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Assessing the State of Knowledge Regarding the Effectiveness of Interventions to Contain Pandemic Influenza Transmission: A Systematic Review and Narrative Synthesis

Assessing the State of Knowledge Regarding the Effectiveness of Interventions to Contain Pandemic Influenza Transmission: A Systematic Review and Narrative Synthesis

  • Patrick Saunders-Hastings, 
  • Jane Reisman, 
  • Daniel Krewski
PLOS
x

Abstract

Background

Influenza pandemics occur when a novel influenza strain, to which humans are immunologically naïve, emerges to cause infection and illness on a global scale. Differences in the viral properties of pandemic strains, relative to seasonal ones, can alter the effectiveness of interventions typically implemented to control seasonal influenza burden. As a result, annual control activities may not be sufficient to contain an influenza pandemic.

Purpose

This study seeks to inform pandemic policy and planning initiatives by reviewing the effectiveness of previous interventions to reduce pandemic influenza transmission and infection. Results will inform the planning and design of more focused in-depth systematic reviews for specific types of interventions, thus providing the most comprehensive and current understanding of the potential for alternative interventions to mitigate the burden of pandemic influenza.

Methods

A systematic review and narrative synthesis of existing systematic reviews and meta-analyses examining intervention effectiveness in containing pandemic influenza transmission was conducted using information collected from five databases (PubMed, Medline, Cochrane, Embase, and Cinahl/EBSCO). Two independent reviewers conducted study screening and quality assessment, extracting data related to intervention impact and effectiveness.

Results and Discussion

Most included reviews were of moderate to high quality. Although the degree of statistical heterogeneity precluded meta-analysis, the present systematic review examines the wide variety of interventions that can impact influenza transmission in different ways. While it appears that pandemic influenza vaccination provides significant protection against infection, there was insufficient evidence to conclude that antiviral prophylaxis, seasonal influenza cross-protection, or a range of non-pharmaceutical strategies would provide appreciable protection when implemented in isolation. It is likely that an optimal intervention strategy will employ a combination of interventions in a layered approach, though more research is needed to substantiate this proposition.

Trial Registration

PROSPERO 42016039803

1. Introduction

Each year, influenza infection is responsible for hundreds of thousands of hospitalizations, tens of thousands of deaths, and billions of dollars in healthcare costs and lost productivity in the United States alone [1, 2]. At the same time, there is an ever-present threat of an antigenic shift occurring in the influenza virus, producing a new strain to which humans possess little or no immunity and causing an influenza pandemic with even more catastrophic potential. This has occurred four times in the past hundred years, at unpredictable intervals and with varying degrees of severity. The 1918 Spanish flu remains one of the worst public health catastrophes in recorded human history [3], resulting in between 20 and 50 million deaths globally [47].

Key concerns surrounding a future pandemic relate to surges in community illness attack rates and, by extension, hospitalization demand [810]. The just-in-time nature of resource delivery in hospitals could make it difficult to adapt to such surges [11, 12]. Taken together, these risks could lead to disruption of health services, compounding the social, economic, and health burdens associated with a pandemic. The inherent uncertainty surrounding such pandemics presents challenges in mounting an appropriate and effective response. Integration of best practices as informed by past influenza pandemics may help in developing effective responses to future pandemics.

This study examines the effectiveness of any intervention to contain human transmission of influenza infection during a future pandemic of unknown severity. To accomplish this, we conducted a systematic review of existing systematic reviews (SR) and meta-analyses (MA) on pandemic influenza interventions. Recognizing that there is substantial variation in where, how, and when interventions are implemented, we sought to better understand the impact of such interventions. Given continuing fears surrounding the threat of avian influenza virus (H5N1 and H7N2) infection in poultry and humans [13, 14], increasing viral diversity of influenza strains circulating in swine populations [15], and escalating human-animal proximity and interaction [16, 17], this article provides timely insight to support future pandemic planning efforts.

2. Methods

2.1 Overview

The review methodology was developed in keeping with PRISMA [18] guidelines for systematic reviews (S1 Table); a protocol developed a priori is published in the National Institute for Health Research International Prospective Register of Systematic Reviews (PROSPERO). Briefly, we conducted a systematic review of existing SRs and MAs dealing with pharmaceutical and non-pharmaceutical interventions to interrupt pandemic influenza transmission and infection. Pharmaceutical interventions include vaccination policies and antiviral use. Non-pharmaceutical interventions include school and work closures, social distancing and contact reduction, use of masks, hand hygiene, and cough etiquette. Where feasible and appropriate, differential effectiveness according to age was noted during data extraction.

2.2 Search strategy

Systematic literature searches were conducted on July 5, 2016 using PubMed (all dates), Medline (1946-present), Embase (1947-present), Cochrane Library (all dates) and the Cumulative Index to Nursing and Allied Health (CINAHL; all dates). The general search strategy is presented in Table 1, with database-specific variations documented in the supplemental material (S2 Table).

The search excluded research on seasonal influenza and non-influenza disease outbreaks, which would both be of reduced applicability in studying interventions specifically targeting pandemic influenza. The search was conducted on 5 July, 2016, with no language or date restrictions. In cases where a full report was not available, we contacted the authors to request any manuscripts based on the identified abstract. The search was complemented by searching the reference lists of included reviews and ad hoc grey literature searches using Google Scholar.

2.3 Eligibility criteria and study inclusion

Articles were imported into Endnote X7.5 and were subjected to blind title and abstract appraisal by two independent reviewers. Discrepancies automatically pushed articles to full review. Full texts were sought for articles retained for full review, and again subjected to blind review by two independent reviewers. Conflicts were resolved by consensus and third-party arbitration as necessary. Articles were excluded if they met one of the a priori exclusion criteria listed in Table 2. Studies were considered to address an influenza “pandemic” if they assessed an intervention implemented during the first or second wave of a pandemic, after which the annually circulating strain was viewed as a “seasonal” influenza.

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Table 2. Exclusion criteria for systematic reviews and meta-analyses of pandemic influenza interventions.

https://doi.org/10.1371/journal.pone.0168262.t002

2.4 Data extraction and analysis

Data from retained articles were extracted to a piloted Excel spreadsheet by two independent reviewers. Spreadsheet categories offer information pertaining to the study populations, interventions, and outcomes. The principal summary measures of relative intervention effect are risk and odds ratios. Methodological heterogeneity of the included systematic reviews—particularly with respect to research questions, inclusion criteria, intervention specifics, and outcome measures—precluded pooling of data for a new meta-analysis, as well as the use of funnel plots to assess the potential for publication bias. Instead, a narrative synthesis is presented for each of the interventions evaluated in a past review, highlighting current knowledge and unfilled data gaps.

2.5 Quality assessment

The quality of articles retained for data extraction was assessed by two independent reviewers using the AMSTAR tool (S3 Table). The 11-item questionnaire was developed for application across a broad range of public health interventions [19, 20] and has been widely applied over the past decade [21, 22], including for reviews of seasonal influenza interventions [2325]. An SR can achieve a maximum score of 10, and an MA a maximum score of 11. Following the approach set out in past publications [21, 23], reviews receiving a score of 9–11 were classified as high quality, 5–8 as moderate-quality, and 0–4 as low-quality. Inter-reviewer disagreements regarding scoring were resolved by consensus only when they resulted in differential quality categorization (low, moderate, high). Although review quality was not used as an exclusion criterion, the level of evidence was noted and integrated into a discussion of results and formulation of conclusions.

3. Results

A total of 348 citations were retrieved from the execution of the search strategy discussed. Following the removal of duplicates, 185 articles were subject to title and abstract review, with 64 retained for full review. An additional 9 articles were identified from searches of reference lists and the grey literature; all were reviewed in full. Of these 73 articles, 17 were selected for quality assessment and data extraction. Fig 1 summarizes the study selection process; articles omitted during full review are summarized in S4 Table, along with the reason for their omission.

3.1. Included reviews

In total, 17 reviews were retained, covering six types of intervention to prevent pandemic influenza infection. Eight [2633] review the effectiveness of pandemic influenza vaccine in preventing influenza and influenza-like illness (ILI); three [3436] examine the impact of antivirals; two [32, 37] review the effectiveness of seasonal influenza vaccines in preventing pandemic influenza infection; two evaluate the impact of personal protective measures (hand-washing, mask use) [38, 39]; one [40] analyzes the impact of school closure; and another [41] reviews the efficacy of traditional Chinese medicine (TCM). One review [42] evaluates the economic viability of a wide range of pharmaceutical and non-pharmaceutical measures, concluding that social distancing, antiviral prophylaxis, school closure, and vaccination are likely to be cost-effective in all settings, while quarantine is never cost-effective. Across these reviews, 33 meta-analyses of intervention impact were conducted. The characteristics of individual reviews are summarized in Table 3, with results and associated implications for intervention impact described in subsequent intervention-specific subsections. Tables summarizing the results of the quantitative analyses performed in the included reviews are available in the appendices for pandemic vaccination (S5 Table), antiviral prophylaxis and treatment (S6 Table), seasonal influenza vaccination (S7 Table), and personal protective measures (S8 Table). Results from the reviews on school closure and TCM are not reported in Tables, as only a single review was available for each.

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Table 3. Summary of reviews included in the systematic review of pandemic influenza interventions.

https://doi.org/10.1371/journal.pone.0168262.t003

3.2 Quality assessment

Inter-reviewer agreement on the quality of the systematic reviews assessed was strong. Of the 17 reviews collected, 10 were rated as being of high methodological quality; 6 were of moderate quality; and one was of low quality (S9 Table). It should be noted, however, that the quality of the systematic reviews alone does not suggest that the conclusions drawn can be viewed with a high degree of certainty. Rather, insufficient data, appreciable heterogeneity, and wide confidence intervals were noted across many of the reviews. Comments on the quality of evidence obtained from the review, as well as an independent assessment of the methodological rigor of that review, are also included in Table 3.

3.3. Pandemic influenza vaccine effectiveness

Of the eight reviews assessing the effectiveness of pandemic influenza vaccines, seven report on the effectiveness of the 2009 pH1N1 vaccine [26, 2833], one reports on the 1968 pandemic vaccine [28], and one reports on the efficacy of killed bacterial vaccines used during the 1918 pandemic [27]. With few exceptions—notably the 1918 bacterial vaccines, used prior to identification of the influenza virus—there appears to be a general consensus that pandemic vaccines were effective across age groups in preventing pandemic influenza infection.

With regard to the 2009 H1N1 pandemic, Breteler et al. [26] report on a study of schoolchildren in China [43], where a vaccine effectiveness of 87% (95% CI: 75%-93%) was found. The review by Demicheli et al. [28] included a single pandemic study [44], which estimated a risk ratio of 0.11 (95% CI 0.06–0.21) associated with the 2009 inactivated pandemic vaccine in pregnant Japanese women. A 2014 review by Jefferson et al. [29] did not pool the results of five pandemic vaccination studies [4549], but reported a consensus across studies that pandemic vaccines provided a significant protective effect against infection, with vaccine efficiency ranging from 71.9%-96%. Similarly, Osterholm et al. [31] did not pool the results of five observational studies of the effectiveness of monovalent pandemic H1N1 vaccination, but reported a median effectiveness of 69% (range: 60%-93%). Yin et al. [32] examined 11 case-control studies reporting on pandemic influenza vaccination and laboratory-confirmed influenza, calculating a combined odds ratio of 0.14 (95% CI 0.07–0.27).

Both Manzoli et al. [30] and Yin et al. [33] reviewed the seroprotective effect of different H1N1 pandemic vaccines. Manzoli et al. [30] found a significant impact of higher vaccine concentrations for single-dose vaccines (RR of seroconversion 1.05; 95% CI 1.03–1.07 per dose step increase), but no significant effects were associated with higher concentrations in two-dose vaccines, administration of a second dose (except in children), or addition of vaccine adjuvants such as aluminum. Yin et al. [33] did not report quantitative effects on infection, but concluded that pandemic vaccination significantly impacted seroconversion, regardless of administration of one or two doses or the addition of aluminum hydroxide as an adjuvant, neither of which significantly improved the immune response.

Demicheli et al. [28] reported that all forms of the 1968 inactivated vaccine were effective in preventing both confirmed influenza and ILI. While the effect was greater for influenza than ILI, it should be noted that all results for confirmed influenza derived from a single study [50]. The authors found no significant effect of live aerosol vaccines. Lastly, Chien et al. [27] evaluated the effectiveness of mixed killed bacterial vaccines in reducing influenza incidence during the 1918 pandemic, finding no significant protective effect; this is not surprising given that bacterial vaccines are likely to be ineffective against viral pathogens.

3.4 Antiviral effectiveness

Three systematic reviews evaluated studies on the role of antiviral prophylaxis and treatment in reducing pandemic influenza infection [3436]. Fielding et al. [34] found that oseltamivir treatment received within 48 hours of symptom onset tended to reduce the duration of viral shedding (3–5 days) relative to no treatment (4–9 days) and to treatment received over 48 hours after onset (5–7 days). This contraction of the infectious period of the index case could reduce secondary infections [34]. Mizumoto et al. [36] reported that secondary infection rates generally decreased in situations where mass oseltamivir prophylaxis had been employed, with a median secondary infection risk of 2.1% (relative to 16.6% among those not receiving prophylaxis). In both cases differences in study design, exposure, and treatment strategies precluded pooled estimates of effectiveness. Jefferson et al. [35] evaluated the effectiveness of amantadine prophylaxis during the 1968 influenza pandemic, reporting significant protective effects against confirmed influenza (RR 0.27; 95% CI 0.17–0.46) and ILI (RR: 0.78; 95% CI 0.74–0.83). However, the authors point out that amantadine significantly increased adverse gastrointestinal and nervous system effects, suggesting that they should only be used in emergency situations, and may not be appropriate for mass prophylaxis.

3.5 Seasonal influenza vaccine effectiveness

Two systematic reviews, both from the 2009 pandemic, report on the cross-protection of seasonal influenza vaccines against pandemic influenza infection for the three Northern hemisphere influenza seasons between 2007 and 2010 and the two Southern hemisphere influenza seasons between 2008 and 2009 [32, 37]. Li et al. [37] report a non-significant risk increase across four randomized control trials (RR: 1.13; 95% CI 0.56–2.29), though we argue that these findings should be interpreted with caution, due to small sample size (n = 1,515). They also report a non-significant protective effect across 16 case-control studies (n = 40,868, OR: 0.80; 95% CI 0.61–1.05). Yin et al. [32] report a similar, non-significant protective effect across 11 case-control studies (n = 31,699, OR: 0.81; 95% CI 0.58–1.13), but found a significant effect when five studies with a high risk of bias were excluded (n = 28,292; OR: 0.66; 95% CI 0.48–0.91). Taken together, these two reviews suggest that seasonal influenza vaccination had a moderate, though non-significant effect in protecting from influenza infection during the 2009 pandemic.

3.6 Personal protective measure effectiveness

Of the two systematic reviews analyzing personal protective measures an influenza epidemic, one [39] reported on its effectiveness in preventing infection, while the other [38] discussed its economic benefit. Wong et al. reviewed ten studies of hand hygiene and facemask use in developed countries, and obtained an insignificant estimate of risk reduction associated with hand hygiene alone (RR: 0.82; 95% CI 0.66–1.02) but a significant risk reduction when hand hygiene was practiced in conjunction with facemask use (RR: 0.73; 95% CI 0.53–0.99). However, only one of these ten studies [51] was performed in a pandemic setting, with the other nine dealing instead with seasonal influenza control. With small sample size limiting generalizability (n = 149), insignificant risk reductions associated with hand hygiene and facemask use for laboratory-confirmed influenza (RR: 0.64; 95% CI 0.32–1.29) and influenza-like illness (RR: 0.52; 95% CI 0.21–1.29) were found in the pandemic study [51]. Mukerji et al. [38] do not report quantitative data on the effectiveness of interventions in preventing infection, but reviewed past cost-effectiveness studies of mask use. Noting important limitations in the studies reviewed, these authors suggest that masks and respirators may be cost-effective, though there is insufficient data to inform more specific interventions.

3.7 School closure effectiveness

A single systematic review [40] assessed the impact of school closure across 57 pandemic studies from the 1918, 1968, and 2009 pandemics. Despite reporting a contact rate reduction of 30%-78% in school-aged children, statistical and methodological differences precluded the authors from pooling data for meta-analysis, comparing of optimal intervention strategies, or commenting on statistical significance.

3.8 Traditional chinese medicine effectiveness

A review by Li et al. [41] examined the effect of Chinese medicines, herbs, extracts, or other ingredients in reducing the duration of viral shedding in individuals infected with pandemic H1N1, both alone and in combination with oseltamivir treatment. In a meta-analysis of 12 studies (n = 1,469), using oseltamivir treatment as a control, the mean duration of viral shedding did not differ significantly between the TCM and oseltamivir treatment groups (mean difference 0.07 days; 95% CI -0.07–0.21). However, a significant reduction in duration of viral shedding was noted in a comparison between a group receiving both TCM and oseltamivir and an oseltamivir control (mean difference −0.52 days; 95% CI −0.96–−0.09).

4. Discussion

The present systematic review is the first assess the state of knowledge regarding interventions to prevent pandemic influenza transmission as reported in existing systematic reviews and meta-analyses. This is an important information gap, as the high degree of uncertainty and heterogeneity regarding pandemic outbreaks and response suggests value in analyzing overarching trends in intervention effectiveness. Variability in pandemic environments, including the degree of infectiousness, population demographics and susceptibility, and intervention strategies and timing, inhibit the generalizability of effectiveness measures reported from a small number of studies to other settings and future pandemics.

Some authors [35, 52] have proposed that intervention effectiveness can be expected to mirror what is observed during seasonal influenza epidemics. This viewpoint is problematic for several reasons. First, seasonal influenza epidemics tend not to be considered as emergency situations, and extreme response measures are not employed [42]. This limits the ability to evaluate the effectiveness of interventions such as school closure, facemask use, or quarantine of infected individuals, which would be inappropriate during standard seasonal influenza seasons. As a consequence, there is no conclusive evidence on the impact of these strategies: there was, in fact, substantial uncertainty about which measures to implement during the 2009 pandemic [53, 54]. Second, the assertion that seasonal influenza research remains relevant to pandemic influenza situations remains controversial [55]. Some suggest that intervention effectiveness may increase in pandemic situations, due to media attention and public anxiety increasing rates of adherence [56]; this was the case during the SARS epidemic [53, 57]. Additionally, the uncertain timing of pandemic influenza outbreaks, relative to usual influenza seasons, may alter non-pharmaceutical intervention effectiveness by impacting the relative importance of different modes of transmission, which have been suggested to vary with ambient temperature and relative humidity [39, 58]. In short, there is a need for more targeted reviews examining the empirical data from past pandemic events, where high viral loads, transmission rates, and public anxiety [55, 59] may have impacted the effectiveness of interventions that were implemented.

The results of this review were insufficient to draw concrete conclusions on the effectiveness of most interventions. Of the 17 reviews included, only seven specifically reviewed pandemic influenza situations, while the other ten conducted subgroup analyses: two of these [26, 39] found only a single pandemic study that met their inclusion criteria. The most commonly investigated intervention was pandemic influenza vaccination, which was found to be highly effective in preventing pandemic influenza infection and ILI. This is not surprising, as the 2009 pandemic vaccine was a very close match with the circulating strain [31]. Rather, the concern with pandemic vaccines is that they may not be available in time for the early stages of a pandemic, as vaccine production, development and distribution can take over six months [60, 61]. The few reviews of the interventions that may be employed in the interim reported mixed results. Where measures of statistical significance were reported, only antiviral prophylaxis with amantadine, a drug with known adverse side effects, demonstrated a significant protective effect. A lack of primary data precluded reporting of statistical significance for non-pharmaceutical measures such as hand hygiene, facemask use, and school closure. It is likely that the most impactful and cost-effective approach to interrupting pandemic influenza transmission involves a layered approach combining multiple pharmaceutical and non-pharmaceutical intervention strategies, although this notion is not well explored in the quantitative analysis of included reviews. The overall lack of quantitative primary data on intervention effectiveness supports the crucial role of mathematical modelling in charting pandemic transmission dynamics and supporting the assessment of public health interventions under conditions of uncertainty.

Though not a focus of this article, several reviews were noted that dealt with the effectiveness of treatment options for pandemic influenza [6270]. While these were beyond the scope of the present review, assessments of four major treatment strategies were found. Results suggest that early treatment with neuraminidase inhibitors can reduce hospitalization [69], ventilator support [71], and death [6365]. Two reviews [66, 68]—based on a single study—mention a benefit of convalescent plasma for treating severe pandemic influenza cases. Three reviews [62, 66, 68] conclude that there is insufficient evidence to comment on the potential benefit of extracorporeal membrane oxygenation to treat influenza-associated respiratory failure. Two reviews [66, 68] found no benefit of corticosteroid therapy to treat acute lung injury, while another [70] found that it significantly increases nosocomial infection and mortality.

The executed search strategy found no systematic reviews relating to either border control measures or hospital triage protocols. Additional searches of the primary literature suggested a low efficacy associated with border control measures. These include the use of non-contact infrared thermometers in airports to detect infected passengers, where studies from the 2009 pandemic found that the positive predictive value ranged from 0.9% to 76.0%, and was likely to be too low to effectively detect and contain pandemic infection [72, 73]. A study of entry screening for pandemic H1N1 at Auckland International Airport, which focused on encouraging infection reporting and did not use thermal scanning or active screening, reported a screening sensitivity of 5.8%, which the authors concluded to be insufficient to delay the spread of pandemic influenza [74]. The general consensus appears to be that even rigorous and expensive border control measures are unlikely to delay the spread of pandemic influenza by more than a few days [75, 76]. No empirical studies were found that quantified the effectiveness of alternate models of care—such as hospital triage protocols—in containing pandemic influenza.

This present systematic review is subject to certain limitations. First, a decision was made to review existing systematic reviews and meta-analyses, rather than primary literature. This was done in an effort to account for the clinical, methodological, and statistical heterogeneity in this field, while summarizing and assessing current, high-quality research regarding preventative interventions for pandemic influenza, and is consistent with past health intervention research methodologies [77]. While it is possible that this approach omits some primary research, this was deemed unlikely to substantially affect results, given the broad search and inclusion criteria and considering that the last pandemic occurred seven years ago, meaning that recent reviews are likely to have captured all relevant primary literature. This approach provided an efficient means of summarizing and assessing the results of numerous reviews in a single study, allowing a more fulsome discussion of the quality of existing evidence on pandemic influenza interventions than would have been feasible from a review of the primary literature. Second, as high heterogeneity both within and between included studies prevented further meta-analysis, we were necessarily restricted to a narrative synthesis of current research and persisting knowledge gaps. The potential for publication biases was noted, as the marginally protective role of interventions such as hand hygiene and mask use may have been overestimated by the disproportionate publication of significant results (the association was still not found to be significant, however). Location bias was also present, as most results included in the reviews were from higher-income countries, and some interventions, such as mass antiviral prophylaxis, may not be feasible in low-resource settings. Another limitation of this review was that most of the available data were obtained from studies of the relatively mild 2009 H1N1 pandemic; this precluded analysis of the how intervention effectiveness is affected by disease characteristics, and may limit to generalizability of findings to future pandemics of unknown severity. Lastly, outcome reporting bias may have influenced the results, given the variability of influenza case definitions that were used in the primary studies, sometimes with little clinical basis.

5. Conclusion

This systematic review provides the first synthesis of existing systematic reviews and meta-analyses on interventions to prevent pandemic influenza infection, comparing findings to advance knowledge and understanding of optimal intervention strategies. Important knowledge gaps persist in this area, particularly with regard to the effect of non-pharmaceutical interventions in limiting transmission and infection. While pandemic vaccination appears to be effective in preventing influenza, it is crucial to prepare for the early phases of a pandemic where vaccines may be unavailable. Future work could focus on the impact of personal protective measures in reducing transmission rates; an important avenue for primary research is the prospective study of intervention effectiveness in infectious disease emergency situations. In the meantime, it is hoped the results of the present review will be of value in informing the development of future pandemic intervention strategies.

Supporting Information

S2 Table. Database-specific search strategies.

https://doi.org/10.1371/journal.pone.0168262.s002

(PDF)

S4 Table. Articles Excluded During Full Review.

https://doi.org/10.1371/journal.pone.0168262.s004

(PDF)

S5 Table. Results of Pandemic Vaccination Analyses Reporting Relative Effects.

https://doi.org/10.1371/journal.pone.0168262.s005

(PDF)

S6 Table. Results of Antiviral Analyses Reporting Relative Effects.

https://doi.org/10.1371/journal.pone.0168262.s006

(PDF)

S7 Table. Results of Seasonal Vaccination Analyses Reporting Relative Effects.

https://doi.org/10.1371/journal.pone.0168262.s007

(PDF)

S8 Table. Results of Personal Protective Measure Analyses Reporting Relative Effects.

https://doi.org/10.1371/journal.pone.0168262.s008

(PDF)

S9 Table. AMSTAR Scoring of Included Studies.

https://doi.org/10.1371/journal.pone.0168262.s009

(PDF)

Acknowledgments

The authors thank Can Chen and Katherine Saunders-Hastings for their assistance in translating foreign language articles. DK is the Natural Sciences and Engineering Council of Canada Chair in Risk Science at the University of Ottawa.

Author Contributions

  1. Conceptualization: PSH.
  2. Data curation: PSH.
  3. Formal analysis: PSH JR.
  4. Investigation: PSH JR.
  5. Methodology: PSH.
  6. Resources: PSH.
  7. Supervision: DK.
  8. Validation: PSH.
  9. Visualization: PSH.
  10. Writing – original draft: PSH.
  11. Writing – review & editing: PSH JR DK.

References

  1. 1. Longini IM Jr. A theoretic framework to consider the effect of immunizing schoolchildren against influenza: implications for research. Pediatrics. 2012;129 Suppl 2:S63–7. Epub 2012/03/06.
  2. 2. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086–96. Epub 2007/06/05. pmid:17544181
  3. 3. Waring J. A history of medicine in South Carolina. South Carolina Medical Association 1971.
  4. 4. Jordan EO. Epidemic influenza: a survey. Chicago, IL: American Medical Association; 1927.
  5. 5. Patterson KD, Pyle GF. The geography and mortality of the 1918 influenza pandemic. Bulletin of the History of Medicine. 1991;65(1):4–21. pmid:2021692
  6. 6. Johnson N, Mueller J. Updating the accounts: Global mortality of the 1918–1920 "Spanish" influenza pandemic. Bulletin of the History of Medicine. 2002;76(1):105–15. pmid:11875246
  7. 7. Humphries M. Paths of infection: The First World War and the origins of the 1918 influenza pandemic. War in History. 2013;21(1):55–81.
  8. 8. Cruz AT, Tittle KO, Smith ER, Sirbaugh PE. Increasing out-of-hospital regional surge capacity for H1N1 2009 influenza a through existing community pediatrician offices: a qualitative description of quality improvement strategies. Disaster Medicine and Public Health Preparedness; Special issue. 2012;6(2):113–6.
  9. 9. Nap R, Andriessen P, Meesen N, Werf T. Pandemic influenza and hospital resources. Emerging Infectious Diseases. 2007;13(11):1714–9. pmid:18217556
  10. 10. Meltzer MI, Patel A, Ajao A, Nystrom SV, Koonin LM. Estimates of the demand for mechanical ventilation in the United States during an influenza pandemic. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2015;60 Suppl 1:S52–7.
  11. 11. Barbisch DF, Koenig KL. Understanding Surge Capacity: Essential Elements. Academic Emergency Medicine. 2006;13(11):1098–102. pmid:17085738
  12. 12. Schultz CH, Koenig KL. State of Research in High-consequence Hospital Surge Capacity. Academic Emergency Medicine. 2006;13(11):1153–6. pmid:16946288
  13. 13. Jiao HU X L. Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry industry and public health. Front Agr Sci Eng. 2016;3(1):11–24.
  14. 14. Li X, Zhang Z, Yu A, Ho SYW, Carr MJ, Zheng W. Global and local persistence of influenza A(H5N1) virus. Emerging Infectious Diseases. 2014;20(8):1287–95. pmid:25061965
  15. 15. Watson SJ, Langat P, Reid SM, Lam TT-Y, Cotten M, Kelly M, et al. Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013. Journal of Virology. 2015;89(19):9920–31. pmid:26202246
  16. 16. Murray KA, Allen T, Loh E, Machalaba C, Daszak P. Emerging Viral Zoonoses from Wildlife Associated with Animal-Based Food Systems: Risks and Opportunities. In: Jay-Russell M, Doyle PM, editors. Food Safety Risks from Wildlife: Challenges in Agriculture, Conservation, and Public Health. Cham: Springer International Publishing; 2016. p. 31–57.
  17. 17. Hollenbeck JE. Interaction of the role of Concentrated Animal Feeding Operations (CAFOs) in Emerging Infectious Diseases (EIDS). Infection, Genetics and Evolution. 2016;38:44–6. http://dx.doi.org/10.1016/j.meegid.2015.12.002. pmid:26656834
  18. 18. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLos Medicine. 2009;6(7):e1000097. pmid:19621072
  19. 19. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10. pmid:17302989
  20. 20. Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, Grimshaw J, et al. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol. 2009;62(10):1013–20. pmid:19230606
  21. 21. Malik VS, Hu FB. Sugar-sweetened beverages and health: where does the evidence stand? The American Journal of Clinical Nutrition. 2011;94(5):1161–2. pmid:21993436
  22. 22. Bahia L, Coutinho ESF, Barufaldi LA, de Azevedo Abreu G, Malhão TA, Ribeiro de Souza CP, et al. The costs of overweight and obesity-related diseases in the Brazilian public health system: cross-sectional study. BMC public health. 2012;12(1):1–7.
  23. 23. Remschmidt C, Wichmann O, Harder T. Methodological quality of systematic reviews on influenza vaccination. Vaccine. 2014;32(15):1678–84. http://dx.doi.org/10.1016/j.vaccine.2014.01.060. pmid:24513008
  24. 24. Michiels B, Van Puyenbroeck K, Verhoeven V, Vermeire E, Coenen S. The Value of Neuraminidase Inhibitors for the Prevention and Treatment of Seasonal Influenza: A Systematic Review of Systematic Reviews. PloS one. 2013;8(4):e60348. pmid:23565231
  25. 25. Michiels B, Govaerts F, Remmen R, Vermeire E, Coenen S. A systematic review of the evidence on the effectiveness and risks of inactivated influenza vaccines in different target groups. Vaccine. 2011;29(49):9159–70. http://dx.doi.org/10.1016/j.vaccine.2011.08.008. pmid:21840359
  26. 26. Breteler JK, Tam JS, Jit M, Ket JC, De Boer MR. Efficacy and effectiveness of seasonal and pandemic A (H1N1) 2009 influenza vaccines in low and middle income countries: a systematic review and meta-analysis. Vaccine. 2013;31(45):5168–77. pmid:24012574
  27. 27. Chien YW, Klugman KP, Morens DM. Efficacy of whole-cell killed bacterial vaccines in preventing pneumonia and death during the 1918 influenza pandemic. Journal of Infectious Diseases. 2010;202(11):1639–48. pmid:21028954
  28. 28. Demicheli V, Jefferson T, Al-Ansary Lubna A, Ferroni E, Rivetti A, Di Pietrantonj C. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews [Internet]. 2014; (3). Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001269.pub5/abstract http://onlinelibrary.wiley.com/store/10.1002/14651858.CD001269.pub5/asset/CD001269.pdf?v=1&t=ir6by811&s=02e43e5110d2a788f3e1c4fe190b9f1808bafd70.
  29. 29. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. Cochrane Database of Systematic Reviews. 2014;(8):N.PAG-N.PAG 1p. Language: English. Entry Date: 20101029. Revision Date: 20150711. Publication Type: Journal Article.
  30. 30. Manzoli L, De Vito C, Salanti G, D'Addario M, Villari P, Ioannidis JP. Meta-analysis of the immunogenicity and tolerability of pandemic influenza A 2009 (H1N1) vaccines. PloS one. 2011;6(9):e24384. Epub 2011/09/15. pmid:21915319
  31. 31. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. The Lancet Infectious Diseases. 2012;12(1):36–44. pmid:22032844
  32. 32. Yin JK, Chow MYK, Khandaker G, King C, Richmond P, Heron L, et al. Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent influenza vaccines and A(H1N1)pdm09 vaccines: Systematic review and meta-analyses. Vaccine. 2012;30(21):3209–22. pmid:22387221
  33. 33. Yin JK, Khandaker G, Rashid H, Heron L, Ridda I, Booy R. Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: Systematic review and meta-analysis. Influenza and other respiratory viruses. 2011;5(5):299–305. pmid:21668694
  34. 34. Fielding JE, Kelly HA, Mercer GN, Glass K. Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age. Influenza and other respiratory viruses. 2014;8(2):142–50. Epub 2013/12/05. pmid:24299099
  35. 35. Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D. Amantadine and rimantadine for influenza A in adults. Cochrane Database of Systematic Reviews [Internet]. 2008; (2). Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001169.pub3/abstract http://onlinelibrary.wiley.com/store/10.1002/14651858.CD001169.pub3/asset/CD001169.pdf?v=1&t=ir6bylaj&s=b0aacaf87cdd4dc2312ad17684d1317203e2b03b.
  36. 36. Mizumoto K, Nishiura H, Yamamoto T. Effectiveness of antiviral prophylaxis coupled with contact tracing in reducing the transmission of the influenza A (H1N1-2009): a systematic review. Theor Biol Med Model. 2013;10:4. Epub 2013/01/18. pmid:23324555
  37. 37. Li ZY, Chen JY, Zhang YL, Fu WM. Partial protection against 2009 pandemic influenza A (H1N1) of seasonal influenza vaccination and related regional factors: Updated systematic review and meta-analyses. Human Vaccines Immunother. 2015;11(6):1337–44.
  38. 38. Mukerji S, MacIntyre CR, Newall AT. Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission. BMC infectious diseases. 2015;15:413. Epub 2015/10/16. pmid:26462473
  39. 39. Wong VWY, Cowling BJ, Aiello AE. Hand hygiene and risk of influenza virus infections in the community: A systematic review and meta-analysis. Epidemiology and Infection. 2014;142(5):922–32. pmid:24572643
  40. 40. Jackson C, Vynnycky E, Hawker J, Olowokure B, Mangtani P. School closures and influenza: Systematic review of epidemiological studies. BMJ open. 2013;3 (2) (no pagination)(002149).
  41. 41. Li JH, Wang RQ, Guo WJ, Li JS. Efficacy and safety of traditional Chinese medicine for the treatment of influenza A (H1N1): A meta-analysis. Journal of the Chinese Medical Association: JCMA. 2016;79(5):281–91. pmid:26935853
  42. 42. Perez Velasco R, Praditsitthikorn N, Wichmann K, Mohara A, Kotirum S, Tantivess S, et al. Systematic review of economic evaluations of preparedness strategies and interventions against influenza pandemics. PloS one. 2012;7(2):e30333. Epub 2012/03/07. pmid:22393352
  43. 43. Wu J, Xu F, Lu L, Lu M, Miao L, Gao T, et al. Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing. New England Journal of Medicine. 2010;363(25):2416–23. pmid:21158658
  44. 44. Yamada T, Yamada T, Morikawa M, Cho K, Endo T, Sato SS, et al. Pandemic (H1N1) 2009 in pregnant Japanese women in Hokkaido. The journal of obstetrics and gynaecology research. 2012;38(1):130–6. Epub 2011/10/01. pmid:21955086
  45. 45. Ortqvist A, Berggren I, Insulander M, de Jong B, Svenungsson B. Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza A(H1N1)v, in Stockholm County, Sweden. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2011;52(10):1203–11. Epub 2011/04/22.
  46. 46. Gilca R, Deceuninck G, De Serres G, Boulianne N, Sauvageau C, Quach C, et al. Effectiveness of pandemic H1N1 vaccine against influenza-related hospitalization in children. Pediatrics. 2011;128(5):e1084–91. Epub 2011/10/12. pmid:21987710
  47. 47. Mahmud S, Hammond G, Elliott L, Hilderman T, Kurbis C, Caetano P, et al. Effectiveness of the pandemic H1N1 influenza vaccines against laboratory-confirmed H1N1 infections: population-based case-control study. Vaccine. 2011;29(45):7975–81. Epub 2011/09/03. pmid:21884747
  48. 48. Van Buynder PG, Dhaliwal JK, Van Buynder JL, Couturier C, Minville-Leblanc M, Garceau R, et al. Protective effect of single-dose adjuvanted pandemic influenza vaccine in children. Influenza and other respiratory viruses. 2010;4(4):171–8. Epub 2010/07/16. pmid:20629771
  49. 49. Valenciano M, Kissling E, Cohen J-M, Oroszi B, Barret A-S, Rizzo C, et al. Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study. PLoS Med. 2011;8(1):e1000388. pmid:21379316
  50. 50. Mogabgab WJ, Leiderman E. Immunogenicity of 1967 polyvalent and 1968 Hong Kong influenza vaccines. Jama. 1970;211(10):1672–6. Epub 1970/03/09. pmid:4984268
  51. 51. Suess T, Remschmidt C, Schink S, Luchtenberg M, Haas W, Krause G, et al. Facemasks and intensified hand hygiene in a German household trial during the 2009/2010 influenza A(H1N1) pandemic: adherence and tolerability in children and adults. Epidemiol Infect. 2011;139(12):1895–901. Epub 2011/01/08. pmid:21211103
  52. 52. Jefferson T, Del Mar CB, Dooley L, Ferroni E, Al-Ansary LA, Bawazeer GA, et al. Physical interventions to interrupt or reduce the spread of respiratory viruses. The Cochrane database of systematic reviews. 2011;(7):Cd006207. Epub 2011/07/08. pmid:21735402
  53. 53. Torner N, Soldevila N, Garcia JJ, Launes C, Godoy P, Castilla J, et al. Effectiveness of non-pharmaceutical measures in preventing pediatric influenza: a case-control study. BMC public health. 2015;15:543. Epub 2015/06/10. pmid:26055522
  54. 54. Suess T, Remschmidt C, Schink S, Luchtenberg M, Haas W, Krause G, et al. Facemasks and intensified hand hygiene in a German household trial during the 2009/2010 influenza A(H1N1) pandemic: adherence and tolerability in children and adults. Epidemiology and infection. 2011;139(12):1895–901. pmid:21211103
  55. 55. Thomas Roger E, Lorenzetti Diane L. Interventions to increase influenza vaccination rates of those 60 years and older in the community. Cochrane Database of Systematic Reviews [Internet]. 2014; (7). Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005188.pub3/abstract http://onlinelibrary.wiley.com/store/10.1002/14651858.CD005188.pub3/asset/CD005188.pdf?v=1&t=ir6c06k5&s=3382482ed0f8dff440f6910a1d4115f85c83b825.
  56. 56. Cowling BJ, Chan KH, Fang VJ, Cheng CK, Fung RO, Wai W, et al. Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial. Annals of internal medicine. 2009;151(7):437–46. Epub 2009/08/05. pmid:19652172
  57. 57. Lau JT, Yang X, Tsui H, Kim JH. Monitoring community responses to the SARS epidemic in Hong Kong: from day 10 to day 62. Journal of epidemiology and community health. 2003;57(11):864–70. Epub 2003/11/06. pmid:14600111
  58. 58. Lowen A, Palese P. Transmission of influenza virus in temperate zones is predominantly by aerosol, in the tropics by contact: A hypothesis. PLoS Currents. 2009;1:RRN1002. pmid:20025197
  59. 59. Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database of Systematic Reviews. 2014b;(4):N.PAG-N.PAG 1 p Language: English. Entry Date: 20110325. Revision Date: 20151007. Publication Type: Journal Article.
  60. 60. Madhav N. Modelling a modern-day spanish flu pandemic. 2013.
  61. 61. Longini I, Halloran ME, Nizam A, Yang Y. Containing pandemic influenza with antiviral agents. American Journal of Epidemiology. 2004;159:623–33. pmid:15033640
  62. 62. Mitchell MD, Mikkelsen ME, Umscheid CA, Lee I, Fuchs BD, Halpern SD. A systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the H1N1 influenza pandemic. Critical Care Medicine. 2010;38(6):1398–404. pmid:20400902
  63. 63. Muthuri SG, Myles PR, Venkatesan S, Leonardi-Bee J, Nguyen-Van-Tam JS. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009–2010 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients. Journal of Infectious Diseases. 2013;207(4):553–63. pmid:23204175
  64. 64. Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. The Lancet Respiratory Medicine. 2014;2(5):395–404. pmid:24815805
  65. 65. Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Lim WS, Al Mamun A, et al. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: An individual participant data meta-analysis. Influenza and other respiratory viruses. 2016;10(3):192–204. pmid:26602067
  66. 66. Ortiz JR, Rudd KE, Clark DV, Jacob ST, West TE. Clinical research during a public health emergency: a systematic review of severe pandemic influenza management. Critical Care Medicine. 2013;41(5):1345–52. pmid:23399939
  67. 67. Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam JS, Lim WS. Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis. Journal of Infectious Diseases. 2015;212(2):183–94. pmid:25406333
  68. 68. Rudd KE, Ortiz JR, Clark DV, Jacob ST, West TE. A systematic review of clinical interventions for patients with severe pandemic influenza a (H1N1) virus infection. American Journal of Respiratory and Critical Care Medicine Conference: American Thoracic Society International Conference, ATS. 2012;185(no pagination).
  69. 69. Venkatesan S, Myles PR, Leonardi-Bee J, Nguyen-Van-Tam JS. Impact of outpatient neuraminidase inhibitor treatment on hospitalisation in patients infected with influenza A (H1N1)pdm09: An IPD analysis. International Journal of Infectious Diseases. 2016;45:248.
  70. 70. Yang JW, Fan LC, Miao XY, Mao B, Li MH, Lu HW, et al. Corticosteroids for the treatment of human infection with influenza virus: A systematic review and meta-analysis. Clinical Microbiology and Infection. 2015;21(10):956–63. pmid:26123860
  71. 71. Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Lim WS, Al Mamun A, et al. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis. Influenza & Other Respiratory Viruses. 2016;10(3):192–204.
  72. 72. Bitar D, Goubar A, Desenclos JC. International travels and fever screening during epidemics: a literature review on the effectiveness and potential use of non-contact infrared thermometers. Eurosurveillance. 2009;14(6). Epub 2009/02/14.
  73. 73. Nishiura H, Kamiya K. Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan. BMC infectious diseases. 2011;11(1):111.
  74. 74. Hale MJ, Hoskins RS, Baker MG. Screening for Influenza A(H1N1)pdm09, Auckland International Airport, New Zealand. Emerging Infectious Diseases. 2012;18(5):866–8. pmid:22516105
  75. 75. Yu H, Cauchemez S, Donnelly CA, Zhou L, Feng L, Xiang N, et al. Transmission Dynamics, Border Entry Screening, and School Holidays during the 2009 Influenza A (H1N1) Pandemic, China. Emerging Infectious Diseases. 2012;18(5):758–66. pmid:22515989
  76. 76. Cowling BJ, Lau LL, Wu P, Wong HW, Fang VJ, Riley S, et al. Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1). BMC infectious diseases. 2010;10(1):82.
  77. 77. Smith V, Devane D, Begley CM, Clarke M. Methodology in conducting a systematic review of systematic reviews of healthcare interventions. BMC Medical Research Methodology. 2011;11(1):1–6.