The risk of acquisition and transmission of respiratory infections amplifies at mass gatherings (MGs) straining healthcare of the host country. For instance, in Hajj, one of the largest annual MG events in the world, more than 2 million people attend each year in Makkah, and over 90% suffer from at least one respiratory symptom, the risk of viral respiratory infections increases several folds and more severe respiratory infections such as pneumonia are the leading causes of hospital admission. [1] [2] [3] Likewise, a number of influenza outbreaks were reported during the World Youth Day 2008, a large catholic gathering in Sydney. 4 MGs are also linked to globalisation of various infections. For instance, the Iztapalapa Play Passion, a religious festival in Mexico, was believed to spark the outbreak of swine flu leading to its accelerated dissemination across the world. 5 Therefore, international public health agencies, including World Health Organization (WHO), have issued guidelines on mass gathering preparedness to minimise the possible risks. 6 From a public health perspective, one of the key concerns is to prevent global spread of respiratory infections during MGs. Interventions like vaccinations against viral and bacterial respiratory infections, anti-influenza prophylaxis and hand hygiene are considered as preventive measures but the measures have limitations. For instance, vaccinations against respiratory infections, such as influenza, are recommended for travellers to MGs such as Hajj, 7 and even though a recent systematic review generally supports its effectiveness against laboratory-confirmed influenza at Hajj, 8 frequent mismatch between vaccine strains and circulating strains is an important concern. 9 Soaring antiviral resistance against both adamantanes and neuraminidase inhibitors is an issue that limits their widespread use in MGs. 4, 10 Similarly, while hand hygiene has been recommended as a protective measure for attendees of MGs, its effectiveness is not fully evaluated in a mass gathering setting and the efficacy is debatable. 11 Therefore, the role of another protective measure, facemask, should be explored in the prevention of respiratory infections. 12 Facemask is believed to have a protective role in preventing nosocomial infections since the time of Spanish influenza. 13 Several studies have assessed the usefulness of facemask in household, community and healthcare settings, the findings of which have been summarised in a few reviews. [14] [15] [16] Noticeable disparities of facemask effectiveness between these studies were observed. Studies conducted in community or health care settings found facemasks to be generally effective against influenza-like illness (ILI) or even against severe acute respiratory syndrome (SARS) but its effectiveness against respiratory infections at MGs remains unknown. 15, 17 A review of non-pharmaceutical interventions against respiratory tract infections among Hajj pilgrims presented data on the uptake of facemask and acknowledged that compliance was generally poor, but did not evaluate its effectiveness during Hajj. 11 Subsequently, further data on the uptake and effectiveness have become available, especially from a pilot randomised controlled trial (RCT). 18 The aim of this systematic review is to explore the uptake and effectiveness of facemask against respiratory infections in MGs.
Studies were identified through searching electronic databases including; Medline (PubMed and Ovid), EMBASE, SCOPUS and CINAHL from database inception to February 8, 2016. We used a combination of MeSH terms and text words including: 'crowding' OR 'mass gathering' OR 'large event' OR 'group assembly' OR 'holiday' OR 'travel' OR 'sport' OR 'Olympic' OR 'FIFA' OR 'festival' OR 'Hajj' (also alternative spelling 'Hadj' or 'Haj') OR 'pilgrimage' AND 'mask' OR 'facemask' OR 'surgical mask' OR 'medical mask' OR 'simple mask' AND 'infection' OR 'respiratory tract diseases' OR 'disease outbreaks' OR 'infectious disease' OR 'respiratory tract infections' OR 'influenza' OR 'pneumonia'. Additionally, an online search of pertinent epidemiology journals, including those not indexed in the mentioned databases (e.g. Saudi Epidemiology Bulletin) was carried out through free hand Google engine search. Finally, manual search was performed reviewing reference lists of included studies to identify additional potentially relevant studies. The search result was presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines ( Figure 1 ). 19 In the first phase, three authors (OB, SM and HB) identified the potential titles, and sifted the titles and abstracts against the inclusion criteria. Titles of all studies published in English language and reported the use or effectiveness of facemask against respiratory infections in MGs were preliminarily included. Studies that dealt with attendees of MGs of any age, gender and country were considered for inclusion. At the end of the screening phase, full texts of potentially relevant studies were retrieved for detailed study. Finally studies that met the inclusion criteria were included for data synthesis. Duplicates were excluded.
Five authors (OB, MA, HB, SM and JA) independently extracted the data from each study into a data extraction sheet which was divided in two sections, 'facemask uptake' and 'facemask effectiveness' and five authors subsequently cross-checked the entries (OB, AA, HB, SM and JA),while a sixth author (HR) arbitrated when a discrepancy occurred. The following data were abstracted in each extraction sheet: study design, year of conducting the study, sample size, country of origin, age, gender, diagnostic method used, definitions of study end point, and history of participants' chronic diseases, if available. The quality of the included studies were categorised according to a modified ranking criteria based on Oxford Evidence Based Medicine (http://www.cebm.net/) into groups (e.g., A, B, C, D) where A was for RCTs of adequate sample size, B for observational studies of adequate sample size with good quality or pilot RCTs or non-randomised trial, C for observational studies of inadequate sample size or of poor quality, and D for cases series, such as focus groups or qualitative surveys.
The search results are summarised in Figure 1 The study sample sizes varied widely ranging from 10 to 1717 participants. The included studies contained the pooled data of 12710 participants aged between 11 and 89 years (mean age ranged from 33.5 to 61.7 years in individual studies). About 37% of the pooled samples were females, in individual studies the proportion of females ranged from 10% to 63%. Excluding three studies, which involved HCWs deployed at Hajj, [23] [24] [25] all other included studies involved Hajj pilgrims. The origin of the participants varied depending on the study, seven studies included multinational participants, while the other 18 were exclusive to participants from a single country of origin; seven out of 18 (38.9%) were from Saudi Arabia, 20,23-28 According to study types 11 out of 25 were cohort studies, 1,2,22-24,28-33 another 11 cross-sectional studies, 21,25-27,34-40 two trials (not necessarily RCTs) 18, 20 and one case-series conducted as a qualitative study 41 (Table 1) .
The median uptake of facemask in pooled sample was 53.5%. The lowest reported uptake was 0.02% by Elachola et al. among pilgrims in a unique study that involved quantification of facemasks through photo frames from surveillance camera during the Hajj in 2013, therefor it is considered as an outlier. 21 The highest uptake was 92.8% observed by Al-Asmary et al. among health care workers during Hajj in 2005. 24 Excluding these two studies (Elachola et al 21 and Al-Asmary et al 24 ) , uptake rate among pilgrims has remained generally steady with gradual increase from 24% in 1999 to 64% in 2014 with minor fluctuations (Figure 2 ). Studies involving HCWs reported an uptake from 50% in 2009 to 92.8% in 2005. According to the pilgrims' country of origin, Malaysian pilgrims were noticed to be most compliant to using facemasks (70.9%), 37,40 followed by French (60.5%) 1,2,32,33 and Iranians (60%) 31 (Table 1) .
Only three studies, all involving Australian pilgrims, evaluated the reasons of compliance (or non-compliance) of using facemask during Hajj. 18, 29, 41 The most reported reasons for wearing facemask were to avoid transmission of infectious organisms and protection from air pollution. 29 However, discomfort and difficulty in breathing were the most reported reasons for not wearing facemask. 18,41
Thirteen studies investigated the effectiveness/efficacy of facemask against respiratory infections, but the endpoints varied very widely. Most of these studies (9 out of 13) used a combination of respiratory symptoms (syndromic) as endpoints with varying definitions. For instance, acute respiratory infections (ARI) was used as an endpoint in three studies, 20,24,28 ILI in two, 18, 37 upper respiratory tract infection (URTI) in two, 22, 26 respiratory illness in two 30, 40 and respiratory tract infections in one. 31 However a couple of studies used only one respiratory symptom as an endpoint: fever 39 and cough. 32 Only one study established laboratory-proven viral infections 25 as an endpoint. Definitions for the endpoints are detailed in Table 2 .
In regards to the effectiveness of facemask, four out of thirteen studies demonstrated significant effect against respiratory infections, 18, 20, 22, 28 two others showed some effect but did not reach statistical significance. 25, 26 One study assessed its effectiveness against fever but ruled out its protectiveness, 39 and the other six studies did not show effectiveness but results were not statistically significant. 24, [30] [31] [32] 37, 40 The pooled data from all studies revealed significant protectiveness of facemasks against respiratory infections in general at Hajj (relative risk [RR] = 0.89, 95% CI: 0.84-0.94, p < 0.01) ( Table 2) .
According to the ranking system we used, most of the studies were of average quality (C) whereas two studies were ranked above average (B): a pilot RCT 18 and a large cross-sectional study, 26 the other seven studies were of below average quality (D) either because of small sample size or poor study quality (Table 1) .
This systematic review shows that the use of facemask among the attendees of MGs remains essentially unchanged for decades although exceptionally in one study a very high uptake (about 93%) 24 or a very low uptake rate (0.02%) 21 has been reported but such variability can be explained by their unique study designs or population characteristics. The pooled data of this systematic review suggest that facemask is generally effective against respiratory infections at Hajj, however the endpoints varied widely.
The uptake of facemask among HCWs deployed at Hajj was generally higher than that among ordinary Hajj pilgrims with average compliance among HCWs being 72% compared to 46% among pilgrims. This finding is similar to what have been found in other studies that examined the uptake of facemask in other settings such as health care and community settings. For instance, the uptake of facemask among HCWs in several studies ranged from 56.6% to 84.3% (average 70.7%). [42] [43] [44] [45] On the other hand, the uptake of facemask among ordinary population in diverse household and community settings ranged from 38% to 80.7% (average 55%). [46] [47] [48] [49] [50] [51] [52] This could be explained by several individual or organisational factors. For example, HCWs have firsthand knowledge about the risk of respiratory infections and the role of preventive measurements in Hajj. 25 Similarly, studies in non-MGs settings showed a positive relationship between HCWs' knowledge about the risk of infectious diseases and their compliance to preventive measures including the use of facemask. [53] [54] [55] Organisational factors such as ready availability of facemask in health care settings, proper training programs and supportive policy of health care system could have played an important role in improving the compliance of HCWs to facemask use. [54] [55] [56] [57] On the other hand, limited studies explored these individual and organisational factors among Hajj pilgrims. A few studies showed that providing educational session on protective measures against respiratory infections (including facemask) before Hajj was associated with significantly higher uptake of facemasks among pilgrims. 18, 20, 27, 36, 38 Moreover, adequate accessibility and availability of facemask during Hajj may enhance the compliance of pilgrims. Abdin et al and Barasheed et al revealed a higher uptake of facemask among groups who were provided with sufficient quantity of free facemask (81.3% versus 33.6%, p < 0.01, and 76% versus 12%, p < 0.01, respectively). 18, 20 However, reasons for not using facemask during Hajj have not been explored adequately. While use of facemask at Hajj has been officially recommended by Saudi Ministry of Health since 2014, it is too early to have a significant impact on pilgrims' practice of facemask use. 58 Although Hajj took place in different seasons (spring, winter and autumn), the uptake of facemask among Hajj pilgrims during the last decade remained generally stable (Figure 2) . Findings also showed that there was no significant change in facemask uptake among Hajj pilgrims during the course of influenza A (H1N1) pandemic outburst in 2009, and the Middle East respiratory syndrome corona virus (MERS-CoV) outbreak since 2012. This does not concur with what has been reported in published studies involving the members of general public over the several outbreaks of respiratory infections in non-MG settings. [59] [60] [61] [62] [63] [64] Those studies showed an increase in facemask use during the outbreaks due to participants' perceived threat of infection. Poor awareness among many pilgrims of contemporary outbreaks might explain why their uptake of facemask did not increase even during an ongoing outbreak. [65] [66] [67] Interestingly, pilgrims of Asian origin (e.g. Malaysians) had higher facemask uptake compared to pilgrims from other regions. 37, 40 A polling study that evaluated the uptake of non-pharmaceutical measures during the pandemic influenza A (H1N1) of 2009 found that participants of Asian origin (e.g. Japan) had the higher facemask uptake (71%) compared to the uptake of participants of Western or Latin American origin. 68 Presence of several peaks of influenza seasons in some Asian countries, overcrowding, dense smog and air pollution in many cities may explain the higher uptake of facemask among people from Asian countries; 69,70 additionally, cultural acceptance practice of the population around facemask while in public may make a difference. 68 Focused studies are required to investigate factors influencing facemask compliance among attendees of Hajj and other MGs.
In this systematic review, pooled data of facemask effectiveness showed that participants who used facemask during Hajj are about 20% less likely to suffer from respiratory infections compared to those who do not use it. This effectiveness of facemask is inconclusive due to great heterogeneity in study questions, assessment methods, study designs and qualities, and endpoints. In regards to the research questions, three out of 13 studies investigated facemask effectiveness as the primary research objective: all three studies yielded significant results; whereas only one out of the other 10 studies that assessed facemask as a secondary or indirect outcome, yielded significant results.
Further, there was great heterogeneity in how the frequency and duration of facemask use were assessed. Although, most of the studies used a self-reported questionnaire to quantify facemask uptake among participants, the qualitative descriptive terms that the studies used (e.g. ''always'', ''mostly'', ''sometimes'' or ''never'') may have introduced subjective bias, since qualitative description varies depending on participants' perception about the frequency and duration of use. However, only one study used measurable criteria in their questionnaires to quantify the number of facemasks used including the duration (in hours) and frequency of use, finding that using facemask more than eight hours per day was associated with significant decrease in ILI symptoms among Hajj pilgrims. 18 Using surveys with more objective options may decrease bias, 71 and provide more accurate estimate of compliance to facemask use in MGs. Study designs also may have contributed to variability in results. For instance, two trials, a pilot RCT and a non-randomised trial, reported facemask to be significantly effective against respiratory infections at Hajj, whereas only two out of six cohort studies reported significant results. In contrast, none of the crosssectional studies yielded significant results. This may indicate that a higher quality study is more likely to produce convincing results.
Finally, facemask effectiveness also differed depending on the study endpoints. For example, studies that examined effectiveness of facemask against a single respiratory symptom (such as cough, sore throat or fever) either ruled out or did not fully support its effectiveness. 32, 37, 39 This is most likely because singular endpoints are often prone to subjective biases due to their non-specificity. In addition, solitary respiratory symptoms may result from causes other than infections; for instance, cough may result from exposure to dust or smoke during Hajj or may be a manifestation of a chronic respiratory condition of non-infectious aetiology, e.g., bronchial asthma. 29 On the other hand, most of the studies that used syndromic criteria (constellation of symptoms) as an endpoint reported facemasks to be effective against respiratory infections during Hajj. 18, 20, 22, 26, 28 This is most likely due to the fact that syndromic endpoints are more specific for an illness than a singular symptom. Only one study used laboratory-confirmed infection as an endpoint, but its sample size was relatively small (n = 104) and it failed to demonstrate statistically significant protectiveness of facemasks against respiratory viral infections among Hajj HCWs. 25 Similarly, in non-MG settings, effectiveness of facemask varied depending on the study endpoint. [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [72] [73] [74] Metaanalysis of RCTs involving facemask in non-MGs showed efficacy against ILI but not against laboratory-confirmed influenza. 14, 15, 75 This study is the first focussed systematic review that describes both the uptake and effectiveness of facemasks against respiratory infections in MGs, and it compiles a data pool of 12710 participants originating from more than 50 countries. However, the main limitation is that most of the studies were of 'average' or 'below average' quality. There was only one RCT but that was a pilot trial of small sample size, and there was another 'trial' published in a nonindexed journal that did not report methodological details including whether and how randomisation was done. As all included studies were conducted only in the context of Hajj, it is not possible to generalise the results to other MGs. A large scale clustered RCT is currently in its final phase that will measure the efficacy of facemasks against both 'syndromic' and laboratoryconfirmed viral infections. 75 The full results of the trial, once available, are likely to provide firmer evidence on the usefulness of facemask against respiratory infections among attendees of MGs.
In summary, the use of facemask among attendees of a particular MG (Hajj) remains almost steady with negligible increase throughout the last decade with an average uptake of 50%. Facemasks seem to be beneficial against certain respiratory infections during Hajj but not definitively proven.
Professor Robert Booy has received funding from Baxter, CSL, GSK, Merck, Novartis, Pfizer, Roche, Romark and Sanofi Pasteur for the conduct of sponsored research, travel to present at conferences or consultancy work; all funding received is directed to research accounts at The Children's Hospital at Westmead. Dr Harunor Rashid received fees from Pfizer and Novartis for consulting or serving on an advisory board. The other authors have declared no conflict of interest in relation to this work.