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Findings, Gaps, and Future Direction for Research in Nonpharmaceutical Interventions for Pandemic Influenza

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Charles J Vukotich at University of Pittsburgh
Charles J Vukotich
Rebecca M Coulborn
Rebecca M Coulborn
Rebecca M Coulborn
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Tomas J Aragon
Tomas J Aragon
Tomas J Aragon
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Michael G Baker
Michael G Baker
Michael G Baker
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Abstract

In June 2006, the Centers for Disease Control and Prevention (CDC) released a request for applications to identify, improve, and evaluate the effectiveness of nonpharmaceutical interventions (NPIs) to mitigate the spread of pandemic influenza within communities and across international borders (RFA-CI06-010) (1). Eleven studies (Table 1) were funded to identify optimal, discrete, or combined NPIs for implementation during an influenza pandemic. During March 4-6, 2009, the principal investigators met to share results, identify research gaps, and define future research needs in 9 areas as described here. A total of 16 research gaps were identified (Table 2).
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Findings, Gaps, and Future Direction for Research in Nonpharmaceutical Interventions for Pandemic Influenza | CDC EID
http://www.cdc.gov/eid/content/16/4/e2.htm[6/24/2010 2:35:11 PM]
Volume 16, Number 4–April 2010
Conference Summary
Findings, Gaps, and Future Direction for
Research in Nonpharmaceutical Interventions
for Pandemic Influenza
Charles J. Vukotich, Jr., Rebecca M. Coulborn, Tomas J. Aragon, Michael G. Baker,
Barri B. Burrus, Allison E. Aiello, Benjamin J. Cowling, Alasdair Duncan, Wayne
Enanoria, M. Patricia Fabian, Yu-hui Ferng, Elaine L. Larson, Gabriel M. Leung, Howard
Markel, Donald K. Milton, Arnold S. Monto, Stephen S. Morse, J. Alexander Navarro,
Sarah Y. Park, Patricia Priest, Samuel Stebbins, Alexandra M. Stern, Monica Uddin, and
Scott F. Wetterhall
Author affiliations: University of Pittsburgh, Pennsylvania, USA (C.J. Vukotich, S. Stebbins); University of
Michigan, Ann Arbor, Michigan, USA (R.M. Coulborn, A.E. Aiello, H. Markel, A.S. Monto, J.A. Navarro, A.M.
Stern, M. Uddin); University of California, Berkeley, California, USA (T.J. Aragon, W. Enanoria); University of
Otago, Dunedin, New Zealand (M.G. Baker, A. Duncan, P. Priest); RTI International, Research Triangle Park,
North Carolina, USA (B.B. Burrus, S.F. Wetterhall); University of Hong Kong, Hong Kong, People's Republic
of China (B.J. Cowling, G. M. Leung); University of Massachusetts, Lowell, Massachusetts, USA (M.P.
Fabian); Columbia University, New York, New York, USA (Y. Ferng, E.L. Larson, S.S. Morse); University of
Maryland, College Park, Maryland, USA (D.K. Milton); and Hawaii Department of Health, Honolulu, Hawaii
(S.Y. Park)
Suggested citation for this article
In June 2006, the Centers for Disease Control and Prevention (CDC) released a request for applications to
identify, improve, and evaluate the effectiveness of nonpharmaceutical interventions (NPIs) to mitigate the
spread of pandemic influenza within communities and across international borders (RFA-CI06-010) (1).
Eleven studies (Table 1) were funded to identify optimal, discrete, or combined NPIs for implementation
during an influenza pandemic. During March 4–6, 2009, the principal investigators met to share results,
identify research gaps, and define future research needs in 9 areas as described here. A total of 16 research
gaps were identified (Table 2).
NPI behaviors can be successfully taught to and adopted by a variety of persons through community health
education, interactive classroom teaching, or Internet-based instruction (3). Urban Hispanics had
misunderstandings about influenza (e.g., 88% thought that influenza was caused by bacteria). Their
knowledge, attitudes, and practices improved through a community education program (4). Acceptability of
NPIs also depends on early planning, consistent and targeted communication during implementation, and
clear delineation of responsibilities and authority. Acceptability further requires communication from traditional
(i.e., emergency response organizations) and nontraditional (i.e., churches) sources.
Behaviors perceived as typical daily behavior were more readily accepted than nontypical daily behaviors.
Hand sanitizing with alcohol-based preparations, washing with soap, covering sneezes and coughs, and
Findings, Gaps, and Future Direction for Research in Nonpharmaceutical Interventions for Pandemic Influenza | CDC EID
http://www.cdc.gov/eid/content/16/4/e2.htm[6/24/2010 2:35:11 PM]
being aware of one's hands (e.g., touching face) showed relatively high compliance. Only 1 of 5 projects had
good adherence to face mask use, which is not a typical behavior (2).
In addition, efficacy of face masks for preventing transmission of influenza viruses has yet to be fully
determined. Influenza virus nucleic acid was present in fine-particle aerosols from influenza patients in tidal
breathing (14%–33%) and coughing (64%) (5). Preliminary results demonstrate that surgical ear-loop face
masks limit the generation of droplets (>5.0 µm in diameter) containing influenza virus RNA.
NPIs can be efficacious for reducing rates of influenza and influenza-like illness (ILI) in community settings.
Household secondary attack ratios were substantially reduced (adjusted odds ratio 0.33, 95% CI 0.13–0.87)
if all household members practiced frequent hand washing and wore face masks within 36 hours after
symptom onset in the index patient (6). University students had a 50%–65% reduced rate of ILI over a 6-
week intervention period, using hand hygiene and masks (7). Mask use was substantial (4–5 hours per day
average), which was attributed to adoption of masks as a daily behavior, rather than as a response to illness.
Elementary school students using a 5-layered NPI approach, including hand hygiene and cough etiquette,
had 53% fewer laboratory-confirmed influenza A infections and 26% fewer total absences compared with a
control group.
Household crowding (measured as a deficit of >2 bedrooms) can be a factor in community influenza
transmission, significantly increasing the relative risk (RR) for hospitalization for pneumonia or influenza (RR
= 1.20, 95% CI 1.05–1.37; age standardized). The mean serial interval (i.e., the time between successive
cases of infectious diseases in the chain of transmission) was 3.6 days, based on pairs of persons in 14
households (8).
School dismissal is part of CDC's pandemic planning, but dismissed students may congregate elsewhere.
The number of social contacts by children dropped 67% (p<0.05) during school holidays, suggesting that
recongregation may not be a factor in school closure and that school dismissal might increase social
distancing during pandemic influenza.
Three studies assessed the use of Quidel QuickVue Influenza A+B Rapid Test in the community and found a
median sensitivity of 27%, despite manufacturer reports of 73%. No cause for this sensitivity has been shown
(9).
Rapid, large-scale risk-based entry screening of air travelers for ILI that used questionnaires and health
assessments was conducted successfully at 2 airports for 177 flights. Seventy-five percent of passengers
who provided contact details were followed up, but few of those with symptoms were prepared to go to a
laboratory for collection of a respiratory specimen. On the basis of preliminary analysis, investigators
concluded that voluntary travel restrictions would sufficiently protect only isolated populations with low
numbers of visitors (10).
Investigators have collected newspapers, official health reports at all levels, scholarly literature, and archived
material from governments and agencies. This material is being compiled into The American Influenza
Epidemic of 1918–1919: A Digital Encyclopedia, an archive of historical material (11,12).
Meeting participants concluded that evidence exists of the effectiveness of NPIs, including face masks, hand
hygiene, cough etiquette, reduced crowding, and school closures, in reducing the spread of influenza.
Insufficient sample sizes, exacerbated by a mild influenza season during the first funding year, underreporting
of disease, and challenges faced by influenza surveillance limited the statistical power of most studies.
Further studies with larger sample sizes, common methods to allow pooling of data, and study durations that
cover multiple influenza seasons are needed to address these limitations. In addition, studies using
Findings, Gaps, and Future Direction for Research in Nonpharmaceutical Interventions for Pandemic Influenza | CDC EID
http://www.cdc.gov/eid/content/16/4/e2.htm[6/24/2010 2:35:11 PM]
engineering controls, such as upper-room ultraviolet C lighting, in populations with naturally acquired infection
are needed to address the relative contribution of transmission modalities, e.g., small vs. large respiratory
droplets and contact transmission.
Acknowledgments
We thank all the meeting participants for their thoughtful presentations and discussions. We
also thank Leslie Fink for editing of and review of the manuscript.
This research was supported by the Centers for Disease Control and Prevention under a
series of cooperative agreements named herein, emanating from RFA-CI06-010, issued on
June 16, 2006.
References
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in an urban elementary school setting. J Public Health Manag Pract. In press.
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cities during the 1918–19 influenza pandemic [discussion 138–42]. Trans Am Clin Climatol Assoc.
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Tables
Findings, Gaps, and Future Direction for Research in Nonpharmaceutical Interventions for Pandemic Influenza | CDC EID
http://www.cdc.gov/eid/content/16/4/e2.htm[6/24/2010 2:35:11 PM]
Table 1. List of projects funded during 2007–2009 under Centers for Disease Control and Prevention
Nonpharmaceutical Intervention Studies for Pandemic Influenza RFA-CI06-010
Table 2. Research gaps in identifying, improving, and evaluating the effectiveness of NPIs in mitigating the
spread of pandemic influenza
Suggested Citation for this Article
Vukotich CJ Jr, Coulborn RM, Aragon TJ, Baker MG, Burrus BB, Aiello AE, et al. Findings, gaps, and future
direction for research in nonpharmaceutical interventions for pandemic influenza [conference summary].
Emerg Infect Dis [serial on the Internet]. 2010 April [date cited]. www.cdc.gov/EID/content/16/4/e2.htm
DOI: 10.3201/eid1604.090719
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  • Apr 2009
  • BMC INFECT DIS
Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).
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Public health - Next flu pandemic: What to do until the vaccine arrives?
Article
Full-text available
  • Dec 2006
  • SCIENCE
Most scientists consider another influenza pandemic inevitable, but there is little information on how best to protect the public before a vaccine can be made available.
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Mask Use Reduces Seasonal Influenza-like Illness in The Community Setting
Conference Paper
  • Oct 2008
Background: This study examined whether use of face masks reduces incidence of influenza like illness (ILI) symptoms among young adults. Methods: A randomized trial during the 2007 flu season. Participants (N=1,417) living in 7 randomized university residence halls were assigned to 1 of 2 intervention groups or a control group. At the start of the influenza season, halls were randomly assigned to 6 weeks of mask use alone, mask and hand hygiene, or control and followed for incidence of ILI. Results: The protective effect of face mask/hand hygiene and face mask only intervention groups compared to the control group increased over time (Figure). By week 4, the face mask only group showed a 29% lower rate of ILI than control group (95% CI: 3% to 47%) and face mask/hand hygiene group had 26% lower rate than control group (95% CI: 0% to 45%), adjusted for covariates. The rate continued to decrease: compared to control, 45% (95% CI: 6% to 67%) lower rate in face mask only and 41% (95% CI: 1% to 65%) lower rate in face mask/hand hygiene group at 6 weeks. Conclusions: Even during a mild influenza season, mask use was associated with a reduction in rate of ILI from 29% to 45%. These findings indicate that mask use may be an effective means of reducing influenza in shared living settings. During year 2 of the study, a major outbreak of influenza took place. Forthcoming studies will examine influenza virus identification as an additional outcome.
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Compliance With a Multilayered Nonpharmaceutical Intervention in an Urban Elementary School Setting
Article
  • Jul 2010
The purpose of this study was to determine to what extent school-aged children can learn hygiene-based nonpharmaceutical interventions (NPIs) and persist in these behavioral changes over the duration of an influenza season. If this can be done successfully, it may be a preferable pandemic mitigation strategy to much more disruptive strategies such as whole-scale school closure. The Pittsburgh Influenza Prevention Project (PIPP) is a prospective, controlled, randomized trial of the effectiveness of a suite of hygiene-based NPIs in controlling influenza and related illnesses in elementary schools in the City of Pittsburgh. During the 2007-08 school year, the project measured adoption of NPIs by students in five elementary schools through surveys of home-room teachers before, during, and after influenza season. Results showed highly statistically significant improvement in students' daily practice of nearly all of the NPIs, including hand washing and sanitizer use and covering coughs and sneezes. The study provides evidence that children can learn, implement, and persist in the behaviors of a multilayered suite of NPIs over a typical flu season. These results will be useful to public health policy makers and practitioners considering methods of infectious disease prevention in school-based settings.
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Estimation of the Serial Interval of Influenza
Article
  • Apr 2009
: Estimates of the clinical-onset serial interval of human influenza infection (time between onset of symptoms in an index case and a secondary case) are used to inform public health policy and to construct mathematical models of influenza transmission. We estimate the serial interval of laboratory-confirmed influenza transmission in households. : Index cases were recruited after reporting to a primary healthcare center with symptoms. Members of their households were followed-up with repeated home visits. : Assuming a Weibull model and accounting for selection bias inherent in our field study design, we used symptom-onset times from 14 pairs of infector/infectee to estimate a mean serial interval of 3.6 days (95% confidence interval = 2.9-4.3 days), with standard deviation 1.6 days. : The household serial interval of influenza may be longer than previously estimated. Studies of the complete serial interval, based on transmission in all community contexts, are a priority.
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Using Nonpharmaceutical Interventions to Prevent Influenza Transmission in Elementary School Children
Article
  • Mar 2009
Schools act as "amplifying sites" for the spread of infectious diseases, outbreaks, and pandemics. This project assessed which nonpharmaceutical interventions (NPIs) are most acceptable to parents and teachers of school children in grades K-5 to K-8 in Pittsburgh public schools. During the spring of 2007, the Pittsburgh Influenza Prevention Project surveyed 134 teachers and 151 parents representing nine elementary schools regarding attitudes toward NPIs and their usage by adults and school children during seasonal influenza outbreaks. General etiquette practices such as covering coughs, handwashing, and using hand sanitizer were highly acceptable to both groups, while masks and gloves were not. The success of an NPI or a set of NPIs depends on both its efficacy and the feasibility of implementing it with relevant populations. If masks, gloves, and other more intrusive NPIs are to be used in community settings during a severe influenza season or pandemic, it is clear that there is significant preparatory work needed to increase acceptability on the part of the adults. Without such acceptance, it is highly unlikely that children and their supervising adults will participate.
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