The French Epidemic Intelligence System: comparing disease surveillance at the national and international level using data from the Program for Monitoring Emerging Diseases.

In a context of globalisation and climate change, the risk of emerging infectious diseases spreading around the world has significantly increased in the past decades. In response to this growing threat, an epidemic intelligence team has been set up within the framework of the French animal health epidemiological surveillance platform (ESA platform). The French Epidemic Intelligence System (FEIS) monitors animal health risks in Europe and beyond that threaten animal populations in France (emerging and exotic diseases not yet present). The FEIS expert network covers all 53 category 1 health hazards identified as priority diseases by the French authorities. From January 2016 to December 2017, the FEIS published 126 reports on animal health events related to infectious diseases, of which 76.2% were related to events in Europe. When comparing FEIS reports to posts from the Program for Monitoring Emerging Diseases (ProMED), an FEIS report was produced for 52.6% of ProMED themes (combinations of disease and country) posted in 2016-2017 on events in Europe. The remaining European ProMED themes did not meet the criterion for the production of an FEIS report because either the disease was already present in France, the risk of introduction into France was considered low or negligible, or the introduction of the pathogen would have low or negligible economic and societal impacts. The FEIS efficiently detected and reported on all health hazards identified by ProMED to alert health authorities and stakeholders when needed (according to the criterion). Compared with international epidemic intelligence systems such as ProMED, which provide general information, the FEIS adds another layer of filtering and interpretation to available information on animal health threats tailored to France's specific needs, in order to communicate only essential information to health authorities.

Dans un contexte caractérisé par la mondialisation et le changement climatique, le risque de propagation mondiale des maladies infectieuses émergentes s'est significativement accru en quelques décennies. Pour répondre à cette menace croissante, une équipe de veille épidémique a été mise en place dans le cadre de la Plateforme française d'épidémiosurveillance en santé animale (Plateforme ESA). Le système de Veille sanitaire internationale (VSI) surveille les risques sanitaires en santé animale présents en Europe, voire au-delà, dès lors qu'ils représentent une menace pour les populations animales sur le territoire français (maladies émergentes et maladies exotiques jamais introduites en France). Le réseau d'experts de la VSI couvre les 53 risques sanitaires de catégorie 1 définis par les autorités françaises comme maladies prioritaires. De janvier 2016 à décembre 2017, 126 rapports de la VSI ont été publiés sur des événements de santé animale liés à des maladies infectieuses, dont 76,2 % concernaient des événements survenus en Europe. La comparaison entre les rapports émanant de la VSI et ceux du Programme de suivi des maladies émergentes (ProMED) fait apparaître que 52,6 % des thématiques publiées en 2016-2017 par ProMED (associant une maladie et un pays) relatives à des événements survenus en Europe avaient également fait l'objet d'un rapport par la VSI. Les thématiques restantes sur ProMED correspondant à des événements européens ne répondaient pas aux critères de la VSI, soit parce qu'il s'agissait d'une maladie déjà présente en France, soit parce que le risque d'introduction de l'agent pathogène en France était considéré comme faible ou négligeable, soit enfin parce que l'impact économique et sociétal d'une telle introduction, si elle survenait, aurait été faible ou négligeable. La VSI a détecté (en fonction de ses critères) l'ensemble des risques sanitaires identifiés par ProMED et les a notifiés avec efficacité aux autorités et acteurs en charge de la santé, chaque fois que nécessaire. Par rapport aux systèmes de veille sanitaire internationaux tels que ProMED qui fournissent des informations générales, la VSI, qui est spécifiquement adaptée aux besoins français, ajoute une strate supplémentaire de filtrage et d'interprétation des données disponibles sur les menaces de santé animale, afin de ne transmettre aux autorités sanitaires que les informations qui leur sont essentielles.

De unos decenios a esta parte, en un contexto marcado por la mundialización y el cambio climático, ha aumentado sustancialmente el riesgo de propagación por todo el mundo de enfermedades infecciosas emergentes. Para responder a esta creciente amenaza se ha establecido, dentro del dispositivo francés de vigilancia epidemiológica zoosanitaria (plataforma ESA), un equipo de inteligencia epidemiológica. El Sistema Francés de Información Epidemiológica (épidémiologique) está dedicado a seguir de cerca los riesgos zoosanitarios que, desde Europa u otras partes del mundo, amenacen a las poblaciones animales de Francia (enfermedades emergentes y exóticas que aún no estén presentes en el país). La red de especialistas de la VSI cubre la totalidad de los 53 peligros sanitarios de categoría 1 que las autoridades francesas tienen definidos como enfermedades prioritarias. Entre enero de 2016 y diciembre de 2017, la VSI publicó 126 informes sobre episodios zoosanitarios relacionados con enfermedades infecciosas, de los que un 76,2% tenían que ver con episodios ocurridos en Europa. Al comparar los informes de la VSI con las notas publicadas por el Programa de Vigilancia de Enfermedades Emergentes (ProMED) se constató que ela VSI había elaborado un informe en relación con el 52,6% de los temas (combinación de enfermedades y países) tratados por el ProMED en sus notas de 2016 y 2017 sobre episodios ocurridos en suelo europeo. Los restantes temas europeos tratados por el ProMED no cumplían el criterio de que hubiera un informe de la VSI al respecto, ya fuera porque la enfermedad ya estaba presente en Francia, porque se consideró bajo o insignificante el riesgo de penetración en Francia o porque la llegada del patógeno tendría una repercusión escasa o insignificante en la economía o la sociedad. La VSI detectó y comunicó con eficacia todos los peligros sanitarios identificados por el ProMED para alertar a las autoridades sanitarias y demás interlocutores cada vez que fue necesario (con arreglo al criterio). En comparación con los sistemas internacionales de información epidemiológica, como el ProMED, que proporcionan información general, la VSI agrega un filtro y un nivel de interpretación suplementarios a la información disponible sobre amenazas zoosanitarias, adaptándola así a las necesidades específicas de Francia, con el fin de comunicar únicamente información esencial a las autoridades sanitarias.

Spread rate of lumpy skin disease in the Balkans, 2015-2016.

After its introduction in Turkey in November 2013 and subsequent spread in this country, lumpy skin disease (LSD) was first reported in the western Turkey in May 2015. It was observed in cattle in Greece and reported to the World Organization for Animal Health (OIE) in August 2015. From May 2015 to August 2016, 1,092 outbreaks of lumpy skin disease were reported in cattle from western Turkey and eight Balkan countries: Greece, Bulgaria, The Former Yugoslav Republic of Macedonia, Serbia, Kosovo, and Albania. During this period, the median LSD spread rate was 7.3 km/week. The frequency of outbreaks was highly seasonal, with little or no transmission reported during the winter. Also, the skewed distribution of spread rates suggested two distinct underlying epidemiological processes, associating local and distant spread possibly related to vectors and cattle trade movements, respectively.

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1.

Trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front-line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active against equine Gram-positive and Gram-negative bacteria, without cytotoxicity against mammalian cells at bacteriolytic concentrations. In the present study, we show that eCATH1 exhibits an in vitro 50% inhibitory concentration (IC50) of 9.5 µM against Trypanosoma brucei brucei, Trypanosoma evansi, and Trypanosoma equiperdum Its trypanocidal mechanism involves plasma membrane permeabilization and mitochondrial alteration based on the following data: (i) eCATH1 induces the rapid influx of the vital dye SYTOX Green; (ii) it rapidly disrupts mitochondrial membrane potential, as revealed by immunofluorescence microscopy using the fluorescent dye rhodamine 123; (iii) it severely damages the membrane and intracellular structures of the parasites as early as 15 min after exposure at 9.5 µM and 5 min after exposure at higher concentrations (19 µM), as evidenced by scanning and transmission electron microscopy. We also demonstrate that administration of eCATH1 at a dose of 10 mg/kg to T. equiperdum-infected mice delays mortality. Taken together, our findings suggest that eCATH1 is an interesting template for the development of novel therapeutic agents in the treatment of trypanosome infections.

Assessment of the safety and immunogenicity of Rhodococcus equi-secreted proteins combined with either a liquid nanoparticle (IMS 3012) or a polymeric (PET GEL A) water-based adjuvant in adult horses and foals--identification of promising new candidate antigens.

Rhodococcus equi is the most common infectious cause of mortality in foals between 1 and 6 months of age. Because of an increase in the number of antibiotic-resistant strains, the optimization of a prophylactic strategy is a key factor in the comprehensive management of R. equi pneumonia. The objectives of this study were to assess the safety and immunogenicity of R. equi-secreted proteins (ReSP) co-administered with either the nanoparticular adjuvant Montanide™ IMS 3012 VG, or a new polymeric adjuvant Montanide™ PET GEL A, and to further investigate the most immunogenic proteins for subsequent immunization/challenge experiments in the development of a vaccine against rhodoccocal pneumonia. The approach involved two phases. The first phase aimed to investigate the safety of vaccination in six adult horses. The second phase aimed to determine the safety and immunogenicity of vaccination in twelve 3-week-old foals. We set out to develop a method based on ultrasound measurements for safety assessment in adult horses in order to evaluate any in situ changes at the injection site, in the skin or the underlying muscle, with quantitative and qualitative data revealing that administration of ReSP combined with the Pet Gel A adjuvant led to an increase in local inflammation, associated with 4- to 7-fold higher levels of anti-R. equi IgGa, IgGb and IgGT, compared to administration of ReSP associated with IMS 3012 adjuvant, but without any impact on animal demeanor. Investigations were then performed in foals with serological and clinical follow-up until 6 months of age. Interestingly, we observed in foals a much lower incidence of adverse local tissue reactions at the injection site than in adult horses, with transient and moderate swelling for the group that received ReSP combined with Pet Gel A. Immunized foals with Pet Gel A adjuvant exhibited a similar response in both IgGa and IgGT levels, but a lower response in IgGb levels, compared to adult horses, with a subisotype profile that may however reflect a bias favorable to R. equi resistance. From the crude extract of secreted proteins, dot-blot screening enabled identification of cholesterol oxidase, mycolyl transferase 3, and PSP (probable secreted protein) as the most immunogenic candidates. Taken together, these results are encouraging in developing a vaccine for foals.

Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection.

Rhodococcus equi causes severe pneumonia in foals and has recently gained attention as a significant opportunistic pathogen in immunocompromised humans. However, no effective vaccine to prevent rhodococcosis is currently available. In this study, we have engineered the food-grade bacterium Lactococcus lactis to secrete the virulence-associated protein A from R. equi (LL-VapA). The immunogenic potential of LL-VapA strain was then evaluated after either intragastric or intranasal immunization in mice either alone or in combination with LL-Lep, a recombinant strain of L. lactis secreting biologically active leptin, a pleiotropic hormone with significant immunomodulatory properties. Intragastric administration of LL-VapA led to the highest VapA-specific mucosal response whereas intranasal administration led to the highest systemic immune responses. Cytokines released from in vitro-stimulated spleen cells show both a strong IFN-γ response and an increase of IL-4 level in all immunized groups, except for the group intranasally co-administered with both LL-VapA and LL-Lep. Strikingly, a significant reduction in R. equi viable counts in liver and spleen was observed four days after intravenous challenge with a virulent strain of R. equi in all immunized groups except for the group vaccinated by intragastric route with LL-VapA. Altogether, our results demonstrate that LL-VapA can evoke a T(H)1-based protective immune response in intranasally immunized mice. This response is enhanced when co-administered with LL-Lep strain, whereas only co-administration of LL-VapA and LL-Lep can induce a protective immune response in intragastric vaccinated mice, associated with a T(H)1/T(H)2 cytokine response.

[Action of an extract of Vanda coerulea on the senescence of skin fibroblasts]. / Action d'un extrait de Vanda coerulea sur la sénescence de fibroblastes cutanés.

The family of the orchids to date is poorly studied as a potential source of molecules with biological activity. The phytochemical analysis of extracts of Vanda coerulea stems (Orchidaceae), the isolation and the purification of the secondary metabolites realized by CLHP followed with high-resolution mass spectrometry and mono and two-dimensional nuclear magnetic resonance made it possible to identify the joint presence in an orchid of three stilbenoïds i.e, imbricatin, methoxycoelonin and gigantol. By flow cytometry, it is shown that the replicative senescence of human normal skin fibroblasts involves a reduction in the number of cells in phase S. A proteins chips technology dedicated to cell cycle proteins makes it possible to correlate this decrease of the number of cells in phase S to a decrease in cyclin E and cyclin dependant kinase 2, cdk2. The treatment by an ethanolic extract of stems of Vanda coerulea titrated in the three stilbenoids restores the percentage at an equivalent rate to that of young cells and the rate of cyclin E and, cdk2, thus bringing a beginning of explanation of their mechanism. These activities let predict an interesting potential as active ingredients to fight against the visible signs of cutaneous ageing.

Antimicrobial properties of the equine alpha-defensin DEFA1 against bacterial horse pathogens.

Defensins are small effector molecules of the innate immune system, synthesised by various organisms including plants and animals. The peptides act as endogenous antibiotics with an antimicrobial activity against a broad spectrum of microbes including bacteria, fungi and viruses. alpha-Defensins are a subgroup of the defensin family, their synthesis is limited to some tissues and furthermore to some mammalian species including the horse. Equine DEFA1 is an enteric alpha-defensin exclusively produced in Paneth cells. The peptide showed an activity against a broad spectrum of microbes, but typical pathogens of the horse were not included in the previous antimicrobial studies. Here, we report the antibacterial properties of DEFA1 against clinical isolates of typical horse pathogens including Rhodococcus equi, various streptococci strains, Salmonella choleraesuis, and Pasteurella multocida. The recombinantly expressed DEFA1 peptide exerted potent activity against these pathogenic bacteria. The highest susceptibility showed R. equi. Three genetically different strains of R. equi were killed at low micromolar concentrations, comparable with conventionally used antibiotics.

Elastokine-mediated up-regulation of MT1-MMP is triggered by nitric oxide in endothelial cells.

Membrane-type I matrix metalloproteinase (MT1-MMP) has been previously reported to be up-regulated in human microvascular endothelial cell-1 line (HMEC) by elastin-derived peptides (elastokines). The aim of the present study was to identify the signaling pathways responsible for this effect. We showed that elastokines such as (VGVAPG)(3) peptide and kappa elastin induced nitric oxide (NO) production in a time-, concentration- and receptor-dependent manner as it could be abolished by lactose and a receptor-derived competitive peptide. As evidenced by the use of NO synthase inhibitors, elastokine-mediated up-regulation of MT1-MMP and pseudotube formation on Matrigel required NO production through activation of the PI(3)-kinase/Akt/NO synthase and NO/cGMP/Erk1/2 pathways. Elastokines induced both PI(3)-kinase p110gamma sub-unit, Akt and Erk1/2 activation, as shown by a transient increase in phospho-Akt and phospho-Erk1/2, reaching a maximum after 5 and 15 min incubation, respectively. Inhibitors of PI(3)-kinase and MEK1/2 suppressed elastokine-mediated MT1-MMP expression at both the mRNA and protein levels, and decreased the ability of elastokines to accelerate pseudotube formation. Besides, elastokines mediated a time- and concentration-dependent increase of cGMP, suggesting a link between NO and MT1-MMP expression. This was validated by the use of a guanylyl cyclase inhibitor, a NO donor and a cGMP analog. The guanylyl cyclase inhibitor abolished the stimulatory effect of elastokines on MT1-MMP expression. Inversely, the cGMP analog, mimicked the effect of both elastokines and NO donor in a concentration- and time-dependent manner. Overall, our results demonstrated that such elastokine properties through NO and MT1-MMP may be of importance in the context of tumour progression.