Q fever : Problems and health risks

Q fever is a zoonosis caused by Coxiella burnetii. Domestic ruminants are the main reservoirs for human contamination, as infected female ruminants shed the bacteria in parturition products, milk and faeces. Several studies describe the natural evolution of bacterial shedding by domestic ruminants. AFSSA proposed recommandations on Q fever risks and on reasoned measures applicable to infected sheep, cattle, and goat herds (Rodolakis et al. 2004). Veterinary researches for the disease are designed to limit the contamination of the environment and of the population. The major challenge is to determine the best diagnostic strategies and to implement control programs. Vaccination appears to be the best way to combat Q fever. A phase I inactivated vaccine, whose preventive efficacy has been experimentally demonstrated, is authorised in France since 2004. Several research teams and professional organisations are currently evaluating the benefit of this vaccine in herds.La fièvre Q est une zoonose causée par Coxiella burnetii. Les ruminants domestiques sont les réservoirs principaux à l'origine de la contamination de l'homme car les femelles infectées excrètent la bactérie dans les produits de mises bas, le lait et les fèces. Plusieurs études contribuent à décrire l'évolution naturelle de l'excrétion bactérienne par les ruminants domestiques. Un avis de l'AFSSA a présenté un état des lieux sur les risques de la fièvre Q et sur les mesures raisonnées et applicables dans les troupeaux ovins, bovins et caprins infectés (Rodolakis et al. 2004). Les recherches vétérinaires visent à limiter la contamination de l'environnement et de la population. L'enjeu actuel majeur est de déterminer les meilleures démarches de diagnostic et de mettre en oeuvre des plans de maîtrise. La vaccination apparaît être un moyen de lutte primordial contre la fièvre Q. Un vaccin inactivé de phase I, dont l'efficacité préventive a été démontrée expérimentalement, peut être employé depuis 2004 en France. Les études en cours permettront une évaluation de ce vaccin dans les élevages

International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients

Objectives. The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. Methods. We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. Results. Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. Conclusion. We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be propose

Photobiocatalytic Oxyfunctionalization with High Reaction Rate using a Baeyer-Villiger Monooxygenase from Burkholderia xenovorans in Metabolically Engineered Cyanobacteria

Baeyer-Villiger monooxygenases (BVMOs) catalyze the oxidation of ketones to lactones under very mild reaction conditions. This enzymatic route is hindered by the requirement of a stoichiometric supply of auxiliary substrates for cofactor recycling and difficulties with supplying the necessary oxygen. The recombinant production of BVMO in cyanobacteria allows the substitution of auxiliary organic cosubstrates with water as an electron donor and the utilization of oxygen generated by photosynthetic water splitting. Herein, we report the identification of a BVMO from Burkholderia xenovorans (BVMOXeno) that exhibits higher reaction rates in comparison to currently identified BVMOs. We report a 10-fold increase in specific activity in comparison to cyclohexanone monooxygenase (CHMOAcineto) in Synechocystis sp. PCC 6803 (25 vs 2.3 U g(DCW)(-1) at an optical density of OD750 = 10) and an initial rate of 3.7 +/- 0.2 mM h(-1). While the cells containing CHMOAcineto showed a considerable reduction of cyclohexanone to cyclohexanol, this unwanted side reaction was almost completely suppressed for BVMOXeno, which was attributed to the much faster lactone formation and a 10-fold lower KM value of BVMOXeno toward cyclohexanone. Furthermore, the whole-cell catalyst showed outstanding stereoselectivity. These results show that, despite the self-shading of the cells, high specific activities can be obtained at elevated cell densities and even further increased through manipulation of the photosynthetic electron transport chain (PETC). The obtained rates of up to 3.7 mM h-1 underline the usefulness of oxygenic cyanobacteria as a chassis for enzymatic oxidation reactions. The photosynthetic oxygen evolution can contribute to alleviating the highly problematic oxygen mass-transfer limitation of oxygendependent enzymatic processes

Experimental infection of pregnant Pyrenean chamois (Rupicapra pyrenaica) with border disease virus subtype 4.

International audienceBorder disease virus (BDV) causes high mortality in Pyrenean chamois (Rupicapra pyrenaica) on the French and Spanish sides of the Pyrenees Mountains. We investigated the pathology induced by BDV in pregnant chamois via experimental infection. Three females were inoculated during the second third of pregnancy with a BDV-4 subgroup strain isolated from a wild Pyrenean chamois during an acute epizootic. A fourth pregnant chamois and one nonpregnant ewe were kept as negative controls. Animals were monitored to assess clinical signs, hematology, viremia, and serology. Postmortem examinations included necropsy, histopathology, and quantification of viral RNA in organs. Pregnancy was unsuccessful in all inoculated animals. One died 24 days postinoculation (dpi) without showing any precursory clinical signs. The second animal had profuse diarrhea from 13 dpi to its death at 51 dpi. The third aborted at 46 dpi and was euthanized at 51 dpi. All animals were viremic from 4 dpi until death. Neutralizing antibodies against BDV-4 were detected from 12 dpi. Necropsies showed generalized lymphadenomegaly, associated in one case with disseminated petechial hemorrhages in the digestive tract. Seventy-eight of 79 organs from inoculated adults and their fetuses had detectable viral RNA. The main histologic lesions in adults were mild lymphohistiocytic encephalitis associated with moderate or moderately severe lymphoid depletion. Control animals remained negative for virus (in blood and organs), antibody, and lesions upon postmortem examination. BDV infection during pregnancy in Pyrenean chamois causes severe disease leading to abortion, then death. Despite 100% fetal death following inoculation, viral RNA was recovered from all organs of infected fetuses, suggesting that persistently infected offspring could be born. Our results may help explain the reported decrease in chamois populations in several areas and suggest that great care must be taken when interpreting infection status for wildlife

Experimental infection of pregnant pyrenean chamois (rupicapra pyrenaica) with border disease virus subtype 4

Border disease virus (BDV) causes high mortality in Pyrenean chamois (Rupicapra pyrenaica) on the French and Spanish sides of the Pyrenees Mountains. We investigated the pathology induced by BDV in pregnant chamois via experimental infection. Three females were inoculated during the second third of pregnancy with a BDV-4 subgroup strain isolated from a wild Pyrenean chamois during an acute epizootic. A fourth pregnant chamois and one nonpregnant ewe were kept as negative controls. Animals were monitored to assess clinical signs, hematology, viremia, and serology. Postmortem examinations included necropsy, histopathology, and quantification of viral RNA in organs. Pregnancy was unsuccessful in all inoculated animals. One died 24 days postinoculation (dpi) without showing any precursory clinical signs. The second animal had profuse diarrhea from 13 dpi to its death at 51 dpi. The third aborted at 46 dpi and was euthanized at 51 dpi. All animals were viremic from 4 dpi until death. Neutralizing antibodies against BDV-4 were detected from 12 dpi. Necropsies showed generalized lymphadenomegaly, associated in one case with disseminated petechial hemorrhages in the digestive tract. Seventy-eight of 79 organs from inoculated adults and their fetuses had detectable viral RNA. The main histologic lesions in adults were mild lymphohistiocytic encephalitis associated with moderate or moderately severe lymphoid depletion. Control animals remained negative for virus (in blood and organs), antibody, and lesions upon postmortem examination. BDV infection during pregnancy in Pyrenean chamois causes severe disease leading to abortion, then death. Despite 100% fetal death following inoculation, viral RNA was recovered from all organs of infected fetuses, suggesting that persistently infected offspring could be born. Our results may help explain the reported decrease in chamois populations in several areas and suggest that great care must be taken when interpreting infection status for wildlife

Auto-sufficient enzymatic cascade combining a non selective and promiscuous ADH and BVMOS: Application for dihydrocoumarin synthesis

International audienceDihydrocoumarin is a plant metabolite widely used as flavoring agent in agro-food industries and also as common fragrance in cosmetics. As a lot of flavor chemicals, dihydrocoumarin is found in minor quantities in its natural plant sources, the sweet clover (Melilotus officinalis) and tonka beans (Dipteryx odorata) so processes are needed to produce this natural flavor in a efficient and eco-friendly manner. Baeyer-Villiger MonoOxygenases (BVMOs) are well known flavoenzymes able to transform efficiently ketone into ester or lactone with high regio-and stereoselectivities. Nevertheless, BVMOs are strictly NADPH-dependent, and therefore require a stoichiometric amount of the expensive nicotinamide cofactor. To address this issue, the multi-enzyme syntheses provide the opportunity to generate efficient auto-sufficient systems and only a limited number of such systems involving BVMOs has been reported to date. We will present here a new efficient access to dihydrocoumarin via a two-enzyme mediated oxidation of Indanol involving Alcohol Dehydrogenase (ADH) and BVMO. The originality of our approach comes from the features of ADH, an enzyme discovered from the biodiversity via a dedicated High Throughput Screening. The ADH is a NADP-dependent and non-enantioselective enzyme which enables on the one hand cofactor recycling and on the other hand a complete transformation of the racemic alcohol. Moreover, it presents a quite large scope of substrates. Several plasmid constructions and combinations have been tested first for the formation of e-caprolactone and compared in order to elaborate a versatile platform using ADH and different BVMOs. Then to optimize the formation of Dihydrocoumarin and limit the hydrolysis, we investigated the composition of the biotransformation medium in whole-cell process as well as in purified enzyme system.Still exploring the diversity of BVMOs activities, we wish to expand the range of potentially valued compounds obtained using these systems. (Ménil et al.

Auto-sufficient enzymatic cascade combining a non selective and promiscuous ADH and BVMOS: Application for dihydrocoumarin synthesis

Dihydrocoumarin is a plant metabolite widely used as flavoring agent in agro-food industries and also as common fragrance in cosmetics. As a lot of flavor chemicals, dihydrocoumarin is found in minor quantities in its natural plant sources, the sweet clover (Melilotus officinalis) and tonka beans (Dipteryx odorata) so processes are needed to produce this natural flavor in a efficient and eco-friendly manner. Baeyer-Villiger MonoOxygenases (BVMOs) are well known flavoenzymes able to transform efficiently ketone into ester or lactone with high regio-and stereoselectivities. Nevertheless, BVMOs are strictly NADPH-dependent, and therefore require a stoichiometric amount of the expensive nicotinamide cofactor. To address this issue, the multi-enzyme syntheses provide the opportunity to generate efficient auto-sufficient systems and only a limited number of such systems involving BVMOs has been reported to date. We will present here a new efficient access to dihydrocoumarin via a two-enzyme mediated oxidation of Indanol involving Alcohol Dehydrogenase (ADH) and BVMO. The originality of our approach comes from the features of ADH, an enzyme discovered from the biodiversity via a dedicated High Throughput Screening. The ADH is a NADP-dependent and non-enantioselective enzyme which enables on the one hand cofactor recycling and on the other hand a complete transformation of the racemic alcohol. Moreover, it presents a quite large scope of substrates. Several plasmid constructions and combinations have been tested first for the formation of e-caprolactone and compared in order to elaborate a versatile platform using ADH and different BVMOs. Then to optimize the formation of Dihydrocoumarin and limit the hydrolysis, we investigated the composition of the biotransformation medium in whole-cell process as well as in purified enzyme system.Still exploring the diversity of BVMOs activities, we wish to expand the range of potentially valued compounds obtained using these systems. (Ménil et al.

Simulation of Wood Logs Combustion in a Stove at Peak Pyrolysis Conditions

Transient wood combustion may lead to excessive carbon monoxide and particle emissions, that could hinder the use of wood in small scale applications. The development of innovative and advanced designs meeting the future standards requires a more detailed knowledge of the flow, temperature, and species fields. Steady fluid dynamics numerical simulations of wood log combustion in a stove have been carried out at peak pyrolysis conditions. The ANSYS Fluent software has been used with a simplified kinetic model for the combustion of the pyrolysis gases. While the numerical model is rather simplified in terms of heat transfer, the essential features of the flow and combustion are well caught thanks to the detailed input for the pyrolysis gases. However, the carbon monoxide concentration at the chimney is higher compared to experimental data

Auto-sufficient enzymatic cascade combining a non selective and promiscuous ADH and BVMOS: Application for dihydrocoumarin synthesis

Dihydrocoumarin is a plant metabolite widely used as flavoring agent in agro-food industries and also as common fragrance in cosmetics. As a lot of flavor chemicals, dihydrocoumarin is found in minor quantities in its natural plant sources, the sweet clover (Melilotus officinalis) and tonka beans (Dipteryx odorata) so processes are needed to produce this natural flavor in a efficient and eco-friendly manner. Baeyer-Villiger MonoOxygenases (BVMOs) are well known flavoenzymes able to transform efficiently ketone into ester or lactone with high regio-and stereoselectivities. Nevertheless, BVMOs are strictly NADPH-dependent, and therefore require a stoichiometric amount of the expensive nicotinamide cofactor. To address this issue, the multi-enzyme syntheses provide the opportunity to generate efficient auto-sufficient systems and only a limited number of such systems involving BVMOs has been reported to date. We will present here a new efficient access to dihydrocoumarin via a two-enzyme mediated oxidation of Indanol involving Alcohol Dehydrogenase (ADH) and BVMO. The originality of our approach comes from the features of ADH, an enzyme discovered from the biodiversity via a dedicated High Throughput Screening. The ADH is a NADP-dependent and non-enantioselective enzyme which enables on the one hand cofactor recycling and on the other hand a complete transformation of the racemic alcohol. Moreover, it presents a quite large scope of substrates. Several plasmid constructions and combinations have been tested first for the formation of e-caprolactone and compared in order to elaborate a versatile platform using ADH and different BVMOs. Then to optimize the formation of Dihydrocoumarin and limit the hydrolysis, we investigated the composition of the biotransformation medium in whole-cell process as well as in purified enzyme system.Still exploring the diversity of BVMOs activities, we wish to expand the range of potentially valued compounds obtained using these systems. (Ménil et al.