Content uploaded by David K Shay
Author content
All content in this area was uploaded by David K Shay on Feb 03, 2014
Content may be subject to copyright.
Mask Use and Hand Hygiene Mitigates ILI •JID 2010:201 (15 February) •491
MAJOR ARTICLE
Mask Use, Hand Hygiene, and Seasonal Influenza-
Like Illness among Young Adults: A Randomized
Intervention Trial
Allison E. Aiello,
1,2
Genevra F. Murray,
3
Vanessa Perez,
1,2
Rebecca M. Coulborn,
1,2
Brian M. Davis,
1,2
Monica Uddin,
1,2
David K. Shay,
4
Stephen H. Waterman,
4
and Arnold S. Monto,
1
1
Department of Epidemiology and
2
Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan,
Ann Arbor, Michigan;
3
Department of Sociology, Anthropology, and Social Work, University of South Alabama;
4
Centers for Disease Control
and Prevention, Atlanta, Georgia
(See the editorial commentary by Daniels and Talbot, on pages 483–5.)
Background. During the influenza A(H1N1) pandemic, antiviral prescribing was limited, vaccines were not
available early, and the effectiveness of nonpharmaceutical interventions (NPIs) was uncertain. Our studyexamined
whether use of face masks and hand hygiene reduced the incidence of influenza-like illness (ILI).
Methods. A randomized intervention trial involving 1437 young adults living in university residence halls
during the 2006–2007 influenza season was designed. Residence halls were randomly assigned to 1 of 3 groups—
face mask use, face masks with hand hygiene, or control— for 6 weeks. Generalized models estimated rate ratios
for clinically diagnosed or survey-reported ILI weekly and cumulatively.
Results. We observed significant reductions in ILI during weeks 4–6 in the mask and hand hygiene group,
compared with the control group, ranging from 35% (confidence interval [CI], 9%–53%) to 51% (CI, 13%–73%),
after adjusting for vaccination and other covariates. Face mask use alone showed a similarreduction inILI compared
with the control group, but adjusted estimates were not statistically significant. Neither face mask use and hand
hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI cumulatively.
Conclusions. These findings suggest that face masks and hand hygiene may reduce respiratory illnesses in
shared living settings and mitigate the impact of the influenza A(H1N1) pandemic.
Trial Registration. ClinicalTrials.gov identifier: NCT00490633.
In February 2007, the Centers for Disease Control and
Prevention (CDC), in collaboration with other federal
agencies and with educational institutions, businesses,
health care providers, and private enterprises, devel-
oped an interim planning guide on the use of non-
pharmaceutical interventions (NPIs) to mitigate an in-
fluenza pandemic [1]. These measures include volun-
tary home quarantine, social distancing, personal pro-
tection (use of face masks and hand hygiene), and
school dismissal; similar measures have been recom-
Received 16 September 2009; accepted 2 November 2009; electronically
published 20 January 2010.
Reprints or correspondence: Dr Allison E. Aiello, John G. Searle Assistant
Professor of Public Health and Assistant Professor of Epidemiology, Center for
Social Epidemiology and Population Health, 1415 Washington Heights, Ann Arbor,
MI 48109 (aielloa@umich.edu).
The Journal of Infectious Diseases 2010;201:491–8
2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20104-0004$15.00
DOI: 10.1086/650396
mended for mitigating severe acute respiratory syn-
drome (SARS). Use of NPIs occurred during the in-
ternational SARS outbreak that began in early 2003 [2]
and is ongoing in the current novel influenza A(H1N1)
(hereafter “nH1N1”) pandemic.
Although several of these measures can be evaluated
Potential conflicts of interest: none reported.
Presented in part: Workshop on personal protective equipment for health care
workers in the workplace against novel H1N1 influenza, Institute of Medicine–
Board on Health Sciences Policy, Washington, DC, 12–13 August 2009. The 48th
Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and
46th Annual Meeting of the Infectious Disease Society of America, Washington,
DC, 25–28 October 2008.
Financial support: Centers for Disease Control and Prevention (grant U01
C1000441) (PIs: A.S.M. and A.E.A.).
The findings and conclusions in this report are those of the authors and do not
necessarily represent the views of the Centers for Disease Control and Prevention
(CDC). The CDC had a role in the design and conduct of the study, interpretation
of data, and preparation, review, and approval of the manuscript; they did not
have a role in the collection, management, or analysis of the data. WarnerLambert
provided hand sanitizer without any involvement in the study design, analysis,
results, or writing of the manuscript.
492 •JID 2010:201 (15 February) •Aiello et al
during seasonal influenza outbreaks, many are difficult or im-
possible to evaluate in advance of a pandemic. School closure
has been implemented during seasonal influenza outbreaks and
the current nH1N1 pandemic, but it has been difficult to assess
this intervention on a large enough scale or before the peak of
illness to provide inferences for future pandemics [3–5]. In
contrast, use of face masks and hand hygiene interventions can
be evaluated during seasonal influenza outbreaks to provide
concrete evidence for the potential effectiveness of these mea-
sures during the current nH1N1 pandemic. We conducted a
cluster randomized intervention study to assess the impact of
face masks and hand hygiene on the incidence of influenza-
like illness (ILI) symptoms among students living in university
residence halls during the 2006–2007 influenza season. We ex-
amined the effects of face masks alone and face masks with
provision of alcohol-based hand sanitizer, compared with a
control group that received no intervention.
METHODS
Study design and eligibility. The study design was a cluster
randomized trial with 3 arms, conducted among university
students living in residence halls. The CONSORT checklist is
available in Table A1 in the Appendix, which is not available
in the print edition of the Journal. On the basis of the size
(1100 residents) and demographic similarity of the residential
halls, 7 of 15 available residence halls were included as potential
intervention or control units.
The largest of the 7 residence halls housed 1240 residents.
The 6 smaller residence halls ranged from 110 to 830 residents.
The 6 smaller halls were combined into 2 similar sized units,
to create a comparable size to the largest residence hall; all 3
similar sized units were then randomized to the intervention
or control arms. The residence hall units were randomized by
blindly selecting a uniform ticket with the name of each hall
out of a container (A.S.M. and A.A.) for randomization as-
signment to each study arm. The largest single residence hall
was randomized to the mask plus alcohol-based hand sanitizer
(62% ethyl alcohol in a gel base) group (hereafter, the “face
mask and hand hygiene” group), a cluster composed of 4 res-
idence halls was randomized to the face mask–only group, and
the remaining 2 residence halls served as the control group
(Figure A1 in the Appendix, which is not available in the print
edition of the Journal).
We estimated a sample size of 750 participants per inter-
vention group to demonstrate a reduction in ILI incidence of
40% between each intervention and the control group [6],
based on a 10% ILI attack rate in the control group, with an
alevel of 0.05 and statistical power of at least 80%. The total
number of eligible participants was 1372 (96% retention rate
among allocated participants). Additional details on the sample
size are available in Section A1 of the Appendix.
Students living in these residence halls were eligible for par-
ticipation if they were at least 18 years of age and willing to
wear a face mask, use alcohol-based hand sanitizer, have a
throat swab specimen collected when ill, and complete thebase-
line and weekly surveys over the 6-week study period. Potential
participants reporting a skin allergy to alcohol were excluded.
Written informed consent was obtained from all participants.
The study was approved by the University of Michigan Insti-
tutional Review Board.
Recruitment and intervention methods. Recruitment be-
gan in November 2006 and continued until 2 weeks after the
intervention period started. The intervention started during the
week of 22 January 2007, after laboratory confirmation of in-
fluenza infection on the University of Michigan campus. The
intervention materials and educational component were pro-
vided to participants on 26 and 27 January, and enrollment
continued until 16 February. The study ended on 16 March
2007. Over the study period, a majority of residents leftcampus
(24 February to 4 March) during a 1-week spring break. Ex-
cluding spring break, the intervention lasted 6 weeks total.
All participants received basic hand hygiene education
(proper hand hygiene practices and cough etiquette) through
an email video link and the study Web site. In addition, face
mask and hand hygiene group participants received written
materials detailing appropriate hand sanitizer and mask use;
mask group participants received written materials regarding
proper face mask use only. Participants in the mask intervention
residence halls received standard medical procedure masks with
ear loops (TECNOL procedure masks; Kimberly-Clark), which
they were asked to wear as much as possible in their residence
hall during the intervention period and encouraged to use out-
side the halls as well. Compliance with masks while sleeping
was optional. Participants were instructed in correct and in-
correct mask use, change of provided masks daily, and use of
provided resealable plastic bags for mask storage when not in
use (eg, eating) and for disposal. Mask and hand hygiene group
participants also received alcohol-based hand sanitizer (port-
able 2 oz squeeze bottle; 8 oz pump) for use throughout the
study. Additional information on supply distribution is avail-
able in Section A1 of the Appendix.
Weekly surveys. At baseline, participants were asked to self-
report data on demographic information (age, sex, and race/
ethnicity), hand hygiene behavior (handwashing frequency, du-
ration, and hand sanitizer ownership), health behaviors (sleep
quality, alcohol consumption, smoking habits, and influenza
vaccination status), and levels of perceived stress. Additional
details on behavioral measures are available in Section A1 of
the Appendix. Participants were also asked to complete the
baseline and weekly Web-based surveys concerning the occur-
rence of respiratory illness symptoms and the use of interven-
tions during the study. The weekly surveys included questions
Mask Use and Hand Hygiene Mitigates ILI •JID 2010:201 (15 February) •493
regarding ILI symptoms, intervention compliance, and health
and hygiene behaviors. In addition, trained staff stationed in
residence hall common areas observed participant compliance.
A detailed description of all compliance measures is available
in Section A1 of the Appendix.
Report of ILI symptoms and laboratory testing. All resi-
dents in participating halls received promotional materials de-
scribing the ILI case definition (presence of cough and at least
1 constitutional symptom [fever/feverishness, chills, or body
aches]) [7] and phone numbers for contacting the nursing staff
to assess for ILI symptoms. During scheduled participant visits,
study nurses ascertained date of illness onset, temperature, use
of antipyretics, and reported symptoms (cough, feverishness,
chills, body aches, headache, nasal congestion, and sore throat).
Students with ILI were offered $25.00 for providing a throat
specimen. With a cotton swab, nurses collected specimens and
transferred them to veal infusion broth. Samples wereprocessed
and analyzed using standard laboratory methods as described
in Section A1 of the Appendix.
Statistical analyses. Of the 1372 eligible participants, 1297
with a complete baseline survey and at least 1 weekly survey
were included in analyses. Several potential covariates were ex-
amined across intervention and control groups, including age,
sex, self-reported race/ethnicity, hand hygiene behaviors at
baseline, sleep quality, alcohol use, smoking habits, physical
activity, levels of perceived stress, reported influenza vaccination
history, and mask and hand hygiene compliance over the study
period. Data describing variable derivation and categorization
are available in Sections A1 and A2 of the Appendix.
To test for potential covariate differences among intervention
and control groups, baseline characteristics and hand hygiene
variables were compared, using x
2
tests and analysis of variance
adjusted for clustering within the 7 residence halls [8]. Intra-
cluster correlation coefficients were calculated using theDonner
method to account for grouping at the residence hall level [9].
Covariates that were significantly related to ILI rate (sex, race/
ethnicity, perceived stress, sleep quality, alcohol consumption,
and vaccination) at the level or that were imbalanced
P⭐.10
across study arms at baseline (age and handwashing) at the
level were included as covariates in adjusted survival
P⭐.05
models described below.
Survival analysis. The main predictor variable was the in-
tervention arm (ie, mask and hand hygiene or mask alone
compared with control). The main outcome variable was the
first reported ILI that was based on clinical ascertainment or
survey report (if no available clinical report) over the 6-week
study period. A small number of cases reported 11 ILI (15
cases); only the first ILI was included in our analyses.
Discrete-time survival analysis using the Proc genmod pro-
cedure in SAS (version 9.1; SAS) was used to estimate rate
ratios because log-log plots demonstrated nonproportionality
of the hazard lines over time [10]. A robust model-based stan-
dard error was used, assuming an exchangeable correlation
structure because the number of residence hall cluster units
was small (7 units) [10, 11]. Analyses were conducted using
intention-to-treat [12–14]. Rate ratios and corresponding CIs
were estimated for each week of the study period and cumu-
latively over the entire study period by fitting interaction terms
between intervention group and week. Results were considered
significant at to account for comparisons across the 2P!.025
intervention and control study arms by week.
RESULTS
The total number of participants analyzed was 1297 with 367
in the face mask and hand hygiene group (9 deemed ineligible
and 26 lost to follow-up), 378 in the face mask–only group (11
deemed ineligible and 52 lost to follow-up), and 552 in the
control group (19 deemed ineligible and 21 lost to follow-up)
(Figure A1 in the Appendix). In total, 1297 (97%) of 1331
participants completed a baseline and at least 1 weekly survey.
Baseline characteristics of the study participants are shown
in Table 1. The mean age of participants was 18.7 years (stan-
dard deviation [SD], 0.8). Sex, self-reported race/ethnicity, sleep
quality, perceived stress, smoking, alcohol use, exercise, influ-
enza vaccination, and hand sanitizer ownership were not sig-
nificantly different across study arms at baseline. However, there
was a significant difference between groups in the proportion
of subjects who reported optimal handwashing practices, de-
fined as handwashing for ⭓20 s at least 5 times per day; control
and face mask–only groups reported a higher proportion of
optimal handwashing practices than those in the face mask and
hand hygiene group. Additional results on survey-reported and
observed compliance are presented in Section A2 of the
Appendix.
ILI symptom reports are shown in Table 2. At baseline, 147
of 1297 participants reported ILI and were therefore excluded
from survival analyses. Of the 1150 who were available for
analysis, 368 (32%) of 1150 participants met the definition for
ILI on either their survey (274 participants) or clinical report
(94 participants) and were analyzed in survival analyses. Cul-
ture and polymerase chain reaction (PCR) results of 94 clinical
samples were obtained from subjects with ILI symptoms. Of
these, 8 samples were positive by cell culture and 10 were pos-
itive by reverse-transcription PCR (RT-PCR) (7 for influenza
A and 3 for influenza B). All specimens that tested positive by
cell culture also tested positive by RT-PCR. RT-PCR–positive
samples included 2 in face mask and hand hygiene, 5 in face
mask alone, and 3 in the control group. The cluster-adjusted
x
2
Pvalue comparing the proportion of positive samples across
study groups was .Pp.44
Survival analysis. Univariate analyses of characteristics
with respect to the first report of ILI are shown in Table 3.
Table 1. Baseline Characteristics of the Study Population (np1297)
Characteristics Overall ICC
Face mask and
hand hygiene Face mask only Control P
a
No. of residence halls 7 1 4 2
Average residence hall size 185 367 95 276
Total no. of participants 1297 367 378 552
Age at baseline, mean year SD 18.7 0.8 .024 18.6 0.8 18.7 0.8 18.4 0.9 .04
Sex .219 .43
Female 861 (66) 179 (49) 230 (61) 452 (82)
Male 436 (34) 188 (51) 148 (39) 100 (18)
Ethnicity .039 .13
b
White 857 (67) 270 (75) 209 (56) 378 (70)
Black 102 (8) 17 (5) 50 (14) 35 (6)
Hispanic 44 (3) 9 (2) 16 (4) 19 (4)
Asian 204 (16) 51 (14) 74 (20) 79 (15)
Other
c
63 (5) 14 (4) 21 (6) 28 (5)
Sleep quality .015 .69
Very or fairly bad 300 (23) 73 (20) 95 (26) 132 (24)
Very or fairly good 981 (77) 291 (80) 276 (74) 414 (76)
Time sleeping,
d
mean h SD 6.4 1.6 .011 6.6 1.5 6.4 1.7 6.4 1.5 .37
Perceived stress score,
e
mean SD 23.5 7.4 .010 22.5 7.1 23.9 7.5 23.9 7.4 .30
Smoking .0004 .61
Current 33 (3) 8 (2) 8 (2) 17 (3)
Nonsmoker 1254 (97) 357 (98) 366 (98) 531 (97)
Alcohol consumption, drinks per week .059 .72
0–1 823 (67) 213 (61) 259 (72) 351 (68)
⭓2 401 (33) 134 (39) 102 (28) 165 (32)
Exercise
f
.006 .09
Low rate 820 (65) 210 (58) 233 (65) 377 (70)
High rate 439 (35) 151 (42) 128 (35) 160 (30)
Flu vaccine .004 .97
Never 689 (53) 194 (53) 199 (53) 296 (54)
Ever 605 (47) 173 (47) 178 (47) 254 (46)
Recent flu vaccine .014 .91
Yes 175 (14) 47 (14) 47 (14) 81 (15)
No 1047 (86) 300 (86) 301 (86) 446 (85)
Optimal handwashing
g
.006 .03
Yes 336 (26) 66 (18) 95 (25) 175 (32)
No 953 (74) 300 (82) 279 (75) 374 (68)
Hand sanitizer ownership .046 .65
Yes 707 (55) 184 (50) 228 (60) 295 (54)
No 587 (45) 182 (50) 150 (40) 255 (46)
NOTE. Data are no. (%) of participants, unless otherwise indicated. ICC, intracluster correlation coefficient.
a
Pvalues computed using cluster-adjusted x
2
test for categorical characteristics and cluster-adjusted analysis of variance for continuous
characteristics. Variables added to the final adjusted model at .P⭐.05
b
Pvalue for percentage of white participants. All other race/ethnic categories were compared, and there were no statistically significant
differences for any race/ethnic comparison (all categories, ).P⭓.05
c
Includes American Indian, Alaskan Native, and Multiethnic.
d
Time sleeping was defined as time spent in bed minus the amount of sleep lost and the amount of time spent intentionally awake in
bed. A total of 193 participants were missing time sleeping: 33 in the face mask and hand hygiene (FMHH) group, 71 in the face mask
(FM)–only group, and 89 in the control group.
e
Total of 21 participants were missing perceived stress score: 5 in the FMHH group and 8 each in the FM-only and control groups.
f
High rate defined as exercising at a very or extremely hard rate for at least 20 min, ⭓3 times per week or exercising at an easy, medium,
or hard rate for at least 30 min, ⭓5 times per week.
g
Optimal handwashing defined as washing ⭓5 times per day and for at least 20 s.
Mask Use and Hand Hygiene Mitigates ILI •JID 2010:201 (15 February) •495
Table 2. Symptom Characteristics for Influenza-like Illness Cases by Intervention Arm
Symptoms Overall
Face mask and
hand hygiene Face mask only Control P
a
Total number of participants 368 92 99 177
Cough
Yes 368 (100) 92 (100) 99 (100) 177 (100)
No 0(0) 0(0) 0(0) 0(0)
Feverish .99
Yes 164 (45) 40 (44) 44 (45) 80 (45)
No 202 (55) 51 (56) 54 (55) 97 (55)
Body aches .22
Yes 284 (78) 67 (73) 78 (79) 139 (80)
No 81 (22) 25 (27) 21 (21) 35 (20)
Chills .16
Yes 185 (52) 53 (60) 52 (53) 80 (47)
No 173 (48) 36 (40) 46 (57) 91 (53)
NOTE. Data are no. (%) of participants, unless otherwise indicated. First report of influenza-like illness (ILI)
was obtained from participants who met with a nurse or otherwise from a survey report. This table excludes ILI
cases identified at baseline ( ).np147
a
Pvalues were computed using a cluster-adjusted x
2
test.
Table 3. Univariate Characteristics and Rate of Influenza-like
Illness Symptoms
Characteristic
a
RR (95% CI) P
Age at baseline 0.92 (0.81–1.04) .19
Sex, female vs. male 1.22 (0.98–1.53) .08
Race/ethnicity (ref White)
Black 1.08 (0.74–1.58) .69
Asian 0.70 (0.50–0.97) .03
Other 1.16 (0.82–1.66) .40
Sleep quality bad vs. good 1.41 (1.12–1.77) .004
Stress score 1.03 (1.01–1.04) !.001
Smoking, current vs. non 0.94 (0.48–1.83) .86
Alcohol consumption
(0 to 1 drink per week)
⭓2 drinks per week 1.41 (1.13–1.74) .002
Physical activity, high vs. low 1.13 (0.91–1.41) .26
Flu shot, ever vs never 1.32 (1.07–1.62) .01
Recent shot, yes vs no 1.23 (0.92–1.63) .16
Optimal handwashing at baseline 1.11 (0.89–1.40) .35
NOTE. CI, confidence interval; RR, rate ratio.
a
Variables added to the final adjusted model at .P⭐.10
Over the 6-week study period, both intervention groups showed
a∼10% reduction in cumulative ILI incidence compared with
the control group in unadjusted analyses, although theseresults
did not reach statistical significance in either group (Table 4).
In addition to cumulative ILI rate over the study period, dis-
crete-time survival analysis allowed estimation of the rate ratio
over each week of the study. After the participant enrollment
ended (ie, week 3 onward), significant reductions in ILI inci-
dence were observed in the mask and hand hygiene group
(weeks 4–6) and in the face mask–only group (weeks 3–5)
compared with the control group. After covariate adjustment,
ILI incidence was significantly lower among the mask and hand
hygiene group compared with the control group from week 4
onward (Table 4; Figure 1). In the face mask–only group, ad-
justed results also showed a reduction in ILI incidence during
week 4 onward but were not statistically significant at P!
..025
DISCUSSION
Intervention studies of face masks in open, noninstitutionalized
populations to protect healthy individuals from primary res-
piratory infections have, to our knowledge, not been previously
reported. We found a significant reduction in the rate of ILI
among participants randomized to the face mask and hand
hygiene intervention during the latter half of this study, ranging
from 35% to 51% when compared with a control group that
did not use face masks.
Our results are consistent with a previous review of studies
examining the effectiveness of mask use in reducing the trans-
mission of respiratory viruses [15]. However, much of the data
on natural infection derives from studies of SARS. The trans-
mission characteristics of this pathogen may be different from
those of influenza and other seasonal respiratory illnesses. Al-
though few data are available to evaluate the efficacy of face
mask use in the community setting, 2 recent randomized mask
intervention studies, one in Hong Kong and the other in Aus-
tralia, reported no significant reductions in secondary trans-
mission of ILI [16, 17]. However, important methodological
differences exist between our study assessing the prevention of
primary infections and these earlier studies that asked partic-
496 •JID 2010:201 (15 February) •Aiello et al
Table 4. Intervention Rate Ratios, Unadjusted and Adjusted for Covariates
Week
Face mask only
vs control
Face mask and hand
hygiene vs control
RR (95% CI) P
a
RR (95% CI) P
a
Unadjusted for covariates
b
1 0.89 (0.61–1.30) .54 0.98 (0.67–1.44) .92
2 0.81 (0.61–1.08) .16 0.86 (0.65–1.15) .31
3 0.75 (0.58–0.96) .02 0.76 (0.59–0.98) .03
4 0.68 (0.51–0.92) .01 0.67 (0.49–0.91) .01
5 0.63 (0.42–0.93) .02 0.59 (0.38–0.89) .01
6 0.57 (0.34–0.97) .04 0.51 (0.30–0.90) .02
Week x treatment 0.92 (0.79–1.06) .25 0.88 (0.75–1.03) .10
Adjusted for covariates
c
1 0.98 (0.65–1.46) .92 1.01 (0.66–1.53) .98
2 0.88 (0.65–1.20) .42 0.87 (0.63–1.20) .39
3 0.80 (0.61–1.04) .09 0.75 (0.57–1.00) .05
4 0.72 (0.53–0.98) .03 0.65 (0.47–0.91) .01
5 0.65 (0.43–0.98) .04 0.56 (0.36–0.88) .01
6 0.58 (0.34–1.00) .05 0.49 (0.27–0.87) .02
Week x treatment 0.90 (0.77–1.05) .19 0.87 (0.73–1.02) .08
NOTE. Week x treatment describes the cumulative influenza-like illness rate ratio over the study period
according to intervention arm. CI, confidence interval; RR, rate ratio.
a
Significance level set at .P!.025
b
(316 in the face mask and hand hygiene [FMHH] group; 347 in the face mask [FM]–onlyNp1150
group; 487 in the control group). Intracluster correlation coefficient, ⫺0.0006; negative correlations set to
0.
c
(289 in the FMHH group; 315 in the FM-only group; 438 in the control group). IntraclusterNp1042
correlation coefficient, ⫺0.0005; negative correlations set to 0. All models adjusted for age, sex, race/
ethnicity, handwashing practices at baseline, sleep quality, stress, alcohol consumption,and flu vaccination.
Figure 1. Adjusted Kaplan-Meier survival curve. The figure shows the
proportion of participants that are ILI-free by intervention arm over the
6-week study period adjusted for age, sex, race/ethnicity, handwashing
practices, sleep quality, stress, alcohol consumption, and influenza vac-
cination ( ).np1042
ipants to don masks only after identification of an influenza
case residing in the household for assessment of the prevention
of secondary infections. We asked participants to begin wearing
the mask and using hand sanitizer at the beginning of the
influenza season just after identification of the first case of
influenza on campus. This fundamental study design difference
may have improved our ability to identify an effect of mask
and hand hygiene use, compared with studies of secondary
transmission in which household members may already have
been infected by the time of mask adoption.
Several factors may explain why we observed a statistically
significant reduction in ILI incidence ( ) only duringP!.025
the latter half of the 6-week study period. First, we continued
recruitment 2 weeks after the study started, which increased
our sample size by 11%. The greater participation rates later
during the study may have resulted in reduced transmission of
respiratory viruses within the intervention residence halls. Sec-
ond, there was an almost 10% increase in the proportion of
subjects in the mask and hand hygiene group who reported
wearing their masks for more than average (3.5 h per day)
during weeks 3–6 of the study. In contrast, this proportion only
increased by 2% in the face mask–only group during the same
period. Another factor that may have influenced the results
included a late and mild influenza season. Laboratory-con-
firmed cases in Michigan and reports of ILI to University Health
Services (UHS) did not substantially increase until the second
week of the study. The greatest frequency of cases of ILI re-
ported to UHS occurred during week 6, and the largest number
of laboratory-confirmed cases of influenza in Michigan oc-
Mask Use and Hand Hygiene Mitigates ILI •JID 2010:201 (15 February) •497
curred during weeks 4 and 5 of the study. In addition, spring
break travel may have influenced our results. As most students
left campus during spring break (between weeks 4 and 5 of the
intervention period) and were not required to continue their
protective measures during this time, potential exposures dur-
ing spring break may have increased illness in residence halls
toward the end of the study, after break. Spring break exposures
may therefore represent a confounding factor, limiting our abil-
ity to demonstrate the effectiveness of interventions. Thus, fu-
ture studies are needed to identify whether the protective effects
observed here can be generalized to larger influenza outbreaks,
as well as the potential influence of intervention start time and
interruption.
ILI incidence between the face mask and hand hygiene group
and the face mask–only group were not substantially different,
suggesting that the addition of a hand sanitizer component did
not appreciably decrease the rate of ILI in this study population.
Because the value of hand hygiene has not been established for
influenza or ILI prevention during periods of confirmed viral
transmission, we decided to include a trial arm in which both
interventions (mask and hand hygiene) were combined. Our
study, however, was not powered to detect small differences
between the intervention groups, which would be expected
during mild influenza seasons. Although some studies have
reported a reduced risk of illness when using alcohol-based
hand sanitizer in conjunction with handwashing [6, 18], the
incremental effect of adding antiseptics to regular handwashing
is unknown [19]. Indeed, a recent metaanalysis of community-
based hand hygiene interventions reported a nonsignificant
pooled reduction in respiratory illnesses based on 5 studies of
alcohol-based hand sanitizer interventions in the community
setting [20].
Although the mask and hand hygiene group used hand san-
itizer more often, and a greater proportion of participants ap-
plied the recommended amount compared with the other study
groups, this group also had a greater proportion of participants
with suboptimal handwashing practices at baseline. Although
we controlled for handwashing habits in our regression models,
it is possible that the overall hand hygiene practices (ie, sig-
nificantly higher use of hand sanitizer yet significantly lower
number of handwashes per day in the face mask and hand
hygiene group) were counterbalanced, such that the incremen-
tal, potentially protective effect of using alcohol-based hand
sanitizer in the layered arm was matched by a greater number
of handwashes per day in the mask-only arm. Nonetheless,
alcohol-based hand sanitizers are more effective for inactivating
a wide range of respiratory viruses, including influenza virus,
compared with plain soap and water [21, 22]. It is important
to note that handwashing habits were the same in both the face
mask–only and control groups at baseline and over the study
period, which suggests that mask use alone may provide a
reduction in respiratory illnesses regardless of handwashing
practices. Future work should address which particular com-
binations of interventions are effective in reducing ILI or other
respiratory viruses, in both the health care and community
settings.
Several demographic characteristics and health factors were
associated with risk of ILI in our study population, including
ever having an influenza vaccination, being white versus Asian
race, higher levels of stress, and increased alcohol intake. Pos-
sibly, reports of “ever having an influenza vaccination” may be
associated with increased ILI because young individuals who
seek vaccination may be more health-conscious and likely to
report ILI symptoms, compared with those who have never
had a vaccination. This bias has been reported in other studies
of vaccination and ILI symptom reporting [23, 24]. Reported
seasonal vaccination status, on the other hand, was not pro-
tective of ILI rates. However, only 14% of the total study pop-
ulation reported vaccination acquisition during the corre-
sponding influenza season. Additional discussion of demo-
graphic variables is available in the supplemental materials(Sec-
tion A3 of the Appendix).
This study has several limitations. First, influenza incidence
was low, so it is likely that most ILI cases were not associated
with influenza infection, even though the study was conducted
during the influenza season. Second, the study was underpow-
ered to detect low reductions in the rate of ILI and across study
arms. The number of clusters in this study was small, thus
suggesting some potential for inflation of variance estimates
[25]. However, there are several factors that support the validity
of our methods and results. First, there were no significant
differences in rates of ILI across the 7 residence halls at baseline,
which suggests that naturally occurring differences in ILI rates
across halls are unlikely to explain our findings. In addition,
we observed consistent reductions in both the face mask–only
and face mask and hand hygiene groups over the study period.
Given that the mask-only group was composed of 4 residence
hall clusters and the changes in the rates of ILI were also com-
parable to the mask and hand hygiene group, it is unlikely that
natural variation could account for the consistency in results
across study arms over time. Second, the magnitude of the
design effect (ie, intracluster correlation coefficient) for both
the adjusted and unadjusted models was well below 1 (see
footnotes in Table 4), which suggests a lack of significant clus-
tering of ILI by residence hall. Therefore, control for clustering
along with conservative P-value cutoffs used in this study may
have potentially masked statistically significant results [25].
Next, the bulk of the data was collected through Web-based
weekly surveys in which participants reported their activities,
symptoms, and other events during the prior week. By relying
largely upon self-reported data, this study may be susceptible
to reporting bias; some individuals could have reported what
498 •JID 2010:201 (15 February) •Aiello et al
they thought was expected of them. The similarity in reported
behavioral habits and hand hygiene practices across interven-
tion and control groups argues against differential reporting
biases. Because of the inability to blind participants to study
interventions, compliance with these interventions must be
considered carefully. We assessed compliance as described in
Sections A1 and A2 of the Appendix, but it was not possible
to gather observational data on all participants at all times and
venues. Finally, given the limited age range and specialized
living setting of study participants, we are not able to generalize
our results to other, nonuniversity aged, community-dwelling
populations. However, our findings should be applicable to
individuals living in similar crowded and close-quarter living
settings.
We demonstrated a protective effect of the intervention even
with relatively moderate use of face masks throughout the day.
We believe that during an influenza pandemic, compliance with
interventions will be higher than what we found in this study,
particularly if rates of serious complications are high or well
publicized. If our findings also apply to laboratory-confirmed
influenza infections, the effect on influenza transmission could
be substantial, particularly early in a pandemic when vaccine
supply will almost certainly be limited, as with the current
nH1N1 pandemic [26]. Our results indicate that interventions
to reduce the transmission of ILI during a winter season may
have substantial effects among individuals who share crowded
living conditions.
Acknowledgments
We gratefully acknowledge the thousands of participants who made this
study possible and the efforts on behalf of staff volunteers, recruitment
coordinators, and laboratory assistants. We are especially thankful for the
assistance of the nursing staff and the generous help provided byUniversity
Health Services and University Housing. Alcohol-based hand sanitizer was
generously provided by Warner Lambert, a subsidiary of Pfizer.
References
1. Centers for Disease Control and Prevention. Interim pre-pandemic
planning guidance: Community strategy for pandemic influenza mit-
igation in the United States—early, targeted, layered use of nonphar-
maceutical interventions. 2007
2. Smith RD. Responding to global infectious disease outbreaks: lessons
from SARS on the role of risk perception, communication and man-
agement. Soc Sci Med 2006; 63:3113–3123.
3. Johnson AJ, Moore ZS, Edelson PJ, et al. Household responses to school
closure resulting from outbreak of influenza B, North Carolina. Emerg
Infect Dis 2008; 14:1024–1030.
4. Cauchemez S, Ferguson NM, Wachtel C, et al. Closure of schools
during an influenza pandemic. Lancet Infect Dis 2009; 9:473–481.
5. Markel H, Lipman HB, Navarro JA, et al. Nonpharmaceutical inter-
ventions implemented by US cities during the 1918–1919 influenza
pandemic. JAMA 2007; 298:644–654.
6. White C, Kolble R, Carlson R, et al. The effect of hand hygiene on
illness rate among students in university residence halls. Am J Infect
Control 2003; 31:364–370.
7. Thursky K, Cordova SP, Smith D and Kelly H. Working towards a
simple case definition for influenza surveillance. J Clin Virol 2003;27:
170–179.
8. Donner A, Klar N. Cluster randomization trials: theory andapplication.
J Stat Plan Inference 1994; 42:37–56.
9. Donner A. Statistical methods in opthalmology: an adjusted x
2
ap-
proach. Biometrics 1989; 45:605–611.
10. Allison PD. Discrete-time methods for the analysis of event histories.
Sociol Methodol 1982; 13:61–98.
11. Zeger SL, Liang KY. Longitudinal data analysis for discrete and con-
tinuous outcomes. Biometrics 1986; 42:121–130.
12. Fisher LD, Dixon DO, Herson J, et al. Intention-to-treat in clinical
trials. New York: Marcel Dekker, 1990.
13. Hollis S, Campbell F. What is meant by intention to treat analysis?
Survey of published randomised controlled trials. BMJ 1999;319:
670–674.
14. Piantadosi S. Clinical trials: a methodologic perspective. New York:
Wiley & Sons, 2005.
15. Jefferson T, Foxlee R, Del Mar C, et al. Physical interventions to in-
terrupt or reduce the spread of respiratory viruses: systematic review.
BMJ 2008; 336:77–80.
16. Cowling BJ, Fung RO, Cheng CK, et al. Preliminary findings of a
randomized trial of non-pharmaceutical interventions to prevent in-
fluenza transmission in households. PLoS ONE 2008; 3:e2101.
17. MacIntyre CR, Cauchemez S, Dwyer DE, et al. Face mask use and
control of respiratory virus transmission in households. Emerg Infect
Dis 2009; 15:233–241.
18. Morton JL, Schultz AA. Healthy hands: use of alcohol gel as an adjunct
to handwashing in elementary school children. J Sch Nurs 2004;20:
161–167.
19. Jefferson T, Foxlee R, Del Mar C, et al. Interventions for the inter-
ruption or reduction of the spread of respiratory viruses. Cochrane
Database Syst Rev 2007:(4)CD006207.
20. Aiello AE, Coulborn RM, Perez V, Larson EL. Effect of hand hygiene
on infectious disease risk in the community setting: a meta-analysis.
Am J Public Health 2008; 98:1372–1381.
21. Kampf G, Kramer A. Epidemiologic background of hand hygiene and
evaluation of the most important agents for scrubs and rubs. Clin
Microbiol Rev 2004; 17:863–893, table of contents.
22. Sattar SA, Springthorpe VS, Tetro J, Vashon R, Keswick B. Hygienic
hand antiseptics: Should they not have activity and label claims against
viruses? Am J Infect Control 2002;3 0:355–372.
23. Ramadan PA, de Araujo FB, Ferreira Junior M. A 12-month follow-
up of an influenza vaccination campaign based on voluntary adherence:
report on upper-respiratory symptoms among volunteers and non-
volunteers. Sao Paulo Med J 2001; 119:142–145.
24. Millot JL, Aymard M, Bardol A. Reduced efficiency ofinfluenzavaccine
in prevention of influenza-like illness in working adults: a 7 month
prospective survey in EDF Gaz de France employees, in Rhone-Alpes,
1996–1997. Occup Med (Lond) 2002; 52:281– 292.
25. Localio AR, Berlin JA, Ten Have TR, Kimmel SE. Adjustments for
center in multicenter studies: an overview. Ann Intern Med 2001; 135:
112–123.
26. Diekman O, Heesterbeek JAP. The basic reproduction ratio. In: Anon-
ymous, ed. Mathematical Epidemiology of Infectious Diseases: Model
Building, Analysis, and Interpretation. United Kingdom: John Wiley
& Sons, 2000.
