 * 1 Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China, 2 Department of Microbiology, The University of Hong Kong, Hong Kong, China, 3 Queen Mary Hospital, Hospital Authority, Hong Kong, China, 4 Centre for Health Protection, Department of Health, Government of the Hong Kong SAR, China, 5 Hong Kong Sanatorium and Hospital, Hong Kong, China, 6 St Paul’s Hospital, Hong Kong, China, 7 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 8 Division of Global Migration and Quarantine, National Center for Preparedness, Detection and Control of Infectious Diseases, Centers for Disease Control and Prevention, Seattle, Washington, United States of America Abstract Background: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. Methodology/Principal Findings: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of ,48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. Conclusions/Significance: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. Trial Registration: ClinicalTrials.gov NCT00425893, HKClinicalTrials.com HKCTR-365 Citation: Cowling BJ, Fung ROP, Cheng CKY, Fang VJ, Chan KH, et al. (2008) Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households. PLoS ONE 3(5): e2101. doi:10.1371/journal.pone.0002101 Editor: Yang Yang, Fred Hutchinson Cancer Research Center, United States of America Received January 4, 2008; Accepted March 19, 2008; Published May 7, 2008 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Funding: This work has received financial support from the US Centers for Disease Control and Prevention (grant no. 1 U01 CI000439-01), the Research Fund for the Control of Infectious Disease, Food and Health Bureau, Government of the Hong Kong SAR, and the Area of Excellence Scheme of the Hong Kong University Grants Committee (grant no. AoE/M-12/06). The sponsors had no role in data collection and analysis, or the decision to publish, but the CDC was involved in study design and preparation of the manuscript. This work represents the views of the authors and not their institutions, including the Centers for Disease Control and Prevention. Competing Interests: The authors have declared that no competing interests exist. * E-mail: gmleung@hku.hk Introduction The specter of an influenza pandemic continues to threaten, with annual outbreaks of highly-pathogenic H5N1 in birds [1] and continued sporadic human H5N1 cases and clusters [2] with some reports that suggested limited, non sustained human-to-human transmission of H5N1 viruses [3,4]. If a pandemic virus strain were to emerge, pre-pandemic vaccines would be available to some populations although of unknown efficacy, but development and distribution of initial doses of influenza vaccine specifically made against the pandemic strain would not be available for at least 4–6 months [5]. Influenza antiviral medications would likely be in short supply in many regions, particularly in developing countries, and might have modest effectiveness against the pandemic strain, PLoS ONE | www.plosone.org 1 May 2008 | Volume 3 | Issue 5 | e2101