Figure 2. Delays between index case symptom onset, random- ization, and intervention in 128 households. Time intervals a) from symptom onset in the index subject to randomization; b) from randomization to application of the intervention; c) from symptom onset to application of the intervention. doi:10.1371/journal.pone.0002101.g002 Although we found little effect of the interventions in preventing household transmission, our study was underpowered. Neverthe- less, our point estimates are close to null, strongly suggesting true equipoise until a definitive randomized trial with sufficient power (i.e. a much larger sample size) rigorously tests the relative efficacy of these interventions. A larger study will also allow us to explore in more detail the transmission dynamics of influenza in households including finer age stratifications and transmission within and between different age groups, which was not possible in the current study. We observed generally low adherence to interventions. More than one in four household contacts in the face mask group did not wear a surgical mask at all during the follow-up period. Adherence to the face mask intervention was higher in the index subjects, likely due to their intention to reduce the probability of infecting other household members and possibly because of the recent memory of SARS in 2003, during which the majority (76%) of the general public reported that they wore face masks in public, and most engaged in numerous protective practices [28,29]. However more than one in four index cases in the control and hand hygiene intervention arms reported wearing masks at home of their own accord, thereby contaminating this intervention. Effectiveness of NPIs for Flu While self-reported hand-hygiene practices were similar across the three groups, we note that contamination of this intervention may be lower firstly because the control and face mask group did not receive the education component on proper hand hygiene, secondly because those groups did not receive the alcohol sanitizer and hand rub. Overall, adherence to the hand hygiene intervention in terms of soap and alcohol use appeared low when benchmarked against rates recommended in health care settings. However we note that a previous randomized community study found that 38% of households used more than 57 g of alcohol hand sanitizer during a 2-week period [30], whereas more than 50% of the households in our study used more than 56 g in 10 days. Overall, the SAR was lower than we had expected. Only 6% of household contacts developed laboratory-confirmed influenza, whereas 5%–18% of contacts developed clinical influenza, depending on case definitions. This is in contrast to previous studies in France [21], Seattle [31] and other places [19], where SARs were approximately 25% (laboratory-confirmed influenza in the latter two studies). There could be a number of reasons for this. First, there has not been significant antigenic drift in the predominant circulating strains of influenza viruses in recent years, potentially resulting in higher levels of pre-existing immunity among our study population. Secondly, our inclusion criteria specified that an index subject should be the only member of their household to be suffering from ILI, and no other household contacts should have experienced ILI in the past 14 days, to ensure that the index is a true index within the household. However, the latter condition may have biased our recruitment towards households where some members were already immune from infection, since among households where all contacts were susceptible there might be a greater possibility of secondary cases being observed prior to the index case presenting to their primary care provider 1–2 days after symptom onset (Figure 2a). However the French study used similar inclusion criteria and found a much higher SAR [21]. Antiviral prescriptions for index subjects followed with home visits appears to affect transmission as would be expected [19], where there was a relative reduction in the SAR of approxi- mately 30% albeit based on a limited sample size. Vaccination of household contacts might also have reduced the risk of secondary infection (Table 3). Finally, environmental or behavioral differences could lead to differing secondary transmission rates in our study, for example differences in use of air conditioning, high background use of face masks, or differences in the amount of time spent with family members at home. We did not collect the relevant data in the present study however; future studies should consider these externalities. Results from other settings with a similar design would be helpful in assessing, at least qualitatively, these respective effects. The variability in clinical SARs depending on the choice of case definition has been noted in previous studies [21,32,33]. Influenza infection is associated with a wide spectrum of symptoms and severities, and in our study 4 (19%) of the 21 laboratory-confirmed secondary cases were asymptomatic. On the other hand, only 10 (48%) of laboratory-confirmed secondary cases reported fever $38uC. With such a range of symptoms caused by influenza, and when infections with other circulating upper respiratory viruses cause similar symptoms, collectively referred to as influenza-like-illnesses, it is difficult to find a single case definition which is highly sensitive and also highly specific for influenza virus. With a small sample size it is not possible here to derive clinical prediction rules [33–38], however we compared three alternative case definitions and PLoS ONE | www.plosone.org 6 May 2008 | Volume 3 | Issue 5 | e2101