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.

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.

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.

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.

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.

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.

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.

Herpes simplex encephalitis and management of acyclovir in encephalitis patients in France.

This study reports on the clinical profiles of herpes simplex encephalitis (HSE) case-patients and the management of acyclovir prescriptions. We designed a study on the causes of encephalitis in France in 2007. Case-patients fulfilling the inclusion criteria were enrolled in all the hospitals that volunteered to participate. Fifty-five of 253 enrolled case-patients were diagnosed with HSE. Three (5%) HSE patients died and 48 (89%) were discharged with persistent neurological symptoms. All HSE patients were prescribed acyclovir, 10 of whom had a 2-week course; 42 a 3-week course; two received incomplete courses; and one received two courses of 21 days each due to relapse. The acyclovir dosage was reported for 45 adult HSE patients, 25 (53%) of whom received 10 mg/kg t.i.d. and 22 (47%) received 15 mg/kg t.i.d. The mortality rate was low despite 49% of patients being admitted to intensive-care units. A high dose of acyclovir was not associated with a better outcome in HSE patients. Most patients had persisting symptoms on discharge suggesting neuropsychological rehabilitation is an important issue for survivors.

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.

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.

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.

Adult intensive-care patients with 2009 pandemic influenza A(H1N1) infection.

In 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.

Rabid dog illegally imported to France from Morocco, August 2011.

In August 2011, a case of canine rabies was notified to the French veterinary services. The dog was a three-month-old puppy illegally imported from Morocco that presented behavioural changes on 1 August and was admitted to a veterinary clinic on 6 August. It died the following day and the body was shortly sent to the national reference centre where rabies was laboratory-confirmed on 11 August. Contact tracing and post-exposure treatment were initiated immediately.

Severe hospitalised 2009 pandemic influenza A(H1N1) cases in France, 1 July-15 November 2009.

From 1 July 2009 to 15 November 2009, 244 patients with 2009 pandemic influenza A(H1N1) were admitted to intensive care unit (ICU) and were compared with 514 cases hospitalised in medical wards in France until 2 November 2009. Detailed case-based epidemiological information and outcomes were gathered for all hospitalised cases. Infants and pregnant women are overrepresented among cases admitted to ICU with seven per cent for both groups respectively, and twenty per cent of ICU cases did not belong to a risk group. Chronic respiratory disease was the most common risk factor among cases but obesity (body mass index >or= 30 Kg/m(2)), chronic cardiac disease and immunosuppression were risk factors associated with severe illness after adjustment for age and for other co-morbidities.

Is there a need for anti-rabies vaccine and immunoglobulins rationing in Europe?

Rabies is a lethal encephalitis caused by a lyssavirus and transmitted from animals to humans via bite wound, scratch wound, or licking of mucous membranes. It is preventable by timely administration of post-exposure prophylaxis (PEP) consisting of four or five doses of rabies vaccine combined, in the most severe cases of exposures, with anti-rabies immunoglobulin (RIG). Although the rabies incidence in humans remains low, rabies is still present in some European countries. Moreover, rabid animals imported from enzootic areas are reported every year in rabies-free areas. These importations threaten the rabies-free status of terrestrial animals in western European countries and challenge the public health surveillance system and the health structures responsible for rabies prophylaxis and control. The importations frequently result in the prescription of a large number of PEP including RIG, especially in western European countries. The situation is inverted in some central and eastern European countries where RIG is underprescribed. Only a limited number of rabies vaccines and particularly of RIG are licensed for use in Europe. Their availability is also limited, a situation that may become worse in the future. It therefore seems important to study the possibility of comparing and unifying national PEP guidelines in Europe, if needed, and to generate effective solutions in the event of a shortage of anti-rabies biological products and RIG in particular, such as rationing these products.

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.

Haemorrhagic Fever with Renal Syndrome: an analysis of the outbreaks in Belgium, France, Germany, the Netherlands and Luxembourg in 2005.

This article aims to describe the Haemorrhagic Fever with Renal Syndrome (HFRS) situation in 2005 in five neighbouring countries (Belgium, France, Germany, the Netherlands and Luxembourg) and define the most affected areas. The 2005 HFRS outbreaks in these countries were the most significant in the region since 1990, with a total of 1,114 confirmed cases. The main feature of the epidemic was the extension of the known endemic area in several of the affected countries, with the involvement of urban areas for the first time. A significant increase in the number of cases was noted for the first time in the province of Liège in Belgium and in the Jura department in France.

[Infectious encephalitis in France from 2000 to 2002: the hospital database is a valuable but limited source of information for epidemiological studies]. / Encéphalites infectieuses: données et limites du PMSI pour l'étude épidémiologique, France métropolitaine 2000-2002.

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.

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.