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Heterologous prime boost vaccination is a primary vaccination with different vaccines, most often from different vaccine platforms. It combines the immunological properties of the different vaccines and thereby induces humoral, cellular and, in some cases, mucosal response. For Covid prevention, it has been used in primary vaccination, due to safety issues and in boosters. We have evaluated some articles reporting on the results of this type of vaccine, and demonstrating its usefulness.

International audience; BackgroundIn France, each year, influenza viruses are responsible for seasonal epidemics leading to 2–6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010–2018).MethodsInfluenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc—2010–2015) and medical costs.ResultsEach season, the average number of influenza-related hospitalizations was 18,979 (range: 8627–44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza associated) was 31,490 (95% confidence interval [CI]: 24,542–39,012), with an average cost of €141 million (range: 54–217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥65 years of age (65+). More than 90% of excess mortality was in 65+ subjects.ConclusionsThe combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.

Resume Introduction La vaccination constitue une avancee majeure dans la prevention des maladies infectieuses. Le principe des vaccins est d’induire une protection contre un agent pathogene donne en eduquant le systeme immunitaire humain. Le vaccin permet de reduire le risque de complications et la mortalite en cas d’exposition ulterieure a l’agent infectieux. Etat des connaissances Dans cette revue, nous rappelons l’histoire de la vaccination ainsi que les principes immunologiques de base qui sous-tendent la composition des vaccins et la reponse vaccinale. Ainsi, les vaccins permettent au systeme immunitaire de produire une memoire immunologique reposant sur les lymphocytes T et B memoires afin de produire une reponse rapide et efficace lors de l’exposition a l’agent pathogene cible. Perspectives L’amelioration des vaccins deja existants et la decouverte de nouveaux vaccins passent par la comprehension fine des determinants immunologiques de la vaccination. Les defis restent grands, notamment en termes d’agents pathogenes-cibles, de futurs candidat-vaccins mais aussi d’acceptation de la vaccination. Conclusion La comprehension des principes de la vaccination permet ainsi de poursuivre le developpement des vaccins et la lutte contre les maladies infectieuses.

Introduction La grossesse est un facteur de risque connu de grippe grave et malgre la recommandation de vaccination maternelle depuis 2012 la couverture vaccinale (CV) reste insuffisante chez les femmes enceintes. Notre objectif principal etait d’identifier les motifs d’acceptation et de refus vaccinal chez les femmes ayant recu une proposition prealable par un professionnel de sante (PS). Nos objectifs secondaires etaient d’estimer le niveau de connaissance sur la grippe et le vaccin et la confiance dans les differentes sources d’informations. Materiels et methodes Une etude monocentrique a ete realisee entre fevrier et mai 2020 via un questionnaire anonyme administre aux femmes hospitalisees en suite de couche dans une maternite de niveau 3 avec mise a disposition du vaccin. Nous avons recueilli les caracteristiques sociodemographiques, le statut vaccinal, et les connaissances et representations sur la grippe et son vaccin. Des analyses thematiques ont ete realisees pour l’etude des motifs de vaccination et des modeles de regression logistique pour celle des facteurs associes. Resultats Au total, 251 femmes ont ete incluses dans l’etude, 176 (70 %) nees en France, 202 (80 %) âgees de 30 ans et plus, 173 (69 %) avec un haut niveau d’etude ; 31 (12 %) presentaient une pathologie chronique ciblee par les recommandations et 212 (84 %) ont ete vaccinees contre la grippe. La proposition de vaccination, multiple pour une meme femme, emanait de plusieurs PS : sage-femme (55 %), gynecologue-obstetricien (50 %), medecin traitant (18 %). La vaccination a eu principalement lieu a la maternite (61 %), dans des cabinets liberaux (21 %) ou en pharmacie (11 %). Les motifs decisifs d’acceptation retrouves chez les femmes vaccinees etaient la recommandation d’un PS (38 %), la protection du nouveau-ne (36 %) ou la perception d’une maladie grave pendant la grossesse (28 %) ; les motifs de refus etaient la peur des effets indesirables du vaccin (74 %) et des doutes sur son interet (51 %). Un niveau de confiance plus eleve envers les PS etait observe chez les femmes vaccinees. La vaccination etait associee a un score eleve de connaissance sur la grippe et le vaccin (OR = 8,0 ; IC95 % [2,4–50,1], p = 0,005), un antecedent de vaccination grippale (OR = 4,2 ; IC95 % [1,8–11,1], p = 0,002), un âge maternel entre 30–35 ans (OR = 3,6 ; IC95 % [1,3–10,1], p = 0,0013), et la presence d’enfant Conclusion Ces resultats soulignent le role cle de la proposition vaccinale par les PS dans l’acceptation de la vaccination durant la grossesse ainsi que l’importance d’informations personnalisees sur les benefices et la securite du vaccin pour la mere et son futur enfant. Cette etude ouvre aussi la reflexion sur l’acceptabilite d’autres vaccins, notamment contre la COVID-19.

Background Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. Methods In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n = 15) or GLA-SE (n = 15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n = 18) or placebo (n = 18). AMA1-DiCo (50 µg) was administered intramuscularly at baseline, Week 4 and 26. Results AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200–300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26 weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. Conclusion AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. Clinical Trials Registration. ClinicalTrials.gov NCT02014727; PACTR201402000719423.

Introduction La conduite des essais vaccinaux COVID-19 necessite le recrutement d’un nombre important de participants dans un delai court. Dans ce contexte, une plateforme nationale informatisee permettant l’auto-inscription de volontaires a ete mise en place. Ce concept inedit en France permet de cibler les populations correspondant aux criteres d’inclusion, d’assurer une repartition geographique et de garantir aux promoteurs, industriels ou academiques, le recrutement rapide dans les essais. L’objectif du travail presente ici est de decrire les caracteristiques des volontaires inscrits. Materiels et methodes Un appel a volontaires a ete lance le 01/10/2020 sous la forme d’une conference de presse. Il a aussi ete relaye par les medecins generalistes. Tout adulte pouvait s’inscrire sur une plateforme declaree a la CNIL accessible a partir d’un site internet contenant des informations sur le developpement des vaccins COVID-19. Le volontaire devait renseigner son identite et ses coordonnees, donner expressement son consentement puis des informations concernant : – son poids, sa taille et l’existence d’une ou plusieurs comorbidites (diabete, hypertension arterielle, maladie cardiaque et/ou respiratoire, insuffisance renale, transplantation d’organe solide, maladie auto-immune et cancer) ; – la prise d’un traitement au long cours, notamment d’un immunosuppresseur ; – son exposition a la COVID-19 (professionnel de sante, metier au contact du public) ou un antecedent de COVID-19 ; – sa participation anterieure a un essai clinique. Les donnees des volontaires inscrits entre le 01/10/2020 et le 21/12/2020 ayant donne leur consentement et dont les donnees d’identite etaient completes ont fait l’objet de cette analyse, effectuee avec le logiciel STATA®. Resultats Au total, 45503 inscriptions ont ete enregistrees, dont 44611 (98%) analysees ici. Il s’agit d’hommes dans 63% des cas (n = 28049, sexratio : 1,7); l’âge median est de 51 ans (IQR : 35-63 ans). Les personnes âgees de 65 ans et plus representent 22% (n = 9551) des volontaires; 1,2% (n = 507) ont 80 ans et plus. Au moins une comorbidite est presente chez 14609 (39%) volontaires: 16% d’obesite (n = 6054), 16,5 % d’hypertension arterielle (n = 6243), 6% de diabete (n = 2251), 6,6% de maladie cardiaque (n = 2493), 9,9% de maladie respiratoire (n = 3747), 0,4 % d’insuffisance renale (n = 160), 5,2 % de maladie auto-immune (n = 1976), 0,8% de cancer (n = 306) et 0,3% de transplantes (n = 117). Cinq pour cent (n = 2284) ont declare un antecedent de COVID-19 et 13% (n = 5654) sont des professionnels de sante. Conclusion La mise en place d’une plateforme nationale dediee aux essais vaccinaux COVID-19 est une premiere en France et a permis l’inscription d’un grand nombre de participants potentiels grâce a un fort relais par la presse nationale et un accueil positif des francais de tous les âges. Cet outil doit garantir un recrutement rapide dans les essais vaccinaux COVID-19 en cours et pourrait constituer de facon plus generale une approche efficace pour dynamiser le recrutement des essais cliniques en France.

Introduction Un vaccin grippal inactive quadrivalent a haute dose (QIV-HD), c’est-a-dire contenant 60 μg d’hemagglutinine (HA) par souche a ete developpe pour ameliorer la protection des personnes âgees contre la grippe et ses complications. QIV-HD a ete enregistre en France en avril 2020 sur la base d’etudes d’immunogenicite, d’efficacite clinique et de tolerance, comparant la forme trivalente HD (TIV-HD) au vaccin trivalent a dose standard (SD : 15 μg HA/souche) et d’une etude d’immuno-bridging comparant QIV-HD a TIV-HD chez les personnes de 65 ans et +. Nous rapportons ici les donnees d’immunogenicite et de tolerance comparant QIV-HD a QIV-SD chez des sujets de 60 ans et +. Materiels et methodes Un essai clinique de phase III, randomise, en double aveugle et controle versus un comparateur actif a ete menee dans 6 pays d’Europe, 17 centres dont 3 en France (EudraCT no 2019-000655-14). Les sujets ont ete randomises (1:1) pour recevoir une dose de QIV-HD ou de QIV-SD. L’objectif principal etait de demontrer une reponse immunitaire superieure du QIV-HD par rapport a QIV-SD en termes de moyenne geometrique des titres en anticorps (MGT) mesuree par le test d’inhibition de l’hemagglutination (IHA), 28 jours apres vaccination, pour les 4 souches, chez les sujets de 60 a 64 ans et ceux de 65 ans et +. L’objectif secondaire etait de decrire la tolerance. Resultats La superiorite du QIV-HD par rapport au QIV-SD, evaluee par la mesure des MGT par IHA, a ete demontree car la limite inferieure de l’IC bilateral a 95 % du ratio des MGT (QIV-HD divise par QIV-SD) etait > 1 pour toutes les souches dans les deux groupes d’âge. L’etude a montre que les deux vaccins etaient bien toleres chez les sujets de 60 ans et +. Les profils de tolerance du QIV-HD et du QIV-SD se sont reveles similaires quel que soit le groupe d’âge avec un nombre un peu plus eleve de reactions locales rapportees apres QIV-HD; aucune difference majeure en termes de gravite. Conclusion Cette etude a montre que QIV-HD offre une plus grande immunogenicite que QIV-SD et est bien tolere chez les sujets de 60 ans et +. Les reponses immunitaires apres QIV-HD etant similaires chez les personnes de 60 a 64 ans et celles de 65 ans et +. Les resultats des essais d’efficacite clinique et d’efficacite en vie reelle du vaccin TIV-HD s’appliquent au QIV-HD des 60 ans. En France, a date d’avril 2021, QIV-HD est recommande par la HAS pour une utilisation a partir de 65 ans et a ete reconnu comme apportant une meilleure protection par rapport au vaccin trivalent a dose standard. Dans ce cadre, la presente etude a l’interet d’apporter des donnees comparatives QIV-HD vs un QIV-SD utilise en France, en matiere d’immunogenicite et de tolerance.

Summary Background Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies. Methods This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered ( NCT01254630 and EudraCT 2010-023156-89). Findings Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI −1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI −17·8 to 41·3). Interpretation The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies. Funding Merck & Co, Inc.

Introduction Les femmes enceintes presentent un risque plus eleve de grippe grave que les femmes du meme âge non-enceintes. La vaccination antigrippale leur est recommandee en France depuis 2012. Cependant, la couverture vaccinale dans cette population est estimee a moins de 10 %. Les sages-femmes (SF), actrices importantes de prevention vis-a-vis des femmes enceintes, ont, depuis 2016, la possibilite de prescrire et administrer un certain nombre de vaccins donc celui de la grippe a leurs patientes. L’objectif de ce travail etait d’evaluer les connaissances des SF sur la grippe pendant la grossesse, le vaccin, les recommandations vaccinales et d’evaluer leur pratique en termes de proposition, prescription et administration du vaccin ainsi que leur couverture vaccinale (CV) contre la grippe. Materiels et methodes Etude transversale proposee aux SF realisant des consultations de suivi de grossesse dans une des douze maternites (publiques ou privees a but non lucratif) et/ou en activite liberale et/ou dans un centre de protection maternelle et infantile d’une ville francaise. Questionnaire en ligne distribue par mail entre le 1er octobre 2017 et le 31 decembre 2017 contenant 25 questions sur les connaissances sur la grippe pendant la grossesse, le vaccin, les recommandations vaccinales et les pratiques en termes de proposition, prescription et administration du vaccin ainsi que leur CV contre la grippe pour la saison 2016/2017. Resultats Le taux de reponse etait de 31 % (208/669). L’âge median de 34 ans et l’experience professionnelle mediane de 10 ans. La majorite (66 %) travaillait dans une maternite. Plus de 90 % des repondantes connaissaient les risques pour la mere et le fœtus d’une grippe pendant la grossesse et les recommandations vaccinales. Environ 75 % pensaient que le vaccin etait efficace et sur. Moins de la moitie savait que le vaccin pouvait egalement proteger le nourrisson. Environ 25 % pensaient que le vaccin est un vaccin vivant et 50 % qu’il contient un adjuvant. Un tiers des SF estimaient leurs connaissances sur la vaccination antigrippale et la vaccination en general insuffisante. Pres de 20 % des SF ne parlent jamais de la grippe ni du vaccin a leurs patientes principalement par oubli ou manque de temps. Seuls 11 % prescrivent systematiquement le vaccin. La CV des SF etait de 39 %. Les principales raisons de non-vaccination etaient le fait de ne pas se sentir concernee par la grippe, la peur des effets indesirables du vaccin et les doutes sur son efficacite. Le niveau de connaissance sur la vaccination etait correle a la vaccination. Les SF vaccinees proposaient plus frequemment le vaccin a leurs patientes que les non vaccinees. Conclusion Bien que la recommandation de vaccination antigrippale et leur habilite a prescrire et vacciner soient connues, les SF utilisent encore peu leurs nouvelles competences. Les strategies d’information et de formation des SF devraient etre ameliorees pour augmenter la CV des SF et de leurs patientes.

Summary Background Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. Methods In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age ( vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5–60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials.gov (NCT01229267) and EudraCT (2010–020150–34). Findings Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2·4 years (SD 1·3) in the vaccine consistency lot group and 2·3 years (SD 1·3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32·9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91·9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63·8% (95% CI 48·4–74·6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0·2%, 95% CI −5·1 to 5·5) and serious vaccine-related adverse events (five [1%] vs five [1%]; risk difference 0·1%, −1·4 to 1·1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 [29%] vs 36 [7%]; risk difference 22·6%, 95% CI 18·5–26·6; p Interpretation This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated. Funding Merck & Co., Inc.

Vaccination constitutes a major advance in the prevention of infectious diseases. The principle of vaccination is to induce protection against a pathogen by mimicking its natural interaction with the human immune system. The vaccine reduces the risk of complications and mortality following subsequent exposure to an infectious agent.In this review we recall the history of vaccination as well as the basic immunological principles underlying the composition of vaccines and the response to vaccination. In this way, vaccines induce the immune system to produce an immunological memory based on T and B lymphocytes in order to produce a rapid and effective response to exposure to the targeted pathogen.The improvement of existing vaccines and the discovery of new vaccines requires an understanding of the immunological principles of vaccination. Great challenges remain, particularly in terms of target pathogens for future vaccine candidates and also the acceptance of vaccination.Understanding the principles of vaccination allows development of vaccines and the control of infectious diseases.

Objective: To investigate the relationship between the response to influenza vaccination and the ability to produce proinflamatory cytokines in elderly subjects.

Background. Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. Methods. We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed byatreatment switch. We adjusted for patients’ characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. Results. A total of 81738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/µL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997–1998 to 9.7% in 2009–2011 (P

Introduction Cervical discectomy with interbody fusion is a common procedure in spinal surgery. The resultant biomechanical alterations accelerate degeneration of the adjacent segment, but the contribution of natural degeneration to adjacent segment disease is unclear. Objective To assess the long-term rate of surgery to discs adjacent to cervical interbody fusion; and to assess the associated incidence of cervico-brachial neuralgia and radiological degeneration of adjacent discs. Material and method A multicenter retrospective study included anterior cervical discectomy patients at a minimum of 10 years’ follow-up. Clinical variables comprised pain, use of analgesics and surgical revision. Functional assessment was performed on the Neck Disability Index (NDI). Radiologic degeneration was assessed on the Goffin score based on cervical spine X-ray. Results Two hundred and eighty-eight patients were contacted and filled out the clinical questionnaire. Among the patients, 153 underwent radiological reassessment. Mean age was 46 years (range, 16–73 years). Mean follow-up was 14.5 years (12–18 years). The rate of surgical revision on a disc adjacent to the primary level was 5.9%. Frequent attacks of cervico-brachial neuralgia were reported in 20.5% of cases. Radiologic adjacent segment degeneration was found in 81.3% of cases over follow-up. There was a significant correlation between degree of radiologic adjacent segment degeneration and NDI (P = 0.02). Discussion Degeneration adjacent to discectomy/fusion is partly due to aging. The present findings, however, agree with the literature and indicate accelerated degeneration in adjacent segments. These findings should be taken into account in treatment decision-making and suggest a possible interest of more physiological surgery such as arthroplasty. Level of evidence IV – Multicenter retrospective study.

Resume Introduction Les discectomies cervicales avec fusion sont des interventions courantes en chirurgie rachidienne. Les modifications biomecaniques qu’elles entrainent accelereraient la degenerescence du segment adjacent. Cependant, la part de degenerescence naturelle dans la constitution de ce syndrome adjacent est mal connue. Objectif Evaluer le taux de patients operes d’un disque adjacent a une arthrodese cervicale a long terme. Determiner l’incidence des nevralgies cervico-brachiales et la degenerescence radiologique des disques adjacents dans cette population. Materiel et methode Etude retrospective multicentrique des patients operes d’une discectomie cervicale anterieure avec un recul minimum de 10 ans. Les caracteristiques cliniques etudiees etaient la douleur, la prise d’antalgiques et la survenue d’une re-intervention chirurgicale. Une evaluation fonctionnelle etait conduite grâce au Neck Disability Index (NDI). La degenerescence radiologique etait evaluee par le score de Goffin sur des radiographies du rachis cervical. Resultats Deux cent quatre-vingts huit patients ont ete contactes et ont renseignes les questionnaires cliniques. Cent cinquante-trois patients ont ete reevalues radiologiquement. L’âge moyen etait de 46 ans (16–73). Le recul moyen etait 14,5 ans (12–18). Le taux de re-intervention sur un niveau adjacent au niveau initial etait de 5,9 %. Des crises de nevralgies cervico-brachiales considerees comme frequentes etaient presentes dans 20,5 % des cas. Une degenerescence radiologique des segments adjacents au cours du suivi etait retrouvee dans 81,3 % des cas. Une relation significative etait retrouvee entre l’importance de la degradation radiologique des segments adjacents et le NDI (p = 0,02). Discussion La degenerescence adjacente a une discectomie/fusion est en partie liee aux phenomenes de vieillissement. Cependant, les resultats de notre etude concordent avec les donnees de la litterature et sont en faveur d’une acceleration de la degenerescence des niveaux adjacents. Ces donnees doivent etre prises en compte dans la decision therapeutique et faire discuter l’interet de techniques chirurgicales potentiellement plus physiologiques comme l’arthroplastie. Niveau de preuve IV – Etude retrospective multicentrique.

Resume Les spondylolyses lombaires multi-etagees representent moins de 6 % des spondylolyses lombaires et leur prise en charge n’est pas homogene dans la litterature. Moins de 10 cas presentant une triple spondylolyse lombaire sont publies. Nous decrivons le cas d’un homme de 33 ans presentant une lyse isthmique bilaterale L3, L4 et L5 sans spondylolysthesis ni degenerescence discale. L’IRM et le scanner du rachis lombaire ont ete des elements decisifs dans notre choix therapeutique et le traitement chirurgical realise a ete une reparation isthmique bilaterale en L3 et L4 et une arthrodese par voie combinee anterieure et posterieure en L5S1. Les resultats cliniques et radiologiques sont bons au dernier recul.

Introduction Des recommandations pour la vaccination des sujets immunodeprimes ont ete elaborees par le HCSP en 2014 ; leur mise en œuvre est complexe. Nous avons souhaite evaluer l’organisation de la vaccination de ces patients dans les centres hospitaliers ayant un service de maladies infectieuses. Materiels et methodes Du 14/01/2019 au 10/02/2019, nous avons diffuse un questionnaire concernant 3 situations : patients traites par chimiotherapie anti-cancereuse (PCAC), apres greffe de cellules souches hematopoietiques (GCSH), et avant transplantation d’organe solide (TOS). Il etait demande pour chacune de ces populations : (a) si leur parcours comprenait une consultation avec un infectiologue ; (b) comment etait geree leur vaccination (par les infectiologues ; par les autres specialistes en collaboration ou non avec les infectiologues ; ou si elle n’etait pas formalisee) ; et (c) quelle etait la proportion de sujets vaccines (PCAC : pneumocoque, DTP(c), ROR ; apres GCSH : pneumocoque, hexavalent, meningocoque, ROR ; avant TOS : pneumocoque, VHB). Resultats Apres retrait des reponses redondantes (plusieurs formulaires au sein d’un meme centre), 69 reponses ont ete retenues, dont 50,7 % issues d’un CHU, 42 % d’un CH et 7,2 % d’un autre etablissement. Une consultation avec un infectiologue n’existe pas dans la plupart des centres (82,5 % des centres pour les PCAC, 75 % des centres apres GCSH, et 42,5 % des centres avant une TOS). Dans d’autres, elle est realisee de maniere systematique (dans 1 centre pour les PCAC, 11,1 % des centres apres GCSH, et 12,5 % des centres avant TOS). La realisation de la vaccination est principalement geree par les infectiologues seuls dans une minorite de centres (8,1 % des centres pour les PCAC, 16,2 % des centres apres GCSH, et 22,5 % des centres avant TOS). Dans le cas contraire, la vaccination est dans certains centres geree par les specialistes oncologues/hematologues/transplanteurs, avec ou sans collaboration avec les infectiologues (43,5 % des centres pour les PCAC, 64,9 % des centres realisant des GCSH, et 60,0 % des centres realisant des TOS) ; dans d’autres centres, l’organisation de la vaccination n’est pas formalisee du tout (48,4 % des centres pour les PCAC, 18,9 % des centres apres GCSH, et 17,5 % des centres avant TOS). Proportion des patients vaccines La proportion de sujets vaccines dans chaque centre est le plus souvent inconnue des infectiologues (PCAC : 53,2 % des centres ; apres GCSH : 48 % des centres ; avant TOS : 35,4 % des centres). Peu de centres declarent qu’elle est de 90 % ou plus (aucun des centres pour les PCAC, 11,5 % des centres apres GSCH, et 9,8 % des centres avant TOS). A l’inverse, il est souvent rapporte une proportion de patients vaccines inferieure a un tiers (PCAC : 33,9 % des centres, apres GCSH : 24,3 % des centres, avant TOS : 12,2 % des centres). Conclusion L’organisation de la vaccination de ces sujets immunodeprimes est a la fois heterogene et suboptimale ; en decoule une faible couverture vaccinale. Les infectiologues doivent davantage investir ce champ, en collaboration avec les disciplines concernees.

Vaccination in immunocompetent adult mainly concerns booster vaccination against diphtheria, tetanus, polio and pertussis. Some chronic diseases may also require the achievement of pneumococcal and influenza vaccines. In addition, from the age of 65, annual influenza vaccination as well as one dose of a live attenuated shingles vaccine between 64 and 75 years are recommended. Immunocompromised adults, due to the increased risk of serious infections responsible of significant morbidity and mortality, are particularly concerned by vaccination. Main issues in this population are the decreased immunogenicity and efficacy of vaccination and the risk of infection with live attenuated vaccines and. Depending on the type of immunosuppression, the recommended vaccines and vaccination schemes differ. Vaccination of healthy persons caring or residing with immunocompromised patients is an important point in the vaccine strategy. The current perspectives in vaccinology concern the development of vaccines against healthcare associated infections (Clostridium difficile and Staphylococcus aureus in particular), the strategy of vaccination during pregnancy to protect new-borns (respiratory syncytial virus, group B streptococcus) and the development of new adjuvants and new routes of immunization. With the overall decline in immunization coverage and increasing distrust of vaccination, the problem of vaccine hesitancy is also a hot topic. The reasons for doubt in the vaccine usefulness and the solutions to be applied are also crucial issues.

Resume Les traumatismes vertebro-medullaires sont responsables d’une morbi-mortalite majeure. La charniere thoracolombaire constitue une zone de fragilite du fait des contraintes biomecaniques avec des risques d’atteinte du cone medullaire dans certains cas. Une atteinte neurologique est une urgence chirurgicale lorsqu’elle est incomplete et que l’etat du patient le permet. En cas d’atteinte complete, aucun consensus n’est admis, mais il semble logique d’operer ces patients au meme titre afin de permettre la recuperation neurologique et non seulement pour eviter les complications de decubitus. Nous rapportons ici les cas de trois patients presentant une paraplegie de niveau L1 par atteinte du cone medullaire Frankel A traites avant la sixieme heure avec une recuperation neurologique tres favorable puisque les patients pouvaient de nouveau marcher au recul de 2,5 ans. Des troubles vesico-sphincteriens persistaient chez deux de ces patients. Le delai de prise en charge rapide semble etre un facteur preponderant pour une possible recuperation neurologique dans le traumatisme du cone medullaire. L’attitude d’operer dans une urgence differee devant une paraplegie complete nous parait obsolete et merite d’etre reetudiee.

Resume Propos La vaccination, en prevenant les infections, presente un interet certain pour les sujets immunodeprimes. L’objectif de cet article est de faire un etat des lieux des donnees concernant l’efficacite (en termes d’immunogenicite) et la tolerance des vaccins viraux disponibles en France et de synthetiser les recommandations existantes pour quatre grands groupes de patients : transplantes d’organes solides, greffes de moelle, infectes par le VIH et traites par immunosuppresseurs pour une maladie systemique. Actualites et points forts Les donnees disponibles relatives a l’immunogenicite et la tolerance vaccinales chez les adultes immunodeprimes sont peu nombreuses et tres parcellaires. Toutefois, elles montrent que dans le respect des contre-indications et des recommandations du calendrier vaccinal, les vaccins restent le plus souvent bien toleres et immunogenes, meme si le pourcentage de sujets repondeurs reste inferieur a celui observe dans la population non immunodeprimee. Par ailleurs, des recommandations vaccinales specifiques a cette population ont ete elaborees, mais demeurent imprecises et incompletes, refletant la encore un manque de donnees sur ce sujet. Perspectives Des etudes complementaires demeurent necessaires pour preciser l’immunogenicite et la tolerance des vaccins chez les adultes immunodeprimes. En attendant, une harmonisation des pratiques vaccinales des adultes immunodeprimes pourrait etre proposee, afin d’aider les praticiens a mieux vacciner cette population.

Objective: We wanted to describe the epidemiological aspects of infective endocarditis (IE) in a French hospital and identify the prognostic factors. Methods: We reviewed the clinical, echocardiographic and microbiological features, and the outcome of 89 patients (90 episodes, median age 60 years) with IE over 18 months. Logistic regression analysis was used to identify prognostic factors for death. Results: A native valve was involved in 68 cases (75.5%); in 7 of these the patient was an intravenous drug user. A prosthetic valve was involved in 22 cases (24.5%); 5 of these were of early onset. Diagnosis was definite in 87% of cases. Median time to diagnosis was 3 days. Twenty-five patients (28%) were immunocompromised. A portal of entry, usually cutaneous, was identified in 65% of cases. Sixty-two percent of patients had an underlying heart disorder, usually degenerative. The infection involved the left heart in more than 75% of cases. One or more vegetations were detected in 75% of cases. The median size of vegetation was 15 mm. Isolated agents were mainly staphylococci ( n =40 (44%), including 12 coagulase-negative isolates), and streptococci ( n =23 (25%), including 7 enterococci). In 11 cases (12%), cultures remained negative. Nineteen episodes were nosocomial and Staphylococcus aureus was implicated in 11 of them. Fifty percent of patients had at least one complication: heart failure ( n =42), kidney failure ( n =44), embolism ( n =35), septic shock ( n =19). Surgery was performed in 49 cases (54%) due to heart failure ( n =19), cerebral embolism ( n =12), and/or severe valve lesions ( n =27). Eighteen patients died, 10 of whom were infected with S. aureus . Nosocomial IE ( P =0.0008), heart failure ( P =0.004) and prosthetic valve ( P =0.01), but not S. aureus were independently associated with death. Conclusions: S. aureus was the main microorganism isolated in our patients. However, it was not independently predictive of fatal outcome.

Background and purpose Traumatic thoracic spine instability is a rare but difficult-to-treat entity, particularly above T5 where pedicle screwing is widely regarded as an unsatisfactory option and anterior surgery is considered difficult because of the anatomic relationship with the shoulder and large vessels. Methods A case of T4 and T5 pseudarthrosis after posterior fixation is reported. It was treated with transpleural corpectomy and fixation, with bone morphogenic protein used to obtain rapid arthrodesis between T3 and T6. No bracing or second posterior fixation was used. Result At 45 days of follow-up, the patient was without pain and the neurologic examination was normal. The CT scan showed bony bridges across all fracture lines. Complete cure of this pseudarthrosis was achieved with a single surgery. At the 12-month follow-up, the clinical status was normal. Conclusions The use of bone morphogenic proteins might be of great help in rare but challenging cases of spinal pseudarthrosis, with a quick return to normal activity after a single-stage surgery.

Introduction Les malades respiratoires chroniques font l’objet de recommandations vaccinales particulieres. L’objectif de cette etude etait d’evaluer leur couverture vaccinale contre la grippe et le pneumocoque ainsi que leurs connaissances sur la vaccination. Methodes En 2013, les adherents des 60 associations regionales ou departementales de malades respiratoires chroniques regroupees au niveau national par la FFAAIR, ont ete sollicites pour repondre a un questionnaire en ligne sur ces points. Resultats Parmi les 340 repondants (femmes : 42 %, > 50 ans : 88 %), 179 (53 %) etaient atteints d’un syndrome d’apnee obstructive du sommeil (SAOS), 159 (47 %) d’une BPCO et 84 (25 %) d’asthme. La couverture vaccinale contre la grippe etait de respectivement 58 %, 81 % et 84 % dans les groupes SAOS, BPCO et asthme. Concernant la vaccination pneumocoque le taux de couverture etait de 71 % dans le groupe BPCO et 44 % dans le groupe Asthme. Les sources d’informations principales des patients sur la vaccination etaient le corps medical (62 %), les medias (32 %) et les associations de malades (19 %). Seuls 52 % des repondants ont declare disposer d’informations suffisantes sur la vaccination. Le corps medical (89 %) et en particulier le medecin generaliste (74 %) ont ete designes comme les sources les plus susceptibles d’apporter une meilleure connaissance sur la vaccination. Conclusion En depit des recommandations, les couvertures vaccinales contre la grippe et le pneumocoque sont inferieures au niveau attendu chez ces patients souffrant de maladies respiratoires chroniques. Il existe une demande des patients d’obtention, de la part de leurs medecins, d’informations supplementaires concernant la vaccination.

The follow-up of patients with postoperative infection of the spine required a multidisciplinary teamwork under the guidance of the spine surgeon and the infectious disease (ID) specialist. During follow-up, the spine surgeon has to ensure the absence of neurological, mechanical and implant-related complications using clinical parameters and different imaging modalities. The ID physician has to give particular attention to antimicrobial efficacy and toxicity, especially during the first weeks when patients necessitate high-dose intravenous treatment.

Vaccination guidelines in patients with cystic fibrosis associate the usual vaccination schedule with specific recommendations concerning influenza, Pneumococcus, viral hepatitis A and B and varicella. Live attenuated vaccines are not contra-indicated but must be administered before pulmonary transplantation. Clinical studies evaluating vaccine efficacy in this population are still necessary. Development of new vaccines against respiratory infections (Staphylococcus aureus, Pseudomonas aeruginosa and Syncitial Respiratory Virus in particular) is an important challenge for the medical management of these patients.

It remains unclear how the detection of hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) should be interpreted and whether all patients with this pattern need to be tested for hepatitis B virus (HBV)-DNA. This study aimed at reassessing the significance of 'anti-HBc alone' in unselected sera referred to the clinical laboratory and determining whether significant HBV viraemia can be found in this setting. Of the 6431 patients tested for HBsAg, total anti-HBc and anti-HBs in a Paris hospital over a 1-year period, 362 (5.6%) had 'anti-HBc alone' (24.8% of anti-HBc-positive patients). Only 11 of the 362 sera (3.0%) were found to be false positive. One patient was in the resolving phase of acute hepatitis B. HBV-DNA was detected in 10 of 362 (2.8%) patients, using a commercial standardized assay (threshold: 350 IU/mL). Viral loads exceeded 10(4) copies/mL in 6 of 10 patients. Mutations in the HBsAg immunodominant region were identified in seven of the viraemic patients. HBsAg was detected in only two cases when retested by one of the latest, multivalent assays. Neither human immunodeficiency virus nor hepatitis C virus serostatus distinguished between patients with and without HBV-DNA. In conclusion, 'anti-HBc alone' should be considered a risk marker for a so-called 'false occult' HBV infection with significant viraemia. Indeed, results in this hospital population indicate that a small proportion of patients with 'anti-HBc alone' have high viral loads, revealing the occurrence of infection with HBV mutants that escape detection even by multivalent HBsAg assays.

SummarySpinal cord injury is an important contributing factor to morbidity. The thoracolumbar junction is a highly vulnerable axial region due to the biomechanical stresses and the risk of conus medullaris injuries in some cases. In the event of an incomplete neurological injury and if the patient's condition is stable, emergency surgical treatment should be considered. Yet, no clear consensus has emerged regarding the treatment modalities of complete injuries but surgical management is advocated to maximize neurological recovery and reduce the risk of decubitus ulcer formation. We report on the cases of three patients with L1 Frankel A paraplegia resulting from injury to the conus medullaris, treated within the first 6hours from injury and demonstrating a very satisfactory neurological recovery since independent walking could be resumed at 2.5 years follow-up. Persistent urinary sphincter dysfunctions were observed in two of these patients. Early surgical management appears as an important predictive factor for neurological recovery in conus medullaris injuries. We believe that delayed surgical management in patients with complete paraplegia could be an inappropriate treatment option, which should be further studied.

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

Traumatic thoracic spine instability is a rare but difficult-to-treat entity, particularly above T5 where pedicle screwing is widely regarded as an unsatisfactory option and anterior surgery is considered difficult because of the anatomic relationship with the shoulder and large vessels.A case of T4 and T5 pseudarthrosis after posterior fixation is reported. It was treated with transpleural corpectomy and fixation, with bone morphogenic protein used to obtain rapid arthrodesis between T3 and T6. No bracing or second posterior fixation was used.At 45 days of follow-up, the patient was without pain and the neurologic examination was normal. The CT scan showed bony bridges across all fracture lines. Complete cure of this pseudarthrosis was achieved with a single surgery. At the 12-month follow-up, the clinical status was normal.The use of bone morphogenic proteins might be of great help in rare but challenging cases of spinal pseudarthrosis, with a quick return to normal activity after a single-stage surgery.