key: cord-0765835-f53w54et authors: Hoffmann, T.; Bakhit, M.; Krzyzaniak, N.; Del Mar, C.; Scott, A.; Glasziou, P. title: Soap versus sanitiser for preventing the transmission of acute respiratory infections: a systematic review with meta-analysis and dose-response analysis date: 2020-07-24 journal: nan DOI: 10.1101/2020.07.22.20160432 sha: cd0e1297bf55aca693d71bfc5aa22b162dfbbc90 doc_id: 765835 cord_uid: f53w54et Objective: To compare the effectiveness of hand hygiene using alcohol-based hand sanitiser to soap and water for preventing the transmission of acute respiratory infections (ARIs), and assess the relationship between the dose of hand hygiene and the number of ARI, influenza-like illness (ILI), or influenza events. Methods: Systematic review of randomised trials that compared a community-based hand hygiene intervention (soap and water, or sanitiser) with a control, or trials that compared sanitiser with soap and water, and measured outcomes of ARI, ILI, or laboratory-confirmed influenza or related consequences. Searches were conducted in CENTRAL, PubMed, Embase, CINAHL and trial registries (April 2020) and data extraction completed by independent pairs of reviewers. Results: Eighteen trials were included. When meta-analysed, three trials of soap and water versus control found a non-significant increase in ARI events (Risk Ratio (RR) 1.23, 95%CI 0.78-1.93); six trials of sanitiser versus control found a significant reduction in ARI events (RR 0.80, 95%CI 0.71-0.89). When hand hygiene dose was plotted against ARI relative risk, no clear dose-response relationship was observable. Four trials were head-to-head comparisons of sanitiser and soap and water but too heterogeneous to pool: two found a significantly greater reduction in the sanitiser group compared to the soap group; two found no significant difference between the intervention arms. Conclusion: Adequately performed hand hygiene, with either soap or sanitiser, reduces the risk of ARI virus transmission, however direct and indirect evidence suggest sanitiser might be more effective in practice. Acute respiratory infections (ARI) cause a substantial annual health burden, and much more so in the current COVID-19 pandemic. Hand hygiene is one effective and low-cost intervention which reduces the transmission of ARIs [1] and is applicable in all countries and all settings. However, important questions for policy and practice are the "dose-response" of hand hygiene, and relative effectiveness of different materials (alcohol-based hand sanitiser; soap and water). This systematic review aimed to address these questions. Our recent systematic review and meta-analysis of physical interventions to interrupt or reduce the spread of respiratory viruses [2] (an update of the 2011 review [3] ) aimed to synthesise all randomised controlled trials of several physical interventions (including hand hygiene) which measured outcomes of ARI, influenza-like illness (ILI), or laboratoryconfirmed influenza (influenza) or related consequences (e.g. absenteeism). For the current systematic review, trials were eligible if they compared a hand hygiene intervention with a control, or compared hand sanitiser with soap and water. Trials in healthcare settings were excluded. We also screened a new Cochrane review of rinse-free handwashing in school and pre-school children for possible eligible studies [4] . Data were extracted by two authors (MB, NK) independently on: volume or weight of material (e.g. sanitiser or soap) used per person per day, and number of handwashes per person per day. When not reported directly, we estimated usage where possible (see Table 1 ). For estimation purposes, we used data on the average amount of material used per person per handwash as reported; if data were not reported, we assumed 0.035 grams of soap or 1.5ml of liquid used per handwash [5] . The following data were extracted from the parent systematic review [2] : 1) study characteristics; 2) risk of bias assessments; 3) type of handwashing intervention(s) (e.g. soap, sanitiser, gel); and 4) risk ratios (RR), log RR, and standard error values for ARI or ILI or influenza (including the outcome with most events from each study). . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 24, 2020. To assess the relationship between handwashes per person per day and the number of ARI or ILI or influenza events, we conducted the following analyses: 1) only studies whose number of handwashes could be estimated (regardless of the type of handwash material), subgrouped by the type of handwash material (soap vs sanitiser vs combination of sanitiser and soap) and 2) all studies (whether or not the number of handwashes could be estimated), subgrouped by the type of handwash material (soap vs sanitiser vs combination of sanitiser and soap). We used a Chi 2 test to test for subgroup interactions. Meta-analyses were conducted using Review Manager 5. The PRISMA flowchart (Fig 1) shows the number of trials identified from the updated 2020 systematic review [2] , the original 2011 review [3] , and additional sources. Eighteen trials were assessed as eligible; four were head-to-head comparisons of hand sanitiser and soap and water [6] [7] [8] [9] and 16 compared hand hygiene with a control [6, 8, [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] . Table 1 presents study characteristics. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 24, 2020. . . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 24, 2020. . is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 24, 2020. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 24, 2020. . https://doi.org/10.1101/2020.07.22.20160432 doi: medRxiv preprint Combining the three trials of soap and water hand hygiene versus control found a nonsignificant increase in ARI events: risk ratio 1.23 (95% CI 0.78 to 1.93) but with high heterogeneity (Figure 2 ; Appendix A.1 shows forest plot for all trials, regardless of whether number of handwashes could be estimated). Combining the six trials of hand sanitiser versus control found a significant reduction in ARI events: risk ratio 0.80 (95% CI 0.71 to 0.89), providing some indirect evidence in favour of hand sanitiser. Number of handwashes (hws) indicated in brackets after study reference where estimable. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 24, 2020. . Eleven of the trials provided sufficient information to estimate the dose of hand hygiene, which we converted to number of hand hygiene events per day. Plotted against the relative risk of ARIs, there is little dose response relationship evident for hand sanitiser (Figure 3 ). There are only three studies solely of soap and water hand hygiene, making a dose-response analysis impossible. The difference in effectiveness between hand sanitiser and soap and water does not appear to be explained by a difference in frequency. The cluster randomised trial by Little and colleagues [16] primarily used soap and water but also offered participants free hand sanitiser; only 18% report collecting the sanitiser. Colored-in circles= studies using hand sanitiser . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 24, 2020. . https://doi.org/10.1101/2020.07.22.20160432 doi: medRxiv preprint 3.3. Head-to-head trials of hand hygiene with hand sanitiser vs with soap and water Four trials directly compared hand sanitiser with soap and water: two in childcare centres, one at a primary school, and one in workplaces. In a cluster randomised trial of children and staff in Swedish childcare centres, those at centres who were randomised to use an alcoholbased oily disinfectant gel (70% ethanol) after regular hand washing had a reduction in absenteeism rate of 12% (95% CI 4% to 20%) compared to control centres which used only soap and water [7] . The 3-arm cluster randomised trial of 24 childcare centres in Spaineducational and hand hygiene measures (one with soap and water; another with hand sanitiser) and a control group found children in the sanitiser group had a 13% lower (95% CI 6% to 28%) risk of respiratory infection than children in the soap and water group [6] . In Kenya, a cluster randomised trial assigned two primary schools to receive a handwashing with soap and water intervention, two to receive a sanitiser intervention, and two were a control [8] . Compared to control group students, both intervention groups had a reduction in observed rhinorrhea (RR 0.77, 95% CI 0.62-0.95 for both sanitiser vs control and soap vs control). No significant differences between the sanitiser and soap groups were observed for respiratory outcomes. The 3-arm trial in six companies in Finland randomised workplaces to equip workplace bathrooms with liquid hand soap (soap and control arms) or alcoholbased hand rub [9] . Participants in the intervention arms also received guidance on additional strategies for limiting infection transmission. Before the onset of the 2009 influenza pandemic (and the subsequent national hand hygiene campaign), a statistically significant (p = 0.002) difference in the infection episodes was observed between the control (6.0 per year) and the soap-and-water arm (5.0 per year), but not between the control and the alcohol-rub arm (5.6 per year). Neither intervention had an effect on work absenteeism. Based on both indirect and direct (head-to-head) trials, hand hygiene using alcohol-based hand sanitiser appears more effective at reducing ARI transmission than hand hygiene using with soap and water, with the difference in effect not explained by the difference in . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 24, 2020. . frequency of hand hygiene. The apparent greater effectiveness of hand sanitiser may be explained by its greater convenience, less time required to perform hand hygiene, more sustained compliance with hand hygiene, and less irritation to the skin [24] . Limitations of this review are that conclusions are mostly from indirectness evidence, with direct evidence available from only four head-to-head trials, and that it was not possible to estimate the dose of hand hygiene for some trials. A recent Cochrane review of the effect of rinse-free handwashing, compared to traditional hand hygiene, on absenteeism for ARI in preschool and school children reported a significant reduction in absenteeism of 9 days per 1000 available days for children in the rinse-free group, with the results coming from six randomised trials [4] . The effectiveness of handwashing with materials other than sanitiser or soap and water, such as ash, which may be used in low-income countries has mostly been examined in observational studies with uncertain effects [25] . Hand hygiene has a modest but important role in reducing the transmission of viral respiratory infections. Adequately performed hand hygiene, with either soap or sanitiser, reduces the risk of acute respiratory virus transmission. However, from both the direct and indirect comparisons in this review, sanitiser appears more effective in practice. While further head-to-head randomised trials are warranted, the current evidence appears sufficient to promote the use of hand sanitiser as the primary means for many everyday situations. Abbreviations: Acute respiratory infections (ARI), Influenza-like illness (ILI), Risk Ratio (RR), Contributors: TH, PG, and CDM conceived the study. MB and NK screened studies for inclusion in this review and extracted the data. TH, AMS, PG and CDM analysed the data. TH wrote the first draft. All authors approved and revised the final manuscript. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 24, 2020. . This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ethical approval: Ethical approval was not required. Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 2 -Hand hygiene and other hygiene measures: systematic review and metaanalysis Physical interventions to interrupt or reduce the spread of respiratory viruses Physical interventions to interrupt or reduce the spread of respiratory viruses Rinse-free hand wash for reducing absenteeism among preschool and school children Comparing the environmental footprints of home-care and personal-hygiene products: the relevance of different life-cycle phases Effectiveness of a Hand Hygiene Program at Child Care Centers: A Cluster Randomized Trial Alcohol-based hand-disinfection reduced children's absence from Swedish day care centers Access to waterless hand sanitizer improves student hand hygiene behavior in primary schools in Hand washing with soap and water together with behavioural recommendations prevents infections in common work environment: an open clusterrandomized trial Effectiveness of a Behavior Change Intervention with Hand Sanitizer Use and Respiratory Hygiene in Reducing Laboratory-Confirmed Influenza among Schoolchildren in Bangladesh: A Cluster Randomized Controlled Trial A clusterrandomized controlled trial of handrubs for prevention of infectious diseases among children in Colombia Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial Preliminary findings of a randomized trial of non-pharmaceutical interventions to prevent influenza transmission in households Effectiveness of alcoholbased hand disinfectants in a public administration: impact on health and work performance related to acute respiratory symptoms and diarrhoea Impact of non-pharmaceutical interventions on URIs and influenza in crowded, urban households An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial An investigation of the effects of a hand washing intervention on health outcomes and school absence using a randomised trial in Indian urban communities Impact of Intensive Handwashing Promotion on Secondary Household Influenza-Like Illness in Rural Bangladesh: Findings from a Randomized Controlled Trial Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial A randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness transmission in the home Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Reduction in the incidence of influenza A but not influenza B associated with use of hand sanitizer and cough hygiene in schools: a randomized controlled trial A hand hygiene intervention to reduce infections in child daycare: a randomized controlled trial Improving adherence to hand hygiene practice: a multidisciplinary approach Hand cleaning with ash for reducing the spread of viral and bacterial infections: a rapid review