Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review

Search strategy

We sought to identify studies in community settings that examined the effect of a hand hygiene exposure (e.g. hand washing or hand sanitiser) on the risk or rate of developing influenza or an acute respiratory tract infection. Searches were carried out in any language in Medline (1946–), Embase (1974–) and Global Health (1910–) though OvidSP and in the Cochrane Central Register of Controlled Trials on 27 June 2011 and updated on 13 February 2012. Reference lists of relevant review articles were searched by hand. The following search strategy was used:

Medline

Embase and Global Health

Cochrane Central Register of Controlled Trials

Eligibility

Articles describing original research conducted in community settings were eligible for inclusion if they reported a measure of the effect of hand hygiene on influenza or acute respiratory tract infection or the means to calculate it. Community settings included institutions such as schools, childcare centres and workplaces as well as domestic residences. We did not include research conducted in hospitals or care homes as the focus was on non-healthcare settings. We considered individually or cluster randomised controlled trials, quasi-randomised controlled trials, crossover trials, cohort studies, case–control studies and cross-sectional surveys. We excluded before–after and ecological studies. We also excluded studies that described multicomponent hygiene interventions or that tested large numbers of measures of hand hygiene without adjustment for multiple testing.

Study selection and data extraction

Two authors (EF and CWG) independently read all titles and relevant abstracts to determine eligibility for full-text review. Reference lists of relevant articles were hand searched for further references. EF and CWG independently read all articles included in the full-text review, determined which met inclusion criteria and extracted relevant data. Any discrepancies were discussed and if necessary referred to a 3rd author (ACH). Data were extracted on definitions of outcome, descriptions of exposure or intervention, study size, design, population, setting, for example, institutional versus domestic, high versus low or middle-income, duration and effect sizes, for example, risk, rate or odds ratio with 95% confidence intervals. Where possible, the main reported multivariable measures of effect were presented for each study with 95% confidence intervals. If no effect measure was reported but raw figures were given, the most appropriate ratio measure of effect was calculated along with 95% confidence intervals (according to formulae in Appendix S1⁸) by two authors independently. For cluster intervention studies where it was necessary to calculate an effect measure, if possible a design effect was also calculated⁹ (see Appendix S1). The square root of the design effect was then multiplied by the standard error, and 95% confidence intervals were recalculated using the generic inverse variance method in RevMan software to account for the effect of clustering⁹ (see Appendix S1 for further details). This is denoted by the symbol^† in the tables. Where this was not possible, for example, if no intracluster correlation coefficient was reported and none was available from similar studies, 95% confidence intervals were calculated but without adjustment for clustering. This would result in artificially narrowed confidence intervals which are denoted by italics in tables.

Data presentation

Results were presented in Tables 1 (laboratory-confirmed influenza) and Table 2 (acute respiratory tract infection including influenza-like illness). These were adapted from GRADE ‘Summary of Findings’ tables.¹⁰ It was not feasible to meta-analyse these data due to heterogeneity, in particular variable reporting of intracluster correlation coefficients, design effect and adjustment for clustering in cluster intervention trials. Instead, we plotted the effect size against the log of the sample size to compare the effects of hand hygiene on (i) influenza and (ii) acute respiratory tract infection in different settings. Where results were presented by setting income, the World Bank classification of countries as ‘low’, ‘lower–middle’, ‘upper–middle’ and ‘high’-income economies was used. An exception to this was a study in Pakistan (a lower–middle-income economy) that was conducted in squatter settlements; this was described as a ‘low-income’ setting.

Quality assessment

A key feature of the GRADE method is that quality is assessed across outcomes rather than by individual study.¹¹ There are four categories of quality ratings in GRADE –‘high’, ‘moderate’, ‘low’ and ‘very low’. Briefly, the default quality rating is ‘high’ for evidence from randomised controlled (including cluster) trials and ‘low’ for evidence from observational studies. Evidence for each outcome is examined for risks of bias, inconsistency, indirectness, imprecision and publication bias. Quality may be rated down if there is evidence of any of these five factors, for example, a randomised controlled trial where risk of bias is judged to be serious would be rated down by 1 point from ‘high’ to ‘moderate’. Conversely, quality may be modified upward if there is a large magnitude of effect, a dose response observed or if any plausible confounders are likely to minimise the observed effect. Quality was assessed independently by two authors for each outcome following GRADE guidance. Overall quality ratings are shown in Tables 1 and 2 (with ‘low’ and ‘very low’ categories combined). Further information on how ratings were determined for each outcome is given in the table footnotes.

Included studies

Eight hundred and seventy-five citations were found from searches of electronic databases, of which 96 were retrieved for full-text review and 13 met inclusion criteria. Three additional references were found through hand searches – see Figure 1.

Intervention studies were carried out in various community settings including institutions: schools (5), childcare centres (2), an elderly day care centre (1), an office (1) and student halls of residence (1) as well as domestic settings: households (4) and squatter settlements (1). Interventions included hand hygiene education along with provision of either soap (3), hand sanitiser (7) or both (1), education and required washing or sanitising of children’s hands (3), education and training of children, teachers and parents (1). Further details of interventions are given in Table S1. The one included observational study was a matched case–control study in healthy clinic attendees in which usual hand hygiene practices were surveyed.

Hand hygiene and laboratory-confirmed influenza – institutional settings

In two cluster randomised trials of a hand hygiene intervention in schools,^12,13 rates of laboratory-confirmed influenza were lower in those receiving a hand hygiene intervention compared with controls – rate ratio (RR) 0·50 (95% confidence interval 0·38–0·66)¹³ and RR 0·81 (0·54–1·23)¹²– although this was only significant for one study in a lower–middle-income setting. In the second study, there was a significant reduction in incidence of influenza A [RR 0·48 (0·26–0·87)] but not influenza B [RR 1·45 (0·79–2·67)] in subgroup analysis.¹² Overall, this evidence was rated moderate quality.

A small matched case–control study¹⁴ provided low-quality evidence of a protective effect in healthy clinic attendees in an upper–middle-income setting: participants reporting frequent hand washing were significantly less likely to be seropositive to influenza A H1N1 pandemic strain – odds ratio 0·21 (0·06–0·74) – than those who washed their hands less often.

Hand hygiene and laboratory-confirmed influenza – domestic settings

In one household study,¹⁵ there was no evidence of a protective effect of hand hygiene on rates of laboratory-confirmed influenza [RR 1·15 (0·57–2·32)]. The quality of this evidence was low. Two household studies of the effect of implementing a hand hygiene intervention to prevent secondary influenza transmission after a case in the household^16,17 provided moderate-quality evidence of no effect on secondary transmission. See Table 1.

Hand hygiene and influenza-like illness or acute respiratory tract infection – institutional settings

In the same two cluster randomised studies in schools reported above,^12,13 hand hygiene interventions were associated with a reduction in rates of absenteeism due to clinically defined influenza-like illness (a moderate-quality outcome), which was significant in a lower–middle-income setting – RR 0·62 (0·49–0·78). In three non-randomised cluster intervention studies in elementary schools,^18–20 there was low-quality evidence of a trend towards lower rates of absence due to respiratory tract illness in those receiving the hand hygiene intervention, significant for two of three studies.^18,20 One cluster randomised trial of a hand hygiene intervention in childcare centres²¹ found high-quality evidence of a marginal effect – RR 0·95 (0·89–1·01), which was significant for those aged under 24 months [RR 0·90 (0·83–0·97)] and for children who complied best with the hand hygiene intervention [RR 0·89 (0·82–0·97)]. In another cluster intervention study in childcare centres²² where the outcome was rated ‘low quality’, no significant protective effect was seen – risk ratio 0·80 (0·52–1·23).

In an elderly day care centre,²³ providing staff with alcohol hand gel resulted in no change to respiratory tract illness rates in elderly attendees over the winter – RR 1·28 (0·70–2·32). A small individually randomised trial in the workplace²⁴ found a significantly lower risk of a ‘cold’ in those receiving an alcohol hand gel intervention – odds ratio 0·35 (0·17–0·71). In a study in student halls of residence,²⁵ although risk of respiratory tract illness was lower in those receiving a hand hygiene intervention, the effect was not significant – risk ratio 0·80 (0·63–1·01). All evidence for these outcomes was rated ‘low quality’.

Hand hygiene and influenza-like illness or acute respiratory tract infection – domestic settings

A cluster randomised trial of a soap and hand hygiene education intervention in squatter settlements in a low-income setting²⁶ provided high-quality evidence of a significant reduction in rates of cough and difficulty breathing in children aged under 15 – RR 0·49 (0·35–0·63). A household study in the USA¹⁵ provided low-quality evidence of no effect – RR 0·91 (0·69–1·20).

Finally, several cluster randomised studies investigated whether hand hygiene interventions reduced secondary transmission of influenza-like illness (ILI) in households. Two studies from Hong Kong¹⁶ and Thailand¹⁷ provided moderate-quality evidence of no significant reduction in secondary household transmission of ILI when hand hygiene interventions were implemented after identification of a laboratory-confirmed index case. However, in a subgroup analysis in one study, there was a significant reduction in ILI rates in the hand hygiene group when the intervention was implemented within 36 hours of symptom onset in the index case – odds ratio 0·46 (0·22–0·96).¹⁶ There was high-quality evidence of no effect on secondary household transmission of respiratory tract illnesses from a North American study where the intervention was implemented prior to any index case²⁷– RR 0·97 (0·72–1·30). See Table 2.

Results for both influenza and acute respiratory tract infection outcomes are summarised graphically in Figure 2 where effect sizes follow a similar distribution across both types of outcome.

Summary of findings

There was moderate–high-quality evidence that hand hygiene was associated with a large reduction in influenza and acute respiratory tract infections in institutional settings (schools) and a domestic setting (squatter settlements) in two studies in low to middle-income countries. In higher-income countries, one study provided high-quality evidence of a small reduction in acute respiratory tract infections in childcare centres, and there was lower-quality evidence of a protective effect in schools and workplaces. For domestic settings, there was moderate–high-quality evidence that a hand hygiene intervention alone did not prevent secondary influenza transmission in households with an index case.

Strengths and limitations

Our review was carried out systematically with a comprehensive search strategy that identified all studies included in previous similar reviews along with several new studies published after the 2009 H1N1 influenza pandemic. We clearly defined outcomes and separated results by laboratory-confirmed influenza and clinically defined acute respiratory tract infection or influenza-like illness. We also reviewed quality of evidence by outcome according to GRADE criteria¹¹ and gave greater weight in our synthesis to outcomes rated ‘moderate’ or ‘high’ quality. We attempted to present results by setting (institutional versus domestic and high income versus low to middle income), as knowledge of effects expected in different settings would help to inform policymakers, although this approach was limited both by lack of studies and by the poor quality of studies in certain settings.

We decided not to generate a pooled estimate of effect due to heterogeneity of settings, hand hygiene interventions and outcomes across studies. Synthesising evidence was also made more difficult by poor methodology and reporting of some cluster intervention trials. Several studies had design flaws including insufficient numbers of clusters, no formal randomisation of clusters, no control for clustering in the analysis and no reporting of an intracluster correlation coefficient,²⁸ so it was not possible to calculate cluster-adjusted confidence intervals. However, outcome quality from any study with these issues was rated ‘low’ according to the GRADE system and evidence weighted accordingly. Heterogeneity of hand hygiene interventions may have affected results if some interventions were more effective than others. However, evidence suggests that both soap and water and various preparations of alcohol-based hand rub are effective in inactivating H1N1 pandemic strain influenza on human hands.²⁹ Assessing compliance with hand hygiene interventions was not carried out in a consistent way across studies, so apparent lack of effect may have been due to poor compliance rather than lack of effectiveness. In studies where compliance data were used to inform analyses, greater protective effects were seen in those with the best compliance. ^21,27

Comparison with previous reviews

Our results were consistent with earlier findings from a previous review of hand washing with water (±soap) in 2006 that found an overall 16% reduction in respiratory tract infections based on seven intervention studies.⁵ None of these studies examined influenza specifically, and overall quality of included studies was judged to be poor. Another meta-analysis of the effect of various hand hygiene interventions on respiratory tract infection across 13 studies, published in 2008⁶, estimated a pooled reduction of 21% for respiratory tract illness across multiple settings. Again, no study was specific to influenza, and individual studies had many methodological limitations. A Cochrane review of physical interventions to reduce respiratory tract virus transmission⁴ concluded that ‘the highest-quality cluster RCTs suggest respiratory tract virus spread can be prevented by hygienic measures, such as hand washing, especially around younger children’. A final review of the effect of hand gel on elementary school absenteeism did not provide a pooled effect estimate and concluded that studies were of poor quality with high-potential risk of bias.³⁰ We included several newer studies that were not found in any of these reviews,^{12–14,17,24} four of which incorporated the outcome laboratory-confirmed influenza.^12–14,17 We excluded several studies that were included in previous reviews because of (i) use of a before–after study design,³¹ where lack of accounting for seasonal variability of influenza and other external factors could introduce serious risks of bias and confounding and (ii) insufficient data reported on respiratory tract outcomes to calculate an appropriate effect measure.^32,33 In previous reviews, these studies were generally described as having major methodological limitations.

We also excluded studies that examined the effect of multicomponent hygiene interventions, for example, disinfecting surfaces as well as hands and toys^34–37 as it was difficult to isolate the relative effect of hand hygiene from among these interventions. None of these earlier studies examined the effect of influenza specifically. Three newer cluster randomised trials with influenza and influenza-like illness as outcomes were not eligible for inclusion as they examined the effect of hand hygiene only in combination with facemask use. All three studies (two in university halls of residence in the USA^38,39 and one of secondary transmission in German households⁴⁰) suggested a reduction in influenza and/or ILI in groups receiving hand hygiene and facemasks compared with controls but results were generally not statistically significant. A recently published cluster randomised trial⁴¹ of regular hand sanitiser use on ILI absence in Thai pre-schools was not eligible for inclusion because insufficient data were presented on ILI episodes to allow an effect measure to be calculated.

Interpretation and implications

The greatest effect of hand hygiene was seen in two studies in low to middle-income settings, which may partly be explained by differences in access to soap and hand-washing equipment. In higher-income settings, smaller effects were seen, which tended to be in institutions such as childcare centres and schools. This may be unsurprising as young children are both less likely to practise good hand hygiene and more prone to experience a relatively heavy burden of influenza-related morbidity.⁴² There is good biological plausibility for an effect⁴³: improving hand hygiene is likely to reduce transmission of influenza and other respiratory tract viruses by interrupting fomite and to some extent droplet spread,^29,44,45 although it is unlikely to affect aerosol transmission. The likely impact of hand hygiene depends on the relative importance of these different modes of influenza transmission and is likely to be situation-specific, for example, it may be less effective for repeated exposures. Nonetheless, in most domestic and institutional settings such as schools, hand hygiene would be expected to be a safe, acceptable intervention,⁴³ although evidence from schools suggests acceptability is greater if hand hygiene is used as a temporary measure to prevent ongoing disruption to lessons.⁴⁶ Finding interventions that successfully improve hand hygiene remains a challenge; several studies in this review suggested that there was little difference in hand hygiene behaviours between intervention and control groups. In general, interventions designed to improve health that are informed by behavioural change theory are more likely to succeed than others.⁴⁷ Compliance with hand hygiene interventions in particular is likely to depend on context, for example, fear generated during a pandemic situation might drive higher compliance,⁴³ especially if the perceived severity of threat is high. In such a situation, hand hygiene messages might help to promote general awareness of influenza-avoidance strategies such as social distancing and other respiratory tract hygiene behaviours.⁴³ In household settings, it will be important to intervene early either through efforts to improve general hand hygiene behaviour or advice to implement enhanced hand hygiene immediately after development of an index case (rather than waiting for physician confirmation of diagnosis). Taken together, these findings suggest that the effectiveness of hand hygiene at reducing transmission of influenza and acute respiratory tract infections is dependent on various factors including setting, context and compliance.

Future directions

Although hand hygiene has the potential to reduce transmission of influenza and acute respiratory tract infections, good compliance with interventions is essential. Improved understanding of the barriers to hand hygiene in community settings will help to inform development of context-specific interventions based on theories of behaviour change. Future research should seek to develop and evaluate such interventions, recognising that it may be difficult to generalise findings from studies carried out in non-pandemic years to pandemic situations.