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Background Workplace absenteeism increases significantly during influenza epidemics. Sick leave records may facilitate more timely detection of influenza outbreaks, as trends in increased sick leave may precede alerts issued by sentinel surveillance systems by days or weeks. Sick leave data have not been comprehensively evaluated in comparison to traditional surveillance methods. The aim of this paper is to study the performance and the feasibility of using a detection system based on sick leave data to detect influenza outbreaks. Methods Sick leave records were extracted from private French health insurance data, covering on average 209,932 companies per year across a wide range of sizes and sectors. We used linear regression to estimate the weekly number of new sick leave spells between 2016 and 2017 in 12 French regions, adjusting for trend, seasonality and worker leaves on historical data from 2010 to 2015. Outbreaks were detected using a 95%-prediction interval. This method was compared to results from the French Sentinelles network, a gold-standard primary care surveillance system currently in place. Results Using sick leave data, we detected 92% of reported influenza outbreaks between 2016 and 2017, on average 5.88 weeks prior to outbreak peaks. Compared to the existing Sentinelles model, our method had high sensitivity (89%) and positive predictive value (86%), and detected outbreaks on average 2.5 weeks earlier. Conclusion Sick leave surveillance could be a sensitive, specific and timely tool for detection of influenza outbreaks.

International audience; Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.

International audience; Enteroviruses (EV), the major pathogens of hand, foot, and mouth disease (HFMD) and herpangina, affect millions of children each year. Most human enteroviruses cause self-limited infections except polioviruses, enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and several echoviruses (Echo) and coxsackieviruses (CV). Especially, EV-A71 has repeatedly caused large-scale outbreaks in the Asia-Pacific region since 1997. Some Asian countries have experienced cyclical outbreaks of severe EV-A71 infections and initiated development of EV-A71 vaccines. Five EV-A71 vaccine candidates have been clinically evaluated and three of them were approved for marketing in China. However, none of the China-approved products seek marketing approval in other countries. This situation supports a role for collaboration among Asian countries to facilitate clinical trials and licensure of EV-A71 vaccines. Additionally, enterovirus D68 outbreaks have been reported in the US and Taiwan currently and caused severe complications and deaths. Hence, an Asia-Pacific Network for Enterovirus Surveillance (APNES) has been established to estimate disease burden, understand virus evolution, and facilitate vaccine development through harmonizing laboratory diagnosis and data collection. Founded in 2017, the APNES is comprised of internationally recognized experts in the field of enterovirus in Asian countries working to raise awareness of this potentially fatal and debilitating disease. This article demonstrated the summaries of the first expert meeting, 2017 International Workshop on Enterovirus Surveillance and Vaccine Development, held by APNES in Taipei, Taiwan, March 2017.

International audience; Background: Influenza virus circulation is monitored through the Cambodian in- fluenza-like illness (ILI) sentinel surveillance system and isolates are characterized by the National Influenza Centre (NIC). Seasonal influenza circulation has previ- ously been characterized by year-round activity and a peak during the rainy season (June-November).Objectives: We documented the circulation of seasonal influenza in Cambodia for 2012-2015 and investigated genetic, antigenic, and antiviral resistance characteris- tics of influenza isolates.Patients/Methods: Respiratory samples were collected from patients presenting with influenza-like illness (ILI) at 11 hospitals throughout Cambodia. First-line screen- ing was conducted by the National Institute of Public Health and the Armed Forces Research Institute of Medical Sciences. Confirmation of testing and genetic, anti- genic and antiviral resistance characterization was conducted by Institute Pasteur in Cambodia, the NIC. Additional virus characterization was conducted by the WHO Collaborating Centre for Reference and Research on Influenza (Melbourne, Australia).Results: Between 2012 and 2015, 1,238 influenza-positive samples were submitted to the NIC. Influenza A(H3N2) (55.3%) was the dominant subtype, followed by in- fluenza B (30.9%; predominantly B/Yamagata-lineage) and A(H1N1)pdm09 (13.9%). Circulation of influenza viruses began earlier in 2014 and 2015 than previously de- scribed, coincident with the emergence of A(H3N2) clades 3C.2a and 3C.3a, respec- tively. There was high diversity in the antigenicity of A(H3N2) viruses, and to a smaller extent influenza B viruses, during this period, with some mismatches with the north- ern and southern hemisphere vaccine formulations. All isolates tested were suscepti- ble to the influenza antiviral drugs oseltamivir and zanamivir.Conclusions: Seasonal and year-round co-circulation of multiple influenza types/sub- types were detected in Cambodia during 2012-2015.

Contexte : les réseaux de type sentinelle composés de médecins généralistes représentent un outil puissant de la surveillance épidémiologique. Objectif : l’objectif de cette étude, à l’instar d’états des lieux antérieurs, était de réaliser une cartographie des réseaux de surveillance de type sentinelle en médecine générale à l’échelon européen, puis de l’étendre progressivement à l’échelon mondial. Méthode : une étude descriptive prospective des réseaux de surveillance de type sentinelle a été réalisée en Europe et dans le monde, entre juillet 2016 et juin 2017. Les réseaux inclus étaient des réseaux en soins de premier recours composés de médecins généralistes collectant des données de façon continue ou régulière à partir des patients vus en consultation. Chaque réseau identifié devait remplir un questionnaire descriptif pour être inclus dans l’étude. Résultats : au total 42 réseaux sur les 53 identifiés et contactés ont répondu à l’étude (79,2%). Issus de 32 pays différents, 33 étaient européens (76,2%). Tous les réseaux étaient composés de médecins généralistes (de 10 à 2 230). Tous les réseaux sauf un effectuaient une surveillance épidémiologique en continue. Parmi eux 38 (92,7%) surveillaient la grippe. Conclusion : cette étude a permis de réaliser une cartographie des réseaux de surveillance de type sentinelle en médecine générale en Europe. L’extension de ce travail à l’échelon mondial est en cours. La mise en ligne d’un site internet regroupant l’ensemble des données collectées devrait permettre de développer les collaborations entre ces réseaux.

International audience; The presence of major arbovirus vector species, climate change that promotes the expansion and increase of their populations, and potential animal reservoirs mean that vector-borne diseases represent a significant health risk for Mallorca's inhabitants. Microbiological monitoring of circulating arboviruses, particularly flaviviruses causing encephalitis, was initiated using domestic horses from localities near wetlands as “sentinel” hosts. A total of 291 blood samples were taken from 172 horses between 2011 and 2012, using paired samples to highlight seroconversion events. A multiplex immunoassay and confirmatory reference serological assays were used to screen sera for immunoglobulin G antibodies against West Nile (WNV), Usutu (USUV), and tick-borne encephalitis (TBEV) viruses. The seroprevalence was 6.4% (confidence interval [95% CI] 3.2%−11.0%) for WNV, 1.2% (95% CI 0.1%−4.1%) for USUV, and 0.6% (95% CI 0.0%−3.2%) for TBEV. In addition, eight horses (4.6%; 95% CI 2.0%−8.9%) were found positive for unidentified flaviviruses. Seroconversion events were detected for WNV and USUV, reflecting recent arboviral infections. These results highlight the active transmission of zoonotic arboviruses in Mallorca wetlands.

Background : The use of a malaria early warning system (MEWS) to trigger prompt public health interventions is a key step in adding value to the epidemiological data routinely collected by sentinel surveillance systems. Methods : This study describes a system using various epidemic thresholds and a forecasting component with the support of new technologies to improve the performance of a sentinel MEWS. Malaria-related data from 21 sentinel sites collected by Short Message Service are automatically analysed to detect malaria trends and malaria outbreak alerts with automated feedback reports. Results : Roll Back Malaria partners can, through a user-friendly web-based tool, visualize potential outbreaks and generate a forecasting model. The system already demonstrated its ability to detect malaria outbreaks in Madagascar in 2014. Conclusion : This approach aims to maximize the usefulness of a sentinel surveillance system to predict and detect epidemics in limited-resource environments.

I-MOVE/I-MOVE+ study team: Portugal - Baltazar Nunes, Ausenda Machado, Ana Paula Rodrigues, Verónica Gomez, Irina Kislaya, Mafalda Sousa Uva (Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge); Raquel Guiomar, Pedro Pechirra, Paula Cristóvão, Patrícia Conde, Inês Costa (Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Doutor Ricardo Jorge). I-MOVE/I-MOVE+study team - Portugal: Baltazar Nunes, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge; Ausenda Machado, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge; Ana Paula Rodrigues, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge; Verónica Gomez, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge; Irina Kislaya, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge; Mafalda Sousa Uva, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge; Raquel Guiomar, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge; Pedro Pechirra, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge; Paula Cristóvão, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge; Patrícia Conde, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo; Jorge Inês Costa, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge. We measured early 2016/17 season influenza vaccine effectiveness (IVE) against influenza A(H3N2) in Europe using multicentre case control studies at primary care and hospital levels. IVE at primary care level was 44.1%, 46.9% and 23.4% among 0-14, 15-64 and ≥ 65 year-olds, and 25.7% in the influenza vaccination target group. At hospital level, IVE was 2.5%, 7.9% and 2.4% among ≥ 65, 65-79 and ≥ 80 year-olds. As in previous seasons, we observed suboptimal IVE against influenza A(H3N2). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446. info:eu-repo/semantics/publishedVersion

Highly pathogenic avian influenza (HPAI) virus was first detected in Cameroon in February 2006. Analysis of NA sequences of the virus demonstrated that it is closely related to the H5N1 isolates from Northern Nigeria, Sudan and Ivory Coast, suggesting a common virus ancestor.

International audience; BACKGROUND:The seasonal drivers of influenza activity remain debated in tropical settings where epidemics are not clearly phased. Antananarivo is a particularly interesting case study because it is in Madagascar, an island situated in the tropics and with quantifiable connectivity levels to other countries.OBJECTIVES:We aimed at disentangling the role of environmental forcing and population fluxes on influenza seasonality in Madagascar.METHODS:We compiled weekly counts of laboratory-confirmed influenza-positive specimens for the period 2002 to 2012 collected in Antananarivo, with data available from sub-Saharan countries and countries contributing most foreign travelers to Madagascar. Daily climate indicators were compiled for the study period.RESULTS:Overall, influenza activity detected in Antananarivo predated that identified in temperate Northern Hemisphere locations. This activity presented poor temporal matching with viral activity in other countries from the African continent or countries highly connected to Madagascar excepted for A(H1N1)pdm09. Influenza detection in Antananarivo was not associated with travel activity and, although it was positively correlated with all climatic variables studied, such association was weak.CONCLUSIONS:The timing of influenza activity in Antananarivo is irregular, is not driven by climate, and does not align with that of countries in geographic proximity or highly connected to Madagascar. This work opens fresh questions regarding the drivers of influenza seasonality globally particularly in mid-latitude and less-connected regions to tailor vaccine strategies locally.

International audience; BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

International audience; BACKGROUND: Although recent work has described the spatiotemporal diffusion of influenza viruses worldwide, comprehensive data on spatiotemporal patterns of influenza from the African continent and Madagascar are still lacking. METHODS: National Influenza Centers from 5 countries-Cameroon, Côte d'Ivoire, Madagascar, Niger, and Senegal--collected specimens from patients presenting with influenza-like illness who visited sentinel surveillance clinics during a 2-year period (2008-2009). Isolates were genetically and antigenically characterized. RESULTS: Overall, 8312 specimens were tested. Seasonal influenza A virus subtypes H1N1 and H3N2 and influenza B viruses were detected in 329, 689, and 148 specimens, respectively. In 2009, pandemic influenza A virus subtype H1N1 was detected in Madagascar most commonly (98.5% of cases). Influenza activity was either significant year-round or occurred during a specific period of the year in the African countries we evaluated. CONCLUSIONS: Our results demonstrate that, from Madagascar to Senegal, the epidemiologic and virologic characteristics of influenza viruses are diverse in terms of spatiotemporal circulation of the different virus types, subtypes, and strains. Our data highlight the importance of country-specific surveillance and of data and virus sharing, and they provide a rational basis to aid policy makers to develop strategies, such as vaccination at the right moment and with the right formulation, aimed at reducing the disease burden in Africa and Madagascar.

International audience; Census and disposal data provide a multipurpose source of information on cattle mortality. The retrospective analyses we conducted on the data gathered in the National Cattle Register produced relevant information for describing and modelling the cattle mortality baseline and evaluating the impact of the 2007-2008 Blue Tongue epidemic on the French cattle population. This work was conducted retrospectively but showed that monitoring cattle mortality near real time could help detecting unexpected events. We are thus currently working on a timely and automated system to monitor cadaver disposal requests received by rendering plants, thanks to a data interchange system recently implemented between the Ministry of Agriculture and the fallen stock companies. Besides technical and methodological challenges, using these data for surveillance purposes raises epidemiological questions that still need to be answered. The question remains notably as to whether an abnormal increased mortality is a sensitive and timely signal for detecting unexpected health events. It appears also very challenging to identify the most adequate surveillance scale (time, space and population) and the most adequate anomaly detection algorithms to apply when the characteristics of the signals to be detected (shape, amplitude, etc.) are not known a priori. In Human health, similar systems have not yet proven their ability to detect unexpected events earlier than classical surveillance systems currently in place, but they have already demonstrated their value for real time assessment of identified and potentially dangerous events. Combined with traditional surveillance systems, we think that monitoring routinely collected data could improve the surveillance of the animal population health. Even if not used for detection purposes, cattle mortality monitoring could be used to rapidly produce information on the impact and evolution of identified events, what would facilitate decision-making regarding management measures and improve the communication.

International audience; A national laboratory network 'Biotox-Piratox' was created in 2003 in France with the purpose of detecting, confirming and reporting potential biological and chemical threat agents. This network is divided into three levels: Level 1 is dedicated to the evaluation of risks (biological, chemical, radiological), to sampling and packing. Level 2 consists of university and military hospitals, who deal with biological specimens, and of environmental and veterinary laboratories, who deal with environmental and animal samples. Level 3 comprises national reference laboratories and the Jean Mérieux biosafety level (BSL)-4 laboratory in Lyon. This report presents the results of four bio-preparedness exercises to check critical points in the processing of samples. These exercises took place in 2007, 2009, 2010 and 2011. Each of them consisted of two parts. The first part was the identification of an unknown bacterial strain and its susceptibility to antibiotics used as a default in case of a bioterrorist event. The second part was the detection of Class III microorganisms, mainly by molecular techniques. The main lesson learnt in these exercises was that the key to successful detection of biological agents in case of a biological threat was standardisation and validation of the methods implemented by all the laboratories belonging to the network.

International audience; Continuous surveillance of acute diarrhea in France has been conducted by Inserm's sentinel network of general practitioners (GP) since 1991. Similar GP-based studies have been performed in the Netherlands, Austria and the UK. The causes of most cases of acute diarrhea are unclear. In case-controlstudies designed to identify viruses in stools, 35 to 40% of cases and virtually none of the controls were positive for one of 4 major viruses (rotavirus, calicivirus, astrovirus and adenovirus). Thus, no viral cause was identified in more than 60% of patients with acute diarrhea. The causative role of viruses such as torovirus, picobirnavirus, picornavirus and enterovirus 22 has rarely been investigated. Further investigations are needed to identify other viral, bacterial fungal or parasitic causes of acute diarrhea. In France, on average, more than 3 million people (predominantly children) visit a GP for acute diarrhea each year. Most of these patients recover spontaneously within a few days, but the medical, social and economic costs of acute diarrhea are sufficiently high to justify a more aggressive public policy to prevent and control epidemics in Europe.; COMMUNICATION SCIENTIFIQUESéance du 9 novembre 2010Malgré une surveillance permanente et continue des diarrhées aiguës sur le territoire français assurée par les médecins généralistes du réseau Sentinelles de l’Inserm depuis 1991, et la mise en place de systèmes de surveillance similaires ou des études en médecine générale dans d’autres pays d’Europe, notamment aux Pays-Bas, en Autriche et au Royaume-Uni, force est de constater que leur étiologie reste encore largement méconnue. Si des études cas-témoins conduites avec une recherche de virus dans les selles ont permis d’identifier un virus dans 35 à 40 % des cas et chez un faible nombre de témoins, en faveur d’un rôle causal probable de quatre virus principalement retrouvés lors des épidémies (rotavirus, calicivirus, astrovirus et adénovirus), dans plus de 60 % des cas la cause de ces diarrhées aigües hivernales ou estivales reste inconnue. Le rôle de virus actuellement peu ou pas recherchés comme les torovirus, picobirnavirus, picornavirus ou entérovirus 22 mériterait d’être précisé. Des recherches restent donc à conduire, notamment visant à l’identification plus étendue d’agents pathogènes potentiellement responsables, qu’ils soient viraux, bactériens, fongiques ou parasitaires, avant de pouvoir espérer prévenir et contrôler de manière efficace ces épidémies récurrentes en Europe, qui concernent de larges segments de la population. En France environ trois millions de personnes consultent en moyenne chaque année leur médecin généraliste pour un épisode de diarrhée aiguë (ce sont des patients de tous âges, bien que plus souvent des enfants). Si pour l’immense majorité des cas leur évolution favorable est spontanée en quelques jours, le coût sanitaire, social et économique de ces épidémies d’ampleur nationale est très élevé et justifierait une politique de prévention et de lutte plus ambitieuse à l’échelle de l’Europe,.

International audience; PROBLEM:The revision of the International Health Regulations (IHR) and the threat of influenza pandemics and other disease outbreaks with a major impact on developing countries have prompted bolstered surveillance capacity, particularly in low-resource settings.APPROACH:Surveillance tools with well-timed, validated data are necessary to strengthen disease surveillance. In 2007 Madagascar implemented a sentinel surveillance system for influenza-like illness (ILI) based on data collected from sentinel general practitioners.SETTING:Before 2007, Madagascar's disease surveillance was based on the passive collection and reporting of data aggregated weekly or monthly. The system did not allow for the early identification of outbreaks or unexpected increases in disease incidence.RELEVANT CHANGES:An innovative case reporting system based on the use of cell phones was launched in March 2007. Encrypted short message service, which costs less than 2 United States dollars per month per health centre, is now being used by sentinel general practitioners for the daily reporting of cases of fever and ILI seen in their practices. To validate the daily data, practitioners also report epidemiological and clinical data (e.g. new febrile patient's sex, age, visit date, symptoms) weekly to the epidemiologists on the research team using special patient forms.LESSONS LEARNT:Madagascar's sentinel ILI surveillance system represents the country's first nationwide "real-time" surveillance system. It has proved the feasibility of improving disease surveillance capacity through innovative systems despite resource constraints. This type of syndromic surveillance can detect unexpected increases in the incidence of ILI and other syndromic illnesses.

International audience; This article describes a two-year surveillance of neurosurgical site infections and an outbreak of infections in deep brain stimulation (DBS) cases. From April to December 2008, six patients had a DBS surgical site infection (SSI). Audits of hygiene practices, infection control of the healthcare environment, and preoperative antimicrobial prophylaxis characteristics were carried out. The results of surgical audits showed that skin preparation and antimicrobial prophylaxis were not being performed adequately. In 2008, the general SSI rate was 1.8% (27 SSIs/1471 patients). Length of preoperative stay was significantly longer among infected patients (2.7 ± 2.9 months) compared with uninfected patients (2.2 ± 4.6 months) (P=0.01). Based on these results, skin preparation and antimicrobial prophylaxis were reviewed with the neurosurgery team. In 2009, the general SSI rate was reduced to 1.1% (16 SSI in 1410 patients), a reduction from 2008 (P=0.12). Although the overall incidence of SSI in 2008 (1.8%) was within the range of published data, this surveillance of SSIs permitted identification of site operative infected patients surgically treated for DBS. A set of actions was then taken to reduce SSI risk. This work demonstrates how an active surveillance programme can successfully change clinical care practice.

International audience; INTRODUCTION: Web-based applications are a choice tool for general practice based epidemiological surveillance; however their use may disrupt the general practitioners (GPs) work process. In this article, we propose an alternative approach based on a desktop client application. This was developed for use in the French General Practitioners Sentinel Network. METHODS: We developed a java application running as a client on the local GP computer. It allows reporting cases to a central server and provides feedback to the participating GPs. XML was used to describe surveillance protocols and questionnaires as well as instances of case descriptions. An evaluation of the users' feelings was carried out and the impact on the timeliness and completeness of surveillance data was measured. RESULTS: Better integration in the work process was reported, especially when the software was used at the time of consultation. Reports were received more frequently with less missing data. This study highlights the potential of allowing multiple ways of interaction with the surveillance system to increase participation of GPs and the quality of surveillance.

International audience; Demonstrating disease freedom is becoming important in different fields including animal disease control. Most methods consider sampling only from a homogeneous population in which each animal has the same probability of becoming infected. In this paper, we propose a new methodology to calculate the probability of detecting the disease if it is present in a heterogeneous population of small size with potentially different risk groups, differences in risk being defined using relative risks. To calculate this probability, for each possible arrangement of the infected animals in the different groups, the probability that all the animals tested are test-negative given this arrangement is multiplied by the probability that this arrangement occurs. The probability formula is developed using the assumption of a perfect test and hypergeometric sampling for finite small size populations. The methodology is applied to scrapie, a disease affecting small ruminants and characterized in sheep by a strong genetic susceptibility defining different risk groups. It illustrates that the genotypes of the tested animals influence heavily the confidence level of detecting scrapie. The results present the statistical power for substantiating disease freedom in a small heterogeneous population as a function of the design prevalence, the structure of the sample tested, the structure of the herd and the associated relative risks.

International audience; OBJECTIVE: Dengue has been reportable in Cambodia since 1980. Virological surveillance began in 2000 and sentinel surveillance was established at six hospitals in 2001. Currently, national surveillance comprises passive and active data collection and reporting on hospitalized children aged 0-15 years. This report summarizes surveillance data collected since 1980. METHODS: Crude data for 1980-2001 are presented, while data from 2002-2008 are used to describe disease trends and the effect of vector control interventions. Trends in dengue incidence were analysed using the Prais-Winsten generalized linear regression model for time series. FINDINGS: During 1980-2001, epidemics occurred in cycles of 3-4 years, with the cycles subsequently becoming less prominent. For 2002-2008 data, linear regression analysis detected no significant trend in the annual reported age-adjusted incidence of dengue (incidence range: 0.7-3.0 per 1000 population). The incidence declined in 2.7% of the 185 districts studied, was unchanged in 86.2% and increased in 9.6%. The age-specific incidence was highest in infants aged

International audience; Plague affects mainly the rural areas in the central highlands of Madagascar. Rattus rattus is the main rodent host of Yersinia pestis in these localities. Since the introduction of plague, endemic foci have continued to expand, and spatiotemporal variability in the distribution of human plague has been observed. To assess the movements of R. rattus and evaluate the risk of dispersion of the disease, a field study at the scale of the habitats (houses, hedges of sisals, and rice fields) in the plague villages was carried out during high and low seasons of plague transmission to humans. The systemic oral marker Rhodamine B was used to follow rats' movements. Baits were placed in different habitats, and trapping success was carried out once a month for 3 months after the bait distribution. Plague indicators (reservoirs' abundance, flea index, Y. pestis prevalence in fleas, and Y. pestis antibody prevalence in rats) were determined. The highest abundance of rats and marking efficiency were observed in the sisal hedges and the rice fields. Marked rats were captured most commonly near the points where baits were initially placed. The main movements of rats were observed between the houses and sisal hedges. Major differences were observed between the seasons of high and low plague transmission. During the season of low plague transmission, rats were more abundant in the sisal hedges and rice fields, with rats moving from the houses to the rice fields. During the high plague transmission season, rats moved from the hedges of sisal to the rice fields. Important indicators of vector abundance and plague transmission were higher during the high plague transmission season. The three study habitats were the risk areas for plague transmission, but the risk appeared highest in the houses and sisals. Rats' movements according to the season were likely directed by the availability of food.

International audience; This work provides estimates of HZ incidence and HZ-related hospitalization and mortality rates in France, where no immunization programme has been implemented. Herpes zoster data was obtained from the Sentinelles surveillance general practitioners (GPs) network, the PMSI Data processing centre for hospital discharges and from the French National Mortality Database (INSERM CépiDC). The yearly HZ incidence rate averaged 382 cases per 100,000 inhabitants (95% CI 364-405) and exponentially increased with age. The annual rates of hospitalizations and mortality due to HZ varied from 4.14±0.32 to 14.42±0.39 and from 0.11±0.03 to 0.29±0.04 per 100,000 inhabitants, respectively, depending on whether HZ was coded in a 'primary' or 'primary or associated' diagnosis. One or more factors of immunodepression occurred in 43.4% of hospitalized cases and in 21.6% HZ-related deaths.

Continuous surveillance of acute diarrhea in France has been conducted by Inserm's sentinel network of general practitioners (GP) since 1991. Similar GP-based studies have been performed in the Netherlands, Austria and the UK. The causes of most cases of acute diarrhea are unclear. In case-controlstudies designed to identify viruses in stools, 35 to 40% of cases and virtually none of the controls were positive for one of 4 major viruses (rotavirus, calicivirus, astrovirus and adenovirus). Thus, no viral cause was identified in more than 60% of patients with acute diarrhea. The causative role of viruses such as torovirus, picobirnavirus, picornavirus and enterovirus 22 has rarely been investigated. Further investigations are needed to identify other viral, bacterial fungal or parasitic causes of acute diarrhea. In France, on average, more than 3 million people (predominantly children) visit a GP for acute diarrhea each year. Most of these patients recover spontaneously within a few days, but the medical, social and economic costs of acute diarrhea are sufficiently high to justify a more aggressive public policy to prevent and control epidemics in Europe., COMMUNICATION SCIENTIFIQUESéance du 9 novembre 2010Malgré une surveillance permanente et continue des diarrhées aiguës sur le territoire français assurée par les médecins généralistes du réseau Sentinelles de l’Inserm depuis 1991, et la mise en place de systèmes de surveillance similaires ou des études en médecine générale dans d’autres pays d’Europe, notamment aux Pays-Bas, en Autriche et au Royaume-Uni, force est de constater que leur étiologie reste encore largement méconnue. Si des études cas-témoins conduites avec une recherche de virus dans les selles ont permis d’identifier un virus dans 35 à 40 % des cas et chez un faible nombre de témoins, en faveur d’un rôle causal probable de quatre virus principalement retrouvés lors des épidémies (rotavirus, calicivirus, astrovirus et adénovirus), dans plus de 60 % des cas la cause de ces diarrhées aigües hivernales ou estivales reste inconnue. Le rôle de virus actuellement peu ou pas recherchés comme les torovirus, picobirnavirus, picornavirus ou entérovirus 22 mériterait d’être précisé. Des recherches restent donc à conduire, notamment visant à l’identification plus étendue d’agents pathogènes potentiellement responsables, qu’ils soient viraux, bactériens, fongiques ou parasitaires, avant de pouvoir espérer prévenir et contrôler de manière efficace ces épidémies récurrentes en Europe, qui concernent de larges segments de la population. En France environ trois millions de personnes consultent en moyenne chaque année leur médecin généraliste pour un épisode de diarrhée aiguë (ce sont des patients de tous âges, bien que plus souvent des enfants). Si pour l’immense majorité des cas leur évolution favorable est spontanée en quelques jours, le coût sanitaire, social et économique de ces épidémies d’ampleur nationale est très élevé et justifierait une politique de prévention et de lutte plus ambitieuse à l’échelle de l’Europe,.

Background Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available. This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases. Methods The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2nd version (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest. Results The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED). Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data. Conclusion Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained "epidemiology watchers". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on "image walls" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.

Objective.To describe the French program for the prevention of healthcare-associated infections and antibiotic resistance and provide results for some of the indicators available to evaluate the program. In addition to structures and process indicators, the 2 outcome indicators selected were the rate of surgical site infection and the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates among the S. aureus isolates recovered.Design.Descriptive study of the evolution of the national structures for control of healthcare-associated infections since 1992. Through national surveillance networks, process indicators were available from 1993 to 2006, surgical site infection rates were available from 1999 to 2005, and prevalence rates for MRSA infection were available from 2001 to 2007.Results.A comprehensive national program has gradually been set up in France during the period from 1993 to 2004, which included strengthening of organized infection control activities at the local, regional, and national levels and developing large networks for surveillance of specific infections and antibiotic resistance. These achievements were complemented by instituting mandatory notification for unusual nosocomial events, especially outbreaks. The second phase of the program involved the implementation of 5 national quality indicators with public reporting. Surgical site infection rates decreased by 25% over a 6-year period. In France, the median proportion of MRSA among S. aureus isolates recovered from patients with bacteremia decreased from 33.4% to 25.7% during the period from 2001 to 2007, whereas this proportion increased in many other European countries.Conclusions.Very few national programs have been evaluated since the Study on the Efficacy of Nosocomial Infection Control. Although continuing efforts are required, the French program appears to have been effective at reducing infection rates.

International audience; Parasite requires an understanding of complex transmission systems where individual, population and environmental factors and their interactions can hardly been considered separately. Moreover, the importance of space and time in host population and parasite transmission processes is increasingly recognised. The present review illustrates how epidemiology and transmission ecology have evolved in a multidisciplinary framework to a systems approach that includes both spatial and temporal dimensions. Focusing on population processes, three significant challenges are discussed: (i) integration of landscape ecology concepts and modelling across time-space scales, (ii) development of molecular methods that permits easy parasite/host identification and process tracking (e.g. host and parasite movements), and (iii) integration of sociology methods to estimate zoonotic risk and exposure.

International audience; Hepatocellular carcinoma is a deadly cancer with growing incidence for which immunotherapy is one of the most promising therapeutic approach. Peptide-based vaccines designed to induce strong, sustained CD8+ T cell responses are effective in animal models and cancer patients. We demonstrated the efficacy of curative peptide-based immunisation against a unique epitope of SV40 tumour antigen, through the induction of a strong CD8+ T cell-specific response, in our liver tumour model. However, as in human clinical trials, most tumour antigen epitopes did not induce a therapeutic effect, despite inducing strong CD8+ T cell responses. We therefore modified the tumour environment to enhance peptide-based vaccine efficacy by delivering mengovirus (MV)-derived RNA autoreplicating sequences (MV-RNA replicons) into the liver. The injection of replication-competent RNA replicons into the liver converted partial tumour regression into tumour eradication, whereas non-replicating RNA had no such effect. Replicating RNA replicon injection induced local recruitment of innate immunity effectors (NK and NKT) to the tumour and did not affect specific CD8+ T cell populations or other myelolymphoid subsets. The local delivery of such RNA replicons into tumour stroma is therefore a promising strategy complementary to the use of peripheral peptide-based vaccines for treating liver tumours.

International audience; Drug resistance surveillance and trend monitoring resistance rates bring some insights into tuberculosis (TB) control. The current study reports the characteristics of TB and drug resistance during a 10-yr prospective surveillance of culture-positive TB in France. Data for the current study was collected from 1995-2004 via a sentinel network of laboratories from university hospitals that complied with the international recommendations for the surveillance of drug resistance. Susceptibility test results were performed in each individual laboratory. Data on 13,283 patients were collected during the 10-yr period, 49% of whom had been born in France, 10% were HIV co-infected and 8% had previously been treated. As expected, previously treated and HIV co-infected patients were more likely to harbour resistant strains, especially rifampicin (RMP)-resistant strains. Among new patients, the mean resistance rate to at least one drug was 8.8%, and there was an upward trend in resistance to isoniazid and RMP (0.8-1%) related to the increase in the proportion of patients who had been born outside of France (38-53%). Among previously treated patients, the mean resistance rate to one drug was 20.6% and there was no significant time trend in resistance rates. The sentinel network provided valuable data on trends regarding the characteristics of tuberculosis and on drug resistance rates and reinforced the interest of analysing data by country of birth and history of treatment.

Objective.To estimate the incidence rate of reported occupational blood and body fluid exposures among French healthcare workers (HCWs).Design.Prospective national follow-up of HCWs from January 1 to December 31, 2004.Setting.University hospitals, hospitals, clinics, local medical centers, and specialized psychiatric centers were included in the study on a voluntary basis.Participants.At participating medical centers, every reported blood and body fluid exposure was documented by the occupational practitioner in charge of the exposed HCW by use of an anonymous, standardized questionnaire.Results.A total of 375 medical centers (15% of French medical centers, accounting for 29% of hospital beds) reported 13,041 blood and body fluid exposures; of these, 9,396 (72.0%) were needlestick injuries. Blood and body fluid exposures were avoidable in 39.1% of cases (5,091 of 13,020), and 52.2% of percutaneous injuries (4,986 of 9,552) were avoidable (5.9% due to needle recapping). Of 10,656 percutaneous injuries, 22.6% occurred during an injection, 17.9% during blood sampling, and 16.6% during surgery. Of 2,065 splashes, 22.6% occurred during nursing activities, 19.1% during surgery, 14.1% during placement or removal of an intravenous line, and 12.0% during manipulation of a tracheotomy tube. The incidence rates of exposures were 8.9 per 100 hospital beds (95% confidence interval [CI], 8.7-9.0 exposures), 2.2 per 100 full-time—equivalent physicians (95% CI, 2.4-2.6 exposures), and 7.0 per 100 full-time—equivalent nurses (95% CI, 6.8-7.2 exposures). Human immunodeficiency virus serological status was unknown for 2,789 (21.4%) of 13,041 patients who were the source of the blood and body fluid exposures.Conclusion.National surveillance networks for blood and body fluid exposures help to better document their characteristics and risk factors and can enhance prevention at participating medical centers.

International audience; BACKGROUND: Living around industrial sites may expose young children to lead and cause elevated blood lead levels (BLLs). Systematic screening for childhood lead poisoning is necessarily invasive but may be appropriate, depending on children's exposure levels. Our objective was to assess the performance of several decision support tools for determining the need for systematic BLL screening in children around industrial sites. METHOD: We used several exposure models to predict BLLs: the pharmacokinetic model IEUBK, the InVS dose model, and an empirical relation (Lewin, 1999) between soil concentrations and BLLs. We tested the BLLs (percentage of children with a BLL >100 micro g/l) that they predicted as well as threshold levels of soil pollution (200, 400, 500 ppm) for 71 situations for which the literature reports both environmental soil concentrations and BLLs in children aged 0-6 years. The tools' performance (sensitivity and specificity) was assessed by the rate of 'correct' (mass screening or not) decisions, judged retrospectively on the basis of measured BLLs, for different tolerated percentages of children with elevated BLLs. RESULTS: Decision support systems based on soil pollution levels were not adequately protective. The IEUBK and (updated) InVS mechanistic exposure models were the most effective in this setting. CONCLUSION: Exposure models may provide decision support if sufficient data about environmental contamination and dietary intake are available. Absolute performance measurement nonetheless remains difficult, in view of the limitations of the input data.

West Nile virus (WNV) is a mosquito-transmitted Flavivirus with a transmission cycle involving birds as amplifying hosts. Wild birds are also believed to carry WNV over large distances and are able to introduce it into new areas during migration and dispersal. In this paper, our objective is to provide lists of birds potentially involved in the introduction, the amplification and the spread of WNV in the Camargue, a Mediterranean wetland in the south of France where several WNV outbreaks have occurred since the 1960s. Bird species were classified according to the following ecological factors: migratory status and provenance area, used biotopes, abundance and period of presence in the Camargue. The obtained lists of bird species potentially involved in the introduction, amplification and spread of WNV should prove useful to determine target species on which further studies on WNV ecology in birds could be focused. Key Words: wild birds—West Nile—Epidemiology—Migration—Amplification— Spreading—Camargue. Vec...

International audience; The recent and rapid spread in the Mediterranean Basin of bluetongue, a viral disease of ruminants transmitted by some species of Culicoides (biting midges), highlights the necessity of determining the conditions of its emergence. This study uses high spatial resolution satellite imagery and methods from landscape ecology science to identify environmental parameters related to bluetongue occurrence in Corsica, a French Mediterranean island where the disease occurred for the first time in 2000. A set of environmental variables recorded in the neighborhood of 80 sheep farms were related to case occurrence through a logistic regression model computed within three subsequent buffer distances of 0.5, 1 and 2 km. The results reveal the role of landscape metrics, particularly those characterizing land-use units such as prairies and woodlands, as well as farm type, latitude and sunshine to explain the presence of bluetongue. Internal and external validation both indicate that the best results are obtained with the 1 km buffer size model (area under Receiver Operating Characteristic curve = 0.9 for internal validation and 0.81 for external validation). The results show that high spatial resolution remote sensing (i.e. 10 m pixels) and landscape ecology approaches contribute to improving the understanding of bluetongue epidemiology.

Performance indicators are variables used to calculate on a continuous basis the operational level of a surveillance network's priority activities. A 10-step process was developed to enable network coordinators to identify specific performance indicators to help them monitor their networks. The methodology was based on a listing of surveillance activities, the definition and choice of network's global priority objectives, the construction of performance indicators and monitoring tables and the implementation of the system within the network. This process was implemented for the bovine clinical digestive salmonellosis surveillance network in France (RESSAB). The process produced a list of 26 activities synthesized into 15 global objectives, from which 12 were retained as priority objectives. This made it possible to develop 12 performance indicators. Indicators retrospectively calculated for the year 2003 indicated that RESSAB was operating according to the objectives set by the network's stakeholders and its financial supporter. The methodology was implemented successfully and was not very time consuming (12 person-days) or expensive. The decision makers and actors in the network quickly appropriated the system. The methodology can thus be considered validated through this example. Nevertheless, the risks inherent in the use of performance indicators must be addressed by ensuring the relevance of the selected indicators through external assessment and by prioritizing an internal and participatory approach to avoid a misuse of the performance indicators. In addition, considering that performance indicators address only the operation of the network, relevance of surveillance procedure should be addressed by external evaluation.

International audience; A sentinel serosurveillance study was conducted in Central African Republic to estimate the prevalence of HIV seropositivity in the general adult population in each province so that the public health authorities can target HIV prevention programmes to the priority areas. Blood samples were collected from women attending 48 antenatal clinics in urban and rural areas of the Central African Republic. These samples were tested for HIV antibodies in an anonymous and unlinked manner using strategy II recommended by WHO. The data were extrapolated to all women of reproductive age in Central African Republic by use of a parity-based adjustment involving the application of correction factors to the observed prevalence rates. A total of 9,305 pregnant women were recruited from November 2001 to October 2002. HIV seroprevalence was high in all age groups (12% in the less than 20 year age group to 17% in the 25-29 year age group). The median prevalence of HIV in antenatal clinics was similar for rural areas, for Bangui and for other urban areas (16.5, 15.0, and 12.5% respectively). Adjustment for parity and fertility pattern increased the prevalence of HIV in all antenatal clinics except in Bangui. This first national study of HIV prevalence in Central African Republic revealed that the HIV epidemic is continuing to spread in both urban and rural areas. Thus, efforts to reduce transmission should be made in every part of the country.

International audience; BACKGROUND:Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia; the 2012 epidemic season was the most severe in the country since 2007, with more than 42,000 reported (suspect or confirmed) cases.METHODS:We report basic epidemiological characteristics in a series of 701 patients at the National Paediatric Hospital in Cambodia, recruited during a prospective clinical study (2011-2012). To more fully explore this cohort, we examined climatic factors using multivariate negative binomial models and spatial clustering of cases using spatial scan statistics to place the clinical study within a larger epidemiological framework.RESULTS:We identify statistically significant spatial clusters at the urban village scale, and find that the key climatic predictors of increasing cases are weekly minimum temperature, median relative humidity, but find a negative association with rainfall maximum, all at lag times of 1-6 weeks, with significant effects extending to 10 weeks.CONCLUSIONS:Our results identify clustering of infections at the neighbourhood scale, suggesting points for targeted interventions, and we find that the complex interactions of vectors and climatic conditions in this setting may be best captured by rising minimum temperature, and median (as opposed to mean) relative humidity, with complex and limited effects from rainfall. These results suggest that real-time cluster detection during epidemics should be considered in Cambodia, and that improvements in weather data reporting could benefit national control programs by allow greater prioritization of limited health resources to both vulnerable populations and time periods of greatest risk. Finally, these results add to the increasing body of knowledge suggesting complex interactions between climate and dengue cases that require further targeted research

International audience; Persistent LCMV infection in wild-derived MAI/Pas mice housed under conventional conditions remained undetected for a decade, despite periodic health monitoring using dirty-bedding sentinels. When MAI/Pas mice were rederived by embryo transfer, recipient mothers produced antiLCMV antibodies, which first revealed the presence of the virus in the colony. Before this information was obtained, MAI/Pas mice had been shipped to another facility, undergone cesarean rederivation there, and been introduced into the recipient barrier. The foster mothers of rederived pups were LCMV-negative according to enzyme-linked immunosorbent assay, but sera of both cesarean-rederived MAI/Pas mice and their foster mothers were positive for LCMV infection by immunofluorescent assay (IFA). LCMV was isolated from the MAI/Pas mice, and its genomic RNA was sequenced. Examination of animal technicians in contact with LCMV-infected mice and of other mouse samples by IFA or a reverse transcriptase-polymerase chain reaction test (or both) revealed that neither the workers nor other animals had been infected with LCMV. Experimental data showed that LCMV transmission from persistently infected mice to naïve ones occurred only after direct contact of animals housed in the same cage. This experience demonstrates the importance of careful viral monitoring in the transfer of laboratory rodents between institutions, the limitation of dirty-bedding sentinels for detection of LCMV infection, and the inadequacy of cesarean rederivation for elimination of enzootic LCMV infection.

International audience; Wild aquatic birds are considered to be the natural reservoir for influenza A viruses, and previous studies have focused mainly on species in the orders Anseriformes and Charadriiformes. In this study, we surveyed a larger spectrum of potential hosts belonging to 10 avian orders. Cloacal swabs (n=1,044) from 72 free-living bird species, were analysed by reverse transcription-polymerase chain reaction for the presence of avian influenza virus. Only two Mediterranean Gulls (Larus melanocephalus) tested positive; one of these viruses was identified as an H9N2 subtype. The absence of infection among passerine birds supports the idea that the prevalence of avian influenza virus infection in terrestrial species is low.