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International audience; CONTEXT: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson’s Chi(2) test, and means were compared using Student’s t-test for continuous variables. RESULTS: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines. more...

This paper was prepared thanks to the collective expertise carried out by the ANSES emergency collective expert appraisal group (GECU) “Monkeypox – Food” (ANSES opinion no 2022-SA-0110), chaired by Nadia Haddad, and whose members are cited in the authors.; International audience; Monkeypox (MPX) is a zoonotic infectious disease caused by Monkeypox virus (MPXV), an enveloped DNA virus belonging to the Poxviridae family and the Orthopoxvirus genus. Since early May 2022, a growing number of human cases of Monkeypox have been reported in non-endemic countries, with no history of contact with animals imported from endemic and enzootic areas, or travel to an area where the virus usually circulated before May 2022. This qualitative risk assessment aimed to investigate the probability that MPXV transmission occurs through food during its handling and consumption. The risk assessment used “top-down” (based on epidemiological data) and “bottom-up” (following the agent through the food chain to assess the risk of foodborne transmission to human) approaches, which were combined. The “top-down” approach first concluded that bushmeat was the only food suspected as a source of contamination in recorded cases of MPXV, by contact or ingestion. The “bottom-up” approach then evaluated the chain of events required for a human to become ill after handling or consuming food. This approach involves several conditions: (i) the food must be contaminated with MPXV (naturally, by an infected handler or after contact with a contaminated surface); (ii) the food must contain viable virus when it reaches the handler or consumer; (iii) the person must be exposed to the virus and; (iv) the person must be infected after exposure. Throughout the risk assessment, some data gaps were identified and highlighted. The conclusions of the top-down and bottom-up approaches are consistent and suggest that the risk of transmission of MPXV through food is hypothetical and that such an occurrence was never reported. In case of contamination, cooking (e.g., 12 min at 70°C) could be considered effective in inactivating Poxviridae in foods. Recommendations for risk management are proposed. To our knowledge, this is the first risk assessment performed on foodborne transmission of MPXV. more...

International audience; Purpose Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. Methods We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) >= 80 years. Results Of the 494 adults with encephalitis enrolled, 258 (52%) were >= 65 years, including 74 (15%) >= 80 years. Patients >= 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm(3)[13-220] in 65-79 years, 62 [17-180] in >= 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in >= 80 years (P < 0.001). Age >= 80 years, coma on admission, CSF protein >= 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality. Conclusion Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group. more...

International audience; BACKGROUND:On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.METHODS:In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done.FINDINGS:The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.INTERPRETATION:We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. more...

Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses. more...

Background New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. Results As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. Conclusions No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis. more...

International audience

Background: Though women increasingly make up the majority of medical-school and other science graduates, they remain a minority in academic biomedical settings, where they are less likely to hold leadership positions or be awarded research funding. A major factor is the career breaks that women disproportionately take to see to familial duties. They experience a related, but overlooked, hurdle upon their return: they are often too old to be eligible for 'early-career researcher' grants and 'career-development' awards, which are stepping stones to leadership positions in many institutions and which determine the demographics of their hierarchies for decades to come. Though age limits are imposed to protect young applicants from more experienced seniors, they have an unintended side effect of excluding returning workers, still disproportionately women, from the running. Methods: In this joint effort by the European Society of Clinical Microbiology and Infectious Diseases, the Federation of European Microbiological Societies, the Infectious Disease Society of America, the International Society for Infectious Diseases and the Swiss Society for Infectious Diseases, we invited all European Congress of Clinical Microbiology and Infectious Diseases-affiliated medical societies and funding bodies to participate in a survey on current 'early-career' application restrictions and measures taken to provide protections for career breaks. Recommendations: The following simple consensus recommendations are geared to funding bodies, academic societies and other organizations for the fair handling of eligibility for early-career awards: 1. Apply a professional, not physiological, age limit to applicants. 2. State clearly in the award announcement that career breaks will be factored into applicants' evaluations such that: • Time absent is time extended: for every full-time equivalent of career break taken, the same full-time equivalent will be extended to the professional age limit. • Opportunity costs will also be taken into account: people who take career breaks risk additional opportunity costs, with work that they did before the career break often being forgotten or poorly documented, particularly in bibliometric accounting. Although there is no standardized metric to measure additional opportunity costs, organizations should (a) keep in mind their existence when judging applicants' submissions, and (b) note clearly in the award announcement that opportunity costs of career breaks are also taken into account. 3. State clearly that further considerations can be undertaken, using more individualized criteria that are specific to the applicant population and the award in question. The working group welcomes feedback so that these recommendations can be improved and updated as needed. more...

BackgroundOn 7 February 2020, French Health authorities were informed of a confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an Englishman infected in Singapore who had recently stayed in a chalet in the French Alps. We conducted an investigation to identify secondary cases and interrupt transmission.MethodsWe defined as a confirmed case a person linked to the chalet with a positive reverse-transcription polymerase chain reaction sample for SARS-CoV-2.ResultsThe index case stayed 4 days in the chalet with 10 English tourists and a family of 5 French residents; SARS-CoV-2 was detected in 5 individuals in France, 6 in England (including the index case), and 1 in Spain (overall attack rate in the chalet: 75%). One pediatric case, with picornavirus and influenza A coinfection, visited 3 different schools while symptomatic. One case was asymptomatic, with similar viral load as that of a symptomatic case. Seven days after the first cases were diagnosed, 1 tertiary case was detected in a symptomatic patient with from the chalet a positive endotracheal aspirate; all previous and concurrent nasopharyngeal specimens were negative. Additionally, 172 contacts were monitored; all contacts tested for SARS-CoV-2 (N = 73) were negative.ConclusionsThe occurrence in this cluster of 1 asymptomatic case with similar viral load as a symptomatic patient suggests transmission potential of asymptomatic individuals. The fact that an infected child did not transmit the disease despite close interactions within schools suggests potential different transmission dynamics in children. Finally, the dissociation between upper and lower respiratory tract results underscores the need for close monitoring of the clinical evolution of suspected cases of coronavirus disease 2019. more...

A French national study on infectious encephalitis enrolled 253 patients in 2007. Fifty-two per cent of patients had a proven etiological diagnosis; 16% had bacterial encephalitis. We aimed to assess the predictive value of CSF lactate concentration to diagnose bacterial encephalitis.Patients from the 2007 cohort whose CSF lactate concentration was available were included. Clinical and biological features associated with a bacterial etiology were assessed using univariate analysis and multivariate logistic regression. The ROC curve of CSF lactate concentration was used to define the most appropriate cut-off associated with bacterial etiology.Fifty-seven patients (37 men, 20 women) were included. Ten patients had bacterial encephalitis, 20 patients had viral encephalitis. The mean CSF white blood cells (WBC), protein, glucose, and lactate levels were respectively 92 cells/mmA high CSF lactate level seems to be a better predictor than WBC or proteins to differentiate bacterial encephalitis from other etiologies. more...

Introduction L’immunodepression (ID) est un facteur de risque de gravite et de mauvais pronostic chez les patients presentant une infection. Nous decrivons les patients immunodeprimes (ID) inclus dans la cohorte ENCEIF, cohorte prospective multicentrique portant sur les encephalites prises en charge en France entre 2016 et 2019. Notre objectif secondaire etait de les comparer avec les patients non-immunodeprimes (NID) de la cohorte, ainsi qu’avec les patients ID d’une cohorte precedente (encephalites 2007). Materiels et methodes Les patients ont ete inclus selon la definition 2013 de l’International Encephalitis Consortium (Venkatessan et al., CID 2013). Les informations demographiques, cliniques et diagnostiques ont ete recueillies de facon standardisee. La definition de l’ID comprenait : une tumeur solide active traitee ou en remission recente, une transplantation d’organe solide ou de cellules souches hematopoietiques, une immunodepression congenitale, un traitement par corticoides a dose elevee, par inhibiteur de calcineurine ou par certains anticorps monoclonaux. L’analyse statistique a utilise le test du Chi2 de Pearson, le test de Student et, si necessaire, les tests non-parametriques. Resultats Au 16 octobre 2019, 476 patients avaient ete inclus, 59 (12 %) etaient ID. Les etiologies les plus frequentes chez ces patients ID etaient VZV (25 %), HSV (21 %), L. monocytogenes (10 %), C. neoformans (5 %) et JC virus (5 %). Quarante et un pour cent de ces patients avaient un antecedent d’hemopathie maligne, 25 % de cancer solide, 25 % etaient receveurs d’une transplantation, 22 % avaient une pathologie inflammatoire systemique, et 11 % etaient traites par un medicament immunosuppresseur pour une autre raison (certains patients cumulaient plusieurs motifs d’ID, expliquant un total superieur a 100 %). Les patients ID etaient significativement plus âges que les patients NID (âge moyen 71 ans vs 58 ans, p Conclusion Seuls 12 % des patients de la cohorte etaient ID mais leur pronostic etait plus souvent defavorable. La frequence de certains pathogenes tels que VZV ou Listeria souligne l’importance de la prevention quand elle est possible (vaccination VZV, chimioprophylaxie, recommandations alimentaires). more...

Herpes simplex virus (HSV) is the most frequent cause of sporadic infective encephalitis in adults. Despite antiviral therapies, the case fatality rate is moderate to high (5 to 30% according studies and countries). Tools for diagnosis are specific polymerase chain reaction testing of the cerebrospinal fluid on one hand and magnetic resonance imaging on the other hand. Guidelines of various countries recommend systematic treatment by acyclovir 10 mg/kg, three times a day, starting before microbiological confirmation. The remaining question is the usefulness of corticosteroids. This question is related to the frequency of late sequalae (30 to 40% of patients) and the recent demonstration of auto-immune encephalitis triggered by HSV encephalitis. These two possible complications suggest the usefulness of steroids as prophylactic treatment but specific clinical trials are needed for confirmation. Genetic features were recently identified, explaining encephalitis occurrence in some patients, but do not explain all cases so far. more...

Introduction Le diagnostic etiologique des encephalites chez les voyageurs est complique, particulierement quand ils reviennent de zones ou certains vecteurs, animaux reservoirs et pathogenes sont endemiques. Cependant, ces patients peuvent tout aussi bien etre exposes a des pathogenes usuels de leur pays de residence habituel, ou avoir ete infectes avant leur voyage. Des donnees solides sont necessaires pour prioriser les investigations etiologiques de premiere intention, chez des voyageurs de retour en France et presentant une encephalite presumee infectieuse. Nous decrivons les patients de retour de voyage inclus dans la cohorte ENCEIF, cohorte prospective multicentrique des encephalites prises en charge en France de 2016 a 2019. Materiels et methodes Les patients ont ete inclus de facon prospective selon la definition de l’International Encephalitis Consortium (2013). Les informations demographiques, cliniques et diagnostiques ont ete recueillies de facon standardisee, ainsi que les etiologies identifiees, les destinations de voyage et les expositions a risque. Les voyageurs etaient definis par un sejour hors de France dans les 6 mois precedant l’encephalite, ou qui etaient residents d’un autre pays mais pris en charge lors d’un sejour en France. Resultats Au 16 octobre 2019, 69/476 (15 %) des patients inclus dans la cohorte correspondaient a cette definition de voyageurs. Ils avaient visite, ou residaient en Europe (n = 34), Afrique (n = 20), Asie (n = 5), Moyen-Orient (n = 4), Amerique du Nord (n = 4), Amerique du Sud (n = 1), et Pacifique Sud (n = 1) ; 18/69 (26 %) avaient sejourne en zone tropicale. Les etiologies des encephalites des voyageurs etaient principalement attribuees a HSV (13 %), tuberculose (9 %), mais 13 (19 %) presentaient une arbovirose (West Nile, Encephalite Japonaise, Tick-borne Encephalitis, Chikungunya, Toscana et Zika). Les arbovirus concernaient 20 % des encephalites au decours d’un sejour en Europe. A leur sortie d’hopital, 66 % avaient des sequelles mineures ou pas de sequelles, selon l’evaluation par le Glasgow Outcome Scale. Aucun deces n’a ete rapporte. Quatre patients ont rapporte avoir ete mordus par un carnivore au cours de leur sejour mais aucun n’a presente de rage ou autre infection zoonotique. Conclusion Dans notre cohorte, les arboviroses representent la premiere cause d’encephalite chez les voyageurs (13 %), devant HSV (13 %) et la tuberculose (9 %). Le diagnostic d’arbovirose devrait etre evoque et recherche en premiere ligne chez les voyageurs, y compris au retour d’Europe. Cependant les etiologies usuelles ne doivent pas etre oubliees. Dans notre cohorte, peu de patients ont ete exposes a des animaux pendant leur voyage, ce qui ne permet pas d’evaluer la pertinence de ce potentiel facteur de risque. more...

Introduction Les infections sont frequentes et potentiellement graves chez les personnes âgees en raison de l’immunosenescence et de la prevalence des comorbidites chroniques. De plus, les patients âges peuvent souffrir de troubles cognitifs lies a l’âge et de signes d’infections moins specifiques rendant la detection et la prise en charge des encephalites plus tardives et compliquees que chez les patients plus jeunes. Nous decrivons les patients âges atteints d’encephalite inclus dans la cohorte ENCEIF, cohorte prospective multicentrique des encephalites prises en charge en France de 2016 a 2019. Materiels et methodes Les patients ont ete inclus de facon prospective selon la definition de cas de l’International Encephalitis Consortium (Venkatessan et al., CID 2013). Les informations demographiques, cliniques et diagnostiques ont ete recueillies de facon standardisee. Les patients âges etaient definis par un âge de 65 ans ou plus. L’analyse statistique pour comparer les patients âges aux plus jeunes a utilise le test du Chi2 de Pearson, le test de Student et, si necessaire, des tests non-parametriques. Resultats Au 16 octobre 2019, parmi les 476 patients inclus, 251 (52 %) etaient âges, 120 (25 %) avaient 75 ans ou plus et 29 (6 %) avaient 85 ans ou plus. Parmi les 251 patients âges, 82 (32 %) etaient traites pour une autre pathologie au moment de l’encephalite, vs 27 chez les patients plus jeunes (12 %, p Conclusion Les patients âges de plus de 65 ans representent plus de la moitie des encephalites en France. Comme pour les plus jeunes, les etiologies les plus frequentes sont HSV et VZV, mais les listerioses sont plus representees. Les patients âges ont une mortalite intra-hospitaliere elevee (12 %), mais la majorite des survivants presente un pronostic favorable a la sortie d’hopital. more...

Introduction L’encephalite a tique (TBE) est une infection virale endemique dans plusieurs pays d’Europe centrale et du Nord, mais rare en France, ou la plupart des cas sont recenses en Alsace. En juin 2017 et aout 2018, deux cas de TBE ont ete diagnostiques par serologie specifique chez des patients du CHU de St-Etienne n’ayant pas quitte la Loire ou la Haute-Loire. Materiels et methodes Une enquete epidemiologique a ete menee afin d’identifier des expositions a risque dans le mois precedant l’apparition des premiers signes cliniques. Resultats L’interrogatoire a distance des patients et de l’entourage du premier cas a permis d’exclure tout sejour en zone endemique en France ou a l’etranger, ainsi que toute consommation de produits a base de lait cru. En revanche, ces deux patients vivent en bordure du massif forestier du Livradois-Forez qu’ils frequentent de maniere occasionnelle ou reguliere, les exposant au risque de piqure de tique. Les dates de debut des signes coincident d’ailleurs avec la saison de proliferation des tiques. Une quinzaine de jours avant le debut des signes cliniques, le premier cas a effectue une randonnee au pied du Mont Bar, en Haute-Loire, au cours de laquelle il a ete pique par des animaux, a priori des arthropodes, qu’il n’a pas identifies. Le second cas est une eleveuse de bovins retraitee, ayant l’habitude de se rendre dans les forets aux alentours de sa ferme situee dans la Loire. Elle rapporte de nombreuses piqures de tiques, notamment le mois precedant les premiers signes cliniques. Conclusion La mise en evidence du virus associe a TBE (TBEV) dans le secteur du Livradois-Forez, avec une transmission a l’homme, necessite l’information des cliniciens susceptibles de prendre en charge des patients de retour ou vivant dans cette zone, et presentant des manifestations cliniques evocatrices de TBE. Un 3e cas d’infection acquise dans la region a ete diagnostique ulterieurement chez un touriste residant dans une autre region. Une estimation de la prevalence du TBEV dans les tiques de la region serait interessante. Enfin, ces cas confirment une zone d’extension du virus plus large qu’historiquement connue. Cette extension du TBEV en France necessite d’etre evaluee, pour adapter si besoin les mesures de prevention, et faciliter la detection des cas humains. more...

SUMMARYBrucellosis is usually acquired by humans through contact with infected animals or the consumption of raw milk from infected ruminants.Brucella suisbiovar 2 (BSB2) is mainly encountered in hares and wild boars (Sus scrofa), and is known to have very low pathogenicity to humans with only two case reports published in the literature. Human cases of brucellosis caused by BSB2 were identified through the national mandatory notification of brucellosis. The identification of the bacterium species and biovar were confirmed by the national reference laboratory. Epidemiological data were obtained during medical follow-up visits. Seven human cases were identified between 2004 and 2016, all confirmed by the isolation of BSB2 in clinical specimens. All patients had direct contact with wild boars while hunting or preparing wild boar meat for consumption. Five patients had chronic medical conditions possibly responsible for an increased risk of infection. Our findings suggest that BSB2 might be an emerging pathogen in hunters with massive exposure through the dressing of wild boar carcasses. Hunters, especially those with chronic medical conditions, should be informed about the risk of BSB2 infection and should receive information on protective measures. more...

Our purpose was to summarize the current knowledge about the neurological presentation of Zika virus infection after the perinatal period. Other Flaviviruses infections, such as West Nile virus (WNV) or Japanese encephalitis virus (JEV), can result in neuro-invasive disease such as myelitis, encephalitis, or meningitis. We aimed at describing the specificities of ZV neurological infection. The recent outbreaks demonstrated clearly the neurotropism of ZV. However, by contrast with other Flaviviruses, the most frequent neurological presentation of ZV infection beyond the perinatal period was Guillain-Barre syndrome, especially the demyelination form of GBS. Encephalitis and myelitis seem to occur less frequently after ZV infection than after WNV or JEV infection. The pathophysiology of neurological ZV infections is still poorly understood and no specific treatment is available. Moreover, no data is available about long-term persisting symptoms and possible impairment of patients after the acute clinical episode. more...

International audience; We performed a literature search in the Medline database, using the PubMed website. The incidence of presumably infectious encephalitis is estimated at 1.5-7 cases/100,000 inhabitants/year, excluding epidemics. Infectious encephalitis and immune-mediated encephalitis share similar clinical signs and symptoms. The latter accounts for a significant proportion of presumably infectious encephalitis cases without any established etiological diagnosis; as shown from a prospective cohort study where 21% of cases were due to an immune cause. Several infectious agents are frequently reported in all studies: Herpes simplex virus (HSV) is the most frequent pathogen in 65% of studies, followed by Varicella-zoster virus (VZV) in several studies. Enteroviruses are also reported; being the most frequent viruses in two studies, and the 2nd or 3rd viruses in five other studies. There are important regional differences, especially in case of vector-borne transmission: Asia and the Japanese encephalitis virus, Eastern and Northern Europe/Eastern Russia and the tick-borne encephalitis virus, Northern America and Flavivirus or Alphavirus. Bacteria can also be incriminated: Mycobacterium tuberculosis and Listeria monocytogenes are the most frequent, after HSV and VZV, in a French prospective study. The epidemiology of encephalitis is constantly evolving. Epidemiological data may indicate the emergence and/or dissemination of new causative agents. The dissemination and emergence of causative agents are fostered by environmental, social, and economical changes, but prevention programs (vaccination, vector controls) help reduce the incidence of other infectious diseases and associated encephalitis (e.g., measles). more...

Introduction En juin 2017, deux cas de fievre Q (FQ) ont ete signales a l’Agence regionale de Sante Centre-Val-de-Loire, dans une famille gerant une ferme ovine avec une activite d’accueil touristique. Selon ces exploitants, plusieurs touristes ayant frequente leur ferme avaient aussi presente des symptomes evoquant une FQ. Une investigation a ete menee afin d’identifier le nombre de personnes atteintes de FQ et confirmer la source d’exposition. Materiels et methodes Les touristes ayant frequente la ferme entre le debut de l’agnelage (mars 2017) et le debut de l’investigation (juillet 2017) ont ete contactes et informes de l’exposition a Coxiella burnetii lors de leur sejour. Ces personnes ainsi que la famille exploitant le site ont ete interrogees via un questionnaire standardise : leurs expositions, la survenue de symptomes apres leur sejour, un eventuel diagnostic de FQ et les facteurs de risques de complication et d’infection chronique ont ete recueillis. La confirmation du diagnostic de FQ a ete recherchee pour les personnes ayant presente des symptomes evocateurs et celles non malades mais presentant des facteurs de risque. Une enquete environnementale et veterinaire a ete menee en parallele. Resultats Au total, 139 personnes sur les 198 contactees ont ete interrogees : 15 etaient des cas confirmes de FQ (serologie ou PCR positive) dont une femme enceinte, et 14 des cas suspects (symptomatologie evocatrice sans diagnostic biologique), soit un taux d’attaque compris entre 11 % (15/139) et 21 % (29/139). Vingt-trois des 27 (85 %) touristes qui etaient des cas suspects ou confirmes ont sejourne sur le site pendant la periode de l’agnelage, entre le 17 avril et le 8 mai, soit un taux d’attaque de 35 % (23/66). Des prelevements environnementaux ont montre une contamination faible mais persistante des parties communes d’un bâtiment, frequentees par les cas. Le troupeau n’etait plus excreteur au moment de l’investigation malgre une vague d’avortements survenus debut 2017, possiblement suite a l’introduction d’animaux infectes. Conclusion Cette investigation a permis l’identification d’un cluster de cas de FQ lie a une exploitation agricole recevant du public ; la mise en place d’une prise en charge adaptee pour les personnes a risque de complications ; la confirmation de la source de cette epidemie, avec des prelevements positifs chez l’homme, chez l’animal, et dans l’environnement ; et la mise en place de mesures de gestion. Cette situation illustre la necessite d’une sensibilisation des eleveurs dans les exploitations recevant du public. more...

Introduction Les infections humaines a Mycobacterium bovis sont principalement zoonotiques ; leur incidence depend de l’existence d’une politique de controle de l’infection dans les troupeaux de ruminants. La France est indemne de tuberculose bovine (prevalence M . bovis sont recueillies par le reseau Azay-Mycobacteries et centralisees par le CNR des mycobacteries. Nous avons realise une investigation de l’origine des infections par M . bovis afin de rechercher si la situation en sante animale a des consequences visibles sur la sante humaine en France. Materiels et methodes L’identification des patients et le recueil d’informations cliniques, bacteriologiques et epidemiologiques ont ete realises aupres des biologistes, des medecins traitants et des patients a partir des informations collectees par le reseau Azay et le CNR entre 2011 et 2016. Les donnees ont fait l’objet d’une analyse descriptive. Resultats Entre 2011 et 2016, 198 cas d’infection par M . bovis ont ete identifies parmi 9397 cas de tuberculose identifies par le reseau et le CNR, soit 33 cas par an (min : 23–max : 42). Les patients etaient âges de 1 a 96 ans (mediane : 39 ans), et le sex-ratio H/F etait de 0,9. Parmi eux, 95 etaient nes dans des pays ou l’incidence des infections a M . bovis est elevee (84 [43 % du total] etaient nes dans un pays du Maghreb, et 11 [6 % du total] en Afrique sub-saharienne), 12 (6 %) en Europe, Asie et Ameriques et 46 (23 %) en France, l’information n’etait pas disponible au moment de la notification pour 45 (23 %) d’entre eux. Cent huit (55 %) patients n’avaient jamais recu de traitement antituberculeux auparavant. Cent trente-neuf des 201 (70 %) souches isolees de ces patients etaient sensibles aux antituberculeux testes (INH, RMP, EMB, SM). L’âge median des 46 patients nes en France etait de 62 ans (min : 7, max : 96 ans), 30 (65 %) n’avaient jamais recu de traitement antituberculeux et 40/46 (87 %) etaient infectes par des souches bacteriennes sensibles a tous les antituberculeux. Les donnees epidemiologiques, en particulier les facteurs de risque zoonotiques, sont en cours de recueil. Conclusion Seuls 23 % des patients avec un diagnostic de tuberculose a M . bovis sont nes en France et donc supposement infectes en France. Les investigations en cours permettront de quantifier les expositions de ces patients a des animaux reservoirs et d’estimer une eventuelle consequence pour la sante publique de la situation des troupeaux. more...

Introduction La tularemie est une zoonose, a declaration obligatoire (DO) depuis 2002. Les cycles epidemiologiques presents en France et les facteurs climatiques ou environnementaux qui les influencent sont mal connus. Des augmentations d’incidence se produisent a intervalles irreguliers, avec des caracteristiques des cas inconstantes. Nous rapportons une epidemie majeure survenue en 2018. Materiels et methodes Les cas de tularemie sont identifies par la DO. Un cas est defini comme un patient presentant des signes cliniques evocateurs de tularemie et un diagnostic biologique confirmant l’infection aigue (PCR, isolement bacterien, serologie). Les informations demographiques et les expositions a risque sont recueillies en routine. Les donnees des cas survenus en 2018 sont decrites et comparees aux annees anterieures (2002–2017). La DO dispose d’une autorisation de la CNIL et est conforme au RGPD. Resultats Au 01/02/19, 109 cas de tularemie survenus en 2018 ont ete declares, c’est l’annee de plus forte incidence depuis 2002. Les formes ganglionnaires et ulcero-ganglionnaires etaient les plus frequentes mais les formes pleuro-pulmonaires etaient plus nombreuses en 2018 que les autres annees (21 % vs 10 %, p = 0,001). Deux patients sont decedes. En 2018, le diagnostic etait plus souvent obtenu par isolement de Francisella que toutes les annees precedentes (21 % vs 11 %, p = 0,02). Les regions Bretagne et Pays de la Loire totalisaient 55 % des cas en 2018 avec respectivement 32 (29 %) et 29 (26 %) cas. Les cas survenus en 2018 etaient moins souvent exposes a des lievres (12 % vs 38 %, p Conclusion La surveillance de la tularemie en 2018 en France est marquee par une epidemie survenue dans l’ouest de la France. IL s’agit de l’annee de plus forte incidence depuis l’inscription sur la liste des DO. La survenue de nombreux cas d’atteinte pleuro-pulmonaire et ne presentant pas les facteurs de risque habituels suggere une modification de l’epidemiologie, d’origine non connue a ce jour. La poursuite de la surveillance de la maladie humaine, en lien avec les acteurs de sante animale, sera utile pour etablir s’il s’agit d’une tendance durable ou d’un evenement isole, et essayer d’en comprendre les ressorts. more...

Introduction An outbreak of shiga-toxin producing Escherichia coli infections occurred in southwest France in June 2012. The outbreak was investigated to identify the source of infection, and guide control measures. Methods Confirmed outbreak cases were patients who developed bloody diarrhoea or haemolytic uremic syndrome (HUS) between 28 May and 6 July 2012, with E. coli O157 isolates showing indistinguishable patterns on pulse field gel electrophoresis (PFGE). A standardized questionnaire was administered to patients to document food consumption and other risk exposures. Their purchase was checked through their supermarket shopper card data. Results Six patients (four with HUS and two with bloody diarrhea) were confirmed outbreak cases. Fresh ground beef burgers from one supermarket were the only common food exposure, identified by interviews and shopper card data. The PFGE profile of shiga toxin-producing E. coli O157 isolated from the suspected beef burgers was identical to those from the human cases. The suspected beef burgers were no longer on sale at the time of investigation but three patients confirmed as outbreak cases had deep-frozen some at home. Conclusion Shopper card data was particularly useful to obtain precise and reliable information on the traceability of consumed food. Despite the expired use-by date, a recall was issued for the beef burgers. This contributed to preventing other cases among consumers who had deep-frozen the beef burgers. more...

Background Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. Methods In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis. more...

Referred to by :Recommandations de prise en charge des encéphalites infectieuses de l’adulte – reprise de la version françaisePratique Neurologique - FMC, Volume 9, Issue 3, September 2018, Pages 195-203; International audience; Recommendations/Recommandations more...

Brucellosis is a bacterial zoonotic disease mainly transmitted to humans by ruminants. In France, brucellosis has disappeared from ruminants herds. Human brucellosis surveillance is performed through mandatory notification and the national reference center. Methods We report the results of human brucellosis surveillance from 2004 to 2013 with regards to epidemiological, clinical and microbiological data. Results A total of 250 cases were notified, making an annual incidence of 0.3 cases per million inhabitants. Brucella melitensis biovar 3 was the most frequently identified bacterium (79% of isolated strains). In total, 213 (85%) cases had been contaminated abroad in endemic countries. In 2012, an episode of re-emergence of brucellosis in cattle occurred in Haute-Savoie, in the French Alps, and was responsible for 2 human cases. Conclusion Brucellosis has become a disease of travelers in France. However, maintaining a stringent epidemiological surveillance is necessary to be able to early detect any local re-emergence in humans or animals. The multidisciplinary surveillance was implemented in France years ago and is a successful example of the One Health Concept. more...

SUMMARYThe French epidemiology of infectious encephalitis has been described in a 2007 prospective study. We compared these results with available data (demographic features, causative agents, case-fatality ratio) obtained through the French national hospital discharge 2007 database (PMSI), in order to evaluate it as a surveillance tool for encephalitis. Causative agents were identified in 52% of cases in the study, and 38% in PMSI (P Listeria monocytogenesandMycobacterium tuberculosiswere less frequent in PMSI than in the study (Listeria: 2%vs.5%,P = 0·001;Mycobacterium: 2%vs.8%,P Listeria(46% in the studyvs.16%). Nevertheless, despite the absence of case definitions and a possible misclassification weakening PMSI data, we suggest that PMSI may be used as a basic surveillance tool at a limited cost. more...

Encephalitis is a rare complication of influenza, mostly reported with influenza A and in children. We report two cases of influenza B meningoencephalitis in adults enrolled in the French encephalitis cohort study (ENCEIF) during the 2015–2016 seasonal influenza outbreak. more...

Introduction Brucella sp. est une bacterie facilement transmissible par aerosol, ce qui justifie son inscription sur la liste des agents infectieux de classe 3. Dans le contexte d’une tres faible incidence de la maladie en France, les echantillons cliniques des patients brucelliques representent une menace pour les personnels des laboratoires si les mesures de protection ne sont pas strictement appliquees. Materiels et methodes Les cas de brucellose acquis au laboratoire ont ete identifies via la declaration obligatoire et le CNR. Une investigation systematique a ete menee pour identifier l’origine et les circonstances de la contamination. Les gestes a risque et points critiques du processus diagnostique ont ete analyses. Resultats De 2004 a 2016, 20 cas acquis au laboratoire ont ete identifies (5 % de tous les cas et 45 % des cas autochtones). Douze cas (60 %) etaient des femmes, 16 cas ont ete diagnostiques par isolement d’une souche et 4 par serologie. Treize cas avaient ete contamines en techniquant les prelevements d’un cas importe, et 2 cas en techniquant les prelevements d’un autre cas de laboratoire lui-meme contamine par un cas importe. L’origine des cas index importes etait l’Algerie (n = 6), la Turquie (n = 5), le Maroc (n = 2), l’Inde et le Portugal (n = 1 chacun). Trois cas travaillaient dans un laboratoire disposant d’une collection propre de souches de Brucella. Enfin, pour 2 cas qui travaillaient dans des LABM non specialises en bacteriologie, le patient/prelevement index a l’origine de leur contamination n’a pas pu etre identifie. Pour chaque cas de contamination au laboratoire identifie, plusieurs collegues exposes aux memes prelevements ont ete identifies et suivis. L’analyse des pratiques et des differents outils diagnostiques disponibles a permis d’identifier des points critiques pre-analytiques et analytiques : absence de suspicion clinique, absence de poste de securite biologique (PSM), reniflement des milieux de cultures, defaut d’identification par les methodes usuelles. Conclusion La manipulation et le traitement de prelevements cliniques restent la premiere cause de brucellose autochtone dans de nombreux pays indemnes de brucellose animale. La contamination se produit en cas de non-respect des mesures de protection standard dans un contexte ou le diagnostic de brucellose est inattendu. Des rappels frequents sur la dangerosite potentielle de tout prelevement diagnostique sont necessaires pour eviter ces cas secondaires. Des recommandations nationales sont necessaires pour assurer une prise en charge et un suivi des personnels exposes non encore malades. more...

Introduction Bacillus anthracis est une bacterie toxinogene dont la sporulation assure la survie plusieurs decennies dans les sols agricoles. Ce reservoir tellurique constitue un risque majeur pour les animaux et pour les personnes des lors qu’une intervention humaine ou qu’un incident climatique fait emerger des spores bacteriennes a la surface des pâturages. Materiels et methodes En France, le charbon est une maladie a DO chez l’homme et chez l’animal. L’origine des foyers animaux est investiguee par les services deconcentres du ministere de l’Agriculture et l’evaluation de risque pour les personnes contact est realisee par l’ARS en lien avec sante publique France et les services de maladies infectieuses. Une recommandation professionnelle de la SPILF est disponible pour les modalites de prophylaxie. En Russie, la surveillance du charbon est effectuee par les autorites agricoles des Oblasts. Les investigations et la gestion des foyers sont menees en lien avec le laboratoire de reference de la Russie et les autorites militaires. Resultats En Moselle, un foyer de charbon a atteint 6 elevages bovins entre aout et septembre 2016, tuant 30 animaux. Une recommandation de prophylaxie a ete emise pour 54 personnes en contact avec les animaux infectes. Une suspicion de charbon cutane chez la proprietaire de bovins infectes n’a pu etre confirmee biologiquement en raison de la prise d’antibiotiques sans prescription avant la consultation medicale. L’epizootie bovine a ete controlee par la vaccination des troupeaux. Des inondations printanieres associees a un ete sec font partie des hypotheses evoquees comme origine de cet episode. En Yamalie, la fonte du permafrost associee a un deficit de vegetation superficielle a conduit a une epizootie inedite dans des elevages de rennes : 2349 rennes sont morts spontanement, 60 000 ont ete abattus et 450 000 vaccines. Quatre cents personnes ont ete evacuees de la zone epizootique, une centaine hospitalisee sous surveillance et un enfant de 12 ans est decede d’une toxi-infection a B. anthracis. Conclusion Ces 2 episodes, d’intensite differente, partagent des caracteristiques epidemiologiques. Des conditions climatiques conduisant a une modification du sol et du comportement des animaux d’elevage constituent un sur-risque d’exposition et d’infection a des bacteries telluriques, en particulier B. anthracis. L’information et la formation des eleveurs sont necessaire dans les zones connues de charbon. Une evaluation du benefice risque d’une vaccination animale dans le contexte d’evenements climatique anormaux (secheresse, canicule, fonte des sols geles) doit egalement etre menee, dans une approche One Health, pour anticiper et prevenir de futurs foyers animaux et humains. more...

Encephalitis is an inflammation of the brain structures: neurons, vessels or glial cells. However, a consensual definition of the syndrome is difficult to obtain, and it is even more difficult to define encephalitis due a specific agent. Most viruses can be responsible for infectious encephalitis, but the number of encephalitis cases is very limited with regards of the incidence of benign infections from these pathogens. Viruses responsible for encephalitis can be animal-borne, vector-borne or human-to-human transmitted, they can infect preferentially immunocompetent or immunosuppressed patients, and some of them have demonstrated their epidemic potential. Herpes simplex encephalitis is recognized worldwide as the most frequent infectious encephalitis, and the only one with a validated specific treatment. Encephalitis following some viral infections such as measles or rabies can be prevented by vaccination. Unfortunately, effective treatment currently lacks for most encephalitic viral agents identified so far. more...

Background Incidence of infectious encephalitis in France is evaluated to be 0.5 to 1/100,000 inhabitants. That means encephalitis are rare infections, and not all physicians do not have expertise about this disease. In case of complex presentations, they may benefit from advices and guidance from a multidisciplinary group. The French infectious diseases society implemented a group of expertise in 2016 to address clinicians’ difficulties with complex cases in a timely manner. Methods Experts were delegated by scientific societies (Infectious Disease, Microbiology, Neurology, Intensive care and Public Health) with regards to their expertise in brain infections. Any physician facing difficulties to manage a patient presenting as a complex case can ask for advice, using a specific e-mail address (encephalite.spilf@infectiologie.com). They have to provide a detailed summary of the clinical case, together with all available biological and etiological results and, when possible, an access to brain images. The case file is then or circulated by mail or discussed in a conference call, within 48 hours. At the end of the discussion, a written answer is produced (detailed recommendations and justification). The traceability of the advice is kept by the French infectious diseases society for both teaching purposes and legal matters. Results So far we had to examine 32 cases, providing from various hospital in mainland France, French West Indies, and Polynesia: 15 from university hospital and 17 from nonuniversity hospitals. Questions (overlapping in some cases) were related to diagnosis procedure (12), to treatment (4), to interpretation of imaging (5), to management of failure (6), and interpretation of test results (10). Our answers were: investigation for autoimmune or inflammatory disease (15); investigation for tuberculosis and/or treatment (14); investigation for tumour (3); complementary tests for an unusual pathogen (10). Pertinence of the advices was adapted in 20 cases (30 evaluated). Conclusion Such a group seems to be useful, and the organization at a national-level works. It is also the opportunity to extend our network in the field of neurological infections, and to use the submitted cases as education material for young ID fellows. Disclosures All authors: No reported disclosures. more...

SUMMARYIn France, the surveillance of hospitalized cases of pandemic influenza was implemented in July 2009 and restricted to intensive-care unit (ICU) patients in November. We described the characteristics of the 1065 adult patients admitted to ICUs and analysed risk factors for severe outcome (mechanical ventilation or death). Eighty-seven percent of cases were aged 15–64 years. The case-fatality ratio was 20%. The risk for severe outcome increased with age and obesity while this association was negative for chronic respiratory disease. Late antiviral therapy was associated with a severe outcome in ICU patients with risk factors (adjusted OR 2·0, 95% CI 1·4–3·0). This study confirms the considerable contribution of young adults to A(H1N1) 2009 mortality. It shows the role of obesity as an independent risk factor for severe disease, and of early antiviral therapy as a protective factor, at least in patients with risk factors. more...

Resume Contexte La tularemie est une zoonose surveillee en France chez l’homme et chez le lievre. Nous rapportons les resultats de la surveillance de la maladie dans ces deux especes au cours des annees 2007 et 2008. Materiels et methode La tularemie est a declaration obligatoire (DO) chez l’homme depuis 2003. Chez le lievre, la surveillance est volontaire et repose sur le reseau des federations de chasse departementales. Les donnees des DO et de la surveillance volontaire en 2007/2008 ont ete analysees et comparees aux donnees anterieures. Resultats En 2007/2008, 144 cas humains de tularemie et 117 cas chez le lievre ont ete rapportes, soit un doublement par rapport aux annees anterieures. Les cas humains ne differaient de ceux des annees anterieures que par la frequence plus elevee de contact avec des animaux d’elevage et la frequence des cas sans aucune exposition a risque connue. Conclusion Un exces de cas est survenu en 2007/2008 dans les deux especes. Des etudes complementaires sont necessaires afin de determiner l’espece reservoir pour l’homme et le lievre, et ainsi comprendre la survenue de ce pic. more...

Many virus and bacteria can cause encephalitis but are rarely identified as the aetiological agent by individual diagnosis. In France, the only continuous source of information about encephalitis is the national hospital medical database (NHMD). Data from the VIH-negative patients recorded in mainland France between 2000 and 2002 with a diagnosis of encephalitis were extracted and analysed according to demographic, geographical and temporal distribution. Hospitalisation details were described. An average of 1200 patients was recorded each year. They were residents of all French districts and equally hospitalized in university hospitals and non university hospitals. Their mean age was 38, and most were men. The aetiological diagnosis was unknown for 80%. The most frequent aetiological diagnosis was herpes simplex virus in adults, and VZV virus in children. These results give us some clues to design a national study on encephalitis. The study will be implemented in mainland France in 2007 and will last one year. We invite all voluntary hospitals to include their encephalitic patients in our study. more...

Resume Contexte. – Les infections a Hantavirus sont presentes dans le Nord-Est de la France. L'homme se contamine en inhalant des poussieres contaminees par les excretas de rongeurs. En fevrier 2003, le centre national de reference (CNR) des fievres hemorragiques virales signalait un nombre accru d'infections. Une investigation etait initiee afin de confirmer l'exces de cas, de les decrire et de proposer des mesures adequates. Materiel et methode. – Les cas, recenses par le CNR, etaient definis par des signes cliniques evocateurs associes a des IgM et des IgG Puumala chez des patients residant en France. Pour chaque patient, des renseignements cliniques et epidemiologiques etaient recueillis. Resultats. – En 2003, 128 cas ont ete identifies contre 61 en 2002. L'âge median etait de 38 ans et 77 % des cas etaient des hommes ; 82 % etaient hospitalises. Les patients residaient dans le quart Nord-Est du pays avec des clusters importants dans les Ardennes et l'Oise. Les expositions a risque retrouvees etaient l'activite professionnelle (35 %) (Bâtiment, secteur forestier et agriculture), la manipulation de bois (35 %), le jardinage (29 %) et les loisirs en exterieur (14 %). Conclusions. – Cette investigation a confirme l'exces de cas en 2003. La localisation geographique et les expositions a risque etaient conformes a celles rapportees lors de precedentes investigations. La prevention des infections a Hantavirus passe par des mesures individuelles contre les rongeurs et l'exposition a des aerosols de poussieres contaminees. Des moyens d'information des professionnels de sante et du grand public dans les zones a risque sont necessaires pour favoriser ces mesures. more...

Twenty people died of rabies in France between 1970 and 2003 (compared to 55,000 yearly worldwide), 80% on returning from Africa. Dogs were the contaminating animals in 90% of the cases and children were the most common victims. The last instance of rabies in a native French animal was reported in 1998. However the illegal importation of animals still poses a risk. The disease is transmitted by saliva, even before the appearance of clinical symptoms, through a bite, scratch, or licks of mucous membranes or broken skin. Person-to-person transmission has only been observed in cases of grafts (cornea). The mean incubation time of 1 to 3 months is long enough to allow passive immunization and vaccination. After its onset, the disease presents as encephalitis or a paralytic syndrome the outcome of which is always fatal. Clinical diagnosis may be difficult in the early stages of the disease. If rabies is suspected, the National Reference Centre is responsible for the sampling and proper transportation of these samples so as to ensure assessment results within 5 days. If stringent hygiene rules are complied to, there is no risk of contamination for those in close contact. Vaccination, which is performed in official rabies centers, is only performed after a diagnosis based on laboratory evidence, and solely for exposed persons or those for whom a reliable history cannot be established (children under 6 years). Prevention is based on information. People traveling abroad, particularly to Africa, are warned not to approach unknown animals (especially dogs) nor to try to import them, and are advised to comply with vaccinal recommendations for travelers, particularly for toddlers. more...

Introduction L’incidence des encephalites en France se situe entre 0,5 et 1/100 000 habitants. Cette relative rarete fait que tous les praticiens n’ont pas une expertise importante sur cette pathologie. Dans les cas complexes, un appui collegial et multidisciplinaire pour la demarche diagnostique et la gestion des patients peut s’averer utile. Materiels et methodes Un groupe d’experts a ete designe, en fonction des criteres suivants : membres du comite de pilotage de la cohorte encephalite francaise (etude ENCEIF), membres du comite scientifique de la RPC encephalites (organisee par la SPILF), representation des competences cliniques (infectiologie, neurologie, reanimation), microbiologiques (bacteriologie, virologie) et epidemiologiques indispensables. Tout clinicien en charge d’une encephalite complexe peut saisir le groupe au moyen d’une adresse mail dediee ( encephalite.spilf@infectiologie.com ). Une reunion telephonique est alors organisee sous 48 h avec les membres du groupe et le demandeur qui expose son dossier et ses besoins specifiques d’aide au diagnostic etiologique ou a la prise en charge. Une proposition formelle et tracable est alors emise. Un compte rendu est adresse apres la reunion au demandeur. Resultats En 2016, 11 dossiers ont ete soumis au groupe, dont 1 a ete discute en incluant des experts internationaux en raison de sa complexite et sa gravite. Les demandes etaient caracterisees par la diversite et la complexite des questions posees par chaque patient : toutes les competences ont ete necessaires pour la discussion (epidemiologie, valeurs des outils diagnostiques, imagerie, pronostic et prise en charge therapeutique). Dans 9 cas, il s’agissait de patients avec evolution prolongee d’etiologie inconnue au moment de la sollicitation, dans 1 cas d’une possible encephalite a EBV et dans 1 cas, il s’agissait d’une demande parvenue apres le deces brutal du patient. Deux conseils de biopsie cerebrale ont ete donnes dont un a abouti a un diagnostic de lymphome cerebral. Pour 5 patients il a ete considere que l’etiologie la plus probable etait une maladie inflammatoire ou auto-immune, avec conseil de traitement par corticoide ou immunosuppresseur. Pour 3 patients, l’hypothese la plus probable etait une tuberculose. Conclusion Ce centre de ressource semble efficace et utile dans la prise en charge des encephalites se presentant comme infectieuses et permet de reorienter l’hypothese initiale vers des pathologies non infectieuses. La multidisciplinarite apparait indispensable. more...

Introduction Seule la moitie des encephalites presumees infectieuses sont documentees, l’autre moitie ne pouvant beneficier d’un traitement specifique et des interventions de sante publique parfois necessaires. En 2016, la cohorte Etude nationale de cohorte des encephalites infectieuses en France (ENCEIF) a ete mise en place sous l’egide de la SPILF pour etudier les caracteristiques des encephalites en France, leur prise en charge et le pronostic a long terme. Nous presentons les resultats preliminaires de la premiere annee de fonctionnement. Materiels et methodes Les centres volontaires ont inclus les patients adultes (≥ 18 ans) qui remplissaient les criteres de definition de cas de l’International Encephalitis Consortium. Des donnees epidemiologiques, cliniques et biologiques ont ete recueillies par un questionnaire dematerialise dans une application securisee (VoozanooO). Les donnees ont ete comparees a celles de la cohorte Encephalite 2007. Resultats Du 1er janvier au 31 decembre 2016, 152 patients ont ete inclus, d’âge median 63 ans (18 a 90 ans), dont 94 hommes (62 %). Onze (9 %) sont decedes durant l’hospitalisation. Les patients de 2016 et 2007 ne differaient pas en termes d’âge, de sexe ratio, de comorbidites avant l’encephalite et de letalite durant l’hospitalisation. Un diagnostic etiologique etait plus frequemment obtenu en 2016 (60 %) qu’en 2007 (52 %) (NS). Les causes les plus frequentes etaient HSV et VZV dans les 2 cohortes. Des causes rares en 2007 ont ete plus frequentes en 2016 : parmi les contaminations autochtones, l’encephalite a tiques (TBE, n = 8), et a virus Influenza (n = 4), et parmi les cas importes, encephalite liee aux virus West Nile (n = 3), Zika (n = 1), et encephalite Japonaise (n = 1). L’emergence des encephalites a tiques autochtones correspond a une epidemie survenue en Alsace durant l’ete. Conclusion La cohorte ENCEIF permet de suivre les tendances des encephalites en France, aussi bien pour des etiologies classiques telles que HSV ou VZV, que pour la detection de phenomenes rares ou emergents, en particulier des Arbovirus. Le recueil prospectif standardise des sequelles a 6 mois et 1 an permettra de progresser dans un domaine encore meconnu. more...

Summary Background For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies directed against different synaptic proteins or receptors in patients with autoimmune encephalitis have recently been described and could indicate a differential diagnosis of infectious encephalitis. Objective The aim of this study was to retrospectively investigate the presence of autoantibodies directed against synaptic proteins or receptors in patients with acute febrile encephalitis. Samples were collected in France in 2007 during a national prospective study. Methods A total of 253 patients with acute febrile encephalitis were enrolled in 2007. Clinical data were collected with a standardized questionnaire. When possible, cerebrospinal fluid CSF was collected and stored at −80 °C. A total of 108 CSF samples were available for retrospective autoantibody screening. Among the 108 patients, infectious etiology had been detected in 38 cases (35%); of these 38 patients, 29 (27%) had viral encephalitis, and 9 (8%) had bacterial encephalitis. No specific diagnosis was indicated for the other 70 patients (65%). Autoantibodies were detected using a cell-based assay in which HEK293 cells were transfected with plasmids coding for different synaptic proteins or receptors. Results Two patients had anti-NMDA receptor antibodies (NMDAR-Abs), and all patients were negative for anti-Lgi1, CASPR2, GABABR, AMPAR, and mGluR5 antibodies. The two patients with NMDAR-Abs presented neurological and psychiatric symptoms typical of NMDAR-Abs encephalitis. Conclusions Autoimmune etiology seems to be rare (less than 2%) in patients with acute febrile encephalitis. However, patients should be systematically screened for the presence of NMDAR-Abs, particularly patients presenting with psychiatric symptoms. more...

Two hundred and fifty-three patients were included in a study on the etiology of encephalitis, carried out in France in 2007. Tuberculosis was the second most frequently identified cause, after HSV and with the same number of cases as VZV. The authors report the specific features of patients presenting with tuberculosis encephalitis (TE).TE patients were defined as patients presenting with encephalitis, with positive culture or PCR for Mycobacterium tuberculosis, or the association of clinical, biological, imaging, and epidemiological evidence (possible cases). Clinical, microbiological, and brain imaging data was analyzed and compared to that of other included patients.Twenty cases of TE were identified. The M/F sex-ratio was 1.5, the mean age 53 years. Four (20%) patients had a history of tuberculosis before the encephalitis. The median delay between the onset of general and neurological symptoms was significantly longer for tuberculosis cases than for others (10 days vs. 2; P10(-10)). The median CSF protein level was significantly higher for tuberculosis cases (2.1 g/L vs. 0.8 g/L, P=0.002). CT scan and MRI were normal on admission for eight patients out of 17. Fourteen isolated strains of M. tuberculosis were susceptible to first-line anti-tuberculosis drugs and one was rifampicin-resistant. Six (33%) patients died during hospitalization and two were lost to follow-up. Ten out of 12 (78.6%) had persisting neurological symptoms on discharge.Despite non-multiresistant MT strains, the case fatality rate among TE patients was high in our series. Early brain imaging is poor contributive for the diagnosis of TE. more...