Influenza Vaccination of Healthcare Workers: a Literature Review of Attitudes and Beliefs

Abstract Background: Influenza vaccination coverage among healthcare workers (HCW) is insufficient despite health authority recommendations in many countries. Numerous vaccination campaigns encouraging HCW to be vaccinated have met with resistance. We reviewed published influenza vaccination programs in healthcare settings to understand the reasons for their success and failure, as well as the attitudes and beliefs of HCW. Methods: Relevant articles published up to June 2004 were identified in the MEDLINE/Pubmed database. Results: Thirty-two studies performed between 1985 and 2002 reported vaccination rates of 2.1–82%. Vaccination campaigns including easy access to free vaccine and an educational program tended to obtain the highest uptake, particularly in the USA. Yet, even this type of campaign was not always successful. Two main barriers to satisfactory vaccine uptake were consistently reported: (1) misperception of influenza, its risks, the role of HCW in its transmission to patients, and the importance and risks of vaccination (2) lack of (or perceived lack of) conveniently available vaccine. Conclusion: To overcome these barriers and increase uptake, vaccination campaigns must be carefully designed and implemented taking account of the specific needs at each healthcare institution.     

Factors associated with influenza vaccination among healthcare workers in acute care hospitals in Canada

Background

Influenza vaccine coverage rates among healthcare workers (HCWs) in acute care facilities in Canada remain below national targets.

Objective

To determine factors associated with influenza vaccine uptake among HCWs.

Methods

This secondary analysis of a prospective cohort study included HCWs aged 18‐69 years, working ≥20 h/wk in a Canadian acute care hospital. Questionnaires were administered to participants in the fall of the season of participation (2011/12‐2013/14) which captured demographic/household characteristics, medical histories, occupational, behavioural and risk factors for influenza. Generalized estimating equation logistic regression was used to determine factors associated with vaccine uptake in the season of participation.

Results

The adjusted odds ratio for influenza vaccination in the current season was highest for those vaccinated in 3 of 3 previous seasons (OR 156; 95% CI 98, 248) followed by those vaccinated in 2 of 3 and 1 of 3 previous seasons when compared with those not vaccinated. Compared with nurses, physicians (OR 4.2; 95% CI 1.4, 13.2) and support services staff (OR 1.8; 95% CI 1.3, 2.4) had higher odds ratios for vaccine uptake. Conversely, HCWs identifying as Black had lower odds of uptake compared with those with European ancestry (OR 0.44, 95% CI 0.26‐0.75) when adjusted for other factors in the model.

Conclusion

Healthcare workers differ in their annual uptake of influenza vaccine based on their past vaccination history, occupation and ethnicity. These findings indicate a need to determine whether there are other vaccine‐hesitant groups within healthcare settings and learn which approaches are successful in increasing their uptake of influenza vaccines.     

The potential economic value of influenza vaccination for healthcare workers in The Netherlands

Background

Despite the clinical evidence, influenza vaccination coverage of healthcare workers remains low. To assess the health economic value of implementing an influenza immunization program among healthcare workers (HCW) in University Medical Centers (UMCs) in the Netherlands, a cost‐benefit model was developed using a societal perspective.

Methods/Patients

The model was based on a trial performed among all UMCs in the Netherlands that included both hospital staff and patients admitted to the pediatrics and internal medicine departments. The model structure and parameters estimates were based on the trial and complemented with literature research, and the impact of uncertainty explored with sensitivity analyses.

Results

In a base‐case scenario without vaccine coverage, influenza‐related annual costs were estimated at € 410 815 for an average UMC with 8000 HCWs and an average occupancy during the influenza period of 6000 hospitalized patients. Of these costs, 82% attributed to the HCWs and 18% were patient‐related. With a vaccination coverage of 15.47%, the societal program’s savings were € 2861 which corresponds to a saving of € 270.53 per extended hospitalization. Univariate sensitivity analyses show that the results are most sensitive to changes in the model parameters vaccine effectiveness in reducing influenza‐like illness (ILI) and the vaccination‐related costs.

Conclusion

In addition to the decreased burden of patient morbidity among hospitalized patients, the effects of the hospital immunization program slightly outweigh the economic investments. These outcomes may support healthcare policymakers’ recommendations about the influenza vaccination program for healthcare workers.     

Low tetanus-diphtheria-acellular pertussis (Tdap) vaccine coverage among healthcare workers in a quaternary university hospital in São Paulo,Brazil: need for continuous surveillance and implementation of active strategies

IntroductionVaccination with tetanus-diphtheria-acellular pertussis (Tdap) has been recommended for healthcare workers (HCWs) by Brazilian Ministry of Health since November 2014.ObjectiveTo describe the strategies implemented to improve Tdap uptake, cumulative vaccine coverage after each intervention, variables associated to Tdap vaccination, and reasons for non-vaccination among HCWs of the main building of a quaternary hospital attached to the Sao Paulo University Medical School.MethodsA list of HCWs eligible for pertussis vaccination was generated. From April to December 2015, the following interventions were implemented: note on intern journal reminding the importance of pertussis vaccination; email to the head nurses strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians of Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. Vaccine coverage was accessed at the end of each month. Multivariate Poisson regression model with a robust error variance was used to evaluate variables associated with Tdap vaccination. Reasons for non-vaccination were evaluated from January to May 2017 through phone calls for HCWs who had not received Tdap.ResultsThe study included 456 HCWs. After the interventions, Tdap coverage raised from 2.8% to 41.2%. In the multivariate analysis, occupation (physician), working place (obstetrics or anesthesiology) and influenza vaccination in 2015 were independently associated to Tdap vaccination. The main reason for non-vaccination was unawareness of Tdap recommendations.ConclusionsTdap uptake among HCWs was low in our hospital. Providing vaccination at convenient places/times for HCW seems to be the most efficient strategy to increase vaccine uptake.     

A nosocomial outbreak of influenza during a period without influenza epidemic activity.

The objective of this study was to describe a nosocomial outbreak of influenza during a period without influenza epidemic activity in the community. Outbreak investigation was carried out in an infectious diseases ward of a tertiary hospital. Presence of two or more of the following symptoms were used to define influenza: cough, sore throat, myalgia and fever. Epidemiological survey, direct immunofluorescence, viral culture, polymerase chain reaction, haemagglutination-inhibition test in throat swabs and serology for respiratory viruses were performed. Twenty-nine of 57 healthcare workers (HCW) (51%) and eight of 23 hospitalised patients (34%) fulfilled the case definition. Sixteen HCW (55%) and three inpatients (37%) had a definitive diagnosis of influenza A virus infection (subtype H1N1). Among the symptomatic HCW, 93% had not been vaccinated against influenza that season. Affected inpatients were isolated and admissions in the ward were cancelled for 2 weeks. Symptomatic HCW were sent home for 1 week. On the seventeenth day of the outbreak the last case was declared. The incidence of cases in this outbreak of influenza, which occurred during a period without influenza epidemic activity in the community, was notably high. Epidemiological data suggest transmission from healthcare workers to inpatients. Most healthcare workers were not vaccinated against influenza. Vaccination programmes should be reinforced among healthcare workers.     

Influenza vaccine coverage for healthcare workers in geriatric settings in France

BACKGROUND AND AIMS: Because of a relative lack of efficiency of influenza vaccine in the elderly population, influenza outbreaks in geriatric healthcare settings are probable, despite high influenza vaccination rates in patients. Nosocomial influenza outbreaks, more probably related to healthcare workers, have also been reported. Therefore, vaccination of healthcare workers is considered to be an important preventive policy, to decrease the in-hospital influenza burden during the viral circulation period. METHODS: This multicenter study measured influenza vaccine coverage of Health Care Worker in 102 geriatric healthcare settings (acute care, rehabilitation care, long-term care) by a first questionnaire. A second questionnaire assessed main factors associated with vaccine acceptance. RESULTS: 102 geriatric healthcare settings (20%) answered the first questionnaire. Vaccine coverage for physicians (n=187), nurses (n=631) and nurse assistants (n=1487) were 48.4%, 30.5% and 27.9%, respectively. Vaccination rates were correlated between occupational categories according to healthcare settings. Vaccination rates were significantly lower in acute care settings compared with rehabilitation and long-term care settings. Local recommendations was reported for 29.9%, but was not correlated with vaccine coverage. The second questionnaire showed that lack of motivation and knowledge, and organizational problems were the three main reasons for reluctance to be vaccinated. CONCLUSIONS: In French geriatric settings, influenza vaccine coverage of healthcare workers is low and highly variable, according to the type of healthcare setting. A group effect was found between occupational categories. However, the reasons for non-acceptance need further evaluation to improve HCW influenza vaccine coverage.     

Cardiovascular Exercise Training Extends Influenza Vaccine Seroprotection in Sedentary Older Adults: The Immune Function Intervention Trial

OBJECTIVES: To determine whether cardiovascular exercise training resulted in improved antibody responses to influenza vaccination in sedentary elderly people who exhibited poor vaccine responses. DESIGN: Single‐site randomized parallel‐arm 10‐month controlled trial. SETTING: University of Illinois at Urbana‐Champaign. PARTICIPANTS: One hundred forty‐four sedentary, healthy older (69.9 ± 0.4) adults. INTERVENTIONS: Moderate (60–70% maximal oxygen uptake) cardiovascular exercise was compared with flexibility and balance training. MEASUREMENTS: The primary outcome was influenza vaccine response, as measured according to hemagglutination inhibition (HI) anti‐influenza antibody titer and seroprotective responses (HI titer ≥40). Secondary measures included cardiovascular fitness and body composition. RESULTS: Of the 160 participants enrolled, 144 (90%) completed the 10‐month intervention with excellent compliance (～83%). Cardiovascular, but not flexibility, exercise intervention resulted in improvements in indices of cardiovascular fitness, including maximal oxygen uptake. Although not affecting peak (e.g., 3 and 6 weeks) postvaccine anti‐influenza HI titers, cardiovascular exercise resulted in a significant increase in seroprotection 24 weeks after vaccination (30–100% dependent on vaccine variant), whereas flexibility training did not. CONCLUSION: Participants randomized to cardiovascular exercise experienced improvements in influenza seroprotection throughout the entire influenza season, whereas those in the balance and flexibility intervention did not. Although there were no differences in reported respiratory tract infections, the exercise group exhibited reduced overall illness severity and sleep disturbance. These data support the hypothesis that regular endurance exercise improves influenza vaccine responses.     

Comparison of two vaccination programmes in preventing influenza-related hospitalization among the elderly during two consecutive seasons

The protective effect of influenza vaccine against influenza related hospitalization is well established at an individual level, but the effect of vaccination programme at the population level is unknown. In this study we compared a risk disease-based free-of-charge influenza vaccination programme in preventing hospitalizations due to influenza or pneumonia and cardiovascular diseases during 2 consecutive influenza seasons 1992/93 and 1993/94 in 43 municipalities in northern Finland. Vaccinations were carried out and reported by local staff in health centres. Data of hospital treatment periods were obtained from the National Hospital Discharge Register. During the influenza seasons the number of hospitalizations due to cardiovascular diseases and influenza/pneumonia increased by 13%. In the 1993/1994 season the increase in the study area with the risk disease-based vaccination programme was 22 per 1000 persons (95% CI 19-24), and with an age-based programme 3.3 per 1000 persons (95% CI 2.5-4.0), while the increase in the 1992/1993 season in both areas was 3-4 per 1000. The excess of hospitalization related to influenza epidemics is mostly due to cardiovascular diseases and varies from y to y, as do the benefits gained by vaccination.     

Knowledge,attitude, and practices about the seasonal influenza vaccination among healthcare workers in Srinagar,India

Please cite this paper as: Bali NK et al. (2012) Knowledge, attitude, and practices about the seasonal influenza vaccination among healthcare workers in Srinagar, India. Influenza and Other Respiratory Viruses 7(4), 540–545. Background Healthcare workers (HCWs) universally have a poor uptake of influenza vaccination. However, no data are available from India. Objective To explore knowledge, attitudes, and practices associated with influenza vaccination in HCWs in a temperate climate area in northern India. Patients and Methods A self‐administered questionnaire was offered to all HCWs in three major hospitals of Srinagar and information sought on motivations, perceptions, preferences and practices regarding influenza vaccination. Results Of the 1750 questionnaires received, 1421 (81%) were returned. Only 62 (4·4%) HCWs had ever received influenza vaccination even as 1348 (95%) believed that influenza poses adverse potential consequences for themselves or their contacts; 1144 (81%) were aware of a vaccine against influenza and 830 (58%) of its local availability. Reasons cited by 1359 participants for not being vaccinated included ignorance about vaccine availability (435; 32%), skepticism about efficacy (248; 18%), busy schedule (166; 12%), fear of side effects (70; 4%), and a perception of not being‐at‐risk (82; 6%). Sixty‐one percent (865) believed that vaccine programs are motivated by profit. Eighty‐eight percent opined for mandatory vaccination for HCWs caring for the high‐risk patients, as a part of ‘employee health program’. Most of the participants intended to get vaccinated in the current year even as 684 (48%) held that vaccines could cause unknown illness and 444 (31%) believed their adverse effects to be underreported. Conclusion Influenza vaccination coverage among HCWs is dismally low in Srinagar; poor knowledge of vaccine availability and misperceptions about vaccine effectiveness, fear of adverse effects and obliviousness to being‐at‐risk being important barriers. Multifaceted, adaptable measures need to be invoked urgently to increase the coverage.     

Influenza vaccination of healthcare workers in acute-care hospitals: a case-control study of its effect on hospital-acquired influenza among patients

Background  

In acute-care hospitals, no evidence of a protective effect of healthcare worker (HCW) vaccination on hospital-acquired influenza (HAI) in patients has been documented. Our study objective was to ascertain the effectiveness of influenza vaccination of HCW on HAI among patients.     

Increased reactions to pediatric influenza vaccination following concomitant pneumococcal vaccination

Please cite this paper as: Van Buynder et al. (2013). Increased reactions to pediatric influenza vaccination following concomitant pneumococcal vaccination Influenza and Other Respiratory Viruses 7(2) 184–190. Background Influenza in children causes significant morbidity and hospitalizations and also some mortality particularly in children <5 years of age. Influenza vaccination in children has been shown to be safe and effective, but in 2010 the pediatric influenza vaccination program was suspended in Western Australia after the rate of febrile convulsions observed (9/1000 doses) was 55 times the previously reported rate. In 2009, over 80% of all children in New Brunswick were vaccinated with an adjuvanted monovalent H1N1 vaccine shown to have very high effectiveness, raising the prospect of potential hyper‐responsiveness because of residual protection. We conducted enhanced post‐marketing surveillance to monitor local and general reactions. Methods Parents of participating children seen at dedicated vaccination clinics were given influenza vaccine survey kits to record local and general symptoms up to 3 days following receipt of season influenza vaccine. Results Febrile reactions of ≥38° occurred in <10% of children who received a first dose of seasonal influenza vaccine (n = 660) and severe febrile incidents with fever ≥39° were uncommon. Concurrent administration of other vaccine(s) including conjugated pneumococcal vaccine appeared to increase reactogenicity. No child in the study had a febrile convulsion. Conclusion Influenza vaccines in children are safe, and this study provides a baseline for rapid assessment studies at the start of a vaccine season. Parents should be aware of increased fevers with concurrent vaccine administration, and antipyretics should be considered.     

Nurses' attitudes and beliefs about influenza and the influenza vaccine: a summary of focus groups in Alabama and Michigan

BACKGROUND: The U.S. Advisory Committee on Immunization Practices (ACIP) recommends influenza immunization among United States health care workers (HCWs) to reduce the spread of influenza to and from workers and patients. Despite these recommendations, influenza immunization coverage of health care workers is less than 50%. PARTICIPANTS AND METHODS: Eight focus groups of registered nurses (RNs) were conducted in Birmingham, Alabama (n = 34) and Detroit, Michigan (n = 37). In each city, the focus groups consisted of 2 groups each of vaccinated and unvaccinated RNs. RESULTS: These focus groups revealed that many nurses were concerned about influenza vaccine effectiveness and safety; their lack of information about the vaccine plays a part in their willingness to promote it to patients. Unvaccinated nurses tended to be less aware of the ACIP recommendations for HCW vaccination, and overall, nurses were not aware of the rationale for HCW vaccination. Attitudes were mixed regarding mandatory influenza vaccination programs, including the hope that such programs would result in higher vaccination rates and concern about potential disciplinary action if vaccine was declined. Participants believed that increasing convenience was the key to increasing HCW vaccination. CONCLUSIONS: Our findings confirm the importance of comprehensive approaches that combine education and convenience, and suggest that emphasizing the rationale for HCW vaccination may contribute to increasing vaccination rates.     

Attitudes towards Anti-SARS-CoV2 Vaccination among Healthcare Workers: Results from a National Survey in Italy

Coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people, fostering and unprecedent effort in vaccine development and distribution. Healthcare workers (HCW) play a key role in vaccine promotion and patient guidance, and it is likely that hesitancy among this population will have a major impact on the adoption of a successful immunization policy. To investigate HCW attitudes towards anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination, we developed an anonymous online cross-sectional survey. 1723 Italian HCW responded. Overall, 1155 (67%) intended to be vaccinated, while 443 (26%) were not sure and 125 (7%) declared refusal. In multivariate analysis, factors associated with hesitancy were using Facebook as the main information source and being a non-physician HCW, while predictors of acceptance included younger age, being in close contact with high-risk groups and having received flu vaccination during the 2019–2020 season. Reasons for hesitancy included lack of trust in vaccine safety (85%) and receiving little (78%) or conflicting (69%) information about vaccines. According to our results, adequate investment in vaccine education for healthcare personnel appears to be urgently needed, prioritizing non-physicians and information quality spread through social media. We hope that our data could help governments and policy-makers to target communication in the ongoing COVID-19 vaccination campaign.     

Influenza vaccination status and influenza-related perspectives and practices among US physicians

BACKGROUND AND OBJECTIVE: The influenza vaccination rate among US healthcare workers (HCWs) remains low. This survey was designed to assess influenza vaccination status and related knowledge, attitudes, and beliefs among a national sample of primary care physicians and subspecialists likely to see patients at high risk for complications from influenza. METHODS: We used a mail survey of a national random sample of 495 family physicians (FPs), 491 internists (IMs), 498 geriatricians (GERs), and 497 pulmonologists (PUDs). RESULTS: The overall response rate was 38%. Almost all respondents (87%) reported receiving an influenza vaccine during the 2003-2004 influenza season, with no significant difference across specialty groups (84% FPs, 87% IMs, 87% GERs, 91% PUDs). In a multivariate model, adjusted for physician specialty and age group, significant predictors of vaccination were: strong agreement that HCWs have professional responsibility to be vaccinated, access to vaccination on site and free of charge, strong worksite recommendation for HCWs to be vaccinated, and strong agreement that benefits of vaccination outweigh risk of side effects. CONCLUSIONS: Physicians reported a high influenza vaccination rate. To improve these rates further, with likely benefits for other HCWs, worksite policies that facilitate access to vaccination and documentation of reductions in nosocomial influenza associated with HCW vaccination should continue to be pursued.     

Marketing paediatric influenza vaccination: results of a major metropolitan trial

Please cite this paper as: Van Buynder et al. (2010) Marketing paediatric influenza vaccination: results of a major metropolitan trial. Influenza and Other Respiratory Viruses 5(1), 33–38. Objectives After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Design Advertising occurred in major statewide newspapers, via public poster displays and static ‘eye‐lite’ displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web‐sites. Parents were subsequently surveyed to assess reasons for vaccination. Main Outcome Results The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Conclusions Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community ‘myths’ about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere.     

Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.     

Strategies to increase influenza vaccine uptake among health care workers in Greece

The aim of the current study was to investigate the contribution of various strategies to increase influenza vaccine uptake among health care workers (HCWs) working in hospitals in Greece during the 2005-2006 season. A total of 132 Greek public hospitals participated in the study. The mean HCWs vaccination rate against influenza during 2005-2006 was 16.36% compared with 1.72% during the previous season. Logistic regression analysis showed that the implementation of the following strategies was significantly associated with influenza vaccination rates above the mean vaccination rate: a mobile vaccination team (OR 2.942, 95% CI 1.154-5.382, p-value 0.016) and lectures on influenza and influenza vaccine (OR 2.386, 95% CI 0.999-5.704, p-value 0.036). In conclusion, in Greece influenza vaccination rates among HCWs remain low; however, the implementation of specific strategies was associated with increased vaccine uptakes.     

Role of neuraminidase inhibitor chemoprophylaxis in controlling nosocomial influenza: an observational study

Please cite this paper as: Higa et al. (2012) Role of neuraminidase inhibitor chemoprophylaxis in controlling nosocomial influenza: an observational study. Influenza and Other Respiratory Viruses 6(4), 299–303. Background An influenza outbreak might result in disruption of services at acute care setting hospitals. Objectives In this study, we retrospectively evaluated the use of neuraminidase inhibitor chemoprophylaxis for prevention of nosocomial spread of influenza in a university hospital. Patients/Methods During the 3‐year study period, 202 index cases of influenza [30 hospitalized patients and 172 healthcare workers (HCW)] and 762 individuals who had had close contact with the index cases (248 hospitalized patients and 514 HCW) were identified. Of these contacts, 416 received neuraminidase inhibitor chemoprophylaxis. Results When both the index cases and the close contacts were hospitalized patients, the incidence of influenza was lower among the close contacts who received chemoprophylaxis than among those who did not (odds ratio, 0·07; confidence interval, 0·01–0·49; P = 0·012). In contrast, when the index cases were HCW, the incidence of influenza was not different between close contacts who did or did not receive chemoprophylaxis. Conclusions This study suggests that chemoprophylaxis might be useful to prevent nosocomial spread of infection between hospitalized patients.     

A coordinated cross‐disciplinary research initiative to address an increased incidence of narcolepsy following the 2009–2010 Pandemrix vaccination programme in Sweden

In response to the 2009–2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03‐adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross‐disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three‐ to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA‐DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon‐gamma production in response to streptococcus‐associated antigens. The chain of patient‐related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross‐disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination‐related adverse events.