Trends in influenza vaccination behaviours – results from the CoPanFlu cohort , France , 2006 to 2011

A L Caille-Brillet (alcailleb@gmail.com)1,2, J Raude1,2, N Lapidus3,4, X De Lamballerie2, F Carrat3,5, M Setbon1,2,6 1. Department of Social and Behavioural Sciences, EHESP School of Public Health, Sorbonne Paris Cité, Rennes, France 2. UMR190 ‘Emergence des Pathologies Virales’ (Aix-Marseille Univ. – IRD French Institute of Research for Development – EHESP French School of Public Health), Marseille, France 3. Institut National de la Santé et de la Recherche Médicale (INSERM; French National Institute of Health and Medical Research), UMR-S 707, Paris, France 4. University Pierre et Marie Curie-Paris 6, UMR-S 707, Paris, France 5. Assistance Publique-Hôpitaux de Paris (Public Assistance – Paris Hospitals), Hospital Saint Antoine, Public Health Unit, Paris, France 6. Centre national de la recherche scientifique (National Center for Scientific Research), Paris France


Introduction
The public health response to the 2009 pandemic of influenza A(H1N1)pdm09, which first appeared in May 2009 in France, as in many European countries, largely focused on vaccination [1].From June 2009, the question of vaccine availability was replaced in France by a growing controversy on the relevance and safety of pandemic vaccination and possible conflicts of interest between pharmaceutical companies and experts [2,3].Two vaccines became available during the 2009/10 pandemic season in France: first a vaccine against seasonal influenza strains (seasonal vaccine), and later a vaccine against the pandemic strain (pandemic vaccine).French health authorities launched campaigns to promote both seasonal and pandemic vaccinations, aimed at protecting the entire population [4], but especially targeting usual and new risk groups [5].In January 2010, the number of influenza infections was under the epidemic threshold in metropolitan France and the vaccination campaigns subsequently stopped.
Only around 8% of the French population got vaccinated against pandemic influenza [2,3].A considerable body of research has been devoted to the failure of the 2009/10 pandemic vaccination campaign [6] and to the determinants of intentions and decisions to get this vaccine [7][8][9].Yet few studies have examined the potential effect of controversies about vaccines on people's general vaccination behaviours and the rare studies addressing change in influenza vaccination behaviours in Europe after the pandemic have mostly focused on high-risk groups [10][11][12].The purpose of this article is to further examine the evolution of influenza vaccination behaviours in relation to the pandemic: (i) whether and how influenza vaccination behaviours after the pandemic changed, and (ii) if some population groups, especially target groups, were particularly affected in their behaviours.

Methods
For this study, longitudinal data from the Cohort for Pandemic Influenza (CoPanFlu) France interdisciplinary consortium were used.The cohort consists of 1,451 individuals from 575 households representative of the French population, and was set up in December 2009 to study the risk of influenza A(H1N1)pdm09 infection and its determinants.Study design, e.g.sampling methods, eligibility criteria and data collection have been described in detail elsewhere [13].The research ethics committee 'Comité de Protection des Personnes Ile-de-France 1' approved the protocol of the study, and informed consent was collected for each subject at the inclusion phase.In 2010/11, 37 subjects had left the study (2.5% of the sample), and a further 94 individuals (131 in total, 9.0% of the sample) had left the study when the research protocol has been extended to the 2011/12 season.Their sociodemographic characteristics were not significantly different from the rest of the cohort.

Measures
This study presents data on vaccination behaviours from the influenza seasons 2006/07 to 2011/12, collected among all 1,451 individuals of the cohort.During the inclusion visit that took place between December 2009 and July 2010, the participants declared whether they had received the influenza vaccination during the three seasons before the pandemic (2006/07, 2007/08 and 2008/09) and the seasonal, pandemic or both influenza vaccinations in 2009/10.During follow-up visits and in questionnaires, cohort subjects were asked to report their vaccination status in 2010/11 and in 2011/12.At inclusion, subjects also provided their sociodemographic characteristics, which are presented in Table 1.
Data on education were divided into four levels using the 1997 International Standard Classification of Education developed by UNESCO and adapted for France by the Eurydice network [14].Information on educational level was mostly unavailable for children under the age of 15 years.Risk groups were defined using criteria for seasonal influenza vaccination before the H1N1 influenza pandemic, as vaccination is recommended by the French health insurance system and free of charge for individuals with a risk factor for complications in case of an infection (65 years or older and some medical conditions) [12,15].Two target (at-risk) groups were differentiated according to their age and clinical data collected during the inclusion visit: subjects aged 65 years and older at the inclusion visit (who may or may not have a condition placing them in a risk group) and those aged younger than 65 years with a risk condition.

Statistical analysis
Differences in independent groups were tested using a two-tailed Pearson's chi-square test.The McNemar test and the Cochran test, respectively, were applied to test the significance of changes in (dependent) vaccination behaviours of the cohort's subjects between two and more than two seasons [16].A series of logistic regression analyses was performed to examine the association between vaccination behaviours and a range of sociodemographic factors.All statistical analysis was executed using IBM SPSS statistics version 20.

Behavioural change during the pandemic in the cohort
Variations in vaccination behaviours before, during and after the pandemic were first investigated (p<0.0001,Tables 2 and 3).Before the pandemic, vaccination behaviours were not significantly different over time, and influenza vaccination coverage (IVC) remained stable over the period from 2006/07 (20.6%, 95% confidence interval (CI): 18. 5

Discussion
As in many industrialised countries during the 2009 influenza A(H1N1)pdm09 pandemic, public health authorities in France faced a climate of distrust toward the pandemic vaccine [6], which was extensively covered by the mass media [2,3].It should also be noted that the pandemic vaccination effort was contested by a number of medical professionals and politicians [3,17].One of the objectives of this article was to ascertain the impact of the controversies on subsequent influenza vaccination behaviours.

An immediate impact on vaccination behaviour
This study shows an immediate impact of the pandemic episode on vaccination uptake rates that lasted for the period of the two following seasons observed in this study.The longitudinal setting of the CoPanFlu cohort enabled us to characterise behaviour changes among the same representative sample of the French population before, during and after the pandemic, which is often lacking in the literature [18,19].A clear immediate effect of the pandemic season on influenza vaccination behaviours could be established (Tables 2 and  3).Despite the low pandemic IVC also recorded in other studies [2,3], cohort subjects were significantly more often vaccinated with the seasonal vaccine in 2009/10 compared with previous seasons, and sometimes got both vaccinations.Altogether, this resulted in a total IVC close to 30%.Vaccination behaviours in the total sample were found to be affected for two years after the pandemic in that IVCs in 2010/11 and 2011/12 were significantly lower than before the pandemic (Table 4).However, this trend can only be confirmed for the people with no risk factor for seasonal influenza, as statistical power was lacking to reveal such an effect among members of the target groups.Regarding the general impact of the pandemic season on vaccination behaviours, this study is to our knowledge the first to reveal such a significant drop in IVC after the pandemic in a longitudinal setting.Whether this trend will continue has yet to be confirmed, as it raises concerns for future vaccination campaigns and among specific population groups.
Pandemic vaccination was in fact recommended for new target groups that were not included in the French definition of target groups before the pandemic: pregnant women, parents of young children, and subjects with other specific pathologies or aged over 19 years with no risk factor [5].Some of these groups were still included in the 2010/11 influenza vaccination recommendations [20].As with the rest of the population, older age groups were more willing to get vaccinated during the pandemic, but less so in the following seasons This is particularly illustrative of the controversial climate during the pandemic: individuals who got vaccinated against seasonal influenza before the pandemic season changed their behaviour.Controversies in 2009/10 and conflicts of interest between pharmaceutical companies and experts could have created doubts about the safety of influenza vaccines among the French population, as these factors have been documented to discourage vaccination behaviours [6][7][8]21].This led not only to a low pandemic IVC in 2009/10 but also to subjects not renewing their vaccination behaviours in 2010/11.Especially concerning is this shift in vaccination behaviour among the age group 55 to 64 years, who will soon belong to the target group of people aged 65 years and over.
These results attest to a specific impact of the pandemic on target groups (Tables 2 and 3).In CoPanFlu data, target groups more frequently adopted both seasonal [22] and pandemic [23,24] vaccines during the pandemic than people with no risk factor (p<0.0001).Target groups were in fact more likely to get both vaccinations than those with no risk factor, but subjects aged 65 years and over almost never relied only on the pandemic vaccine.Since past vaccination behaviours are known to influence later vaccination behaviours [1,6,18,24], and people aged 65 years and over demonstrated high and superior IVCs across time [17], they seemed to have continued their usual seasonal vaccination practices, and adopting the additional protection from the pandemic vaccine.On the other hand, individuals younger than 65 years were more likely to use only the pandemic vaccine and had had a lower adherence to seasonal vaccination before the pandemic than other risk groups.
In the CoPanFlu cohort, the 2009 influenza pandemic did not alter post-pandemic vaccination behaviours among target groups as found in another French study conducted in 2010/11 [17].In fact, individuals with risk factors constitute priority target groups for influenza immunisation programmes in France as in most industrialised countries [25,26] because they benefit most from the protection of the influenza vaccine [27], which would encourage them not to discontinue their vaccination behaviours.It is however, of public health concern that the vaccination coverage in those target groups is still insufficient, below the 75% recommended by the World Health Organization [28], as has already been highlighted in several studies before the pandemic [15,16,25].

Limitations and potential biases
In the CoPanFlu cohort, vaccination behaviours were stable before the 2009 pandemic (Tables 2 and 3), similar to other French studies [15,29].IVCs among people over 65 years were comparable to other data [29,30], yet slightly lower than in the general population compared with previously published (though cross-sectional) results [31].Prepandemic IVCs among individuals under 65 years with a risk condition were significantly lower (i.e.ranging from 34% to 38.3%) than those observed in other studies [29,30].Moreover, the criteria for target groups used in this study were based on less restrictive clinical criteria (suffering or having suffered from a specific condition) those that of the French health insurance (i.e. based on enrolment in the long-term chronic disease programme for these specific diseases).Finally, the 2009/10 pandemic IVC in this cohort was higher than the 8% coverage observed in France [2,3], although in line with the IVC estimate of 11.1% from another French study on IVC during the pandemic [24].
We initially used participants' age at the inclusion as a default and stable variable in the results.When comparing behaviours between two seasons, we considered age at the later season to test for a behavioural change among subjects younger than 65 years who could have entered the risk group of people aged over 65 of age.However, even if some IVCs and results of the paired tests differed, the differences observed over time remained insignificant.
The CoPanFlu France cohort was originally designed to assess the relative risk of infection by the influenza A(H1N1)pdm09 virus, not the uptake of influenza vaccination.As indicated in a methodological paper by Lapidus et al. in 2012 [13]: We first intended to include 1000 households (about 2100 subjects) which would have permitted to detect covariates associated to a relative risk ≥1.4 with a 80% power and 5% significance, assuming a cumulative incidence of 10% and intrahousehold correlation of 0.3.However, due to organisational and financial constraints, only 575 households (1,451 subjects) were eventually included in the cohort.Theoretically, the maximal margin of error with a 95% CI is ± 2.6 for a random sample of 1,451 individuals and ± 2.2 for a random sample of 2,000 individuals.Due to the sample size and the possible subsequent lack of statistical power, changes in vaccination behaviours may have been more substantial in some population groups.

Conclusion
These data illustrate the power of prospective household study designs to investigate behavioural changes in a context of global health crises.Contrary to Guthmann and colleagues [17], our study attests to a more lasting impact of the pandemic over the following two seasons, ultimately causing a decrease in IVC (with the possible exception of certain target groups at risk for complications).Secondly, it highlighted that people with no risk factors, and among them, young adults aged 24 to 34 years and people aged 45 to 64 years, were more affected by this trend.Although these groups could have been targeted by the pandemic vaccination campaign, this may also be influenced by the fact that influenza vaccination is not generally free of charge for these non-risk groups.Further studies should assess if this decreasing post-pandemic IVC trend is a temporary side-effect of the pandemic season or an indicator of a longer-lasting disaffection with the seasonal influenza vaccine or with vaccination in general, especially among at-risk populations.To do so, determinants of vaccination behaviours and motivations to get or not to get vaccinated should be more closely monitored.

Table 2
Influenza vaccination coverage in the CoPanFlu cohort from 2006/07 to 2011/12, all data, France (n=1,451) a Seasonal vaccination only.b Pandemic vaccination only.c Both vaccinations.

Table 3
Influenza vaccination coverage in the CoPanFlu cohort from 2006/07 to 2011/12, excluding missing data, France (n=1,451) a The missing data are excluded.b Seasonal vaccination only.c Pandemic vaccination only.d Both vaccinations.

Behavioural change during the pandemic according to risk factors
FigureInfluenza vaccination coverage from 2006/07 to 2011/12 in the total CoPanFlu cohort and according to risk factors for seasonal influenza, France (n=1,451 until 2009/10, n=1,414 in 2010/11, n=1,320 in 2011/12) : 7.2-10.1)whogotimmunised only against the pandemic strain.Similar to those aged 65 years and over, persons under 65 years with a target condition relied more strongly on both vaccines that year (12.5%, 95% CI: 10.8-14.2) and on the seasonal vaccine only (20.1%, 95% CI: 18.0-22.2).Table4).The change in vaccination behaviours was significantly different according to risk factors (Pearson's chi-square test, p<0.0001): 45.4% of individuals with no risk factor, 21.6% of those under age 65 years with a target condition, and 14.2% of individuals aged 65 years and over abandoned influenza vaccination.In fact, considering individuals who had not left the study, vaccination behaviours in 2010/11 and in 2011/12 among people at high risk for complications were not statistically different from those adopted in the three seasons before the pandemic, whereas a significant IVC decrease was observed after the pandemic among subjects with no risk factor.