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2006
Vaccine 26 (2008) 5612–5618
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Influenza vaccination coverage in patients with cystic fibrosis followed at 12 care centers in the Greater South Region of France for the season 2005/2006 Marlène Murris-Espin a,∗,1,2 , Marie Aubert b,1,2 , Emmanuelle Bosdure c,1,2 , Jean-Christophe Dubus c,1,2 a b c
Cystic Fibrosis Care Center for Adults, Pulmonology Department, Larrey Teaching Hospital, Toulouse, 25 Chemin de Pouvourville, TSA 30030, 31059 Toulouse Cedex 9, France Sanofi Pasteur MSD, Lyon, France Pediatric Cystic Fibrosis Care Center, Infantile Medicine Department, Timone-Enfants Teaching Hospital, Marseille, France
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Article history: Received 9 May 2008 Received in revised form 24 July 2008 Accepted 28 July 2008 Available online 20 August 2008 Keywords: Cystic fibrosis Influenza Vaccination
a b s t r a c t The objective of this observational study was to estimate influenza vaccination coverage for the 2005/2006 season in cystic fibrosis (CF) patients consulting at or hospitalized in 12 CF care centers. Data from 518 CF patients >6 months of age (children: 64.9%) were analyzed: 79.9% were vaccinated. The vaccination coverage was 85.6% in children, 69.4% in adults and 44.4% in transplanted patients. General practitioners vaccinated 67.9% of the patients. “Lack of time” reason was reported by 24.7% non-vaccinated patients. In France, influenza vaccination coverage in CF patients meets the National Health objective (≥75% by 2008), but could be improved in adults and transplanted patients. © 2008 Elsevier Ltd. All rights reserved.
1. Introduction Influenza (flu) is known for its serious consequences in the elderly and those with underlying chronic disease (i.e., chronic heart or lung disease, metabolic or renal disease, or immunodeficiency) [1]. Flu vaccines are safe and effective, and annual
Abbreviations: CF, cystic fibrosis; CI, confidence interval; CRCM, National CF Care Centers (Centres de Ressources et de Compétence de la Mucoviscidose); Flu, influenza; GP, general practitioner; HCP, health care professionals. ∗ Corresponding author. Tel.: +33 567771851; fax: +33 567771475. E-mail address: [email protected] (M. Murris-Espin). 1 The investigators from the French Muco-Sud and Muco-Med networks: Drs Boisserie-Lacroix Vincent, Bui Stéphanie, Ceccato Franc¸oise, Domblides Philippe, Dromer Claire and Fayon Michael from the Adult and Pediatric Cystic Fibrosis Care Centers of Bordeaux; Drs Gautry Philippe and Caporal Pierre from the Mixed Cystic Fibrosis Care Center of Brive; Drs Labbé André, Philippe Pierre, Hager Marie-Odile, Heraud Marie-Christine, and Petit Isabelle from the Mixed Cystic Fibrosis Care Center of Clermont-Ferrand; Drs de Lumbley Lionel, Melloni Boris, Languepin Jeanne, and Menetrey Céline from the Mixed Cystic Fibrosis Care Center of Limoges; Drs Didier Alain, Brémont Franc¸ois, Le Tallec Claire, Rittié Jean-Luc, and Têtu Laurent from the Adult and Pediatric Cystic Fibrosis Care Centers of Toulouse; Drs Mely Laurent and Jubin Virginie from the Mixed Cystic Fibrosis Care Center of Giens; Drs Reynaud-Gaubert Martine, Sarles Jacques, Boniface Stéphanie, and Stremler-Lebel Nathalie from the Adult and Pediatric Cystic Fibrosis Care Centers of Marseille; Drs Chiron Raphaël, Counil Franc¸ois, and Fournier Favre Sébastien from the Mixed Cystic Fibrosis Care Center of Montpellier; and Drs Albertini Marc and Moreau Ludovic from the Pediatric Cystic Fibrosis Care Center of Nice. 2 On behalf of the French Muco-Sud and Muco-Med networks. 0264-410X/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2008.07.095
vaccination of high-risk persons ahead of the flu season is currently the most effective measure for reducing the impact of this disease [2]. The World Health Organization (WHO) recommends annual vaccination of high-risk patients [1]. This recommendation is currently followed by nearly all European countries. In France, one National Health objective for the year 2008 is to achieve at least 75% flu vaccination coverage rate in at-risk populations [3]. Cystic fibrosis (CF) is the commonest genetically inherited disease in white populations (1 in 2500 newborns). Progress in the understanding of the disease and the impact of this on management has been rapid over the past 20 years. The predicted median survival for babies born in the 21st century is now more than 50 years. CF is an autosomal recessive disease, caused by mutations in the CFTR (Cystic Fibrosis Transmembrane conductance Regulator) gene. The commonest mutation (about 70% of CF patients) is the deletion of phenylalanine at codon 508 (known as F508). However, moreover 1600 mutations of the CFTR gene with varying effects on CFTR function and resulting in different CF phenotypes (mild or severe) have been described. The CFTR protein is expressed in many cells and has several functions. The primary function of the CFTR protein is as an ion channel that regulates liquid volume on epithelial surfaces through chloride secretion and inhibition of sodium absorption. CF is a complex multi-system disease affecting upper and lower airways, pancreas, bowel, liver, and reproductive tracts. Lung destruction is caused by airways obstruction due to dehydrated, thickened secretions, resultant endobronchial infection, and exaggerated inflammatory response leading to development
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of bronchiectasis and progressive obstructive chronic airways disease. Lung disease occurs in children and adults, and accounts for nearly 85% of the mortality. The management of such a complex disease takes place in specialist centers [4,5]. Children and adults with CF are at increased risk of pulmonary complications if they contract flu, especially if they receive immunosuppressive treatment for lung and/or liver transplants [6–8]. Flu viruses cause disease progression and lung function worsening, predispose to bacterial infections and increase hospitalization rates [9,10]. Flu vaccination elicits an antibody response in CF patients that is expected to achieve a clinical protection against flu disease [10–12]. This response is maintained with repeated annual vaccination [10,13]. Flu vaccination has been shown to offer protection from its subsequent acquisition in the CF population [9]. Annual flu vaccination is therefore recommended in all CF patients >6 months of age [14,15]. In France, annual flu vaccination is recommended in patients with chronic lung disease since 1986 [16], including specifically CF patients since the year 2000 [17]. In France, there are approximately 6000 CF patients of whom 180 are transplanted each year [18]. In 2004, there were 4533 CF patients (38.4% of adults) followed at one of the 49 approved National CF Care Centers (Centres de Ressources et de Compétence de la Mucoviscidose, CRCMs) [18]. These CRCMs are hospitalbased and organized in networks. Their health objectives are to improve the management, life expectancy and quality of life of CF patients. They bring together medical and paramedical Health Care Professionals (HCPs): e.g., doctors, nurses, physiotherapists, dieticians, psychologists and social workers. The HCP teams coordinate the care both given at home and in hospital. The CRCMs are also meeting places for patients, families, and HCPs [19]. To the best of our knowledge, up to now, no specific data on flu vaccination coverage rate in CF patients are available in France. The present observational descriptive study sought thus to estimate coverage for the 2005/2006 flu season in French CF patients followed in CRCM.
2.3. Flu vaccine
2. Patients and methods
2.5. Statistical analysis
2.1. Study design
All data were analyzed by Mapi-Naxis (Lyon, France). Statistical analyses were performed on SPSS 13.0 software. A description of the population on all the variables of the questionnaire was performed. For each variable, percentages were calculated using available data (missing data ignored). The calculated value of the 2005/2006 flu vaccination coverage rate is given with its 95% confidence interval (95% CI). A statistical analysis by subgroup (age, transplantation status, reception of a free voucher) was performed for the 2005/2006 season on coverage rates, vaccinators, reasons for non-vaccination. The Chi2 test was used for comparisons of proportions; the significance threshold was set at 0.05.
This observational study was conducted from 1 March 2006 to 31 August 2006 (i.e., after the 2005/2006 flu official campaign: from September 2005 to February 2006). The study was initially proposed to the 12 CRCMs of the two networks, Muco-Sud and Muco-Med. The whole 12 CRCMs accepted to participate in the study. These 12 CRCMs represent a quarter of all the French CRCMs, and the totality of the CRCMs located in the nine biggest cities in the Greater South region of France (Fig. 1). These 12 CRCMs follow about 1200 CF patients, including approximately 60 transplant recipients. Three of these CRCMs are specifically devoted to adults, four specifically to children, and five (mixed CRCMs) follow both adult and pediatric patients. Diagnosis of CF in patients followed at CRCMs is made on clinical signs and symptoms, sweat tests results, and/or genetics. 2.2. Patients Each physician included consecutively all patients who met the following inclusion criteria: (a) suffering from CF; (b) >6 months of age at the beginning of the flu vaccination campaign (i.e., September 2005); (c) consulting at or hospitalized in the CRCM; and (d) with a vaccination card available so as to check flu vaccination status.
The vaccines for the 2005–2006 season (Northern Hemisphere) contained the following: an A/New Caledonia/20/99(H1N1)-like virus, an A/California/7/2004(H3N2)-like virus, and a B/Shanghai/ 361/2002-like virus (B/Jiangsu/10/2003 and B/Jilin20/2003). 2.4. Data collection The physician filled in an anonymous questionnaire for each included patient and checked data consistency with the vaccination card. Demographic and clinical data were first collected: birth date, gender, and transplantation status (whether or not transplanted, whether or not included on a transplantation waiting list). In addition, administrative data were collected: whether CF was recognized or not as an underlying chronic disease by the French Health Authorities, and if so, provision or not of a free voucher for flu vaccination from the National Public Health Insurance. In France patients with recognized underlying chronic diseases (from a published list defined by National Public Health Insurance) are eligible for 100% reimbursement for all medical costs (including vaccine costs) related to their illness [20]. Patients were then asked for their 2005/2006 flu season vaccination status (yes or no). If yes, patients were asked for vaccinators (i.e., HCP who had administered the vaccine): CRCM, lung specialist, general practitioner (GP), or pediatrician. If not, they were asked for the following reasons: vaccine useless as the disease is benign, vaccine considered dangerous, afraid of injection, lack of information, vaccine considered ineffective, contra-indication including allergy, or other reason (any spontaneous reported reason). Patients could give one or more than one reason for non-vaccination. For all the patients who should have been vaccinated (i.e., >6 months of age) during the 2001/2002, 2002/2003, 2003/2004, 2004/2005, and 2005/2006 flu seasons, the physician recorded vaccination dates from the vaccination card. Patients were also asked whether they were systematically vaccinated every year.
2.6. Ethical considerations As this study was an observational study without any modification of the patient’s usual medical management, it was not submitted to an ethics committee for approval, in line with current French legislation. All questionnaire data were rendered anonymous using Mapi-Naxis’s data procedure that was validated by the Commission Nationale de l’Informatique et des Libertés (French information protection commission). Before being included in the study, all patients (or parents or guardians for patients <18 years of age) were duly informed of the objectives and requirements of the study (an information sheet was
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Fig. 1. Geographic distribution of the 49 French Cystic Fibrosis (CF) Care Centers (Centres de Ressources et de Compétence de la Mucoviscidose, CRCM) and the 12 CRCMs of the Muco-Sud (double circle) and Muco-Med (single circle) networks who participated in this study (with the kind authorization from the French association Vaincre la Mucoviscidose). Pediatric: CRCM with an active file of at least 30 children (i.e., infants, children and adolescents); Adult: CRCM with an active file of at least 20 adult patients; Mixed: CRCM including children and adults.
given by the physician) and gave their oral consent. Patients (or their parents or guardians) were informed of their rights under the French information protection law. 3. Results From 1 March 2006 to 31 August 2006, data from 527 of the approximately 1200 CF patients followed at the 12 CRCMs were collected and data from 518 patients were analyzed. Data from nine
questionnaires were excluded from analysis because the patients had not received the information sheet (n = 7) or because the patients did not meet all the inclusion criteria (n = 2; one patient was <6 months of age in September 2005, and the age of one patient was missing and could not be checked). The rest of the population (approximately 700 patients) were not included in the study as they did not consult the center during the study period, did not give their consent to participate in the study, or did not comply with the inclusion criteria.
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3.1. Patients’ characteristics The mean age (mean ± standard deviation) of the analyzed population (n = 518) was 15.9 ± 12.0 years (median: 13.1; quartiles: 6.2–22.4) and 50.5% of the CF patients were female. There were more children (<18 years of age) than adults (≥18 years of age): 64.9% versus 35.1%, respectively. Most of the patients (n = 488; 98.0%) had had their CF recognized as an underlying chronic disease by the French Health Authorities, and were therefore eligible for 100% coverage for medical costs, including flu vaccination. A total of 49 (9.7%) CF patients were transplanted and/or on a transplantation waiting list (30 patients were transplanted, 17 were on a transplantation waiting list, and 2 patients had undergone transplantation but were also on a transplantation waiting list). Their mean age was 27.7 ± 9.7 years (median: 28.9; quartiles: 21.3–33.3). There were more adults than children (85.7% versus 14.3%) and 76.1% were female. For 95.8% of them, the CF was recognized as an underlying chronic disease by the French Health Authorities. 3.2. Flu vaccination 3.2.1. Flu vaccination coverage rate for 2005/2006 season Information regarding flu vaccination for the 2005/2006 season was available for 493 of the 518 CF patients (95.2%); 394 had been vaccinated for the 2005/2006 season. The flu vaccination coverage rate for the 2005/2006 season was estimated as 79.9% (95% CI: 76.3%–83.5%). 3.2.2. Frequency of flu vaccination for the previous seasons Of the 518 CF patients, 429, 451, 465, and 484 patients were >6 months of age during the 2001/2002, 2002/2003, 2003/2004, and 2004/2005 flu season, respectively. According to the vaccination card data, at least 74.8% of the CF patients had been vaccinated for the 2001/2002 season, 77.4% for the 2002/2003 season, 76.3% for the 2003/2004 season, and 77.9% for the 2004/2005 season. 75.9% of the 493 CF patients, for whom data were available, were systematically vaccinated each year. Regarding patients over 5 years of age in September 2005 (n = 429), 67.1% were systematically vacci-
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nated each year, 4.1% were vaccinated four times, 1.6% three times, 2.8% twice, and 6.3% once. 3.2.3. Change in flu vaccination coverage rate for the 2005/2006 season according to patient characteristics Among the 320 children (<18 years of age) and 173 adults (≥18 years of age), 274 and 120 respectively were vaccinated for the 2005/2006 season. The flu vaccination coverage rate for the 2005/2006 season was significantly greater in children than in adults: 85.6% (95% CI: 82.6%–90.4%) versus 69.4% (95% CI: 63.3%–77.1%); Chi2 test, p < 0.05 (Fig. 2). Flu vaccination coverage ranged between 88.1% and 80.0% in children: 87.4% (95% CI: 78.9%–93.3%), 80.0% (95% CI: 70.2%–87.7%), and 88.1% (95% CI: 82.6%–93.6%) in the under 5, 5–10, 10–18 age group, respectively. It ranged between 78.8% and 62.5% in adults: 78.8% (95% CI: 66.9%–87.9%), 62.5% (95% CI: 49.5%–74.3%), and 65.1% (95% CI: 49.0%–79.0%) in the 18–25, 25–35, and over 35 age group, respectively. Information regarding flu vaccination during the 2005/2006 season was available for 45 of the 49 CF patients transplanted and/or on a transplantation waiting list. Among these 45 CF patients, 20 had been vaccinated for the 2005/2006 season; flu vaccination coverage rate for the 2005/2006 season was 44.4% (95% CI: 29.6%–60.0%) (Fig. 2). 3.3. Vaccinators and reasons for non-vaccination The vaccinator was known for 346 of the 394 CF patients vaccinated during the 2005/2006 season. 235 of these 346 patients (67.9%) had been vaccinated by their GP, 54 (15.6%) by a nonhospital-based pediatrician, 50 (14.5%) at a CRCM, and 7 (2.0%) by a lung specialist. CF children (n = 243) were mainly vaccinated by a GP (66.7%) or a non-hospital-based pediatrician (21.8%) while CF adults (n = 103) were mainly vaccinated by their GP (70.9%) or at the CRCM (23.3%). Patients who were transplanted and/or on a transplantation waiting list were mainly vaccinated by their GP (72.2%) or at the CRCM (22.2%). In all, 97 of the 99 CF patients not vaccinated for the 2005/2006 season (or their parents or guardians) gave one or more
Fig. 2. Changes in vaccination coverage rate in French Cystic Fibrosis (CF) patients according to age, transplantation status, and provision of voucher for free vaccination*for the 2005/2006 influenza season. *A voucher for free influenza vaccination is provided by the National Public Health Insurance only to patients with CF recognized as an underlying chronic disease by the French Health Authorities.
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Fig. 3. Reasons for non-vaccination given by 97 of the 99 patients with cystic fibrosis who had not been vaccinated against influenza virus for the 2005/2006 influenza season. (Percentages were calculated using the number of patients with available data, n = 97. Each patient could give more than one reason for non-vaccination.)
than one reason for non-vaccination. A total of 109 reasons for non-vaccination were reported: 61 reasons identified in the questionnaire and 48 spontaneously reported reasons (Fig. 3). “Lack of time” (n = 24, 24.7%) was the most frequently reported identified reason for non-vaccination. “Lung-transplanted” (n = 11) or “included on a transplantation waiting list” (n = 4) was the most frequently reported spontaneously reported reason (n = 15, 31.2%). 3.4. Flu vaccination coverage in CF patients who received a voucher for free of charge flu vaccination Information regarding flu vaccination during the 2005/2006 season was available for 465 of the 488 patients with CF recognized as an underlying chronic disease by the French Health Authorities; 375 had been vaccinated. The flu vaccination coverage rate for the 2005/2006 season in these CF patients was thus 80.6%. Information regarding voucher provision for free flu vaccination during the 2005/2006 season was available for 461 patients with CF officially recognized as an underlying chronic disease. Most of them (78.1%, n = 360) declared having received the free voucher. Free voucher provision increased flu vaccination coverage rate from 64.2% to 85.7% (Chi2 test, p < 0.05) in patients with CF recognized as an underlying chronic disease (Fig. 2). It statistically significantly increased flu vaccination coverage in both children (Chi2 test, p < 0.01) and adults (p < 0.05): 91.4% (95% CI: 87.7%–95.1%) of the children with a free voucher versus 69.2% (95% CI: 56.5%–80.1%) without free voucher were vaccinated, and 75.6% (95% CI: 68.1%–83.1%) of the adults with a free voucher versus 53.3% (95% CI: 34.3%–71.7%) without free voucher were vaccinated for the 2005/2006 season. 4. Discussion In CF children, respiratory viruses, and in particular flu viruses are associated with CF exacerbations, and upper respiratory symptoms are strong predictors for the presence of respiratory viruses [21]. In addition, the annual incidence of admissions per adult CF patient associated with viral infection was 4.9% [22]. Vaccination is therefore recommended to CF patients. Moreover it has been showed to play a role in preventing flu subsequent acquisition. However, at the time of manuscript writing, no European or French
data on flu vaccination coverage in CF patients have been published. The present study is, to our knowledge, the first carried out in France. Overall, 79.9% of the patients followed in the 12 CRCMs of the Greater South region of France were vaccinated against flu during the winter of 2005/2006. The coverage rate of flu vaccination was relatively stable with just a slight increase over the four years before this season (from 74.8% to 77.9% from the 2001/2002 to the 2004/2005 season, respectively). Thus, since five years, flu vaccination coverage rate met the national objective of the French Public Health Law Plan for patients at high-risk (i.e., at least 75% by 2008) [3]. The vaccination coverage rate reported in this study (79.9% in all CF patients and 80.6% in patients with CF recognized as an underlying chronic disease by the French Health Authorities) was higher than that reported in other French studies in patients with any disease recognized as an underlying chronic disease by the French Health Authorities [23,24]. For the 2004/2005 flu season, a French postal survey of 6,000 people over 15 years of age found a flu vaccination coverage rate of 52% in patients with the underlying chronic diseases officially recognized [23]. For the 2003/2004 flu season, in French high-risk children (i.e., with officially recognized underlying chronic disease) living in Paris and Paris area, Weil-Olivier et al. reported a 43.7% flu vaccination coverage rate [24]. A flu vaccination coverage rate higher for CF patients than for other at-risk populations was also observed by Marshall et al. [25] for the 1997/1998 flu season in US patients followed in one CF Care Center (the coverage was 76.4%). Such high scores in CF patients can be explained by the fact that the management of such a complex disease takes place in specialist centers (CRCMs). In the last mentioned study [25], during the 1997/1998 flu season, the vaccination rate was higher in children than in adults: 79.4% in patients <18 years of age versus 70.1% in patients ≥18 years of age (Chi2 , p = 0.084). The results from our study (85.6% of patients <18 years of age versus 69.4% of patients ≥18 years of age vaccinated against flu virus, p < 0.05) confirmed the higher flu vaccination coverage rate in children than in adults. Zindani et al. suggest that parental supervision plays a major role in adherence to medical management in CF patients [26]. CF patients who were transplanted and/or on a transplantation waiting list were usually adults (85.7% of the patients were ≥18 years of age; mean age was 27.7 years). According to the data
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from the International Society for Heart and Lung Transplantation (ISHLT) 17,2% of European patients transplanted from January 2006 to January 2007 were suffering from CF and nearly all transplanted European patients were adults (only 2.1% of European patients with a lung transplantation were <18 years of age) [27]. In the present study, the flu vaccination rate of CF patients transplanted and/or on a transplantation waiting list was lower (44.4%) than in the CF population as a whole (79.9%) and in adult patients (69.4%). In addition, “lung transplanted or included on a transplantation waiting list” was the reason for non-vaccination given by 15 patients (11 transplanted patients and 4 patients on a transplantation waiting list). The efficacy in term of immune response (lower antibody response) of any inactivated vaccine, including flu vaccine, may be questionable in immunocompromised patients [28]. Moreover some physicians may be afraid of a possible negative interaction between vaccination and immunosuppression leading to a risk of rejection of the transplant. Indeed attention was called to possible general stimulation of the immune response by flu vaccination in kidney-transplant patients in 1972 by Briggs et al. [29]. Nevertheless, Ballout et al. [30] showed no clear evidence that flu vaccination is likely to provoke rejection. In France, as in all European countries, inactivated flu vaccines are the only available and recommended vaccines in transplant patients [15]. The present study confirms the major role of the GP in flu primary prophylaxis: 67.9% of vaccinated CF patients were vaccinated by their GP. As, in addition, “lack of time” (cited by 24.7% of the nonvaccinated patients who answered the corresponding item) was one of the most frequently reported reasons for non-vaccination, time-saving processes must be developed to increase CF patients’ vaccination. In the US, for example, the vaccination rate is improved by GPs keeping vaccine in their office and thus being able to vaccinate the patient during consultation, which is time-saving for both GPs and patients (and their family). In France, GPs do not have any vaccines (and in particular no flu vaccines) to hand; patients have to first go to the pharmacy to obtain their flu vaccine with either a prescription or a free voucher and then consult for administration. Vaccination rate in this population could also be improved by storing flu vaccine in all CRCMs and offering vaccination to CF patients during any visits or hospitalizations during the fourth term of the year. Due to the relatively short flu vaccination period and the number of CF patients (about 4500 CF patients were followed at 49 centers), not all CF patients could be vaccinated at their CRCM. Vaccination rate could also be improved with other strategies: increased communication with posters and leaflets in the office, open access (walk-in clinics or same day appointments) and reminder phone calls to patients. A recent study by Britto et al. has proved that these strategies were effective [31]. In France, CF is one of the chronic diseases whose followup, treatments and vaccination program including flu vaccine are free of charge after recognition by the French Health Authorities [20]. In addition, the National Public Health Insurance provides an annual voucher for free flu vaccination for some of these underlying chronic diseases, including CF. In this study, although 98.0% of CF patients had had their CF recognized as an underlying chronic disease, only 78.1% said that they had received their voucher for the 2005/2006 season. As voucher provision significantly improved vaccination rates (85.7% versus 64.2% for patients with and without the flu vaccine voucher, respectively), the reasons leading to non-provision of free vouchers need to be analyzed in order to improve vaccination rates: forgetting, loss of the free voucher by the patients, undeclared change of patient’s address, failure to update the database by the National Public Health Insurance, etc.) The limit of the present study concerns the relevance of the generalization of our results to the whole CF French population. No information was collected on patients not included in the study.
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However, physicians had to include all the patients seen consecutively during the inclusion period at the CRCM strictly on the basis of the inclusion criteria only. Thus, this sample of 518 patients can be supposed to be representative of the 1200 patients followed at the 12 CRCMs of the Greater South Region of France (i.e., a quarter of French centers). Although the vaccination practices might not differ according to the geographic location of the centers, the extrapolation of our results to the whole French centers should be done with caution. Moreover, the extrapolation to patients, who, despite the national recommendation, are not yet followed in CRCMs, would require further investigations within this specific population. In conclusion, flu vaccination coverage rate in CF patients followed in the 12 CRCMs in the Greater South Region of France (Muco-Sud and Muco-Med networks) during the 2005/2006 season was 79.9%. This flu vaccination coverage rate met the National Health objective of at least 75% by 2008 [3] and was higher than the rates usually reported in high-risk populations in France (between 43.7% and 52%) [23,24]. There is, however, room for improvement in adults and transplanted patients. Provision of vouchers for free flu vaccination seems to have played a major role in improving vaccination coverage. Acknowledgments This study was supported by Sanofi Pasteur MSD. The authors thank the members of “Avancées Vaccinales” (a French Expert Group in Clinical and Epidemiological Research), and in particular Professor Catherine Weil-Olivier for her informed advice and precious help. Also they thank the staff of the CRCMs of Bordeaux, Brive, Clermont-Ferrand, Giens, Limoges, Marseille, Montpellier, Nice and Toulouse who participated in the study, Yann Bourhis and Remi Gauchoux (Mapi-Naxis) for the data analysis, and Fabienne Péretz (independent medical writer) for their help in preparing this article. References [1] World Health Organization. Influenza vaccines. Wkly Epidemiol Rec 2005;80:279–87. [2] Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports. July 13, 2007/56(RR-6);1–31. Available at: http://www.cdc.gov/ mmwr/preview/mmwrhtml/rr5606a1.htm. Accessed 31 March 2008. [3] Loi relative à la politique de santé publique. Loi n(2004-806 du 9 août 2004. Available at: http://www.legifrance.gouv.fr Accessed 31 March 2008. [4] Flume PA, O’Sullivan BP, Robinson KA, Goss CH, Mogayzel Jr PJ, Willey-Courand DB. Cystic fibrosis pulmonary guidelines chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007;176:957–69. [5] Davies JC, Alton E, Bush A. Cystic fibrosis. Br Med J 2007;335:1255–9. [6] Conway SP, Simmonds EJ, Littlewood JM. Acute severe deterioration in cystic fibrosis associated with influenza A virus infection. Thorax 1992;47:112–4. [7] Ferson MJ, Morton JR, Robertson PW. Impact of influenza on morbidity in children with cystic fibrosis. J Paediatr Child Health 1991;27:308–11. [8] Pribble CG, Black PG, Bosso JA, Turner RB. Clinical manifestations of exacerbations of cystic fibrosis associated with nonbacterial infections. J Pediatr 1990;117:200–4. [9] Wat D, Gelder C, Hibbitts S, Bowler I, Pierrepoint M, Evans R. Is there a role for influenza vaccination in cystic fibrosis? J Cyst Fibros 2008;7:85–8. [10] Ong EL, Bilton D, Abbott J, Webb AK, McCartney RA, Caul EO. Influenza vaccination in adults with cystic fibrosis. BMJ 1991;303:557. [11] Gruber WC, Campbell PW, Thompson JM, Reed GW, Roberts B, Wright PF. Comparison of live attenuated and inactivated influenza vaccines in cystic fibrosis patients and their families: results of a 3-year study. J Infect Dis 1994;169:241–7. [12] Dharmaraj P, Tan A, Smyth R. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database Systematic Reviews 2007, Issue 4. doi:10.1002/14651858. CD001753 Available at: http://www.mrw.interscience. wiley.com/cochrane/clsysrev/articles/CD001753/frame.html. Accessed 31 March 2008. [13] Gross PA, Denning CR, Gaerlan PF, Bonelli J, Bernius M, Dran S. Annual influenza vaccination: immune response in patients over 10 years. Vaccine 1996;14:1280–4.
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[14] Malfroot A, Adam G, Cliofu O, Doring G, Knoop C, Lang AB. for the European Cystic Fibrosis Society (ECFS) vaccination group. Immunisation in the current management of cystic fibrosis patient. J Cyst Fibros 2005;4: 77–87. [15] Calendrier vaccinal 2007–Avis du Haut Conseil de la Santé Publique. BEH 2007; 31–32:269–88. [16] Calendrier vaccinal. BEH 1986; 52:206–7. [17] Calendrier vaccinal 2000. Avis du Conseil Supérieur d’Hygiène Publique de France BEH 2000; 27:115–7. [18] Vaincre la mucoviscidose. La mucoviscidose. Etre muco. Les patients atteints de mucoviscidose en France (French). Available at: http://www. vaincrelamuco.org/ewb pages/e/etre-muco.php. Accessed 31 March 2008. [19] Circulaire DHOS/O 1/DGS/SD 5 n◦ 2001-502 du 22 octobre 2001 relative à l’organisation des soins pour la prise en charge des patients atteints de mucoviscidose. NOR: MESH0130696C. Available at: http://www. sante.gouv.fr/adm/dagpb/bo/2001/01-50/a0503306.htm Accessed 31 March 2008. [20] Sécurité sociale. L’assurance maladie. Qu’est-ce qu’une ALD. Available at: http://www.ameli.fr/assures/droits-et-demarches/par-situation-medicale/encas-d-affection-de-longue-duree/qu-8217-est-ce-qu-8217-une-a.l.d.php Accessed 31 March 2008. [21] Wat D, Gelder C, Hibbitts S, Cafferty F, Bowler I, Pierrepoint M, Evans R, Doull I. The role of respiratory viruses in cystic fibrosis. J Cyst Fibros. 2008 Feb 4. [Epub ahead of print]. [22] Clifton IJ, Kastelik JA, Peckham DG, Hale A, Denton M, Etherington C. Ten years of viral and non-bacterial serology in adults with cystic fibrosis. Epidemiol Infect 2008;136:128–34.
[23] TNS Sofres Santé. Bilan de la vaccination anti-grippale hiver 2004–2005. Press conference of September 19, 2005. 68 BG 16—Mars 2005. pp. 62. [24] Weil-Olivier C, Angoulvant F, Chevallier B, De Montalembert M, Gaudelus J, Quinet B. [Influenza vaccine coverage rate in children with underlying chronic disorders in 7 French pediatric wards] (in French). Arch Pediatr 2006;13:1287–93. [25] Marshall BC, Henshaw C, Evans DA, Bleyl K, Alder S, Liou TG. Influenza vaccination coverage level at a cystic fibrosis center. Pediatrics 2002;109:1–4. [26] Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health 2006;38:13–7. [27] International Society for Heart and Lung Transplantation (ISHLT) Transplant Registry Quarterly Reports for Lung in Europe. Characteristics for Transplants performed between January 1, 2006 and June 30, 2007. Available at: http://www.ishlt.org/registries/quarterlyDataReportResults.asp?organ=LU &rptType=tx demo&continent=3 Accessed 31 March 2008. [28] Soesman NM, Rimmelzwaan GF, Nieuwkoop NJ, Beyer WE, Tilanus HW, Kemmeren MH. Efficacy of influenza vaccination in adult liver transplant recipients. J Med Virol 2000;61:85–93. [29] Briggs JD, Timbury MC, Paton AM, Bell PRF. Viral infection and renal transplant rejection. Br Med J 1972;4:520–2. [30] Ballout A, Goffin E, Yombi JC, Vandercam B. Vaccinations for adult solid organ transplant recipient: current recommendations. Transplant Proc 2005;37:2826–7. [31] Britto MT, Schoettker J, Pandzik GM, Weiland J, Mandel KE. Improving influenza immunization for high-risk children and adolescents. Qual Saf Health Care 2007;16:363–8.
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Influenza vaccination coverage in patients with cystic fibrosis followed at 12 care centers in the Greater South Region of France for the season 2005/2006 Marlène Murris-Espin a,∗,1,2 , Marie Aubert b,1,2 , Emmanuelle Bosdure c,1,2 , Jean-Christophe Dubus c,1,2 a b c
Cystic Fibrosis Care Center for Adults, Pulmonology Department, Larrey Teaching Hospital, Toulouse, 25 Chemin de Pouvourville, TSA 30030, 31059 Toulouse Cedex 9, France Sanofi Pasteur MSD, Lyon, France Pediatric Cystic Fibrosis Care Center, Infantile Medicine Department, Timone-Enfants Teaching Hospital, Marseille, France
a r t i c l e
i n f o
Article history: Received 9 May 2008 Received in revised form 24 July 2008 Accepted 28 July 2008 Available online 20 August 2008 Keywords: Cystic fibrosis Influenza Vaccination
a b s t r a c t The objective of this observational study was to estimate influenza vaccination coverage for the 2005/2006 season in cystic fibrosis (CF) patients consulting at or hospitalized in 12 CF care centers. Data from 518 CF patients >6 months of age (children: 64.9%) were analyzed: 79.9% were vaccinated. The vaccination coverage was 85.6% in children, 69.4% in adults and 44.4% in transplanted patients. General practitioners vaccinated 67.9% of the patients. “Lack of time” reason was reported by 24.7% non-vaccinated patients. In France, influenza vaccination coverage in CF patients meets the National Health objective (≥75% by 2008), but could be improved in adults and transplanted patients. © 2008 Elsevier Ltd. All rights reserved.
1. Introduction Influenza (flu) is known for its serious consequences in the elderly and those with underlying chronic disease (i.e., chronic heart or lung disease, metabolic or renal disease, or immunodeficiency) [1]. Flu vaccines are safe and effective, and annual
Abbreviations: CF, cystic fibrosis; CI, confidence interval; CRCM, National CF Care Centers (Centres de Ressources et de Compétence de la Mucoviscidose); Flu, influenza; GP, general practitioner; HCP, health care professionals. ∗ Corresponding author. Tel.: +33 567771851; fax: +33 567771475. E-mail address: [email protected] (M. Murris-Espin). 1 The investigators from the French Muco-Sud and Muco-Med networks: Drs Boisserie-Lacroix Vincent, Bui Stéphanie, Ceccato Franc¸oise, Domblides Philippe, Dromer Claire and Fayon Michael from the Adult and Pediatric Cystic Fibrosis Care Centers of Bordeaux; Drs Gautry Philippe and Caporal Pierre from the Mixed Cystic Fibrosis Care Center of Brive; Drs Labbé André, Philippe Pierre, Hager Marie-Odile, Heraud Marie-Christine, and Petit Isabelle from the Mixed Cystic Fibrosis Care Center of Clermont-Ferrand; Drs de Lumbley Lionel, Melloni Boris, Languepin Jeanne, and Menetrey Céline from the Mixed Cystic Fibrosis Care Center of Limoges; Drs Didier Alain, Brémont Franc¸ois, Le Tallec Claire, Rittié Jean-Luc, and Têtu Laurent from the Adult and Pediatric Cystic Fibrosis Care Centers of Toulouse; Drs Mely Laurent and Jubin Virginie from the Mixed Cystic Fibrosis Care Center of Giens; Drs Reynaud-Gaubert Martine, Sarles Jacques, Boniface Stéphanie, and Stremler-Lebel Nathalie from the Adult and Pediatric Cystic Fibrosis Care Centers of Marseille; Drs Chiron Raphaël, Counil Franc¸ois, and Fournier Favre Sébastien from the Mixed Cystic Fibrosis Care Center of Montpellier; and Drs Albertini Marc and Moreau Ludovic from the Pediatric Cystic Fibrosis Care Center of Nice. 2 On behalf of the French Muco-Sud and Muco-Med networks. 0264-410X/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2008.07.095
vaccination of high-risk persons ahead of the flu season is currently the most effective measure for reducing the impact of this disease [2]. The World Health Organization (WHO) recommends annual vaccination of high-risk patients [1]. This recommendation is currently followed by nearly all European countries. In France, one National Health objective for the year 2008 is to achieve at least 75% flu vaccination coverage rate in at-risk populations [3]. Cystic fibrosis (CF) is the commonest genetically inherited disease in white populations (1 in 2500 newborns). Progress in the understanding of the disease and the impact of this on management has been rapid over the past 20 years. The predicted median survival for babies born in the 21st century is now more than 50 years. CF is an autosomal recessive disease, caused by mutations in the CFTR (Cystic Fibrosis Transmembrane conductance Regulator) gene. The commonest mutation (about 70% of CF patients) is the deletion of phenylalanine at codon 508 (known as F508). However, moreover 1600 mutations of the CFTR gene with varying effects on CFTR function and resulting in different CF phenotypes (mild or severe) have been described. The CFTR protein is expressed in many cells and has several functions. The primary function of the CFTR protein is as an ion channel that regulates liquid volume on epithelial surfaces through chloride secretion and inhibition of sodium absorption. CF is a complex multi-system disease affecting upper and lower airways, pancreas, bowel, liver, and reproductive tracts. Lung destruction is caused by airways obstruction due to dehydrated, thickened secretions, resultant endobronchial infection, and exaggerated inflammatory response leading to development
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of bronchiectasis and progressive obstructive chronic airways disease. Lung disease occurs in children and adults, and accounts for nearly 85% of the mortality. The management of such a complex disease takes place in specialist centers [4,5]. Children and adults with CF are at increased risk of pulmonary complications if they contract flu, especially if they receive immunosuppressive treatment for lung and/or liver transplants [6–8]. Flu viruses cause disease progression and lung function worsening, predispose to bacterial infections and increase hospitalization rates [9,10]. Flu vaccination elicits an antibody response in CF patients that is expected to achieve a clinical protection against flu disease [10–12]. This response is maintained with repeated annual vaccination [10,13]. Flu vaccination has been shown to offer protection from its subsequent acquisition in the CF population [9]. Annual flu vaccination is therefore recommended in all CF patients >6 months of age [14,15]. In France, annual flu vaccination is recommended in patients with chronic lung disease since 1986 [16], including specifically CF patients since the year 2000 [17]. In France, there are approximately 6000 CF patients of whom 180 are transplanted each year [18]. In 2004, there were 4533 CF patients (38.4% of adults) followed at one of the 49 approved National CF Care Centers (Centres de Ressources et de Compétence de la Mucoviscidose, CRCMs) [18]. These CRCMs are hospitalbased and organized in networks. Their health objectives are to improve the management, life expectancy and quality of life of CF patients. They bring together medical and paramedical Health Care Professionals (HCPs): e.g., doctors, nurses, physiotherapists, dieticians, psychologists and social workers. The HCP teams coordinate the care both given at home and in hospital. The CRCMs are also meeting places for patients, families, and HCPs [19]. To the best of our knowledge, up to now, no specific data on flu vaccination coverage rate in CF patients are available in France. The present observational descriptive study sought thus to estimate coverage for the 2005/2006 flu season in French CF patients followed in CRCM.
2.3. Flu vaccine
2. Patients and methods
2.5. Statistical analysis
2.1. Study design
All data were analyzed by Mapi-Naxis (Lyon, France). Statistical analyses were performed on SPSS 13.0 software. A description of the population on all the variables of the questionnaire was performed. For each variable, percentages were calculated using available data (missing data ignored). The calculated value of the 2005/2006 flu vaccination coverage rate is given with its 95% confidence interval (95% CI). A statistical analysis by subgroup (age, transplantation status, reception of a free voucher) was performed for the 2005/2006 season on coverage rates, vaccinators, reasons for non-vaccination. The Chi2 test was used for comparisons of proportions; the significance threshold was set at 0.05.
This observational study was conducted from 1 March 2006 to 31 August 2006 (i.e., after the 2005/2006 flu official campaign: from September 2005 to February 2006). The study was initially proposed to the 12 CRCMs of the two networks, Muco-Sud and Muco-Med. The whole 12 CRCMs accepted to participate in the study. These 12 CRCMs represent a quarter of all the French CRCMs, and the totality of the CRCMs located in the nine biggest cities in the Greater South region of France (Fig. 1). These 12 CRCMs follow about 1200 CF patients, including approximately 60 transplant recipients. Three of these CRCMs are specifically devoted to adults, four specifically to children, and five (mixed CRCMs) follow both adult and pediatric patients. Diagnosis of CF in patients followed at CRCMs is made on clinical signs and symptoms, sweat tests results, and/or genetics. 2.2. Patients Each physician included consecutively all patients who met the following inclusion criteria: (a) suffering from CF; (b) >6 months of age at the beginning of the flu vaccination campaign (i.e., September 2005); (c) consulting at or hospitalized in the CRCM; and (d) with a vaccination card available so as to check flu vaccination status.
The vaccines for the 2005–2006 season (Northern Hemisphere) contained the following: an A/New Caledonia/20/99(H1N1)-like virus, an A/California/7/2004(H3N2)-like virus, and a B/Shanghai/ 361/2002-like virus (B/Jiangsu/10/2003 and B/Jilin20/2003). 2.4. Data collection The physician filled in an anonymous questionnaire for each included patient and checked data consistency with the vaccination card. Demographic and clinical data were first collected: birth date, gender, and transplantation status (whether or not transplanted, whether or not included on a transplantation waiting list). In addition, administrative data were collected: whether CF was recognized or not as an underlying chronic disease by the French Health Authorities, and if so, provision or not of a free voucher for flu vaccination from the National Public Health Insurance. In France patients with recognized underlying chronic diseases (from a published list defined by National Public Health Insurance) are eligible for 100% reimbursement for all medical costs (including vaccine costs) related to their illness [20]. Patients were then asked for their 2005/2006 flu season vaccination status (yes or no). If yes, patients were asked for vaccinators (i.e., HCP who had administered the vaccine): CRCM, lung specialist, general practitioner (GP), or pediatrician. If not, they were asked for the following reasons: vaccine useless as the disease is benign, vaccine considered dangerous, afraid of injection, lack of information, vaccine considered ineffective, contra-indication including allergy, or other reason (any spontaneous reported reason). Patients could give one or more than one reason for non-vaccination. For all the patients who should have been vaccinated (i.e., >6 months of age) during the 2001/2002, 2002/2003, 2003/2004, 2004/2005, and 2005/2006 flu seasons, the physician recorded vaccination dates from the vaccination card. Patients were also asked whether they were systematically vaccinated every year.
2.6. Ethical considerations As this study was an observational study without any modification of the patient’s usual medical management, it was not submitted to an ethics committee for approval, in line with current French legislation. All questionnaire data were rendered anonymous using Mapi-Naxis’s data procedure that was validated by the Commission Nationale de l’Informatique et des Libertés (French information protection commission). Before being included in the study, all patients (or parents or guardians for patients <18 years of age) were duly informed of the objectives and requirements of the study (an information sheet was
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Fig. 1. Geographic distribution of the 49 French Cystic Fibrosis (CF) Care Centers (Centres de Ressources et de Compétence de la Mucoviscidose, CRCM) and the 12 CRCMs of the Muco-Sud (double circle) and Muco-Med (single circle) networks who participated in this study (with the kind authorization from the French association Vaincre la Mucoviscidose). Pediatric: CRCM with an active file of at least 30 children (i.e., infants, children and adolescents); Adult: CRCM with an active file of at least 20 adult patients; Mixed: CRCM including children and adults.
given by the physician) and gave their oral consent. Patients (or their parents or guardians) were informed of their rights under the French information protection law. 3. Results From 1 March 2006 to 31 August 2006, data from 527 of the approximately 1200 CF patients followed at the 12 CRCMs were collected and data from 518 patients were analyzed. Data from nine
questionnaires were excluded from analysis because the patients had not received the information sheet (n = 7) or because the patients did not meet all the inclusion criteria (n = 2; one patient was <6 months of age in September 2005, and the age of one patient was missing and could not be checked). The rest of the population (approximately 700 patients) were not included in the study as they did not consult the center during the study period, did not give their consent to participate in the study, or did not comply with the inclusion criteria.
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3.1. Patients’ characteristics The mean age (mean ± standard deviation) of the analyzed population (n = 518) was 15.9 ± 12.0 years (median: 13.1; quartiles: 6.2–22.4) and 50.5% of the CF patients were female. There were more children (<18 years of age) than adults (≥18 years of age): 64.9% versus 35.1%, respectively. Most of the patients (n = 488; 98.0%) had had their CF recognized as an underlying chronic disease by the French Health Authorities, and were therefore eligible for 100% coverage for medical costs, including flu vaccination. A total of 49 (9.7%) CF patients were transplanted and/or on a transplantation waiting list (30 patients were transplanted, 17 were on a transplantation waiting list, and 2 patients had undergone transplantation but were also on a transplantation waiting list). Their mean age was 27.7 ± 9.7 years (median: 28.9; quartiles: 21.3–33.3). There were more adults than children (85.7% versus 14.3%) and 76.1% were female. For 95.8% of them, the CF was recognized as an underlying chronic disease by the French Health Authorities. 3.2. Flu vaccination 3.2.1. Flu vaccination coverage rate for 2005/2006 season Information regarding flu vaccination for the 2005/2006 season was available for 493 of the 518 CF patients (95.2%); 394 had been vaccinated for the 2005/2006 season. The flu vaccination coverage rate for the 2005/2006 season was estimated as 79.9% (95% CI: 76.3%–83.5%). 3.2.2. Frequency of flu vaccination for the previous seasons Of the 518 CF patients, 429, 451, 465, and 484 patients were >6 months of age during the 2001/2002, 2002/2003, 2003/2004, and 2004/2005 flu season, respectively. According to the vaccination card data, at least 74.8% of the CF patients had been vaccinated for the 2001/2002 season, 77.4% for the 2002/2003 season, 76.3% for the 2003/2004 season, and 77.9% for the 2004/2005 season. 75.9% of the 493 CF patients, for whom data were available, were systematically vaccinated each year. Regarding patients over 5 years of age in September 2005 (n = 429), 67.1% were systematically vacci-
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nated each year, 4.1% were vaccinated four times, 1.6% three times, 2.8% twice, and 6.3% once. 3.2.3. Change in flu vaccination coverage rate for the 2005/2006 season according to patient characteristics Among the 320 children (<18 years of age) and 173 adults (≥18 years of age), 274 and 120 respectively were vaccinated for the 2005/2006 season. The flu vaccination coverage rate for the 2005/2006 season was significantly greater in children than in adults: 85.6% (95% CI: 82.6%–90.4%) versus 69.4% (95% CI: 63.3%–77.1%); Chi2 test, p < 0.05 (Fig. 2). Flu vaccination coverage ranged between 88.1% and 80.0% in children: 87.4% (95% CI: 78.9%–93.3%), 80.0% (95% CI: 70.2%–87.7%), and 88.1% (95% CI: 82.6%–93.6%) in the under 5, 5–10, 10–18 age group, respectively. It ranged between 78.8% and 62.5% in adults: 78.8% (95% CI: 66.9%–87.9%), 62.5% (95% CI: 49.5%–74.3%), and 65.1% (95% CI: 49.0%–79.0%) in the 18–25, 25–35, and over 35 age group, respectively. Information regarding flu vaccination during the 2005/2006 season was available for 45 of the 49 CF patients transplanted and/or on a transplantation waiting list. Among these 45 CF patients, 20 had been vaccinated for the 2005/2006 season; flu vaccination coverage rate for the 2005/2006 season was 44.4% (95% CI: 29.6%–60.0%) (Fig. 2). 3.3. Vaccinators and reasons for non-vaccination The vaccinator was known for 346 of the 394 CF patients vaccinated during the 2005/2006 season. 235 of these 346 patients (67.9%) had been vaccinated by their GP, 54 (15.6%) by a nonhospital-based pediatrician, 50 (14.5%) at a CRCM, and 7 (2.0%) by a lung specialist. CF children (n = 243) were mainly vaccinated by a GP (66.7%) or a non-hospital-based pediatrician (21.8%) while CF adults (n = 103) were mainly vaccinated by their GP (70.9%) or at the CRCM (23.3%). Patients who were transplanted and/or on a transplantation waiting list were mainly vaccinated by their GP (72.2%) or at the CRCM (22.2%). In all, 97 of the 99 CF patients not vaccinated for the 2005/2006 season (or their parents or guardians) gave one or more
Fig. 2. Changes in vaccination coverage rate in French Cystic Fibrosis (CF) patients according to age, transplantation status, and provision of voucher for free vaccination*for the 2005/2006 influenza season. *A voucher for free influenza vaccination is provided by the National Public Health Insurance only to patients with CF recognized as an underlying chronic disease by the French Health Authorities.
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Fig. 3. Reasons for non-vaccination given by 97 of the 99 patients with cystic fibrosis who had not been vaccinated against influenza virus for the 2005/2006 influenza season. (Percentages were calculated using the number of patients with available data, n = 97. Each patient could give more than one reason for non-vaccination.)
than one reason for non-vaccination. A total of 109 reasons for non-vaccination were reported: 61 reasons identified in the questionnaire and 48 spontaneously reported reasons (Fig. 3). “Lack of time” (n = 24, 24.7%) was the most frequently reported identified reason for non-vaccination. “Lung-transplanted” (n = 11) or “included on a transplantation waiting list” (n = 4) was the most frequently reported spontaneously reported reason (n = 15, 31.2%). 3.4. Flu vaccination coverage in CF patients who received a voucher for free of charge flu vaccination Information regarding flu vaccination during the 2005/2006 season was available for 465 of the 488 patients with CF recognized as an underlying chronic disease by the French Health Authorities; 375 had been vaccinated. The flu vaccination coverage rate for the 2005/2006 season in these CF patients was thus 80.6%. Information regarding voucher provision for free flu vaccination during the 2005/2006 season was available for 461 patients with CF officially recognized as an underlying chronic disease. Most of them (78.1%, n = 360) declared having received the free voucher. Free voucher provision increased flu vaccination coverage rate from 64.2% to 85.7% (Chi2 test, p < 0.05) in patients with CF recognized as an underlying chronic disease (Fig. 2). It statistically significantly increased flu vaccination coverage in both children (Chi2 test, p < 0.01) and adults (p < 0.05): 91.4% (95% CI: 87.7%–95.1%) of the children with a free voucher versus 69.2% (95% CI: 56.5%–80.1%) without free voucher were vaccinated, and 75.6% (95% CI: 68.1%–83.1%) of the adults with a free voucher versus 53.3% (95% CI: 34.3%–71.7%) without free voucher were vaccinated for the 2005/2006 season. 4. Discussion In CF children, respiratory viruses, and in particular flu viruses are associated with CF exacerbations, and upper respiratory symptoms are strong predictors for the presence of respiratory viruses [21]. In addition, the annual incidence of admissions per adult CF patient associated with viral infection was 4.9% [22]. Vaccination is therefore recommended to CF patients. Moreover it has been showed to play a role in preventing flu subsequent acquisition. However, at the time of manuscript writing, no European or French
data on flu vaccination coverage in CF patients have been published. The present study is, to our knowledge, the first carried out in France. Overall, 79.9% of the patients followed in the 12 CRCMs of the Greater South region of France were vaccinated against flu during the winter of 2005/2006. The coverage rate of flu vaccination was relatively stable with just a slight increase over the four years before this season (from 74.8% to 77.9% from the 2001/2002 to the 2004/2005 season, respectively). Thus, since five years, flu vaccination coverage rate met the national objective of the French Public Health Law Plan for patients at high-risk (i.e., at least 75% by 2008) [3]. The vaccination coverage rate reported in this study (79.9% in all CF patients and 80.6% in patients with CF recognized as an underlying chronic disease by the French Health Authorities) was higher than that reported in other French studies in patients with any disease recognized as an underlying chronic disease by the French Health Authorities [23,24]. For the 2004/2005 flu season, a French postal survey of 6,000 people over 15 years of age found a flu vaccination coverage rate of 52% in patients with the underlying chronic diseases officially recognized [23]. For the 2003/2004 flu season, in French high-risk children (i.e., with officially recognized underlying chronic disease) living in Paris and Paris area, Weil-Olivier et al. reported a 43.7% flu vaccination coverage rate [24]. A flu vaccination coverage rate higher for CF patients than for other at-risk populations was also observed by Marshall et al. [25] for the 1997/1998 flu season in US patients followed in one CF Care Center (the coverage was 76.4%). Such high scores in CF patients can be explained by the fact that the management of such a complex disease takes place in specialist centers (CRCMs). In the last mentioned study [25], during the 1997/1998 flu season, the vaccination rate was higher in children than in adults: 79.4% in patients <18 years of age versus 70.1% in patients ≥18 years of age (Chi2 , p = 0.084). The results from our study (85.6% of patients <18 years of age versus 69.4% of patients ≥18 years of age vaccinated against flu virus, p < 0.05) confirmed the higher flu vaccination coverage rate in children than in adults. Zindani et al. suggest that parental supervision plays a major role in adherence to medical management in CF patients [26]. CF patients who were transplanted and/or on a transplantation waiting list were usually adults (85.7% of the patients were ≥18 years of age; mean age was 27.7 years). According to the data
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from the International Society for Heart and Lung Transplantation (ISHLT) 17,2% of European patients transplanted from January 2006 to January 2007 were suffering from CF and nearly all transplanted European patients were adults (only 2.1% of European patients with a lung transplantation were <18 years of age) [27]. In the present study, the flu vaccination rate of CF patients transplanted and/or on a transplantation waiting list was lower (44.4%) than in the CF population as a whole (79.9%) and in adult patients (69.4%). In addition, “lung transplanted or included on a transplantation waiting list” was the reason for non-vaccination given by 15 patients (11 transplanted patients and 4 patients on a transplantation waiting list). The efficacy in term of immune response (lower antibody response) of any inactivated vaccine, including flu vaccine, may be questionable in immunocompromised patients [28]. Moreover some physicians may be afraid of a possible negative interaction between vaccination and immunosuppression leading to a risk of rejection of the transplant. Indeed attention was called to possible general stimulation of the immune response by flu vaccination in kidney-transplant patients in 1972 by Briggs et al. [29]. Nevertheless, Ballout et al. [30] showed no clear evidence that flu vaccination is likely to provoke rejection. In France, as in all European countries, inactivated flu vaccines are the only available and recommended vaccines in transplant patients [15]. The present study confirms the major role of the GP in flu primary prophylaxis: 67.9% of vaccinated CF patients were vaccinated by their GP. As, in addition, “lack of time” (cited by 24.7% of the nonvaccinated patients who answered the corresponding item) was one of the most frequently reported reasons for non-vaccination, time-saving processes must be developed to increase CF patients’ vaccination. In the US, for example, the vaccination rate is improved by GPs keeping vaccine in their office and thus being able to vaccinate the patient during consultation, which is time-saving for both GPs and patients (and their family). In France, GPs do not have any vaccines (and in particular no flu vaccines) to hand; patients have to first go to the pharmacy to obtain their flu vaccine with either a prescription or a free voucher and then consult for administration. Vaccination rate in this population could also be improved by storing flu vaccine in all CRCMs and offering vaccination to CF patients during any visits or hospitalizations during the fourth term of the year. Due to the relatively short flu vaccination period and the number of CF patients (about 4500 CF patients were followed at 49 centers), not all CF patients could be vaccinated at their CRCM. Vaccination rate could also be improved with other strategies: increased communication with posters and leaflets in the office, open access (walk-in clinics or same day appointments) and reminder phone calls to patients. A recent study by Britto et al. has proved that these strategies were effective [31]. In France, CF is one of the chronic diseases whose followup, treatments and vaccination program including flu vaccine are free of charge after recognition by the French Health Authorities [20]. In addition, the National Public Health Insurance provides an annual voucher for free flu vaccination for some of these underlying chronic diseases, including CF. In this study, although 98.0% of CF patients had had their CF recognized as an underlying chronic disease, only 78.1% said that they had received their voucher for the 2005/2006 season. As voucher provision significantly improved vaccination rates (85.7% versus 64.2% for patients with and without the flu vaccine voucher, respectively), the reasons leading to non-provision of free vouchers need to be analyzed in order to improve vaccination rates: forgetting, loss of the free voucher by the patients, undeclared change of patient’s address, failure to update the database by the National Public Health Insurance, etc.) The limit of the present study concerns the relevance of the generalization of our results to the whole CF French population. No information was collected on patients not included in the study.
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However, physicians had to include all the patients seen consecutively during the inclusion period at the CRCM strictly on the basis of the inclusion criteria only. Thus, this sample of 518 patients can be supposed to be representative of the 1200 patients followed at the 12 CRCMs of the Greater South Region of France (i.e., a quarter of French centers). Although the vaccination practices might not differ according to the geographic location of the centers, the extrapolation of our results to the whole French centers should be done with caution. Moreover, the extrapolation to patients, who, despite the national recommendation, are not yet followed in CRCMs, would require further investigations within this specific population. In conclusion, flu vaccination coverage rate in CF patients followed in the 12 CRCMs in the Greater South Region of France (Muco-Sud and Muco-Med networks) during the 2005/2006 season was 79.9%. This flu vaccination coverage rate met the National Health objective of at least 75% by 2008 [3] and was higher than the rates usually reported in high-risk populations in France (between 43.7% and 52%) [23,24]. There is, however, room for improvement in adults and transplanted patients. Provision of vouchers for free flu vaccination seems to have played a major role in improving vaccination coverage. Acknowledgments This study was supported by Sanofi Pasteur MSD. The authors thank the members of “Avancées Vaccinales” (a French Expert Group in Clinical and Epidemiological Research), and in particular Professor Catherine Weil-Olivier for her informed advice and precious help. Also they thank the staff of the CRCMs of Bordeaux, Brive, Clermont-Ferrand, Giens, Limoges, Marseille, Montpellier, Nice and Toulouse who participated in the study, Yann Bourhis and Remi Gauchoux (Mapi-Naxis) for the data analysis, and Fabienne Péretz (independent medical writer) for their help in preparing this article. References [1] World Health Organization. Influenza vaccines. Wkly Epidemiol Rec 2005;80:279–87. [2] Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports. July 13, 2007/56(RR-6);1–31. Available at: http://www.cdc.gov/ mmwr/preview/mmwrhtml/rr5606a1.htm. Accessed 31 March 2008. [3] Loi relative à la politique de santé publique. Loi n(2004-806 du 9 août 2004. Available at: http://www.legifrance.gouv.fr Accessed 31 March 2008. [4] Flume PA, O’Sullivan BP, Robinson KA, Goss CH, Mogayzel Jr PJ, Willey-Courand DB. Cystic fibrosis pulmonary guidelines chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007;176:957–69. [5] Davies JC, Alton E, Bush A. Cystic fibrosis. Br Med J 2007;335:1255–9. [6] Conway SP, Simmonds EJ, Littlewood JM. Acute severe deterioration in cystic fibrosis associated with influenza A virus infection. Thorax 1992;47:112–4. [7] Ferson MJ, Morton JR, Robertson PW. Impact of influenza on morbidity in children with cystic fibrosis. J Paediatr Child Health 1991;27:308–11. [8] Pribble CG, Black PG, Bosso JA, Turner RB. Clinical manifestations of exacerbations of cystic fibrosis associated with nonbacterial infections. J Pediatr 1990;117:200–4. [9] Wat D, Gelder C, Hibbitts S, Bowler I, Pierrepoint M, Evans R. Is there a role for influenza vaccination in cystic fibrosis? J Cyst Fibros 2008;7:85–8. [10] Ong EL, Bilton D, Abbott J, Webb AK, McCartney RA, Caul EO. Influenza vaccination in adults with cystic fibrosis. BMJ 1991;303:557. [11] Gruber WC, Campbell PW, Thompson JM, Reed GW, Roberts B, Wright PF. Comparison of live attenuated and inactivated influenza vaccines in cystic fibrosis patients and their families: results of a 3-year study. J Infect Dis 1994;169:241–7. [12] Dharmaraj P, Tan A, Smyth R. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database Systematic Reviews 2007, Issue 4. doi:10.1002/14651858. CD001753 Available at: http://www.mrw.interscience. wiley.com/cochrane/clsysrev/articles/CD001753/frame.html. Accessed 31 March 2008. [13] Gross PA, Denning CR, Gaerlan PF, Bonelli J, Bernius M, Dran S. Annual influenza vaccination: immune response in patients over 10 years. Vaccine 1996;14:1280–4.
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[14] Malfroot A, Adam G, Cliofu O, Doring G, Knoop C, Lang AB. for the European Cystic Fibrosis Society (ECFS) vaccination group. Immunisation in the current management of cystic fibrosis patient. J Cyst Fibros 2005;4: 77–87. [15] Calendrier vaccinal 2007–Avis du Haut Conseil de la Santé Publique. BEH 2007; 31–32:269–88. [16] Calendrier vaccinal. BEH 1986; 52:206–7. [17] Calendrier vaccinal 2000. Avis du Conseil Supérieur d’Hygiène Publique de France BEH 2000; 27:115–7. [18] Vaincre la mucoviscidose. La mucoviscidose. Etre muco. Les patients atteints de mucoviscidose en France (French). Available at: http://www. vaincrelamuco.org/ewb pages/e/etre-muco.php. Accessed 31 March 2008. [19] Circulaire DHOS/O 1/DGS/SD 5 n◦ 2001-502 du 22 octobre 2001 relative à l’organisation des soins pour la prise en charge des patients atteints de mucoviscidose. NOR: MESH0130696C. Available at: http://www. sante.gouv.fr/adm/dagpb/bo/2001/01-50/a0503306.htm Accessed 31 March 2008. [20] Sécurité sociale. L’assurance maladie. Qu’est-ce qu’une ALD. Available at: http://www.ameli.fr/assures/droits-et-demarches/par-situation-medicale/encas-d-affection-de-longue-duree/qu-8217-est-ce-qu-8217-une-a.l.d.php Accessed 31 March 2008. [21] Wat D, Gelder C, Hibbitts S, Cafferty F, Bowler I, Pierrepoint M, Evans R, Doull I. The role of respiratory viruses in cystic fibrosis. J Cyst Fibros. 2008 Feb 4. [Epub ahead of print]. [22] Clifton IJ, Kastelik JA, Peckham DG, Hale A, Denton M, Etherington C. Ten years of viral and non-bacterial serology in adults with cystic fibrosis. Epidemiol Infect 2008;136:128–34.
[23] TNS Sofres Santé. Bilan de la vaccination anti-grippale hiver 2004–2005. Press conference of September 19, 2005. 68 BG 16—Mars 2005. pp. 62. [24] Weil-Olivier C, Angoulvant F, Chevallier B, De Montalembert M, Gaudelus J, Quinet B. [Influenza vaccine coverage rate in children with underlying chronic disorders in 7 French pediatric wards] (in French). Arch Pediatr 2006;13:1287–93. [25] Marshall BC, Henshaw C, Evans DA, Bleyl K, Alder S, Liou TG. Influenza vaccination coverage level at a cystic fibrosis center. Pediatrics 2002;109:1–4. [26] Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health 2006;38:13–7. [27] International Society for Heart and Lung Transplantation (ISHLT) Transplant Registry Quarterly Reports for Lung in Europe. Characteristics for Transplants performed between January 1, 2006 and June 30, 2007. Available at: http://www.ishlt.org/registries/quarterlyDataReportResults.asp?organ=LU &rptType=tx demo&continent=3 Accessed 31 March 2008. [28] Soesman NM, Rimmelzwaan GF, Nieuwkoop NJ, Beyer WE, Tilanus HW, Kemmeren MH. Efficacy of influenza vaccination in adult liver transplant recipients. J Med Virol 2000;61:85–93. [29] Briggs JD, Timbury MC, Paton AM, Bell PRF. Viral infection and renal transplant rejection. Br Med J 1972;4:520–2. [30] Ballout A, Goffin E, Yombi JC, Vandercam B. Vaccinations for adult solid organ transplant recipient: current recommendations. Transplant Proc 2005;37:2826–7. [31] Britto MT, Schoettker J, Pandzik GM, Weiland J, Mandel KE. Improving influenza immunization for high-risk children and adolescents. Qual Saf Health Care 2007;16:363–8.