Two randomised controlled trials of personal public health measures in Australia and Hong Kong investigating effectiveness of the use of face masks and hand washing in the prevention of secondary cases of influenza-like illness (ILI) or actual influenza in households following diagnosis of a confirmed case of seasonal flu in one family member.  

Australia

Australia - Face mask use and prevention of secondary respiratory virus transmission in households - comparing simple surgical masks, N95 masks versus no masks

MacIntyre CR, Epid MA, Cauchemez S, Dwyer DE, Seale H, Cheung P, et al. Face mask use and control of respiratory virus transmission in households. Emerg Infect Dis [serial on the Internet]. 2009 Feb [date cited]. Available here.

Description

This article describes a study carried out a prospective, cluster-randomized trial of mask use in households in Australia during two winter seasons of 2006 and 2007. The study population comprised households with adults with known exposure (within the household) to a child with fever and respiratory symptoms as diagnosed in the emergency department of a paediatric hospital and a paediatric primary care practice. The participating households were randomized to one of three groups asked to wear ordinary surgical masks, P2 masks (equivalent to N95 masks) and a control group were no masks were offered. Adherence to face mask use was specifically monitored during each household follow-up. The reasons for non-adherence were investigated. The outcome measure was respiratory illness in the adults.  In total, 290 adults were recruited from 145 households and 47 households were randomized to the surgical mask group, 46 to the P2 mask group and 52 to the control group. Samples were collected from 141 children and a variety of respiratory viruses were detected in 79 of the children. In 29 of the 79 influenza viruses A (n=22) or B (n = 7) were detected either singly or in 3 influenza A infections with other viruses. The other viruses included adenoviruses, RSV, PIV and coronaviruses.

Self-reported adherence to mask wearing all o the time in the day at home was never higher than 50% and declined with time with little difference between the surgical mask and P2/N95 mask group.  The main reported problems with mask use were that the mask was uncomfortable, that children did not want the parents wearing masks or that the parents forgot to wear the mask.

An intention to treat analysis was undertaken meaning looking at the proportion of adults that developed respiratory illness according to the allocation by group ignoring whether or not the adults used the mask. Influenza like illness (ILI) was reported in 21/94 (22.3%) in the surgical mask group, 14/92 (15.2%) in the P2/N95 mask group and 16/100 (16.0%) in the control group. Samples were collected from 43/51 (84%) sick adults, with respiratory viruses isolated in 17/43 (40%) sick adults. Viral pathogens were isolated from 6/94 (6.4%) in the surgical mask group, 8/92 (8.7%) in the P2/N95 mask group and 3/100 (3.0%) in the control group. Conversely when the reserchers analysed comparing people who did and did not use masks there seemed to be some protective effect. Irrespective of the assumed value for the incubation period, the relative reduction in the daily risk of acquiring a respiratory infection associated with adherent mask use (P2 or surgical) was in the range of 60%-80%. Though to their credit the researchers correctly did not emphasise this result. The authors concluded that community use of face masks is unlikely to be an effective control police for seasonal respiratory diseases.

Hong Kong

Hong Kong  - Face mask and hand washing for prevention of secondary influenza virus transmission in households - comparing simple surgical masks, hand washing versus neither in a control group Preliminary findings of a randomized trial of non-pharmaceutical interventions to prevent influenza transmission in households

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
This article can be found here.

Description

The objective of the study was to quantify the effectiveness of face masks or hand hygiene in reducing transmission of influenza to household contacts at the individual level. A randomized controlled trial of households (composed of at least three members) was undertaken where an index subject presented with influenza-like illness (ILI) symptoms of less than 48 hours duration. To do this, they enrolled 944 Hong Kong residents aged at least 2 years, from 30 first-contact outpatient clinics in both the private and public sectors. Out of the 944 there were 158 index subjects that were considered to have reasonable evidence of influenza by either a positive rapid test for influenza types A or B (Quickvue test  n = 144) or having a temperature of over 38oc n = 44). The households of the index subjects were randomized to one of three interventions – control, surgical face mask use and hand hygiene though with a ratio of 3:1:1. 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 that subsequently became ill with laboratory confirmed or clinical influenza. The overall laboratory-confirmed SAR was only 6.0% which represented only 21 individuals. A number of clinical case definitions were also used giving higher numbers but whichever definition was done there were no significant differences between the interventions and the control group.  Where there were problems were adherence. After randomisation substantial numbers of families declined to participate 53 of the 127 control households refused to participate as did 13 of 35 face mask household and 4 of 36 hand-washing houeholds. In the face masks households only 45% of the index cases reported wearing a mask often or always. The percentage for other household members was 21%. Hong Kong is a community used to wearing masks and in the control and hand-washing groups 30% and 28% of the index cases reported still wearing masks though their household contacts rarely did so. The authors noted that their study is the first reported community-based randomized trial of these interventions specifically against influenza, with laboratory-confirmed outcomes and that they had learnt many important lessons for the next phase of the study.
           
ECDC Comment (12/03/2009)

There are two key questions here. 1. Do either mask-wearing and routine hand-washing reduce influenza transmission? And 2. should either or both be encouraged or recommended for seasonal or pandemic influenza?  As part of the preparation of its 2005 Pandemic Planning Guidance WHO organised consultations about what non-pharmaceutical public health measures (PHMs) should be recommended for mitigating the impact of a pandemic. There was considerable interest in these following SARS, not least since there was evidence from Hong Kong that the combination of PHMs: self-isolation, school closures, mask wearing, avoiding crowds, cancelling large events, stopping working, hand washing etc etc was clearly associated in Hong Kong at least with a marked decline in seasonal influenza incidence.(1)  However it was equally unclear which of the many interventions were effective and which were  not.  Recommendations were made in the Annex to the 2005 Planning Guidance(2) but a major conclusion of two supporting published reviews was that for many of the measures the evidence simply did not exist concerning which of the many suggested measures were effective and which were a waste of time and money or simply a distraction.  So the reviews concluded more research is needed.(3,4) To their credit groups of researchers, especially stimulated by a call for proposals from the American CDC started doing such work. One of the targets of the research was the personal measures that people can undertake, regular hand-washing and mask wearing. These two papers are some of the first outputs from for two studies employing randomised community based trials against either all respiratory viruses (Australia) or influenza (Hong Kong). Neither trial has been able to come up with clean cut answers indeed both demonstrate the difficulties of undertaking randomised trials of behaviours but both made major methodological advances and the researchers are to be congratulated. Both trials also demonstrate what some have called Monto’s Rule named after the eminent influenza epidemiologist Prof Arnold Monto. He suggested that from his long experience that if you set up a trial of anything to reduce influenza transmission (masks, antivirals, a new vaccine) you can expect that at least in the first season your population of study will experience unusually low incidence of influenza. Indeed the Australian study hardly was able to much influenza at all with A & B influenza viruses representing a minority of the infections they considered. That study is really looking at all and any respiratory infection and is open to the problem that seasonal influenza may not behave like other viruses. However the biggest problem of both studies was that people simply found it hard to adhere to the interventions, many people in the groups randomised to wear masks in the Australian study. The same was true in the Hong Kong study people where many families declined to participate after recruitment and in addition index cases in the non-mask wearing groups still wore masks. Neither study could demonstrate that either mask-wearing reduced influenza transmission and the Hong Kong study could not detect an effect of hand-washing. Is it then fair to conclude that mask wearing and hand washing will not reduce influenza transmission? Or that they should not be encouraged or recommended for seasonal or pandemic influenza? Well from a scientific point of view neither of these studies give evidence that allows one to answer either question. Both were under-powered meaning that they did not have the numbers to answer the questions either way. However they also demonstrate a real problem for these trials with the low adherence to the recommended interventions. Concerning hand washing it should be remembered that there are other earlier trials that did show an effect, though for all respiratory infections.(5,6) There has never been any reported trial of hand-washing reported with influenza as an end-point. There were other important problems. It was difficult to be sure if the household contacts were being infected by the index case.

So what should be the next steps to answer the key questions? The Hong Kong group refined their methods from what was a pilot and have undertaken their main study in 2008. The Australian group did not continue and felt that recommending household use of masks was ineffective for seasonal respiratory disease while noting that motivation of the public for mask wearing would be much higher in a pandemic. Both studies demonstrated the difficulties of conducting these trials and analysing their results. It may be that the mask question best now be approached by highly controlled experiments with volunteers. Such studies are starting in Europe but they may need international support because of their expense.

References

1. Lo JY, Tsang TH, Leung YH, Yeung EY, Wu T, Lim WW. Respiratory infections during SARS outbreak, Hong Kong, 2003. Emerg Infect Dis 2005;11(11):1738-41.
2. World Health Organization. WHO Global Influenza Preparedness Plan. 2005 Annex One Recommendations for non-pharmaceutical public health measures (pages 42-46) 
3. World Health Organization Writing Group. Nonpharmaceutical interventions for pandemic influenza, national and community measures. Emerg Infect Dis [serial on the Internet]. 2006 Jan [date cited].
4. World Health Organization Writing Group. Nonpharmaceutical interventions for pandemic influenza, international measures. Emerg Infect Dis [serial on the Internet]. 2006 Jan [date cited]. Vol 12: 88-94
5. Falsey AR, Criddle MM, Kolassa JE, McCann RM, Brower CA, Hall WJ. Evaluation of a handwashing intervention to reduce respiratory illness rates in senior day-care centers. Infect Control Hosp Epidemiol. 1999;20:200–2.
6. Luby SP, Agboatwalla M, Feikin DR, Painter J, Billhimer W, Altaf A, et al. Effect of handwashing on child health: a randomised controlled trial. Lancet. 2005;366:225–33.

Comment to: influenza@ecdc.europa.eu