Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

OBJECTIVES: We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). METHODS: A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. RESULTS: Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. CONCLUSIONS: The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with QLAIV on public health and economic outcomes in France.

Comparison of NITAG policies and working processes in selected developed countries.

BACKGROUND: Vaccines are specific medicines characterized by two country-specific market access processes: (1) a recommendation by National Immunization Technical Advisory Group (NITAG), and (2) a funding policy decision. OBJECTIVES: The objective of this study was to compare and analyze NITAGs of 13 developed countries by describing vaccination committees' bodies and working processes. METHODS: Information about NITAGs bodies and working processes was searched from official sources from June 2011 to November 2012. Retrieved information was completed from relevant articles identified through a systematic literature review and by information provided by direct contact with NITAGs or parent organizations. An expert panel was also conducted to discuss, validate, and provide additional input on obtained results. RESULTS: While complete information, defined as 100%, was retrieved only for the UK, at least 80% of data was retrieved for 9 countries out of the 13 selected countries. Terms of references were identified in 7 countries, and the main mission for all NITAGs was to provide advice for National immunization programs. However, these terms of references did not fully encompass all the actual missions of the NITAGs. Decision analysis frameworks were identified for 10 out of the 13, and all NITAGs considered at least four criteria for decision-making: disease burden, efficacy/effectiveness, safety and cost-effectiveness. Advices were published by most NITAGs, but few NITAGs published meeting agendas and minutes. Only the United States had open meetings. CONCLUSIONS: This study supports previous findings about the disparities in NITAGs processes which could potentially explain the disparity in access to vaccinations and immunization programs across Europe. With NITAGs recommendations being used by policy decision makers for implementation and funding of vaccine programs, guidances should be well-informed and transparent to ensure National Immunization Programs' (NIP) credibility among the public and health care professionals.

[Is the new vaccination schedule recommended in France adapted to premature babies?]. / Le nouveau calendrier vaccinal est-il adapté à l'ancien prématuré ?

The French 2013 immunization schedule having a goal of simplification with comparable efficacy, has decreased the number of injections and removed the injection performed at three months of age in the general population. Apart from the prevention of invasive pneumococcal infections for which it is recommended to maintain three dose primary immunization, vaccination of premature is not addressed in this new calendar. Can the extremely preterm infants (<33 weeks of gestational age) benefit from this new schedule or should we keep them in three injections schedule? The objective of this paper is to clarify this point through the data available in the literature. Children born prematurely and especially the "extremely premature" born before 33 weeks are at high risk of infections, some of them are preventable by immunization. Although there is no clinical evidence, for pertussis, pneumococcus, Haemophilus influenzae b, hepatitis B, whatever the immunogenicity criteria, immunogenicity is significantly lower in preterm than in term newborn after 3 doses primary schedule. This lower immunogenicity raises concerns about the transition to two doses, about the ability to give short term protection and booster responses. Given these data, GPIP takes the position for maintaining a primary 3-dose vaccination at 2.3 and 4 months for premature infants less than 33 weeks.

Ten years of experience with the pneumococcal conjugate 7-valent vaccine in children.

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30-40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7(®) routine immunization in children below 2 years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13(®), a second-generation vaccine with six new serotypes, replaced Prevenar 7(®) in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France).

[Update on vaccine research. Proceedings of the 15th annual conference on vaccine research organized by the National Foundation for Infectious Diseases]. / Actualités en matière de recherche vaccinale. Compte-rendu de la 15(e) conférence annuelle sur la recherche vaccinale organisée par la National Foundation for Infectious Diseases.

Every year, the National Foundation for Infectious Diseases brings together more than 300 participants to review progress in vaccine research and development and identify the most promising avenues of research. These conferences are among the most important scientific meetings entirely dedicated to vaccine research for both humans and animals, and provide a mix of plenary sessions with invited presentations by acknowledged international experts, parallel sessions, poster sessions, and informal exchanges between experts and young researchers. During the Fifteenth Conference that took place in Baltimore in May 2012, various topics were addressed, including the scientific basis for vaccinology; exploration of the immune response; novel vaccine design; new adjuvants; evaluation of the impact of newly introduced vaccines (such as rotavirus, HPV vaccines); vaccine safety; and immunization strategies. The new techniques of systems biology allow for a more comprehensive approach to the study of immune responses in order to identify correlates of protection and to design novel vaccines against chronic diseases such as AIDS or malaria, against which natural immunity is incomplete.

[Plea for advancement of the age of vaccination against human papillomavirus in France: Position of the Pediatric Infections Pathology Group (GPIP) and the French Association of Ambulatory Pediatrics (AFPA)]. / Plaidoyer pour un avancement de l'âge de la vaccination contre les papillomavirus en France: Position du Groupe de Pathologie Infectieuse Pédiatrique (GPIP) et de l'Association Française de Pédiatrie Ambulatoire (AFPA).

Vaccination against human papillomavirus (HPV) is recommended in France at 14 years. The Groupe de Pathologie Infectieuse Pédiatrique de la Société Française de Pédiatrie takes a clear position for advancement of age of vaccination at 11-12 years based on the following arguments: (i) data on the long-term persistence of protective antibodies are reassuring; (ii) these vaccines can be co-administered with vaccines recommended in the current immunization schedule at this age; (iii) actually, nearly 20% of adolescents have had sexual intercourse when the vaccination schedule is finished; (iv) vaccination beyond 14 years increases the risk of occurrence of coincidental autoimmune diseases; (v) the immunogenicity of vaccines against HPV is better when they are administered before age 15; (vi) finally, especially by reducing the number of injections from 3 to 2, the immunization at 11-12 years could improve immunization coverage which is insufficient nowadays.

[Rotavirus vaccination in 2012. Position of the Pediatric Infections Pathology Group (GPIP) and the French Association of Ambulatory Pediatrics (AFPA)]. / La vaccination rotavirus en 2012. Position du Groupe de Pathologie Infectieuse Pédiatrique (GPIP) et de l'Association Française de Pédiatrie Ambulatoire (AFPA).

In 2008 and 2010, the Comité technique des vaccinations and the Haut Conseil de Santé Publique have not recommended generalized vaccination against rotavirus (RV) in France. The Groupe de Pathologie Infectieuse Pédiatrique (GPIP) and the Association Française de Pédiatrie Ambulatoire (AFPA) believes that it is time to reconsider the recommendation. Indeed, on the one hand, answers were made on the presence of circovirus in vaccines and the risk of intussusception, on the other hand, these vaccines are already implemented in vaccination programs in many developing countries or countries with income intermediate and high. Finally, independent studies have demonstrated the effectiveness in countries with widespread vaccinations (without significant genotypic changes of circulating strains). In addition, implementation would have a major impact on our health care system, changes of the epidemic curve of RV infections (delayed and shortened) to prevent the coexistence of different epidemics occurring during the fall and winter. Remains medico-economic evaluation, which is not of the competence and the responsibility of GPIP and AFPA. However, it seems surprising that developing or middle-income countries have been able to generalize this vaccination and that France can't do it.

[Influenza vaccination coverage in asthmatic children in France in 2006-2007]. / Couverture vaccinale contre la grippe chez les enfants asthmatiques en France en 2006-2007.

In France, an annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Each year, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-2007 influenza vaccination coverage rate in 433 asthmatic children aged six to 17 years (mean age: 9.5 years; male: 61%) who consulted a pediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza vaccination coverage rate was 15.7% for the 2006-2007 season (13.9% for the 2005-2006 season and 10.9% for the 2004-2005 season). General practitioners vaccinated 72.1% of the children. Lack of information (42%) was the most frequently reported reason for non-vaccination. Free vouchers (received by 39.6% of the children) significantly increased the vaccination coverage rate (31% versus 5.9%; p < 0.001). In France, in 2006-2007, the influenza vaccination coverage rate in asthmatic children was far below the national public health objective to achieve for the year 2008 (at least 75%). Concerted action is needed to improve the influenza vaccination coverage rate in asthmatic children.

Low influenza vaccination coverage in asthmatic children in France in 2006-7.

In France, annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Since 1988, each year from September to December, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-7 influenza vaccination coverage rate (VCR) in 433 asthmatic children aged 6 to 17 years (mean age: 9.5 years; male: 61%) who consulted a paediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza VCR was 15.7% for the 2006-7 season (13.9% for the 2005-6 season and 10.9% for the 2004-5 season). General practitioners vaccinated 72.1% of the children. "Lack of information" (42%) was the most frequently reported reason for non-vaccination. Vouchers (received by 39.6% of the children) significantly increased the VCR (31% versus 5.9%; p<0.001). In France, in 2006-7, the influenza VCR in asthmatic children was far below the national public health objective (at least 75% for the year 2008). Concerted action is needed to improve the influenza VCR in asthmatic children.

[Coverage rate of influenza vaccine in healthcare workers in the 12 cystic fibrosis centres of the Greater South Region of France in 2005/2006]. / Couverture vaccinale vis-à-vis de la grippe des soignants des douze Centres de Ressources et de Compétences de la Mucoviscidose du Grand-Sud de la France en 2005-2006.

INTRODUCTION: In France annual influenza vaccination is recommended for healthcare workers but few data regarding coverage are available. The objective of the present study was to evaluate influenza vaccine coverage rate in healthcare workers from the 12 cystic fibrosis centres in the Greater South Region of France during the 2005/2006 'flu season. METHODS: An observational, descriptive telephone survey was performed from February to April 2006 to collect information about the vaccine status of all the healthcare workers in the 12 cystic fibrosis centres of the Muco-Sud and Muco-Med networks. RESULTS: During the 2005/2006 'flu season a 59.4% influenza vaccine coverage rate was achieved in the 128 healthcare workers. The influenza vaccine coverage rate ranged from 81.4% (physicians) to 16.7% (social workers). Vaccination was usually performed in October (42.1%) or November (39.5%) by occupational medicine officers (65.8%). The most frequently reported reason for non-vaccination was "vaccine useless as the disease is benign" (36.7%). CONCLUSIONS: The influenza vaccine coverage rate in healthcare workers from the 12 cystic fibrosis centres in the Greater South Region of France is high, but still too low in view of the risks influenza may incur for cystic fibrosis patients. It fails to meet one of the objectives of French Public Health Law (at least 75% influenza vaccine coverage rate for healthcare workers by 2008).

[Pneumococcal infection among community-acquired pneumonia. A retrospective study of 230 hospitalized children]. / Pneumonies aiguës communautaires: place des pneumonies à pneumocoque. Enquête rétrospective dans un service de pédiatrie d'Ile-de-France.

OBJECTIVES: To find arguments in favour of pneumococcal origin in community-acquired pneumonia. POPULATION AND METHODS: A retrospective analysis of the files of 230 children hospitalized between January 1st 1999 and June 30th 2001 for community acquired pneumonia was performed. The files were classified into 3 subgroups: I (N=7), confirmed (positive blood culture); II (N=134), probable (biological arguments); III (N=89), possible pneumococcal infection. Age of the children was also taken into consideration. RESULTS: All children in the subgroup I had fever>39 degrees C at admission and at least 1 of the 3 criteria (WBC> or=20.10(9)/l, neutrophils > or =10.10(9)/l, C-reactive protein level> or =60 mg/l). Dyspnea was more frequently asthmatiform in the subgroup III. Chest X-ray was not contributive. Before admission, 39% of the children were given one or several antibiotics, and so some of patients belonging to the subgroups II and III could have been infected by pneumococcus without possibility to confirm that. CONCLUSION: Results of this analysis suggest that some criteria may be useful for selecting initial antibiotherapy even though systematic early specific antipneumococcal immunization should reduce the frequency of this infection.

Influenza vaccination: the paediatric perspective.

Influenza in young children represents a significant problem to families and to society, as this population is most susceptible to developing complications and is also a major route of disease spread within communities. However, there is a paucity of European data for the burden of disease in children and the health benefits and cost-effectiveness of vaccination, leading to a lack of awareness by governments, authorities, healthcare professionals and parents. The experience in elderly individuals and the paediatric experience in the US may provide some guidance in developing studies that will provide evidence for the creation of guidelines and educational strategies within Europe.

[Influenza vaccination coverage rate in children with underlying chronic disorders in 7 French pediatric wards]. / Couverture vaccinale vis-à-vis de la grippe chez les enfants de la région parisienne atteints d'une affection de longue durée.

UNLABELLED: In France, annual influenza vaccination is recommended and free of charge for children with chronic disease (chronic lung, heart or kidney disease, diabetes, haemoglobinopathy, immune deficiency). The national goal is to reach 75% influenza vaccination coverage by 2008, but data on coverage in high risk children are limited. OBJECTIVES: To estimate the influenza vaccination coverage in children with an underlying chronic health condition in the Paris region, during in- or out-patient visit at hospital. METHODS: A multicentre cross-sectional descriptive study was carried out over 2 months before the 2004-2005 flu vaccination campaign in 7 French paediatric hospitals (Paris region). Inclusion criteria for this survey were: children aged 6 months to 18 years, with an underlying chronic disease requiring annual influenza vaccination, with a vaccination card available, so as to check their vaccination status. Reasons for non vaccination were recorded. RESULTS: Data from 239 children were analysed. 56% of patients were males (mean age: 8.1 years). Two patients had 2 separate underlying chronic disorders; 69% had a haemoglobinopathy, 16.3% had a chronic respiratory disease, and 7.5% had diabetes. The influenza vaccination rate for 2003-2004 was 43.7% (haemoglobinopathy: 55.5%; chronic respiratory diseases: 12.8%). This rate increased from 20.4% to 43.7% between 1999 and 2003. Less than 16% of parents remembered having received a voucher for free vaccination from the National Health Insurance Agency. CONCLUSION: Efforts are still needed to achieve the 2008 objectives of 75% coverage.