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Inuenza pandemics occur at irregular intervals
when new strains of inuenza A virus spread in
humans (1). Inuenza pandemics cause considerable
health and social impact that exceeds that of typical
seasonal (interpandemic) inuenza epidemics. One
of the characteristics of inuenza pandemics is the
high incidence of infections in all age groups because
of the lack of population immunity. Although inu-
enza vaccines are the cornerstone of seasonal inu-
enza control, specic vaccines for a novel pandemic
strain are not expected to be available for the rst
5–6 months of the next pandemic. Antiviral drugs
will be available in some locations to treat more se-
vere infections but are unlikely to be available in the
quantities that might be required to control trans-
mission in the general community. Thus, efforts to
control the next pandemic will rely largely on non-
pharmaceutical interventions.
Most inuenza virus infections cause mild and
self-limiting disease; only a small fraction of case-
patients require hospitalization. Therefore, inuenza
virus infections spread mainly in the community. In-
uenza virus is believed to be transmitted predomi-
nantly by respiratory droplets, but the size distribu-
tion of particles responsible for transmission remains
unclear, and in particular, there is a lack of consensus
on the role of ne particle aerosols in transmission
(2,3). In healthcare settings, droplet precautions are
recommended in addition to standard precautions for
healthcare personnel when interacting with inuenza
patients and for all visitors during inuenza seasons
(4). Outside healthcare settings, hand hygiene is rec-
ommended in most national pandemic plans (5), and
medical face masks were a common sight during the
inuenza pandemic in 2009. Hand hygiene has been
proven to prevent many infectious diseases and might
be considered a major component in inuenza pan-
demic plans, whether or not it has proven effective-
ness against inuenza virus transmission, specically
because of its potential to reduce other infections and
thereby reduce pressure on healthcare services.
In this article, we review the evidence base for
personal protective measures and environmental
hygiene measures, and specically the evidence
for the effectiveness of these measures in reducing
transmission of laboratory-conrmed inuenza in
the community. We also discuss the implications of
the evidence base for inclusion of these measures in
pandemic plans.
Nonpharmaceutical Measures
for Pandemic Inuenza in
Nonhealthcare Settings—
Personal Protective and
Environmental Measures
Jingyi Xiao,1 Eunice Y. C. Shiu,1 Huizhi Gao, Jessica Y. Wong, Min W. Fong, Sukhyun Ryu, Benjamin J. Cowling
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 5, May 2020 967
Author aliation: University of Hong Kong, Hong Kong, China
DOI: https://doi.org/10.3201/eid2605.190994 1These rst authors contributed equally to this article.
There were 3 inuenza pandemics in the 20th century,
and there has been 1 so far in the 21st century. Local,
national, and international health authorities regularly
update their plans for mitigating the next inuenza pan-
demic in light of the latest available evidence on the
eectiveness of various control measures in reducing
transmission. Here, we review the evidence base on the
eectiveness of nonpharmaceutical personal protective
measures and environmental hygiene measures in non-
healthcare settings and discuss their potential inclusion
in pandemic plans. Although mechanistic studies sup-
port the potential eect of hand hygiene or face masks,
evidence from 14 randomized controlled trials of these
measures did not support a substantial eect on trans-
mission of laboratory-conrmed inuenza. We similarly
found limited evidence on the eectiveness of improved
hygiene and environmental cleaning. We identied sev-
eral major knowledge gaps requiring further research,
most fundamentally an improved characterization of the
modes of person-to-person transmission.
POLICY REVIEW
Methods and Results
We conducted systematic reviews to evaluate the
effectiveness of personal protective measures on in-
uenza virus transmission, including hand hygiene,
respiratory etiquette, and face masks, and a system-
atic review of surface and object cleaning as an en-
vironmental measure (Table 1). We searched 4 data-
bases (Medline, PubMed, EMBASE, and CENTRAL)
for literature in all languages. We aimed to identify
randomized controlled trials (RCTs) of each measure
for laboratory-conrmed inuenza outcomes for each
of the measures because RCTs provide the highest
quality of evidence. For respiratory etiquette and sur-
face and object cleaning, because of a lack of RCTs
for laboratory-conrmed inuenza, we also searched
for RCTs reporting effects of these interventions on
inuenza-like illness (ILI) and respiratory illness out-
comes and then for observational studies on labora-
tory-conrmed inuenza, ILI, and respiratory illness
outcomes. For each review, 2 authors (E.Y.C.S. and
J.X.) screened titles and abstracts and reviewed full
texts independently.
We performed meta-analysis for hand hygiene
and face mask interventions and estimated the ef-
fect of these measures on laboratory-conrmed in-
uenza prevention by risk ratios (RRs). We used a
xed-effects model to estimate the overall effect in
a pooled analysis or subgroup analysis. No overall
effect would be generated if there was considerable
heterogeneity on the basis of I2 statistic >75% (6). We
performed quality assessment of evidence on hand
hygiene and face mask interventions by using the
GRADE (Grading of Recommendations Assessment,
Development and Evaluation) approach (7). We pro-
vide additional details of the search strategies, selec-
tion of articles, summaries of the selected articles, and
quality assessment (Appendix, https://wwwnc.cdc.
gov/EID/article/26/5/19-0994-App1.pdf).
Personal Protective Measures
Hand Hygiene
We identied a recent systematic review by Wong et
al. on RCTs designed to assess the efcacy of hand
hygiene interventions against transmission of labo-
ratory-conrmed inuenza (8). We used this review
as a starting point and then searched for additional
literature published after 2013; we found 3 additional
eligible articles published during the search period of
January 1, 2013–August 13, 2018. In total, we identi-
ed 12 articles (9–20), of which 3 articles were from
the updated search and 9 articles from Wong et al.
(8). Two articles relied on the same underlying data-
set (16,19); therefore, we counted these 2 articles as
1 study, which resulted in 11 RCTs. We further se-
lected 10 studies with >10,000 participants for inclu-
sion in the meta-analysis (Figure 1). We excluded 1
study from the meta-analysis because it provided es-
timates of infection risks only at the household level,
not the individual level (20). We did not generate an
overall pooled effect of hand hygiene only or of hand
hygiene with or without face mask because of high
heterogeneity in individual estimates (I2 87 and 82%,
respectively). The effect of hand hygiene combined
with face masks on laboratory-conrmed inuenza
was not statistically signicant (RR 0.91, 95% CI 0.73–
1.13; I2 = 35%, p = 0.39). Some studies reported being
underpowered because of limited sample size, and
low adherence to hand hygiene interventions was
observed in some studies.
We further analyzed the effect of hand hygiene
by setting because transmission routes might vary
968 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 5, May 2020
Table 1. Summary of literature searches for systematic review on personal and environmental nonpharmaceutical interventions for
pandemic influenza*
Types of interventions
No. studies identified
Study designs included†
Main findings
Hand hygiene
12
RCT
The evidence from RCTs suggested that
hand hygiene interventions do not have a
substantial effect on influenza transmission.
Respiratory etiquette
0
NA
We did not identify research evaluating the
effectiveness of respiratory etiquette on
influenza transmission.
Face masks
10
RCT
The evidence from RCTs suggested that the
use of face masks either by infected
persons or by uninfected persons does not
have a substantial effect on influenza
transmission.
Surface and object cleaning
3
RCT, observational studies
There was a limited amount of evidence
suggesting that surface and object cleaning
does not have a substantial effect on
influenza transmission.
*NA, not available; RCT randomized controlled tri al.
†In these systematic reviews, we prioritized RCTs, and only considered observational studies if there were a small number of RCTs. Our rationale was
that with evidence from a larger number of RCTs, additional evidence from observational studies would be unlikely to change overall conclusions.
Pandemic Inuenza—Personal Protective Measures
in different settings. We found 6 studies in house-
hold settings examining the effect of hand hygiene
with or without face masks, but the overall pooled
effect was not statistically signicant (RR 1.05, 95%
CI 0.86–1.27; I2 = 57%, p = 0.65) (Appendix Figure 4)
(11–15,17). The ndings of 2 studies in school set-
tings were different (Appendix Figure 5). A study
conducted in the United States (16) showed no ma-
jor effect of hand hygiene, whereas a study in Egypt
(18) reported that hand hygiene reduced the risk for
inuenza by >50%. A pooled analysis of 2 studies
in university residential halls reported a marginally
signicant protective effect of a combination of hand
hygiene plus face masks worn by all residents (RR
0.48, 95% CI 0.21–1.08; I2 = 0%, p = 0.08) (Appendix
Figure 6) (9,10).
In support of hand hygiene as an effective
measure, experimental studies have reported that
inuenza virus could survive on human hands for
a short time and could transmit between hands and
contaminated surfaces (2,21). Some eld studies
reported that inuenza A(H1N1)pdm09 and inu-
enza A(H3N2) virus RNA and viable inuenza vi-
rus could be detected on the hands of persons with
laboratory-conrmed inuenza (22,23), supporting
the potential of direct and indirect contact transmis-
sion to play a role in the spread of inuenza. Other
experimental studies also demonstrated that hand
hygiene could reduce or remove infectious inuenza
virus from human hands (24,25). However, results
from our meta-analysis on RCTs did not provide ev-
idence to support a protective effect of hand hygiene
against transmission of laboratory-conrmed inu-
enza. One study did report a major effect, but in this
trial of hand hygiene in schools in Egypt, running
water had to be installed and soap and hand-drying
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 5, May 2020 969
Figure 1. Meta-analysis of risk
ratios for the eect of hand hygiene
with or without face mask use on
laboratory-conrmed inuenza
from 10 randomized controlled
trials with >11,000 participants.
A) Hand hygiene alone; B) hand
hygiene and face mask; C) hand
hygiene with or without face mask.
Pooled estimates were not made if
there was high heterogeneity
(I2 >75%). Squares indicate risk
ratio for each of the included
studies, horizontal line indicates
95% CIs, dashed vertical line
indicates pooled estimation of
risk ratio, and diamond indicates
pooled estimation of risk ratio.
Diamond width corresponds to the
95% CI.
POLICY REVIEW
material had to be introduced into the intervention
schools as part of the project (18). Therefore, the im-
pact of hand hygiene might also be a reection of the
introduction of soap and running water into prima-
ry schools in a lower-income setting. If one considers
all of the evidence from RCTs together, it is useful to
note that some studies might have underestimated
the true effect of hand hygiene because of the com-
plexity of implementing these intervention studies.
For instance, the control group would not typically
have zero knowledge or use of hand hygiene, and
the intervention group might not adhere to optimal
hand hygiene practices (11,13,15).
Hand hygiene is also effective in preventing other
infectious diseases, including diarrheal diseases and
some respiratory diseases (8,26). The need for hand
hygiene in disease prevention is well recognized
among most communities. Hand hygiene has been
accepted as a personal protective measure in >50% of
national preparedness plans for pandemic inuenza
(5). Hand hygiene practice is commonly performed
with soap and water, alcohol-based hand rub, or oth-
er waterless hand disinfectants, all of which are easily
accessible, available, affordable, and well accepted in
most communities. However, resource limitations in
some areas are a concern when clean running water
or alcohol-based hand rub are not available. There are
few adverse effects of hand hygiene except for skin
irritation caused by some hand hygiene products
(27). However, because of certain social or religious
practices, alcohol-based hand sanitizers might not be
permitted in some locations (28). Compliance with
proper hand hygiene practice tends to be low because
habitual behaviors are difcult to change (29). There-
fore, hand hygiene promotion programs are needed
to advocate and encourage proper and effective
hand hygiene.
Respiratory Etiquette
Respiratory etiquette is dened as covering the nose
and mouth with a tissue or a mask (but not a hand)
when coughing or sneezing, followed by proper dis-
posal of used tissues, and proper hand hygiene after
contact with respiratory secretions (30). Other de-
scriptions of this measure have included turning the
head and covering the mouth when coughing and
coughing or sneezing into a sleeve or elbow, rath-
er than a hand. The rationale for not coughing into
hands is to prevent subsequent contamination of oth-
er surfaces or objects (31). We conducted a search on
November 6, 2018, and identied literature that was
available in the databases during 1946–November 5,
2018. We did not identify any published research on
the effectiveness of respiratory etiquette in reducing
the risk for laboratory-conrmed inuenza or ILI.
One observational study reported a similar incidence
rate of self-reported respiratory illness (dened by >1
symptoms: cough, congestion, sore throat, sneezing,
or breathing problems) among US pilgrims with or
without practicing respiratory etiquette during the
Hajj (32). The authors did not specify the type of re-
spiratory etiquette used by participants in the study.
A laboratory-based study reported that common re-
spiratory etiquette, including covering the mouth by
hands, tissue, or sleeve/arm, was fairly ineffective
in blocking the release and dispersion of droplets
into the surrounding environment on the basis of
measurement of emitted droplets with a laser diffrac-
tion system (31).
Respiratory etiquette is often listed as a preven-
tive measure for respiratory infections. However,
there is a lack of scientic evidence to support this
measure. Whether respiratory etiquette is an effective
nonpharmaceutical intervention in preventing inu-
enza virus transmission remains questionable, and
worthy of further research.
Face Masks
In our systematic review, we identied 10 RCTs that
reported estimates of the effectiveness of face masks
in reducing laboratory-conrmed inuenza virus in-
fections in the community from literature published
during 1946–July 27, 2018. In pooled analysis, we
found no signicant reduction in inuenza trans-
mission with the use of face masks (RR 0.78, 95% CI
0.51–1.20; I2 = 30%, p = 0.25) (Figure 2). One study
evaluated the use of masks among pilgrims from
Australia during the Hajj pilgrimage and reported no
major difference in the risk for laboratory-conrmed
inuenza virus infection in the control or mask group
(33). Two studies in university settings assessed the
effectiveness of face masks for primary protection
by monitoring the incidence of laboratory-conrmed
inuenza among student hall residents for 5 months
(9,10). The overall reduction in ILI or laboratory-con-
rmed inuenza cases in the face mask group was
not signicant in either studies (9,10). Study designs
in the 7 household studies were slightly different:
1 study provided face masks and P2 respirators for
household contacts only (34), another study evaluat-
ed face mask use as a source control for infected per-
sons only (35), and the remaining studies provided
masks for the infected persons as well as their close
contacts (11–13,15,17). None of the household studies
reported a signicant reduction in secondary labora-
tory-conrmed inuenza virus infections in the face
970 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 5, May 2020
Pandemic Inuenza—Personal Protective Measures
mask group (11–13,15,17,34,35). Most studies were
underpowered because of limited sample size, and
some studies also reported suboptimal adherence in
the face mask group.
Disposable medical masks (also known as surgi-
cal masks) are loose-tting devices that were designed
to be worn by medical personnel to protect acciden-
tal contamination of patient wounds, and to protect
the wearer against splashes or sprays of bodily u-
ids (36). There is limited evidence for their effective-
ness in preventing inuenza virus transmission either
when worn by the infected person for source control
or when worn by uninfected persons to reduce ex-
posure. Our systematic review found no signicant
effect of face masks on transmission of laboratory-
conrmed inuenza.
We did not consider the use of respirators in the
community. Respirators are tight-tting masks that
can protect the wearer from ne particles (37) and
should provide better protection against inuenza vi-
rus exposures when properly worn because of higher
ltration efciency. However, respirators, such as
N95 and P2 masks, work best when they are t-test-
ed, and these masks will be in limited supply during
the next pandemic. These specialist devices should
be reserved for use in healthcare settings or in special
subpopulations such as immunocompromised per-
sons in the community, rst responders, and those
performing other critical community functions, as
supplies permit.
In lower-income settings, it is more likely
that reusable cloth masks will be used rather than
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 5, May 2020 971
Figure 2. Meta-analysis of risk
ratios for the eect of face mask
use with or without enhanced hand
hygiene on laboratory-conrmed
inuenza from 10 randomized
controlled trials with >6,500
participants. A) Face mask use
alone; B) face mask and hand
hygiene; C) face mask with or
without hand hygiene. Pooled
estimates were not made if there
was high heterogeneity (I2 >75%).
Squares indicate risk ratio for
each of the included studies,
horizontal lines indicate 95% CIs,
dashed vertical lines indicate
pooled estimation of risk ratio,
and diamonds indicate pooled
estimation of risk ratio. Diamond
width corresponds to the 95% CI.
POLICY REVIEW
disposable medical masks because of cost and avail-
ability (38). There are still few uncertainties in the
practice of face mask use, such as who should wear
the mask and how long it should be used for. In the-
ory, transmission should be reduced the most if both
infected members and other contacts wear masks,
but compliance in uninfected close contacts could be
a problem (12,34). Proper use of face masks is essen-
tial because improper use might increase the risk for
transmission (39). Thus, education on the proper use
and disposal of used face masks, including hand hy-
giene, is also needed.
Environmental Measures
Surface and Object Cleaning
For the search period from 1946 through October
14, 2018, we identied 2 RCTs and 1 observational
study about surface and object cleaning measures
for inclusion in our systematic review (40–42). One
RCT conducted in day care nurseries found that bi-
weekly cleaning and disinfection of toys and linen
reduced the detection of multiple viruses, includ-
ing adenovirus, rhinovirus, and respiratory syn-
cytial virus in the environment, but this interven-
tion was not signicant in reducing detection of
inuenza virus, and it had no major protective ef-
fect on acute respiratory illness (41). Another RCT
found that hand hygiene with hand sanitizer to-
gether with surface disinfection reduced absentee-
ism related to gastrointestinal illness in elementary
schools, but there was no major reduction in absen-
teeism related to respiratory illness (42). A cross-
sectional study found that passive contact with
bleach was associated with a major increase in self-
reported inuenza (40).
Given that inuenza virus can survive on some
surfaces for prolonged periods (43), and that cleaning
or disinfection procedures can effectively reduce or
inactivate inuenza virus from surfaces and objects in
experimental studies (44), there is a theoretical basis
to believe that environmental cleaning could reduce
inuenza transmission. As an illustration of this pro-
posal, a modeling study estimated that cleaning of
extensively touched surfaces could reduce inuenza
A infection by 2% (45). However, most studies of in-
uenza virus in the environment are based on detec-
tion of virus RNA by PCR, and few studies reported
detection of viable virus.
Although we found no evidence that surface
and object cleaning could reduce inuenza trans-
mission, this measure does have an established im-
pact on prevention of other infectious diseases (42).
It should be feasible to implement this measure in
most settings, subject to the availability of water and
cleaning products. Although irritation caused by
cleaning products is limited, safety remains a con-
cern because some cleaning products can be toxic or
cause allergies (40).
Discussion
In this review, we did not nd evidence to support a
protective effect of personal protective measures or
environmental measures in reducing inuenza trans-
mission. Although these measures have mechanistic
support based on our knowledge of how inuenza is
transmitted from person to person, randomized tri-
als of hand hygiene and face masks have not dem-
onstrated protection against laboratory-conrmed
inuenza, with 1 exception (18). We identied only
2 RCTs on environmental cleaning and no RCTs on
cough etiquette.
Hand hygiene is a widely used intervention and
has been shown to effectively reduce the transmission
of gastrointestinal infections and respiratory infec-
tions (26). However, in our systematic review, updat-
ing the ndings of Wong et al. (8), we did not nd
evidence of a major effect of hand hygiene on labora-
tory-conrmed inuenza virus transmission (Figure
1). Nevertheless, hand hygiene might be included in
inuenza pandemic plans as part of general hygiene
and infection prevention.
We did not nd evidence that surgical-type face
masks are effective in reducing laboratory-conrmed
inuenza transmission, either when worn by infected
persons (source control) or by persons in the general
community to reduce their susceptibility (Figure 2).
However, as with hand hygiene, face masks might
be able to reduce the transmission of other infections
and therefore have value in an inuenza pandemic
when healthcare resources are stretched.
It is essential to note that the mechanisms of per-
son-to-person transmission in the community have
not been fully determined. Controversy remains over
the role of transmission through ne-particle aero-
sols (3,46). Transmission by indirect contact requires
transfer of viable virus from respiratory mucosa onto
hands and other surfaces, survival on those surfaces,
and successful inoculation into the respiratory mu-
cosa of another person. All of these components of
the transmission route have not been studied exten-
sively. The impact of environmental factors, such as
temperature and humidity, on inuenza transmission
is also uncertain (47). These uncertainties over basic
transmission modes and mechanisms hinder the opti-
mization of control measures.
972 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 5, May 2020
Pandemic Inuenza—Personal Protective Measures
In this review, we focused on 3 personal protec-
tive measures and 1 environmental measure. Other
potential environmental measures include humidi-
cation in dry environments (48), increasing ventila-
tion (49), and use of upper-room UV light (50), but
there is limited evidence to support these measures.
Further investigations on the effectiveness of respi-
ratory etiquette and surface cleaning through con-
ducting RCTs would be helpful to provide evidence
with higher quality; evaluation of the effectiveness of
these measures targeting specic population groups,
such as immunocompromised persons, would also be
benecial (Table 2). Future cost-effectiveness evalu-
ations could provide more support for the potential
use of these measures. Further research on transmis-
sion modes and alternative interventions to reduce
inuenza transmission would be valuable in improv-
ing pandemic preparedness. Finally, although our re-
view focused on nonpharmaceutical measures to be
taken during inuenza pandemics, the ndings could
also apply to severe seasonal inuenza epidemics.
Evidence from RCTs of hand hygiene or face masks
did not support a substantial effect on transmission of
laboratory-conrmed inuenza, and limited evidence
was available on other environmental measures.
This study was conducted in preparation for the
development of guidelines by the World Health Organization
on the use of nonpharmaceutical interventions for pandemic
inuenza in nonmedical settings.
This study was supported by the World Health
Organization. J.X. and M.W.F. were supported by the
Collaborative Research Fund from the University Grants
Committee of Hong Kong (project no. C7025-16G).
About the Author
Ms. Xiao is a postgraduate student at the School of Public
Health, University of Hong Kong, Hong Kong, China.
Her primary research interests are inuenza epidemiology
and the dynamics of person-to-person transmission.
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Table 2. Knowledge gaps for personal protective and environmental nonpharmaceutical interventions for pandemic influenza*
Intervention
Knowledge gaps
Suggested studies
Hand hygiene
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POLICY REVIEW
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Address for correspondence: Benjamin J. Cowling, World Health
Organization Collaborating Centre for Infectious Disease
Epidemiology and Control, School of Public Health, Li Ka Shing
Faculty of Medicine, University of Hong Kong, 1/F Patrick
Manson Bldg (North Wing), 7 Sassoon Rd, Hong Kong, China;
email: bcowling@hku.hk
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