Changing profile of encephalitis: Results of a 4-year study in France.

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 Chi2 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.

Management of infectious encephalitis in adults: Highlights from the French guidelines (short version).

The article highlights the French clinical guidelines for the management of adult patients with acute infectious encephalitis.

Cerebrospinal fluid lactate concentration and bacterial encephalitis diagnosis.

OBJECTIVES: 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 AND METHODS: 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. RESULTS: 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/mm3 (range: 0-450), 1.2g/L (range: 0.2-8.2), 3.9mmol/L (range: 0.8-8.8), and 2.8mmol/L (range: 0-9.4). In univariate analysis, CSF protein level (P<0.01), WBC count (P=0.02), and lactate concentration (P<0.01) were significantly associated with bacterial etiology. The only factor independently associated with bacterial etiology in the multivariate analysis was CSF lactate concentration. The area under the ROC curve of CSF lactate for the diagnosis of bacterial encephalitis was 0.86. The cut-off value of 3.4 mmol/L correctly classified 87.8% of patients with 70% sensitivity, 91.5% specificity, 64% positive predictive value, and 93% negative predictive value. CONCLUSION: A high CSF lactate level seems to be a better predictor than WBC or proteins to differentiate bacterial encephalitis from other etiologies.

Strengthened Ebola surveillance in France during a major outbreak in West Africa: March 2014-January 2016.

Introduction An unprecedented outbreak of Ebola virus diseases (EVD) occurred in West Africa from March 2014 to January 2016. The French Institute for Public Health implemented strengthened surveillance to early identify any imported case and avoid secondary cases. METHODS: Febrile travellers returning from an affected country had to report to the national emergency healthcare hotline. Patients reporting at-risk exposures and fever during the 21st following day from the last at-risk exposure were defined as possible cases, hospitalised in isolation and tested by real-time polymerase chain reaction. Asymptomatic travellers reporting at-risk exposures were considered as contact and included in a follow-up protocol until the 21st day after the last at-risk exposure. RESULTS: From March 2014 to January 2016, 1087 patients were notified: 1053 were immediately excluded because they did not match the notification criteria or did not have at-risk exposures; 34 possible cases were tested and excluded following a reliable negative result. Two confirmed cases diagnosed in West Africa were evacuated to France under stringent isolation conditions. Patients returning from Guinea (n = 531; 49%) and Mali (n = 113; 10%) accounted for the highest number of notifications. CONCLUSION: No imported case of EVD was detected in France. We are confident that our surveillance system was able to classify patients properly during the outbreak period.

Brucella suis biovar 2 infection in humans in France: emerging infection or better recognition?

Brucellosis is usually acquired by humans through contact with infected animals or the consumption of raw milk from infected ruminants. Brucella suis biovar 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.

Update and new insights in encephalitis.

Infectious encephalitis is a rare but severe medical condition resulting from direct invasion of the brain by viruses, bacteria, fungi or parasites, or indirect post-infectious immune or inflammatory disorders when the infectious agent does not cross the blood-brain barrier. Infectious encephalitis cases represent an interesting and accurate sentinel to follow up on trends in infectious diseases or to detect emerging infections. Using Pubmed and Embase, we searched the most relevant publications over the last years. We present here an update on the important findings and new data recently published about infectious encephalitis.

Epidemiology of infectious encephalitis causes in 2016.

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).

Human brucellosis in France in the 21st century: Results from national surveillance 2004-2013.

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.

Travel-associated and autochthonous Zika virus infection in mainland France, 1 January to 15 July 2016.

During summer 2016, all the conditions for local mosquito-borne transmission of Zika virus (ZIKV) are met in mainland France: a competent vector, Aedes albopictus, a large number of travellers returning from ZIKV-affected areas, and an immunologically naive population. From 1 January to 15 July 2016, 625 persons with evidence of recent ZIKV infection were reported in mainland France. We describe the surveillance system in place and control measures implemented to reduce the risk of infection.

10 years of surveillance of human tularaemia in France.

Tularaemia has been mandatorily notifiable in France since October 2002. The surveillance aims to detect early any infection possibly due to bioterrorism and to follow up disease trends. We report the results of national surveillance from 2002 to 2012. A case is defined as a patient with clinical presentation suggestive of tularaemia and biological confirmation of infection or an epidemiological link with a biologically confirmed case. Clinical, biological and epidemiological data are collected using a standardised notification form. From 2002 to 2012, 433 cases were notified, with a median age of 49 years (range 2 to 95 years) and a male­female sex ratio of 1.8. Most frequent clinical presentations were glandular tularaemia (n=200; 46%) and ulceroglandular tularaemia (n=113; 26%). Most frequent at-risk exposures were handling hares (n=179; 41%) and outdoor leisure exposure to dust aerosols (n=217; 50%). Tick bites were reported by 82 patients (19%). Ten clusters (39 cases) were detected over the 10-year period, as well as a national outbreak during winter 2007/2008. The tularaemia surveillance system is able to detect small clusters as well as major outbreaks. Surveillance data show exposure to dust aerosols during outdoor leisure activities to be a major source of contamination in France.

Shopper cards data and storage practices for the investigation of an outbreak of Shiga-toxin producing Escherichia coli O157 infections.

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.

Encephalitis due to Mycobacterium tuberculosis in France.

PURPOSE: 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). METHODS: 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. RESULTS: 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; P<10(-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. DISCUSSION: 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.

Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium.

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.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Epidemiology of infectious encephalitis, differences between a prospective study and hospital discharge data.

The 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 < 0·001). The incidence of encephalitis in France in 2007 was estimated as 2·6 cases/100 000 inhabitants. HSV and VZV were the most frequent aetiological agents in both databases with similar rates. Listeria monocytogenes and Mycobacterium tuberculosis were less frequent in PMSI than in the study (Listeria: 2% vs. 5%, P = 0·001; Mycobacterium: 2% vs. 8%, P < 0·001). The case-fatality ratios were similar, except for Listeria (46% in the study vs. 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.

Re-emergence of brucellosis in cattle in France and risk for human health.

A case of human brucellosis was diagnosed in France in January 2012. The investigation demonstrated that the case had been contaminated by raw milk cheese from a neighbouring dairy farm. As France has been officially free of bovine brucellosis since 2005, veterinary investigations are being conducted to determine the origin of the infection and avoid its spread among other herds. Hypotheses about the source of this infection are discussed.

Outbreak of haemolytic uraemic syndrome due to Shiga toxin-producing Escherichia coli O104:H4 among French tourists returning from Turkey, September 2011.

Eight cases of diarrhoea, including two cases of haemolytic uraemic syndrome (HUS), were identified among 22 French tourists who travelled to Turkey in September 2011. A strain of Escherichia coli O104:H4 stx2-positive, eae-negative, hlyA-negative, aggR-positive, ESBL-negative was isolated from one HUS case. Molecular analyses show this strain to be genetically similar but not indistinguishable from the E. coli O104:H4 2011 outbreak strain of France and Germany. Although the source of infection was not identified, we conclude that the HUS cases had probably been infected in Turkey.