Effectiveness of NPIs for Flu Table 3. Factors affecting the laboratory-confirmed influenza and clinical influenza secondary attack ratios in the 350 household contacts. Laboratory-confirmed influenza Clinical influenza* Definition 1 Definition 2 Definition 3 95% CI for OR 95% CI for OR 95% CI for OR 95% CI for OR OR{ 1.00 0.88 0.86 1.00 0.59 1.00 0.87 1.00 1.42 1.00 0.83 1.00 0.95 (0.34, 2.27) (0.39, 1.91) (0.31, 1.15) (0.51, 1.47) (0.72, 2.79) (0.42, 1.66) (0.48, 1.88) OR{ 1.00 0.87 0.88 1.00 1.40 1.00 0.76 1.00 1.30 1.00 0.82 1.00 0.79 (0.30, 2.51) (0.36, 2.14) (0.56, 3.53) (0.39, 1.48) (0.55, 3.08) (0.36, 1.87) (0.35, 1.80) OR{ 1.00 2.00 0.80 1.00 1.28 1.00 0.99 1.00 0.63 1.00 0.55 1.00 1.44 (0.57, 7.02) (0.22, 2.89) (0.36, 4.60) (0.38, 2.58) (0.10, 4.07) (0.16, 1.84) (0.43, 4.85) Control group Face mask group Hand hygiene group Child (aged#15) Adult (aged 16+) Female Male Not vaccinated Vaccinated in past 1 year 37 Child (aged#15) index Adult (aged 16+) index Female index Male index n 202 60 83 54 291 211 134 308 52 70 68 54 OR{ 1.00 1.16 1.07 1.00 1.75 1.00 1.10 1.00 0.46 1.00 0.51 1.00 0.80 (0.31, 4.34) (0.29, 4.00) (0.43, 7.16) (0.52, 2.33) (0.07, 2.98) (0.18, 1.43) (0.30, 2.13) *Clinical influenza definition 1 is fever$38uC or at least 2 of headache, runny nose, sore throat, aches or pains in muscles or joints, cough, or fatigue. Clinical influenza definition 2 is at least 2 of fever$37.8uC, cough, headache, sore throat, aches or pains in muscles or joints. Clinical influenza definition 3 is the standard CDC classification of fever$37.8uC plus cough or sore throat. {OR = odds ratio. doi:10.1371/journal.pone.0002101.t003 no indication of greater efficacy in this subgroup. Thirdly, there is the potential for recruited households to be biased towards including household contacts with pre-existing immunity, as discussed above. An alternative approach would have been to randomize a much larger cohort of initially uninfected households, who were then followed throughout an influenza season. However such a longitudinal study would require greater resources by several orders of magnitude than the one proposed here, due to the low attack rate of influenza. In conclusion, there remains a serious deficit in the evidence base of the efficacy of non-pharmaceutical interventions. The US Centers for Disease Control and Prevention have awarded grants to study non pharmaceutical interventions in community settings [40], including this study. Other funded study designs include symptom-based recruitment (as in our study) and longitudinal studies of initially uninfected cohorts, in children and adults and in various settings including households, schools and student halls of residences. We eagerly anticipate that conclusive evidence will become available as these studies proceed in the coming months, finally allowing empirically-driven pandemic planning. Supporting Information Table S1 Performance of alternative definitions of clinical influenza versus the gold standard of laboratory-confirmed influenza infection in household contacts. Found at: doi:10.1371/journal.pone.0002101.s001 (0.03 MB DOC) Figure S1 Study recruitment versus local influenza activity. a) daily recruitment rate (patients per working day); b) Local sentinel surveillance data of influenza-like-illness (number of ILI consul- tations per 1000 consultations) by the Centre for Health Protection; c) rate of positive influenza isolations among specimens submitted to the WHO reference laboratory of Queen Mary Hospital, Hong Kong. Found at: doi:10.1371/journal.pone.0002101.s002 (1.23 MB EPS) Text S1 Appendix with additional details of laboratory proce- dures Found at: doi:10.1371/journal.pone.0002101.s003 (0.02 MB PDF) Protocol S1 Trial protocol Found at: doi:10.1371/journal.pone.0002101.s004 (0.17 PDF) Checklist S1 CONSORT checklist Found at: doi:10.1371/journal.pone.0002101.s005 (0.03 PDF) MB MB Acknowledgments We thank all the doctors, nurses and staff of participating centers for facilitating recruitment; Conrad Lam, Winnie Wai, Yolanda Yan and Eileen Yeung for research support; and all field nurses and health care workers for assistance with recruitment and conducting the home visits. Author Contributions Conceived and designed the experiments: JP GL BC WS RY. Performed the experiments: JP KC BC RF CC. Analyzed the data: JP GL KC BC VF. Contributed reagents/materials/analysis tools: JP KC. Wrote the paper: JP GL KC TU BC RF CC VF WS RY BC PL PH. PLoS ONE | www.plosone.org 8 May 2008 | Volume 3 | Issue 5 | e2101