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RSV is an almost obligatory virus responsible for upper (rhinitis and otitis) and lower (bronchiolitis and asthma attack) respiratory infections in children under 5 years of age. Reinfections are frequent at all ages because immunity is only partial and does not last long. Young children under the age of 1 are the most affected. The majority of these children are healthy. Having a risk factor (premature birth, heart disease, bronchopulmonary dysplasia, but also passive smoking) increases the severity of RSV pathology. Very few children currently benefit from prevention by anti-RSV monoclonal antibodies. The annual cost of care, the various socio-economic costs are a public health reality in three care sectors: out-patient, pediatric emergencies, hospitalization. Subsequent consequences: repeated wheezing and asthma, should also be taken into consideration and integrated into public health decisions. Progress in recognizing this pathology is desirable: distribution of diagnostic tests in the city; providing parents with information.Le VRS est un virus quasi obligatoire responsable d’infections respiratoires hautes (rhinite et otite) et basses (bronchiolite et crise d’asthme) chez l’enfant de moins de 5 ans. Les réinfections sont fréquentes du fait d’une immunité partielle, peu durable, à tous les âges de la vie. Les jeunes enfants de moins de 1 an sont les plus touchés. La majorité de ces enfants sont bien portants. Avoir un facteur de risque (prématurité, cardiopathie, dysplasie bronchopulmonaire mais aussi tabagisme passif) majore la sévérité de la pathologie à VRS. Très peu d’enfants bénéficient actuellement d’une prévention par les anticorps monoclonaux anti-VRS. La charge annuelle en soins, les coûts socioéconomiques variés constituent une réalité de santé publique portant sur les trois secteurs de soins : ambulatoire, urgences pédiatriques, hospitalisation.Les conséquences ultérieures : répétition de wheezing, asthme, devraient aussi être pris en considération et intégrés dans les décisions de santé publique.Des progrès dans la reconnaissance de cette pathologie sont souhaitables : diffusion des tests diagnostiques en ville ; information aux parents.

Online ahead of print; International audience; The highly contagious respiratory syncytial virus (RSV) is responsible for up to approximately 50,000 hospitalisations during each RSV season in children aged under 5 years in France, with the burden greatest in infants younger than 1 year who were born at term. There is a need for a strategy to universally protect young children from RSV infection, and thereby reduce the pressure that RSV places every year on RSV-infected children, their parents, and French healthcare systems. Potential strategies currently undergoing clinical investigation include passive immunisation via maternal vaccination or administration of long-acting monoclonal antibodies at or soon after birth, followed by vaccination later in infancy or childhood. An ongoing partnership and collaboration between parents, public health authorities, and frontline primary healthcare will need to be reinforced once these new RSV prevention strategies are available, to facilitate their use and ensure that all children receive adequate protection from the start of their first RSV season.

Introduction Invasive meningococcal disease (IMD) is an uncommon but serious infectious disease. Its economic burden is known to be high but is poorly characterised. The objective of this study was to determine costs, as captured in the healthcare claims database, incurred by all patients hospitalised for IMD in France over a 6-year period. Methods This case–control study was performed using the French national public health insurance database (SNDS). Cases comprised all individuals hospitalised with acute IMD in France between 2012 and 2017 inclusive. For each case, three controls were identified, matched for age, gender and region of residence. All healthcare resource consumption by cases and controls during the follow-up period was documented. Costs were analysed for the index hospitalisation in cases, 1 year following the index date and then for 5 years following the index date. Costs were assigned from national tariffs. The analysis was performed from a societal perspective. IMD sequelae were identified from hospital discharge summaries. Results A total of 3532 cases and 10,590 controls were evaluated. The mean per capita cost of the index IMD hospitalisation was €11,256, and increased with age and with the presence of sequelae. In the year following the index date, mean per capita direct medical costs were €6564 in cases and €2890 in controls. Annual costs were €4254 in cases without sequelae, €10,799 in cases with one sequela and €20,096 in cases with more than one sequela. In the fifth year of follow-up, mean per capita costs were €2646 in cases and €1478 in controls. The excess cost in cases was principally due to the management of sequelae. Amputation, skin scarring and mental retardation generated per capita costs in excess of €20,000 in the first year and in excess of €10,000 for subsequent years. Conclusion The economic burden of IMD in France is high and, over the long-term, is driven by sequelae management. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00468-w.

Respiratory syncytial virus (RSV) infects nearly all infants at least once by their second birthday (1). It spreads through coughs, sneezes, or close physical contact (2). RSV infections are associated with morbidity and mortality, ranging from mild upper respiratory illness to life threatening lower respiratory tract infections (LRTIs). More than 97% of RSV-attributable deaths occur in low- and middle-income countries (LMICs) (3), reflecting that healthcare infrastructure and resources in these countries is limited and may present issues in dealing with RSV disease burden.

Vaccination of at-risk populations against Neisseria meningitidis is an important strategy to prevent invasive meningococcal disease (IMD). The objective of this study was to characterize preexisting risk factors in patients with IMD and to compare their relative importance. This case-control analysis was performed in the French national public health insurance database (SNDS). Cases consisted of all people hospitalized for IMD in France over a six-year period (2012–2017). Controls were matched by age, gender, and district of residence. Medical risk factors were identified from ICD-10 codes in the SNDS. Socioeconomic risk factors studied were low household income and social deprivation of the municipality of residence. Associations of these risk factors with hospitalization for IMD were quantified as odds ratios (ORs) between cases and controls with their 95% confidence intervals (95%CI). The medical risk factors showing the most robust associations were congenital immunodeficiency (OR: 39.1 [95%CI: 5.1–299], acquired immunodeficiency (10.3 [4.5–24.0]) and asplenia/hyposplenia (6.7 [3.7–14.7]). In addition, certain chronic medical conditions, such as autoimmune disorders (5.4 [2.5–11.8]), hemophilia (4.7 [1.8–12.2]) and severe chronic respiratory disorders (4.3 [3.1–6.2]) were also strongly associated, as was low household income (1.68 [1.49–1.80]). In conclusion, this study has documented potential risk factors associated with hospitalization for IMD in a large and comprehensive sample of individuals with IMD in France. Several of the risk factors identified may help identify groups who could benefit from targeted prevention measures (such as vaccination) in order to reduce the burden of IMD.

Worldwide, lifestyle and resource disparities among adolescents contribute to unmet health needs, which have crucial present and future public health implications for both adolescents and broader communities. Risk of infection among adolescents is amplified by biological, behavioral, and environmental factors; however, infectious diseases to which adolescents are susceptible are often preventable with vaccines. Beyond these concerns, there is a lack of knowledge regarding adolescent vaccination and disease risk among parents and adolescents, which can contribute to low vaccine uptake. Promising efforts have been made to improve adolescent vaccination by programs with motivational drivers and comprehensive communication with the public. In May 2017, a multidisciplinary group of experts met in Amsterdam, Netherlands, to discuss adolescent vaccine uptake, as part of an educational initiative called the Advancing Adolescent Health Spring Forum. This article presents consensus opinions resulting from the meeting, which pertain to the burden of vaccine-preventable diseases among adolescents, reasons for low vaccine uptake, and common characteristics of successful strategies for improving adolescent vaccination.Conclusion: There is an urgent “call to action,” particularly targeting healthcare providers and public health authorities, for the prioritization of adolescent vaccination as a necessary element of preventive healthcare in this age group. What is Known:• Despite increased risk of certain infectious diseases, adolescent vaccination uptake remains low. What is New:• Barriers to adolescent vaccine uptake include lack of information regarding vaccines and disease risk, health system inadequacies, and insufficient healthcare follow-up.• Successful efforts to improve adolescent vaccine uptake need cohesive leadership and involvement of multiple stakeholders, as well as youth-friendly messaging; healthcare providers and policymakers should prioritize adolescent vaccination and implement proven program strategies to improve adolescent health worldwide.

This review considers the pathogenesis, diagnosis, and epidemiology of invasive meningococcal disease in infants, to examine and critique meningococcal disease prevention in this population through vaccination. High rates of meningococcal disease and poor outcomes, particularly for very young infants, highlight the importance of meningococcal vaccination in early infancy. Although effective and safe meningococcal vaccines are available for use from 6 weeks of age, they are not recommended globally. Emerging real-world data from the increased incorporation of these vaccines within immunization programs inform recommendations regarding effectiveness, appropriate vaccination schedule, possible long-term safety effects, and persistence of antibody responses. Importantly, to protect infants from IMD, national vaccination recommendations should be consistent with available data regarding vaccine safety, effectiveness, and disease risk.

Invasive meningococcal disease (IMD) carries a high burden in terms of mortality, long-term complications, and cost, which can be significantly reduced by vaccination. The objectives of this case-control study were to document the care pathways of patients with IMD before, during, and after hospitalization and to assess in-hospital complications and long-term sequelae. Cases consisted of all people hospitalized for IMD in France between 2012 and 2017. Controls were matched by age, gender, and district of residence. Data were extracted from the French national public health insurance database on demographics, hospitalizations, mortality and potential sequelae of IMD. Overall, 3,532 cases and 10,590 controls were assessed and followed up for 2.8 years (median). During hospitalization, 1,577 cases (44.6%) stayed in an intensive care unit, 1,238 (35.1%) required mechanical ventilation, and 43 (1.2%) underwent amputation; 293 cases (8.3%) died in hospital and a further 163 (4.6%) died following discharge; 823 cases (25.4% of survivors) presented ≥1 sequela and 298 (9.2%) presented multiple sequelae. The most frequently documented sequelae were epilepsy (N = 205; 5.8%), anxiety (N = 196; 5.5%), and severe neurological disorders (N = 193; 5.5%). All individual sequelae were significantly more frequent (Benefits of providing optimal medical care for IMD patients.Importance of minimising the delay before hospitalization.IMD remains challenging to diagnose, and vaccination is the most efficient way to prevent the disease and its complications.

Respiratory syncytial virus (RSV)—the most common viral cause of bronchiolitis—is a significant cause of serious illness among young children between the ages of 0–5 years and is especially concerning in the first year of life. Globally, RSV is a common cause of childhood acute lower respiratory illness (ALRI) and a major cause of hospital admissions in young children and infants and represents a substantial burden for health-care systems. This burden is strongly felt as there are currently no effective preventative options that are available for all infants. However, a renaissance in RSV prevention strategies is unfolding, with several new prophylactic options such as monoclonal antibodies and maternal vaccinations that are soon to be available. A key concern is that health decision makers and systems may not be ready to take full advantage of forthcoming technological innovations. A multi-stakeholder approach is necessary to bridge data gaps to fully utilise upcoming options. Knowledge must be made available at multiple levels to ensure that parents and doctors are aware of preventative options, but also to ensure that stakeholders and policymakers are given the necessary information to best advise implementation strategies.

Conflict of Interest Statement: SE has received consultancy fees and independent research grants from GlaxoSmithKline group of companies, Sanofi-Pasteur, Merck, Vifor, and DMG. MK was member of advisory boards for GSK, Pfizer, Baxter, Novartis, Astra Zeneca, MedImmune, SPMSD, Sanofi, MSD, Jansen, and performed for these companies presentations during industry symposia. These activities were done as a service task for his employer. Personally, he did not receive any fees from companies. There was also no target agreement with his employer in this respect. MO has received an investigator initiative research grant from Merck to evaluate population perception on hexavalent vs. heptavalent vaccines in Chile. KF is on the vaccine advisory boards for Sanofi Pasteur and Seqiris and have received honoraria from AstraZeneca and Pfizer for giving talks. PP has received research funding from the National Institute for Health Research and from GlaxoSmithKline, and has received honorariums from Sanofi Pasteur and Pfizer. CR has received consultancy fees and independent research grants from GlaxoSmithKline group of companies, Sanofi-Pasteur MSD, Wyeth, Pfizer, Astra-Zeneca, and Astellas. Pertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedule was associated with a marked reduction in pertussis cases in the vaccinated cohort. However, due to the frequency of local and systemic adverse events after immunization with wPV, work on a less reactive vaccine was undertaken based on isolated B. pertussis components that induced protective immune responses with fewer local and systemic reactions. These component vaccines were termed acellular vaccines and contained one or more pertussis antigens, including pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN), and fimbrial proteins 2 (FIM2) and 3 (FIM3). Preparations containing up to five components were developed, and several efficacy trials clearly demonstrated that the aPVs were able to confer comparable short-term protection than the most effective wPVs with fewer local and systemic reactions. There has been a resurgence of pertussis observed in recent years. This paper reports the results of a Consensus Conference organized by the World Association for Infectious Disease and Immunological Disorders (WAidid) on June 22, 2018, in Perugia, Italy, with the goal of evaluating the most important reasons for the pertussis resurgence and the role of different aPVs in this resurgence.

International audience; Currently, circulating viruses responsible for annual seasonal influenza epidemics belong to two influenza A subtypes, A(H1N1) and A(H3N2), and to two antigenically distinct type B lineages, B/Yamagata and B/Victoria lineages. Like diseases due to influenza A virus, influenza B virus diseases may have severe consequences and should be prevented. Until now, in France, the vaccines used to prevent seasonal influenza were trivalent, systematically targeting viruses belonging to both A subtypes and to one or other of the B lineages. The protective efficacy of trivalent vaccines is diminished during the seasons when viruses belonging to both B lineages cocirculated or when the circulating dominant type B virus belonged to a lineage different from that targeted by the vaccine strain. By targeting viruses belonging to both B lineages, quadrivalent vaccines improve the antigenic concordance between circulating and vaccine type B strains. Three inactivated quadrivalent vaccines are authorized for marketing in France and should be available for the 2018-2019 season. It is expected that, by providing enlarged protection, these quadrivalent influenza vaccines will improve vaccine efficacy, the confidence in immunization of the public, the satisfaction of health professionals, and ultimately will help to complete immunization coverage.

Currently, circulating viruses responsible for annual seasonal influenza epidemics belong to two influenza A subtypes, A(H1N1) and A(H3N2), and to two antigenically distinct type B lineages, B/Yamagata and B/Victoria lineages. Like diseases due to influenza A virus, influenza B virus diseases may have severe consequences and should be prevented. Until now, in France, the vaccines used to prevent seasonal influenza were trivalent, systematically targeting viruses belonging to both A subtypes and to one or other of the B lineages. The protective efficacy of trivalent vaccines is diminished during the seasons when viruses belonging to both B lineages cocirculated or when the circulating dominant type B virus belonged to a lineage different from that targeted by the vaccine strain. By targeting viruses belonging to both B lineages, quadrivalent vaccines improve the antigenic concordance between circulating and vaccine type B strains. Three inactivated quadrivalent vaccines are authorized for marketing in France and should be available for the 2018-2019 season. It is expected that, by providing enlarged protection, these quadrivalent influenza vaccines will improve vaccine efficacy, the confidence in immunization of the public, the satisfaction of health professionals, and ultimately will help to complete immunization coverage.

Resume Le calendrier vaccinal 2013 repondant a un objectif de simplification a efficacite comparable, a diminue le nombre d’injections recommandees et a en particulier supprime l’injection effectuee a l’âge de trois mois en population generale. En dehors de la prevention des infections invasives a pneumocoque pour laquelle il est recommande de maintenir trois doses en primovaccination, la vaccination du premature n’est pas abordee dans ce nouveau calendrier. Les grands prematures peuvent-ils beneficier de ce nouveau calendrier ou doit-on maintenir chez eux trois injections ? L’objectif de ce travail est de preciser ce point a travers les donnees disponibles dans la litterature. Les enfants nes prematurement et surtout les « grands prematures » nes avant 33 SA sont des enfants a haut risque de contracter des infections dont certaines peuvent etre prevenues par la vaccination. Pour les valences coqueluche, pneumocoque, Hib, hepatite B quels que soient les criteres d’immunogenicite retenus, elle est nettement moins bonne chez les grands prematures que chez les nouveau-nes a terme. Bien qu’il n’y ait pas de preuve clinique, ceci fait craindre que le passage a deux doses ne permette pas d’une part, de proteger suffisamment a court terme et, d’autre part, laisse craindre une moins bonne reponse immunitaire apres le rappel a 11 mois. Compte tenu de ces donnees, le GPIP prend position pour le maintien d’une primo-vaccination a 3 doses a 2,3 et 4 mois pour les prematures de moins de 33 semaines.

Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children. As highlighted in this paper, differences exist between children and adults for PD manifestations (incidence, morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and diseases, so benefits from adult vaccination must be considered in this light. PCV13 induces an immune response in adults that is non-inferior for all serotypes common with the 23-valent plain polysaccharide vaccine that is currently recommended for adults and even superior for many serotypes. Although there is no evidence that this immune response translates to clinical efficacy in adults as seen in children, the results from a randomised trial in The Netherlands, expected in 2014, should provide the missing evidence. This evidence and efficient surveillance systems should provide the necessary data, essential for policy makers in their decisions on adult pneumococcal vaccination policies.

In 2008 and 2010, the Comite technique des vaccinations and the Haut Conseil de Sante Publique have not recommended generalized vaccination against rotavirus (RV) in France. The Groupe de Pathologie Infectieuse Pediatrique (GPIP) and the Association Francaise de Pediatrie 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.

Key points The Committee for the Prevention and Control of Influenza (Comite de lutte contre la Grippe - CLCG) is an advisory committee to the French Health Minister for a medical and scientific collective expertise on the measures to be implemented to control or to reduce the impact of an epidemic or a pandemic of influenza. Appointed by decree, the CLCG consists of ex-officio members; representatives of French Agencies strongly involved by influenza and qualified personalities, representing various fields of expertise. Collective expertise is based on consensus after thorough collective discussion. A notice is drafted in reply to every official question and passed on either to the Chief Medical Officer, or, when the question concerns vaccines, to the Technical Committee of the vaccinations for which the CLCG acted as a working group. The CLCG was extremely active throughout the pandemic. The objective of this article is to describe in a factual way its output throughout this period of sanitary crisis. This article presents and compare chronologically and in a factual way the state of the scientific knowledge about influenza due to the A(H1N1)pdm09 virus and the CLCG notices. Between the alert launched by the WHO the 24th of April and the 31st of December 2009, CLCG met on 40 occasions. Its work dealt in particular with patient care, recommendations on medical treatment (antivirals, seasonal and pandemic vaccines), and on virological diagnosis. Whatever the defects of its expertise delivered in a context of urgency, which was a difficult exercise, the CLCG fulfilled its advisory to the health authorities. However, the pandemic experience showed that this expertise must be improved by insuring the recognition and the visibility of the advisory committee and by defining their exact position in the chain of decision.

For a number of years now, GEIG, the Groupement d’Expertise et d’Information sur la Grippe (Influenza Expertise and Information Group) has conducted surveys to monitor seasonal trivalent vaccine uptake in France in adults. During the H1N1 pandemic in 2009, this survey was conducted to determine vaccination uptake for both pandemic and seasonal vaccines. An additional specific questionnaire was used to collect data on vaccination in children under 15 years of age. This additional study was carried out because pandemic vaccination (PV) was offered to the French population and children were listed as a priority target group by the national health authorities, whereas seasonal trivalent inactivated vaccines (TIV) are not recommended in children in France. Overall, we collected 2443 questionnaires on children, including children with underlying conditions (9.2%) for whom TIV vaccination was recommended. Overall, 17.9% of children (438/2443) received at least one shot of PV, compared to 3.4% (83/2443) who received at least one shot of TIV. PV uptake was statistically different between non at-risk and at-risk children (366/2218 [16.5%] vs. 71/225 [31.8%], p < 0.0001). This difference was even more significant in the subgroup of children with severe underlying diseases (42.7%, p < 0.0001). This confirms that despite the low overall PV uptake in the French population (9%), the specific recommendation for PV for children increased vaccine uptake in this specific population, suggesting that the disease burden of influenza in children is recognised by both practitioners and parents. The next few years will tell us whether TIV uptake in children increases as a consequence of the specific recommendations made for children during the 2009 pandemic wave, or whether it will return to the very low level of 3.4% observed before the pandemic.

Resume En France, la vaccination saisonniere annuelle contre la grippe est recommandee depuis 2000 chez les patients souffrant d’affections bronchopulmonaires chroniques graves, dont l’asthme. Chaque annee, l’Assurance maladie adresse un bon de prise en charge a 100 % du vaccin contre la grippe aux patients souffrant d’insuffisance respiratoire chronique grave, parmi lesquels les patients atteints d’asthme severe. En novembre 2006, la prise en charge gratuite du vaccin grippe a ete etendue a toutes les personnes atteintes d’asthme, quelle que soit la severite de leur asthme. Cette etude evalue la couverture vaccinale contre la grippe pour la saison 2006–2007 chez 433 enfants asthmatiques âges de six a 17 ans (âge moyen : 9,5 ans ; garcons : 61 %) ayant consulte un pneumopediatre a l’hopital entre mars et septembre 2007. Le taux de couverture vaccinale contre la grippe pour la saison 2006–2007 etait de 15,7 % (13,9 % en 2005–2006 et 10,9 % en 2004–2005). Dans 72,1 % des cas, les enfants etaient vaccines par un medecin generaliste. Le motif de non-vaccination le plus souvent rapporte etait le manque d’information (42 %). La reception du bon de prise en charge (recu par 39,6 % des enfants) augmentait significativement le taux de couverture vaccinale (31 % versus 5,9 % ; p

During the past years, the number of tonsillectomies (only palatine tonsils are taken off) has decreased, indications for surgery have changed. A multi-disciplinal group of paediatricians tried to elaborate the state of the art in the field. Tonsils are the first line defense of high respiratory tract. The immune functions of their lymphoid tissue are multiple: mucosal antigens capture, presentation to lymphocytes, antigens specific proliferation of lymphocytes T and B, differentiation of lymphocytes in effectors lymphocytes and immune lymphocytes. Epithelial cells on the tonsils' surface express non-specific defense. These facts explain partly tonsils' hypertrophy. Tonsillectomy has no general immune consequences. In 2002, in France, 75,000 tonsillectomies were realized, of which 90% were in children. Tonsil's hypertrophy is the major indication, mandatory when sleep apnoeas exist. The main historical tonsillectomy indication for recurrent tonsillitis should decrease due to a more precise diagnostic (rapid test at bed site), an efficient antibiotics therapy and better care for pain. Other indications are scarce. Surgery, feasible from 9 months of age, requires a brief general anaesthesia and has very few contra-indications. The technique, operator dependent, relies on his experience. The only potentially severe complication is an haemorrhage due to scab fall between the eighth and twelfth days. It requires explanation and a written note given to parents. The possibility of lack of feeding and voice modification, usually transitory, should be known. Multiple consequences of tonsillectomy especially allergy have been alleged. Since the years 1980, it is well established that pre-existing allergy or asthma are not a contraindication. More, its deleterious impact on allergic children has not been demonstrated. Last, a gain of weight post-tonsillectomy is possible and could become a risk if excessive.

Influenza is often regarded as an illness of the elderly portion of the population because most of the excess mortality associated with influenza epidemics occurs in that age group. However, evidence derived from a large number of clinical studies carried out in different countries and various settings has clearly demonstrated that the burden of influenza is also substantial in children. The attack rates of influenza during annual epidemics are consistently highest in children, and young children are hospitalized for influenza-related illnesses at rates comparable to those for adults with high-risk conditions. Especially among children younger than 3 years of age, influenza frequently predisposes the patient to bacterial complications such as acute otitis media. Children also serve as the main transmitters of influenza in the community. A safe and effective vaccine against influenza has been available for decades, but the vaccine is rarely used even for children with high-risk conditions. Despite several existing problems related to influenza vaccination of children, the current evidence indicates that the advantages of vaccinating young children would clearly outweigh the disadvantages. Considering the total burden of influenza in children, children younger than 3 years of age should be regarded as a high-risk group for influenza, analogously with the age-based definition of high risk among persons 65 years of age or older. Annual influenza vaccination should be recommended to all children from 6 months to 3 years of age.

For the first time, a live attenuated varicella vaccine with an indication for universal vaccination is licensed in all EU countries. It is now time to consider whether in Europe there should be widespread vaccination against varicella to prevent this common and highly infectious disease. Increasing numbers of countries are adopting vaccination programmes against the disease. In those countries where a routine vaccination policy has been adopted, the success of the vaccine has been significant. The USA, which prior to the launch of a universal vaccination programme in 1995 had 4 million cases of varicella per year, has seen a dramatic reduction in varicella morbidity and mortality rates. A universal varicella vaccination policy is an option that needs to be considered for Europe not only in medical terms but also because it would be socially and economically appropriate.

Four steps are usually necessary before population access to vaccination programmes. Marketing authorization, appropriation by national agencies of the data, recommendation and policy-decision steps on funding and implementation. Using rotavirus vaccination as an illustrative case, this study aims at better understanding picture of population access, and identifying lessons learnt from current experience.Systematic review of national vaccination policies in 20 countries.12 countries have included rotavirus vaccination in their childhood national vaccination programme, two decided not to include it, decision is pending in three countries, while it has not started in the three remaining countries. Published evaluations and/or advice were available in 16 countries. Many differences in content and outcomes were identified.Rotavirus vaccination implementation across industrialized countries was disparate, leading to unequal population access over time. Comparative analyses of the decision-making process suggest different interpretations of available evidence, raising the need for a similar decision integrated framework, using a structured and systematic approach.

Two-dose varicella vaccination is recommended for optimal control of varicella in populations with high (90%) 1-dose coverage. Optimal timing of the second dose may depend on whether breakthrough varicella results from primary vaccine failure (no protective immunity after vaccination) or secondary vaccine failure (waning protective immunity).Published literature (1995 to 2012) on vaccine failure after varicella vaccination cited in PubMed and other online sources was reviewed.Nineteen publications detailed 21 varicella outbreaks with breakthrough varicella rates ranging from 0% to 42%; the publications showed no consistent trend between breakthrough varicella rate and time since vaccination.Literature to date indicates a relatively high rate of primary vaccine failure and limited evidence of secondary vaccine failure among 1-dose varicella vaccine recipients, suggesting that a short interval between 2 doses might be preferable in countries considering implementation of universal varicella vaccination to reduce breakthrough varicella. However, any potential disruption to well-established vaccination schedules should be considered.

International audience; 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.

BMC infectious diseases 12, 207 (2012). doi:10.1186/1471-2334-12-207, Published by BioMed Central, London

Based on an increasingly extensive literature expressing the large interest in the field, this paper gives an overview of different aspects of influenza prevention in children. It relies on paradoxes. First, the heaviest part of the burden is well demonstrated in the youngest infants by numerous epidemiological data elsewhere. On the contrary, with older children, the prevention by influenza vaccines is more efficacious-without notable side effects. Second, the available TIV vaccines are 60 years old and the requests of registration and regulation of vaccines have evolved. There is a specific need in children: it is time to re-discuss the pragmatic utilization of influenza vaccines (full dose in the youngest patient? More flexibility regarding the interval between the two required doses in vaccine-naïve children), and to change from a compassionate use to a targeted research and adapted vaccines considering the limits of TIV in the youngest children. Third, influenza virus transmission is the highest in children in semi-close communities (day-care centers, schools), diffusing to households and more largely to the population. A restricted policy on high risk groups (roughly 10% in a pediatric population, all medical conditions including asthma, for whom influenza vaccine coverage is a 15-75% range) is far below the estimated threshold of 45% coverage rate to limit the virus circulation by an indirect impact during seasonal epidemics. Fourth, public health decisions in the vaccination field are usually taken from top to bottom. The pandemic A/H1N1 has toughly demonstrated that "forgetting" about the perception and expectations of the public and the parents nearly created conflicts and at least a strong resistance impeding the quality of a program worked on for a long time ahead. Fifth, and not the least, HCPs are pivotal in influenza vaccination mostly trusted by the parents. Too often, they are not backed by a national and clear support and they need to reinforce their knowledge on the disease and the vaccines.

Influenza virus A/H1N1 2009 is a specific combination of internal genes explaining its pandemic character. Compared with seasonal influenza, influenza like illnesses were more frequent in young healthy people (children and adults). In France, among 1 329 severe cases, 20% had no risk factors and 312 subjects (23.5%) died. Compared with young adults without RF, the risk of severe case was 10-fold in pregnant women or 5-fold in infants (1 yr). A risk factor (in similar age group/without risk factor) multiplied the risk by 20 to 30 between 2 and 64 yrs, by 18 after 64 yrs, by 130 in infants1 yr, by over 300 between 1 and 2 yrs, and by 20 in pregnant women. A/H1N1 vaccination, proposed to the French population, was organized by the State in dedicated vaccination centers, in a staggered approach relying on pre-established priority groups, the sequential arrival of vaccines, the type of available vaccines, most often in multidoses. The official recommendations were adapted over time (age group, number of doses, type of vaccine utilized). Pandemrix and Focetria were the most casual; from mid-November 2009, Panenza was available. There was a 3 weeks interval between seasonal vaccination and pandemic one. Global coverage rate achieved is 8%. No peculiar severe adverse events and no signal of Guillain Barré syndrome were notified to the national pharmacovigilance net.

This study identified and characterized a novel delta beta fusion gene in which the delta-globin gene promoter is linked to intact beta-globin coding sequences in a Senegalese family. It results from a 7.4-kb deletion that removes the delta-globin coding sequences, the delta beta intergenic region as well as the beta-globin gene promoter and causes delta(0)beta(+) thalassemia with hemoglobin A expressed at the 11% to 15% range. The phenotype of this naturally occurring delta beta hybrid gene not only clarifies, in an in vivo context, the respective strength of delta- and beta-globin gene promoters, but also emphasizes the importance of beta-globin intragenic sequences in the expression of beta-globin chains. (Blood. 2001;98:1261-1263)

International audience; Background: Neisseria meningitidis meningitis represents approximately one-half of the meningococcal cases in French children. To explore the contribution of bacterial typing in improving the management of cases, we aimed to describe clinical characteristics and mortality of meningococcal meningitis in children reported to the multicenter survey system, GPIP/ACTIV, in association with phenotypes/genotypes of bacterial isolates.Methods: From 2001 to 2005, 259 pediatric wards and 168 microbiology laboratories enrolled all children with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded.Results: A total of 962 cases of Neisseria meningitidis meningitis among a total of 2131 bacterial meningitis (45%) were recorded (mean age, 4.5 ± 4.7 years). Serogroup distribution of the isolates was 62.3%, 33.7%, 2.9%, 0.6%, and 0.6% for serogroups B, C, W135, A and Y, respectively. The major clonal complexes were ST-41/44 (32.2%), ST-11 (21.9%), ST-32 (20.8%), ST-8 (8.2%), and ST-269 (4.9%). Despite global heterogeneity of the isolates, 2 phenotypes/genotypes were of interest. Isolates of the phenotype/genotype B:14:P1.7,16/ST-32 (56% clustered in the region of Haute Normandie) were observed in older children (8.6 years) and were associated with a higher case fatality rate (12%) than were other phenotypes of serogroup B. The phenotype/genotype C:2a:P1.5/ST-11 was found in 26.3% of serogroup C cases and was possibly associated with a higher mortality among serogroup C (9.9% for C and 5.9% for B, P = 0.04).Conclusions: This large survey provides data that could be important for implementation of future vaccines. Typing of meningococcal isolates could contribute to an understanding of prognosis in meningococcal meningitis.

Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely.

Influenza in children is now recognized as a yearly burden, with severe symptoms or complications responsible for hospitalizations in young children and at risk groups. Clinical diagnosis, similar to adults in children over 4-5 years of age, is much less feasible in young infants due to overlap of symptoms with other respiratory or digestive viral epidemics. Rapid diagnostic tests could thus be useful. Prevention relies on vaccination but recommendations are restricted (at risk groups, professional and familial surroundings), vaccine schedule is a constraint, and the vaccine protective efficacy is increasing with the children age. Thus, specific anti-virals could be useful as curative treatment or even prophylaxis.

International audience; 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

Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5–10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasability of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

Background Although vaccination has been proved to be a safe, efficacious, and cost-effective intervention, immunisation rates remain suboptimal in many European countries, resulting in poor control of many vaccine-preventable diseases. Discussion The Summit of Independent European Vaccination Experts focused on the perception of vaccines and vaccination by the general public and healthcare professionals and discussed ways to improve vaccine uptake in Europe. Despite the substantial impact and importance of the media, healthcare professionals were identified as the main advocates for vaccination and the most important source of information about vaccines for the general public. Healthcare professionals should receive more support for their own education on vaccinology, have rapid access to up-to-date information on vaccines, and have easy access to consultation with experts regarding vaccination-related problems. Vaccine information systems should be set up to facilitate promotion of vaccination. Summary Every opportunity to administer vaccines should be used, and active reminder systems should be set up. A European vaccine awareness week should be established.

In children, community acquired pneumonia represent less than 10% of respiratory tract infections. In infants and toddlers, the diagnosis is difficult as, at any age, in case of isolated fever. Typical features of pneumonia are rare. Chest radiograph is necessary for confirmation and mandatory in children under 2 years of age, other diagnosis suspision or recurrent pneumonia. Identification of risk factors and/or severity criteria will guide the hospitalisation decision. Epidemiological data have a collective usefulness but help very little for the individual decision. Pneumococcus is observed at any age. Before 3 years of age, viruses and pneumococcus are predominant. After 3 years of age pneumococcus, Mycoplasma pneumoniae and Chlamydia pneumoniae are possible. Viral or virobacterial co-infections exist in 15 up to 25% of cases. An empiric and rapid antibiotherapy is given, pending on age, national or regional epidemiology, initial severity, risk factors. A clinical evaluation is mandatory at H48-72. Routine vaccination with the 7-valent conjugate anti-pneumococcal vaccine will modify the strategy of use of antibiotics in children's pneumonia.

Despite the proven safety and efficacy of vaccines, common vaccine-preventable diseases such as measles are not yet controlled in all European countries. This is largely due to three factors. First, vaccination systems differ widely throughout Europe and they vary between highly centralised and totally decentralised systems. Both have advantages and disadvantages, but without doubt they can all work locally. "Harmonisation" in this field is neither a prerequisite nor a guarantee for success. Second, perception of vaccination--and this includes education of the public--is most crucial. In this field the media play an important part, but their ability or will to communicate complicated scientific matters in an appropriate way to the public is often insufficient. Third, political will may be the single most important factor for success in vaccination. Only if the European Union comes up with and implements common vaccination goals with firm deadlines can the best health through vaccination of all Europeans be accomplished. The system as well as the schedule used would then be of minor importance.

Objectif L’objectif est d’evaluer le taux de couverture vaccinale (CV) contre la grippe chez les enfants asthmatiques pour la saison 2006-2007. La vaccination annuelle contre la grippe est recommandee en France pour les patients asthmatiques. Un bon de prise en charge gratuite du vaccin grippe est adresse par la Caisse Nationale d’Assurance Maladie (CNAM) aux patients atteints de certaines affections de longue duree, dont l’asthme severe. En novembre 2006, cette mesure a ete etendue a l’asthme quel que soit son degre de severite. En 2008, l’objectif national de la loi de sante publique est d’atteindre pour les populations a risque, incluant les patients asthmatiques, un taux de CV contre la grippe d’au moins 75 %. Methodes Etude multicentrique, observationnelle, realisee de mars a septembre 2007 dans huit hopitaux repartis sur l’ensemble du territoire francais. Criteres d’inclusion : enfants âges de 6 a 17 ans revolus, consultant un pneumo-pediatre a l’hopital, dont le diagnostic d’asthme datait de plus de 6 mois et disposant d’un carnet de sante ou d’un dossier medical. Le medecin remplissait un questionnaire pour chaque enfant inclus. Resultats Les donnees de 433 enfants ont ete analysees (moyenne : 9,5 ans, 61 % de sexe masculin). Le taux global de CV contre la grippe etait de 15,7 % en 2006-2007. Parmi ces enfants, 39,6 % avaient recu un bon CNAM. La reception du bon CNAM augmentait la CV (31 % de vaccines parmi les enfants ayant recu le bon, versus 5,9 % de vaccines parmi les enfants n’ayant pas recu le bon, p Conclusions En France, en 2006-2007, le taux de CV grippe chez les enfants asthmatiques (15,7 %) est tres inferieur a l’objectif national d’au moins 75 % en 2008. L’extension recente de la prise en charge gratuite du vaccin grippe a tous les patients asthmatiques pourrait ameliorer ce taux. Une information plus importante des patients sur les risques de la grippe en cas de maladie asthmatique et sur les benefices de la vaccination devrait aussi contribuer a l’amelioration de ce taux.

Objectives: To estimate the public health impact of annual vaccination of children with a quadrivalent live-attenuated influenza vaccine (QLAIV) across Europe. Methods: A deterministic, age-structured, dynamic model was used to simulate influenza transmission across 14 European countries, comparing current vaccination coverage using a quadrivalent inactivated vaccine (QIV) to a scenario whereby vaccination coverage was extended to 50% of 2–17 year-old children, using QLAIV. Differential equations described demographic changes, exposure to infectious individuals, recovery and immunity dynamics. For each country, the basic reproduction number (R0) was calibrated to published influenza incidence statistics. Assumed vaccine efficacy for children was 80% (QLAIV) and 59% (QIV). Symptomatic cases cumulated over 10 years were calculated per 100 000 person-years. One-way sensitivity analyses were conducted on QLAIV efficacy in 7–17 year-olds (59% instead of 80%), durations of natural (±3 years; base case: 6, 12 years for influenza A, B respectively) and QLAIV vaccine-induced immunity (100% immunity loss after 1 season; base case: 30%), and R0 (+/-10% around all-year average value). Results: Across countries, annual QLAIV vaccination additionally prevents 1366–3604 symptomatic cases per 100 000 population (average 2495 /100 000, ie, a reduction of 47.6% of the cases which occur in the reference scenario with QIV vaccination only). Among children (2–17 years), QLAIV prevents 551–1555 cases per 100 000 population (average 990 /100 000, ie, 67.2% of current cases). Among adults, QLAIV indirectly prevents 726-2047 cases per 100 000 population (average 1466 /100 000, ie, 40.0% of current cases). The most impactful drivers of total protection were duration of natural immunity against influenza A, R0 and QLAIV immunity duration and efficacy. In all evaluated scenarios, there was a large direct and even larger indirect protection compared with the reference scenario. Conclusions: The model highlights direct and indirect protection benefits when vaccinating healthy children with QLAIV in Europe, across a range of demographic structures, contact patterns and vaccination coverage rates.