World Medical & Health Policy www.psocommons.org/wmhp
Vol. 2: Iss. 2, Article 4 (2010)
Influenza Immunization: Synthesizing and Communicating the Evidence
Arnauld Nicogossian, MD, FACPM, FACP, George Mason University
Nelya Ebadirad, BS, George Mason University Thomas Zimmerman, PhD, International Society of Microbial
Resistance Gary Kreps, PhD, FAAHB, George Mason University
Edward J. Septimus, MD, FACP, FIDSA, FSHEA, Texas A&M Health Science Center
Abstract
Objective: To synthesize the evidence underpinning the benefits and risks of influenza vaccination for inclusion in communication and outreach campaigns.
Background: Influenza A virus is a seasonal contributor to worldwide morbidity and mortality. Children, the immunocompromised, and the elderly are at higher risk of influenza complications. Compliance with vaccination remains below the optimum effectiveness level despite an estimated annual global mortality of 300,000 to 500,000.
Methods: Publications describing concerns and objections to the influenza vaccination were reviewed. Based on these reviews, Medical Subject Heading (MeSH) terms were selected to query major databases for relevant information on effectiveness, risks, compliance, and acceptance of seasonal and 2009 pandemic influenza vaccines. A standardized approach to the rating of the evidence was developed. The synthesized evidence on vaccine effectiveness, enacted medical and public health policies, and communication practices was discussed with a group of experts and subjected to an external peer review.
Results: Prior surveys identified poor understanding of influenza health risks and lack of access to the vaccine as major objections to immunization. There is good evidence that the seasonal vaccine provides protection against influenza, and vaccine complications are rare. Influenza vaccination rates remain low suggesting that the potential economic and health benefits of the vaccine have not yet been realized. Epidemiological studies quantifying the success of the general public’s use of precautionary practices are lacking. Prospective studies on vaccine efficacy were not found in the published literature. Few cross-sectional studies on immunization compliance among healthcare workers (HCWs) and different population groups were found in our literature searches. Well-designed epidemiological studies on the benefits and risks of influenza vaccination programs are available for a limited number of countries and select population groups. Discussion: It is postulated that the success of an immunization program depends on advanced planning and sustained communication campaigns. Evidence-based education on the benefits of vaccination can help improve compliance among HCWs and the public. Interpreting and explaining scientific data end knowledge is complex, and conveying this information to the public should target primarily the benefits and risks of vaccination. Educational campaigns should include well-defined strategies compatible with cultural, behavioral, and social constructs of each community. Conclusions: There is good evidence that seasonal influenza vaccination is a reliable and effective public health tool for reducing the adverse health and economic consequences of this disease. This evidence should be clearly articulated in all influenza educational and outreach campaigns. Evidence supporting the added efficacy of influenza vaccines, together with physical and sanitary measures to interrupt transmission, should be the subject of additional studies. Physical countermeasures should form the basis for a sustained outreach campaign since they also offer protection against other infections. The availability of effective influenza vaccines in the late summer or early fall could help maintain public confidence and improve compliance. Large-scale international epidemiological studies of influenza vaccine acceptance are required to plan successful immunization campaigns. Applicability: Clear, concise and understandable evidence-based information, coupled with sustained education campaigns, is critical for promoting vaccination. Immunization campaigns should involve the participation and support of all HCWs to promote public confidence, minimize confusion and improve compliance. After the events of September 11, 2001, and the mailing of anthrax-laced letters, all U.S. critical infrastructure personnel and vulnerable individuals should receive the seasonal influenza vaccine for biodefense purposes. The use of the influenza vaccine can help differentiate a bioterrorist incident involving pulmonary anthrax from seasonal and pandemic influenza.
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Study Limitations: This study used published information on the benefits and risks of vaccination in select population groups: the elderly, residents in long-term care facilities, and patients with chronic afflictions who were already under medical care before receiving the vaccination. Proper caution should be exercised when extrapolating these findings to other demographic groups or a healthy population in the absence of specific epidemiological data. Ethical, societal and religious concerns, beliefs and controversies surrounding influenza immunization policies were not addressed.
Keywords: influenza, global burden of the infection, vaccine benefits and risks, vaccine efficacy, vaccine acceptance, public confidence, communication campaigns, outreach and education, evidence-based information, economic consequences, biodefense
Author Notes: Disclaimer: The presented findings and conclusions are those of the authors and do not necessarily represent the views of George Mason University or any other organization. This publication primarily focuses on seasonal influenza. The 2009 A(H1N1) pandemic influenza is included since it has generated a wealth of information relevant to the objectives of this study. This manuscript has not been published elsewhere. No human or animal subjects were used in this study. Conflict(s) of interest: None declared. The authors wish to recognize the contributions of the many experts who participated in advising and reviewing this paper, and also thank Tia Beritashvili, MD, Jenny Mitchell, and Kate O’Rourke for their help with the editing of this manuscript.
Recommended Citation: Nicogossian, Arnauld; Nelya Ebadirad; Thomas Zimmerman; Gary Kreps; and Edward J. Septimus (2010) “Influenza Immunization: Synthesizing and Communicating the Evidence,” World Medical & Health Policy: Vol. 2: Iss. 2, Article 4. DOI: 10.2202/1948-4682.1090 http://www.psocommons.org/wmhp/vol2/iss2/art4
Introduction Influenza is a persistent contributor to societal suffering and economic burden worldwide (Szucs 1999; Carrat et al. 2002). Despite acknowledged concerns by many healthcare workers (HCWs) and the public, a large segment of the population continues to resist vaccination. Public confusion and fear of vaccination side effects persist as the debate over influenza vaccination policies continues (Weber-Morgan Health Department 2010).
Influenza and influenza-like illnesses (ILI) have been reported since ancient times. Historically it appears that pandemics occur every 10 to 50 years (World Health Organization - WHO Outbreak Communication – 2009a). The deadliest was the 1918–1919 influenza pandemic, with over 50 million deaths—3.8% of the estimated 1918 world population (Allwin et al. 2002). Since 1919, the influenza A virus has afflicted people around the world on a seasonal basis. In the Northern Hemisphere, the number of patients presenting with influenza symptoms begins to increase in November, peaks around February, and decreases by late April of each year (CDC – The Flu Season - 2009a). The months of May through late November make up the influenza season in the Southern Hemisphere. Implicated viruses are thought to spread primarily in crowded conditions, mainly from person to person through respiratory droplets or contact with soiled surfaces (Chen et al. 2009; Agolini 2008). Up to 50% of cases remain clinically asymptomatic and can contribute to the spread of the illness through viral shedding (Allwin et al. 2002). Recent studies suggest that these “silent spreaders” may be play a major role in the spread of influenza than previously believed (Lincoln et al. 2010).
Influenza was responsible for an estimated over 100 million deaths in the twentieth century (Ho, Wang, and Liu 2010). Between 5% and 20% of the population of the United States (15–50 million) contract influenza annually (National Foundation for Infectious Diseases 2009). Each year, over 200,000 individuals are hospitalized and up to 36,000 die from influenza-related complications (Meltzer et al. 1999). The annual global burden is estimated at over one billion cases, with three to five million hospitalizations and over 300,000 deaths. The mortality risk among debilitated individuals older than 65 years can reach 90% (Roche Laboratories 2009). No other infection poses a similar threat, with such a rapid rise in acute illness and death (U.S. Department of Health and Human Services 2009).
On June 11, 2009, the Geneva-based World Health Organization (WHO) declared the 2009 A(H1N1) influenza a pandemic. This decision was primarily based on the extent of the global spread of the virus and not
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on the severity of the illness (CDC – 2009 H1N1 Flu (Swine Flu) and You - 2009b). As of January 2010, the 2009 A(H1N1) virus had become the predominant strain circulating worldwide (CDC - 2009 H1N1 Flu: International Situation Update - 2009c). The 2009 A(H1N1) virus was initially thought to be a novel strain, but was later shown to carry a common epitope (antigenic similarity) bridging the 1918 and 2009 strains, which could explain the partial immunity observed in elderly groups (Xu et al. 2010). The 2009 A(H1N1) virus resulted in high morbidity, but low mortality (1% to 4%) (CDC - Update: Influenza Activity—United States, August 30, 2009–March 27, 2010, and Composition of the 2010–11 Influenza Vaccine – 2010a). Its infectivity is similar to that of seasonal influenza, spreading fast among young and older individuals (Jain et al. 2009; CDC - 2009 H1N1 Flu (Swine Flu) and You - 2009b). The U.S. Centers for Disease Control and Prevention (CDC) has reported a total of 115,226 confirmed influenza cases, with 27,553 hospitalizations and 1,936 related deaths (324 children) since August 30, 2009 (CDC - CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009–January 16, 2010 - 2010b). There is a discrepancy among different reporting sources due to inadequate laboratory sample collection and testing (CDC - 2009 H1N1 Flu: Situation Update - 2010c). The global 2009 mortality, as reported by the WHO and based on laboratory validation through sample analysis, was 14,142 individuals in 209 countries (WHO - Pandemic (H1N1) 2009—update 80 - 2010c).
Methods
A standardized protocol for the literature review process was developed and followed by the GMU research team. Publications addressing describing influenza vaccination concerns and objections (surveys) were reviewed (Akan H et al. 2010; Hofmann et al. 2006). Based on these reviews, Medical Subject Heading (MeSH) terms were used to query different databases such as PubMed, Ovid Medline, and the Cochrane Library. Publications for the preceding 15 years (1995-2010) were included in our study. The searches used general terms for seasonal and pandemic influenza vaccination, including evidence communications. The focus of the searches was primarily on meta-analyses and Randomized Controlled Trials (RCTs). Properly designed and executed meta-analysis and RCTs are considered to be the most robust sources for evidence (Ebell et al. 2004). Other relevant studies on the subject matter and those published prior to 1995 were also considered as appropriate.
MeSH terms consisted of global and U.S. influenza mortality and morbidity, physical precautionary measures, number of vaccine doses delivered, produced, and administered, vaccine efficacy, immunity, demographics, ethical considerations in scarce resource allocations, immunization priority setting, and vaccine acceptance among the general public and HCWs, chronically ill patients, and hospital and hospice patients. International and national immunization guidelines for “healthy” and “ill” individuals with chronic or acute medical conditions were also included in the searches.
A major screening criterion, used for the selection and review of a publication, was the author’s description of the evidence underpinning current or proposed public health policies, practices, and/or standards for influenza vaccination. A total of 180 articles, reports, reviews, and websites of interest were identified. Following a preliminary screening of abstracts and citations, 163 publications were judged relevant and selected for further evaluation. All publications were organized according to the major MeSH terms used in the literature searches. After accounting for duplication in the number of publications, which contained information on several MeSH terms, 115 met the screening criteria and were selected for further in-depth reviews.
Table 1 displays the number of publications in each of the major MeSH terms category, including meta-analyses and RCTs, found in the literature and selected for further in-depth evaluations. The largest number of publications dealt with the type and composition of the influenza vaccines, immunization and vaccination strategies. Only 17 meta-analyses and/or RCTs were found during our searches.
All publications were evaluated for the quality of research primarily based on the relevance and experimental design. Four basic levels describing the strength of evidence were assigned to each publication. Table 2 describes these levels, provides qualitative description for each category and corresponding justification which also considers the risks and benefits relationship of the proposed interventions (USPSTF 2003; Pawson R. et al 2010). Though reviewed Level 4 publications were not included in the discussions.
Table 3 shows only the number of publications subjected to the in-depth analysis in each search category and associated levels of evidence. The influenza vaccine, vaccination, immunization and relevant meta-analysis and RCT studies formed the major portion of the Level 1 evidence found.
In November 2009 the literature reviews and primoinary findings were subjected to a peer review by a group of experts from academia, government and the private sector. (The names of the experts and reviewers
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and their affiliations can be found in the “Influenza Immunization: Communicating Evidence in an Era of Confusion” report, at www.policy-csimpp.gmu.edu). For completeness during the preparation of this publication periodic literature surveys were conducted to minimize controversy in reporting of our results. Some of these articles are included and cited as appropriate in the text of this publication.
Table 1. Final Number of Publications (Including Meta-analyses and RCTs) Addressing Influenza Vaccination Selected for In-depth Reviews
Table 2.Explanation of the Levels of Evidence and Corresponding Justifications (Adapted from USPSTF 2000-2003)
Level Explanation Justification and Categories of Recommendations
1 Good evidence
Studies with minimal experimental bias demonstrating clear relationship between the risks and benefits (High Quality Meta- analysis, or RCTs)
2 Fair evidence
Limited scientific information with potential for significant bias and some evidence of the risks/ benefits relationship (case-control studies, extrapolation from level 1 reports, case series or reports)
3 Inconclusive evidence Limited scientific information with potential for significant bias and/or benefits balancing the risks.
4 Poor Evidence No scientific evidence published, poor quality or descriptive studies, expert opinions, committee or single case reports
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Effectiveness of combined preventive measures for seasonal influenza
0 3 0 0 3
Seasonal influenza and antiviral drugs 6 0 1 0 7
Spread of seasonal influenza 1 3 0 0 4
HCWs vaccination against influenza 0 1 7 0 8
HCWs transmission of influenza to patients 0 0 4 0 4
Meta-analysis and RCTs 17 0 0 0 17 Number of Publications in Each Search Category and Total Number of Publications Evaluated
61 44 75 0
180 (115 after
adjusting for duplications)
Results
The most common objections to the influenza vaccination in the U.S. included the fear of side effects, risks for contracting the infection from the Live Attenuated Influenza Vaccine (LAIV), confidence in not being at risk of infection, inconvenient operating schedules and locations of vaccination sites, doubts regarding seriousness of influenza and efficacy of the vaccine, and fear of injections (Hofmann et al. 2006).
Influenza Vaccines Types and Route of Administration U.S. Trivalent Influenza Vaccine (TIV) and LAIV are the two vaccines available for seasonal influenza in the United States. Each contains two live attenuated influenza A viruses and one influenza B virus, selected on the basis of the prevailing strains circulating in both hemispheres. Monovalent Influenza Vaccine and LAIV, containing only the A(H1N1) strain of the virus, were used against the 2009 pandemic virus. Currently, five major pharmaceutical companies manufacture influenza vaccines. Cell-based vaccines are approved in several countries, but not in the United States. Vaccines are administered intramuscularly (IM) or through the nasal passages. All routes of administration are shown to elicit similar immune responses (Chi, Rock, and Neuzil 2010). International Pub Med and WHO website searches on the international rate of influenza immunization did not yield useful results. Recently, the recombinant influenza cell-based vaccine, using virus-like particles (VLPs) with high immunogenicity and efficacy, has been introduced (Quan et al. 2010; Huang, Lowe, and Batt 2010). VLPs were used to protect against the 2009 A(H1N1) influenza pandemic. Adenovirus-based influenza vaccine is capable of generating robust immune response against A(H1N1) virus and may be considered as a promising future immunization modality (Steitz et al. 2010). Current Recommendations Regarding Influenza Immunization The CDC and WHO recommend that all individuals requesting vaccination should be immunized (CDC - 2009 H1N1 Vaccination Recommendations - 2010g; WHO - Pandemic (H1N1) vaccines and vaccination 2010b). However, the CDC suggests that individuals with a life-threatening allergy to chicken eggs should not receive influenza vaccination (CDC - General Questions and Answers on 2009 A(H1N1) Influenza Vaccine Safety – 2009e).1 1 Published studies recommend vaccinating individuals allergic to chicken eggs, based on the determination that the risk for immediate allergic reactions is quite low (.James et al., “Safe Administration of Influenza Vaccine to Patients with Egg Allergy,” Journal of Pediatr. 133 [1998]: 624-628), and the amount of ovalbumin contained in the influenza vaccines is small (John M. Kelso, “Administration of Influenza Vaccines to Patients with Egg Allergy,” Journal of Allergy and Clinical Immunology 125 [April 2010] [4]: 800-802).
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The U.S. Advisory Council on Immunization and Practices (ACIP) recommends vaccination of all age groups for the forthcoming 2010–2011 influenza season (Drugs.com 2010). Despite repeated recommendations, only a fraction of children and young adults, a high risk group for infection and spread of influenza, are vaccinated each season. Representative statistics for seasonal vaccination rates, derived from the 2009 pandemic U.S. influenza vaccination campaign, are shown in Table 4.
Table 4. Percent of the vaccinated U.S. population, by different age groups, during 2009–2010 influenza season (CDC – Interim Results: State-Specific Seasonal Influenza Vaccination Coverage - 2010d)
Age Groups Percent Vaccinated (%)
6 months 40.6 Children 6 months–17 years 41.2 Adults 18–49 years (with high-risk medical condition) 38.3
Adults 18–49 years (without high-risk medical condition) 28.8 (lowest compliance)
Adults 50–64 years 45.5
Adults 65 years and older 69.3
Influenza Vaccine Efficacy
U.S.The seasonal influenza vaccine is reported to be 70% effective (Hsieh et al. 2005). Variations in the host immune response can be influenced by the age, sex, physical environment, and genetic make-up of each individual. Epidemiological data suggest that the duration of the immune system memory is largely determined by the magnitude and complexity of the responses to vaccination (Castellino et al. 2009).
Immunization prevents illness in about 70%–90% of healthy individuals younger than 65 years of age. The vaccine is also 60% effective in preventing hospitalizations and 80% effective in reducing mortality among elderly residents (65 years and older) of nursing homes. The vaccine is 30%–70% effective in preventing hospitalization among the elderly not living in assisted or long-term care facilities, including those with chronic
medical conditions (such as asthma, diabetes, or heart disease) (CDC - Seasonal Flu Shot - 2009f). Few meta-analyses and RCTs on vaccination efficacy were found in the literature. Limited epidemiological studies suggest that vaccinating the most vulnerable population groups will reduce disease transmission and mortality and improve economic outcomes (Medlock and Galvani 2009; Khazeni et al. 2009). International International studies of vaccine effectiveness are limited in number and scope. Studies specific to Asian, African, Canadian, and Australian regions were not found. Information on vaccine effectiveness from the European Union (EU) showed high effectiveness of seasonal influenza vaccine among the elderly (>65 years) only for the 2009–2010 influenza season (Pitigoi et al. 2009). Compliance with Vaccination Recommendations U.S. Vaccines are considered the most effective prevention tool available to public health services (Chua and Chen 2010). However, the success of an immunization program depends on the rate of acceptance and the extent of community coverage (Fidler 2009). Clinicians and HCWs can play a critical role in educating the public. Healthcare providers are cited as the most frequent source of immunization information by parents, including parents of unvaccinated children (Pinquier et al. 2008; Dubé et al. 2010). It is not clear to what extent non-compliance among HCWs does influence the general public attitudes toward seasonal influenza immunizations.
Although some clinicians have considered or actually discontinued their provider relationship with patients who refuse vaccines, the American Academy of Pediatrics Committee on Bioethics (APCB) advises against such practices. Instead, the APCB recommends that clinicians address vaccine refusal by respectfully listening to parental and patient concerns and then discussing the risks of non-vaccination (Omer et al. 2009). While 2009 A(H1N1) influenza was perceived to be more severe than seasonal influenza, its vaccination rate was found to be lower than that for seasonal influenza. The major obstacle was the lack of confidence in vaccine safety (Maurer et al. 2010). Table 5 presents a summary of the U.S. estimated vaccination rates for seasonal and pandemic influenza among HCWs and the general public. These estimates are based on the published evidence. Similar information for the “novel” 2009 pandemic was not found, possibly due to the still ongoing studies.
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Vaccination of HCWs in long-term healthcare facilities is associated with a decreased mortality rates among the patients and residents (Hayward et al. 2006; Carman et al. 2000). The effectiveness of vaccination among HCWs in acute-care settings has not been adequately documented by clinical trials. The short length of hospitalization is probably a contributing factor. Increasing influenza activity in the community contributes to the rise in the risk of nosocomial2 infections, possibly through asymptomatic visitors.
Table 5. Compliance with Influenza Vaccination Guidelines among HCWs and the General Public
Influenza Type HCWs General Public
Seasonal Influenza
Influenza vaccination of U.S. HCWs remains below 40% despite vaccine availability and CDC recommendations. (New strategies to improve the compliance rates among HCWs are needed.) (Simeonsson et al. 2004)
Lower than expected vaccinations among children, adults, and the elderly (the elderly have better overall rates) (Esposito et al. 2007; Heininer 2003; Hutchinson et al. 1995)
Pandemic Influenza Robust studies not founs Robust studies not
identified
Nosocomial outbreaks of influenza are not uncommon and are usually introduced into hospitals by already infected HCWs or visitors (Salgado et al. 2002). Salgado reported that an increased influenza vaccination rate in HCWs is inversely correlated with a significant decrease in nosocomial infections among patients (Salgado et al. 2004). Van den Dool and colleagues developed a model of influenza transmission in an attempt to address the effectiveness of vaccination in acute-care settings. The model predicts that immunizing hospital HCWs can significantly reduce the risk of patients contracting influenza, and the benefit is similar to that of vaccinating nursing home personnel (Van den Dool et al. 2009).
InternationalIn France, the experience with vaccination showed low acceptability of A(H1N1) vaccine among the public. The alarming messages from the
2 Hospital or other healthcare facility acquired infection.
government were counteracted by calm and seemingly harmless personal experiences that failed to substantiate the threat and severity of the disease (Schwarzinger et al. 2010). Reported studies from the United Kingdom showed a similar reluctance towards vaccination among parents of young children (six months to five years old). These unfavorable responses were primarily attributed to vaccine safety concerns and fear of its adverse effects (Brown et al. 2010).
Similar findings were reported in the Australian population during the 2009–2010 influenza season (Seale et al. 2010). Other studies highlighted the importance of providing vaccine safety information to increase the vaccination rate among individuals not yet decided on receiving the vaccine (Eastwood et al. 2010). In Hong Kong, vaccination costs, in addition to availability of information about vaccine efficacy and safety, was one of the deterministic factors in the general public low vaccination rates (39%) (Lau et al. 2009). Vaccine acceptance rates, reported to be low among Hong Kong HCWs, was mainly due to a lack of confidence in vaccine efficacy and fear of vaccine side effects (Chor et al. 2009). The acceptance of vaccine among HCWs in Mexico was high (Esteves-Jaramillo et al. 2009). This finding is attributed to the severity of the 2009–2010 A(H1N1) influenza pandemic, the enacted public health policies and the effectiveness of the communication and awareness campaign in Mexico.
China was the first country to launch a mass vaccination against A(H1N1) in September 2009 (Parry 2009). Reliable evidence for vaccine acceptance and its adverse side effects among the Chinese population was not found. Chinese officials believe that some adverse side effects after immunization are unavoidable (Chang 2009). In Poland the vaccination rates of high risk groups remains bellows the WHO recommended levels (Nitsch-Osuch A. and Wardyn K. 2009) Risks Associated with Influenza Vaccine A potential and still debatable side effect of vaccination is the Guillain-Barré Syndrome (GBS). The association of GBS and the influenza vaccine has been extensively studied, but not adequately documented. It is estimated that the annual incidence of GBS has decreased from 0.17 per 100,000 vaccinations in 1993–1994 to 0.02 per 100,000 vaccinations in 2002–2003 (Haber et al. 2004). GBS can occur in non-vaccinated individuals. On average, 3,000 to 6,000 cases of GBS are reported in the United States each year, or one to two cases for every 100,000 individuals vaccinated (CDC - General Questions and Answers on Guillain-Barré Syndrome - 2009g).
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Post-1976 influenza epidemic studies failed to demonstrate a consistent causal relation between influenza vaccination and GBS. A recent study spanning a 15-year period (1990–2005) documented the lack of a causal relationship between the seasonal influenza vaccination and the appearance of GBS within the first 90 days post-immunization (Stowe et al. 2009).
As of December 11, 2009, a total of 76.3 million A(H1N1) vaccines were distributed in the United States. The exact number of vaccines administered is unknown. The U.S. Vaccine Adverse Event Reporting System (VAERS) received 5,703 individual reports following the use of the 2009 Monovalent A(H1N1) vaccine; of those reports, 333 (5.9%) cases were classified as serious health events (defined as life-threatening or resulting in death, major disability, and abnormal conditions at birth, hospitalization, or extension of a hospitalization). The remainder was classified as non serious or life threatening events such as swelling or irritation of the injection site. Nineteen fatalities (approximately 0.6%) were reported among the 333 serious events VAERS has received 21 reports of GBS (CDC - Summary of 2009 Monovalent H1N1 Influenza Vaccine Data—Vaccine Adverse Event Reporting System - 2010e). Table 6 shows the latest VAERS updates for both seasonal and 2009 A(H1N1) influenza.
Table 6. Reported Adverse Events Following Influenza Vaccinations in the United States (as of November 2009) (CDC - Mortality and Morbidity Weekly Report -2010f)
Despite the evidence and a retraction by Lancet of the original research implicating the vaccine, autism continues to be cited as a concern by opponents of the vaccination (Wakefield et al. 2004). The most recent information from the CDC shows no connection between the influenza vaccine and autism. Furthermore, the number of autistic cases has been decreasing over the past decade, while administration of influenza vaccines
has increased (Medscape 2010). Influenza vaccine has been recently implicated as a possible cause of Bell’s palsy. Also known as the idiopathic facial paralysis (affecting the VII cranial nerve), Bell’s palsy is thought to be linked with viral infections such as influenza (Philippin et al. 2002). Concerns on the association of Bell’s palsy and influenza vaccine were raised following the publication of surveillance data in Switzerland (Stowe et al. 2006; Mutsch et al. 2004). Specifically the data showed a strong association between the intranasal administration of inactivated influenza vaccine and Bell’s palsy within a 90 day period following immunizations. While the incidence of this complication is low, the general public should nevertheless be informed of this side effect (Chou et al. 2007). Information on the association of Bell’s palsy with the uses of injectable seasonal and 2009 A(H1N1) vaccines has not been reported at this time.
In the absence of vaccine or medical contraindications other preventive, therapeutic and physical modalities are used to interrupt transmission or treat influenza. In many instances, and especially in health care settings, a combination of vaccine and physical barriers are necessary to help interrupt the influenza transmission.
Relevant Non-Vaccine Preventive Measures The following represents a summary of current practices on the use of additional measures contributing to the interruption of the influenza transmission: Indication for the Use of Antiviral Medications Targeted antiviral prophylaxis is considered as an alternative prevention tool to contain pandemic influenza until an adequate quantity of the appropriate vaccine is made available (Longini et al. 2004). Several antiviral medications are available to interrupt transmission and minimize disease complications. Such medications include compounds that prevent viral un-coating (Amantadine), are nucleoside inhibitors (Ribavirin), and interfere with viral transcription and inhibit neuraminidase activity (Zanamivir and Oseltamivir) (Saladino et al. 2010). Antiviral agents, especially Oseltamivir and Zanamivir, are primarily used for individuals with an underlying health condition, such as those with allergies to vaccine components, pregnant women, or immunocompromised patients (Narain et al. 2009). These antiviral medications are commonly used for influenza prophylaxis in susceptible or exposed individuals, such as residents of long-term medical care facilities or their caregivers (CDC- Interim Recommendations for the
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Use of Influenza Antiviral Medications in the Setting of Oseltamivir Resistance among Circulating Influenza A(H1N1) Viruses, 2008-09 Influenza Season - 2010g).
Physical Modalities
In the event of a pandemic, where effective vaccine and antiviral medications may be in short supply, physical countermeasures, including distancing, use of facemasks, avoiding the sharing of personal effects and utensils, and hand hygiene are recommended. Fair evidence exists for the use of facemasks as a physical barrier to reduce the rate of influenza transmission by exposed individuals, asymptomatic carriers and patients. Some authors (Aiello et al. 2010) report that facemasks can reduce viral spreading from an infected person, and thus minimize the risk of disease transmission under crowded conditions. The same study showed that the use of facemasks in combination with hand hygiene significantly reduced ILI and influenza transmission compared to no intervention. Evidence suggests that hand hygiene in healthcare settings is more effective in reducing disease transmission than if practiced in the community at large (Cowling et al. 2009).
CDC is now preparing an updated guidance for handling seasonal influenza in healthcare settings. This update is expanding and replacing prior guidance for influenza and infection control measures. Specifically, the use of facemasks around confirmed or suspected cases of influenza, use of respirators during aerosol-generating procedures, and negative pressure rooms during high risk procedures are discussed in this update. Currently, the CDC is seeking public comments on guidance prior to its enactment.
Discussion
Communicating scientific knowledge during epidemics and pandemics is complex (Nelson et al. 2009). Constantly updated, sometimes contradictory, information can result in confusion. Outreach and communication campaigns should include a sustained effort to prepare for seasonal and pandemic influenza. In order to be most effective, evidence-based information should be used in a context relevant to the issue under consideration (McNutt and Livingston 2010). Unfortunately, our searches identified a limited number of meta-analyses or RCTs on this subject. Table
7 summarizes the findings from the meta-analyses on the benefits of vaccinating HCWs and the community.
The data from these studies suggest that until reliable information on the role of unvaccinated HCWs (with or without precautionary physical measures) in transmitting the virus is developed, community vaccination will remain the most effective method for interrupting influenza spread. Due to a lack of community compliance and/or effectiveness of hand hygiene, vaccination will be the most efficient mechanism for interrupting transmission of the virus. This message should be clearly communicated to the general public.
Influenza viruses undergo constant drifts and shifts in their genetic structure and require annual vaccinations to protect against the disease (Garten et al. 2009; Katz et al. 2009). For example vaccination against seasonal influenza generated negligible cross-immunity with the 2009 A(H1N1) virus. To create substantial protection, administration of both vaccines was required during the 2009 pandemic (Hancock et al. 2009).
Limited information on preventive measures and disease surveillance outcomes was found during the literature searches. Evidence for improved vaccination compliance rates explaining complex epidemic/pandemic concepts to the general public is lacking. Media can play an important role in communicating “user-friendly” scientific information in a timely fashion to avoid confusion in the general public (Keogh-Brown and Smith 2008; Perlman 2009). However, the role of the media has not been well documented.
To ensure the consistency and accuracy of all messages, public health officials should provide necessary resources to support the dissemination of relevant, understandable and timely information to all communicating entities (New Brunswick 2010). Epidemiological data on influenza transmissibility and viral shedding should be at the core of all preventative strategies (Gostlin 2006). Such strategies should be tailored to individual communities’ needs and availability of resources. The education of the public on influenza risks should be a sustained effort, not a seasonal event. This will help maximize the effectiveness of the campaign. Educational campaigns should include well-defined strategies that take the specific cultural, behavioral, and social characteristics of each community into consideration (Vaughan and Tinker 2009a). To have a meaningful understanding of the benefits of vaccination, additional investments in research are needed. Areas in need of greater attention include international surveillance on vaccine efficacy and compliance, and post-vaccination health side effects (Patriarca and Cox 1997).
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Table 7. Meta-analyses on the Benefits of Vaccinating HCWs and Community Residents shown by Age Groups
HCWs Community (Age Groups in Years) (2–17): A meta-analysis of 16 RCTs and 18 cohort studies, and 294,159 observations conducted in 2008, illustrated that live influenza vaccine has an efficacy of 82% and an effectiveness of 33%. Inactivated vaccines showed a lower efficacy of 59% but a similar effectiveness of 36% (Jefferson et al. 2008 ; Xing and Liu 2009; Rhorer et al. 2009; Monzoli et al. 2007. (18–60): A meta-analysis of randomized and quasi-randomized studies involving 66,248 people in 2008 suggested that for adults, inactivated influenza vaccines were 30% effective against ILI and 80% efficacious against influenza when the vaccine matched the circulating strain. However, effectiveness decreased to 50% when it did not (Jefferson et al. 2007).
A meta-analysis of two RCTs and one cohort study in 2006 showed good evidence that vaccinating healthy adults under age 60 (including HCWs) reduced the number of influenza cases. Both the elderly in institutions and the HCWs who care for them should be vaccinated for their own protection, but an incremental benefit of vaccinating HCWs for the benefit of the elderly cannot be proven without better studies (Thomas et al. 2006).
(> 60): A 2006 meta-analysis of randomized, quasi-randomized cohort and case control studies showed that in homes for the elderly, well-matched vaccines prevented pneumonia hospital admission and mortality. Vaccinating individuals living in the community was not significantly effective against influenza, ILI, or pneumonia. Well-matched vaccines prevented hospital admission for influenza and pneumonia and all-cause mortality (Rivetti et al. 2006).
The WHO advises that a major component of the planning process should include practices aimed at developing trust and transparency with the public. An example of this would be the use of early communication and general public dialogues with community leaders and HCWs. Compliance by HCWs should be addressed first since it generates the most controversy and distrust in the general public. All messages should be linguistically and culturally appropriate. The best health communication practices should provide opportunities for feedback reinforcing, messages, soliciting feedback and responding to public concerns.
Reaching the most vulnerable of population groups could require strategies aimed at overcoming cultural, linguistic, educational, and health literacy barriers. Timing and procedures to enable these groups to participate in pandemic interventions are important aspects of an effective communication strategy (Vaughan and Tinker 2009b). Targeting vulnerable populations and their healthcare providers is critical (Leon et al. 2009). At-risk populations include individuals with multiple vulnerabilities that are likely to change over time. Hence, continual adaptive communication leads to more successful involvement (Hutchins et al. 2009). Some of the effective communication strategies consist of following (adapted from Vaughan and Tinker 2009b):
• Messages that are
o Evidence-based, integrated, engaging, sensitive and relevant for the intended audience.
o Directed at improving health literacy and public understanding. Multiple channels of communication should be used to provide reinforcing messages over time to audiences.
• Best results can be obtained if efforts regarding communication of epidemics and pandemics are initiated before, during, and after the event.
• Monitoring communities’ attitudes and behaviors to help refine communication strategies.
In a globalizing world, all individuals should understand the
obligation to be vaccinated to protect their own health and the health of others. Public health officials devote significant efforts and resources to curtail the spread of influenza. These resources are not limitless and rationing will eventually happen if proper preventive measures are not complied with. Unfortunately, compliance with influenza vaccination remains problematic (Morbidity and Mortality Weekly Report 2009; Maurer, Uscher-Pines, and Harris 2010). Influenza is a major cause of potentially preventable seasonal morbidity and mortality worldwide. In the United States, mandatory compliance among hospital HCWs continues to face opposition, and at times results in legal action taken by the employees (Kaye 2010). Other factors, such as socioeconomic disparities, tend to contribute to already poor compliance rates and add to the annual burden of healthcare costs (Nowalk et al. 2009).
Public confidence is an important asset in pandemic preparedness. However, in the 2009 A(H1N1) influenza pandemic, mixed messages from
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the U.S. media, policymakers, experts, and researchers, coupled with rationing due to delivery problems (also not well explained to the public), did more to confuse than to educate the public (New York Times 2010). In the United States, when the population was given the correct information and wanted the vaccine, the shortcomings and alarming inadequacy of the U.S. stockpile created concerns followed by mistrust (Larson and Heymann 2010). The “Ready or not? 2009” report also stated that the 2009 A(H1N1) pandemic exposed gaps in the ability of the United States to respond to a public health emergency (Trust for America’s Health 2010).
Conclusion and Policy Implications
The evaluation of the evidence, together with a review of successful communication practices, is summarized in Table 8.
Table 8. Policy Recommendations Based on the Level of Evidence Extracted from the Published Literature
Level of Evidence Category Policy/Recommendation References
1 Immunization Influenza vaccine should be administered annually.
McNutt and Livingston
(2010); Garten et al. (2009); Katz et al. (2009)
2 Use of a barrier
Facemasks can act as a physical barrier for both ill and healthy individuals to reduce the transmission rate.
Hancock et al. (2009)
Communication efforts should be directed at translating, in understandable terms, the complex epidemic/pandemic facts and benefits of preventive measures to the public.
Cowling et al. (2009) 3 Communication
Communication and information sharing with the public should be consistent and timely.
Speculations and opinions, not supported by evidence, should be minimized, and knowledge gaps should be explained in a concise and understandable format.
Brown et al. (2008)
Pandemic preparedness requires timely press releases based on unambiguous, scientific and clinical facts to avoid public confusion.
Aiello et al. (2010); Keogh-
Brown et al. (2008)
Mitigation strategies should be tailored to individual community needs and availability of resources. Over-promising in the face of scarce resources can lead to loss of public confidence, which ultimately affects compliance.
Gostin (2006)
Planning Strategies
Epidemiologic of the influenza transmissibility, virus shedding in asymptomatic carriers and the importance of seasonal vaccinations is at the core of all preventive public health strategies.
New Brunswick
(2010)
Educating the public on handling influenza outbreaks should be an ongoing activity.
Gostin (2006);
Patriarca and Cox (1997)
Knowledge Educational campaigns should include well-defined strategies that take the specific cultural, behavioral, and social characteristics of each community into consideration.
Gostin (2006)
Surveillance
International surveillance should be expanded to include vaccination rates for all regions to have a meaningful understanding of vaccine efficacy.
Vaughan and Tinker (2009a)
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A baseline for all background morbidity and mortality should be developed. This will allow establishing reliable incidence rates for the adverse side effects of vaccination.
Vaughan and Tinker (2009a)
Reaching out to different socioeconomic groups should be the major goal for local and state governments.
Patriarca and Cox (1997); Vaughan and
Tinker (2009b);
Leon et al. (2009)
Role of the Government
State and federal governments should ensure adequate resources to all communicating entities, including nonprofit and media organizations, to ensure consistency and accuracy of the messages. (translating the evidence and training) The WHO should validate and disseminate information on vaccine benefits.
Perlman (2009)
There is good evidence to support the need for policies encouraging and promoting seasonal vaccination of HCWs (reduce absenteeism) and the public (interrupt the viral transmissions). There is also sufficient evidence to promote the use of physical barriers. There is fair evidence to support the consistency of the communication messages, government support to enhance communications, adequacy of the global surveillance, well-designed and implemented communication strategies. Health literacy of immigrants and different ethnic groups should be a major thrust of the outreach campaigns to reduce disparities in mortality and morbidity and achieve full benefits from influenza immunization (Kreps GL. and Sparks L. 2008).
Our findings suggest that developing and communicating evidence-based best practices to combat influenza global impacts should be an integral part of all strategies promoting vaccination compliance. Leadership, participation and contributions of HCWs in the outreach campaigns are required to ensure and sustain public confidence (Abramson ZH and Levi O. 2008)
Prospective studies on influenza vaccine efficacy are complicated by the uncertainty of circulating strains, vaccine availability and compatibility. Proper caution should be exercised when extrapolating published findings to other demographic groups or a healthy population in the absence of specific epidemiological data (Jackson et al 2006).
Additional targeted research and surveillance supporting future communication campaigns should: 1. Develop evidence-based information on vaccine efficacy in the general population and determine the optimal timing for vaccine administration in both hemispheres. . 2. Evaluate the vaccine distribution, delivery and safety practices (including cell-based preparations) to prevent rationing. Vaccine distribution should be well-organized with careful monitoring of the process to avoid over-promising and maintain public confidence (Caplan 2010). 3. Establish requirements for a sustained global surveillance for GBS, autism and other complications to determine the actual risks for these complications. The role of airlines in the spread of influenza globally should be studied 4. Conduct epidemiological studies to establish the best practices in communication. 5. Adopt a consistent nomenclature describing the influenza viral strains, particularly in the case of pandemics, to facilitate future communications with the public (multiple designations for the 2009 pandemic influenza were found). Finally, following the events of September 11, 2001 and the mailing of anthrax-laced letters, all U.S. critical infrastructure personnel and vulnerable individuals should receive the seasonal influenza vaccine for biodefense purposes (Mackler et al. 2007).
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