Clostridium botulinum type C, D, C/D, and D/C: An update.

Clostridium botulinum is the main causative agent of botulism, a neurological disease encountered in humans as well as animals. Nine types of botulinum neurotoxins (BoNTs) have been described so far. Amongst these "toxinotypes," the A, the B and E are the most frequently encountered in humans while the C, D, C/D and D/C are mostly affecting domestic and wild birds as well as cattle. In France for instance, many cases and outbreaks are reported in these animal species every year. However, underestimation is very likely at least for avifauna species where the detection of dead animals can be challenging. Knowledge about BoNTs C, D, C/D, and D/C and the diseases they cause in animals and humans is still scarce and unclear. Specifically, the potential role of animal botulism outbreaks in cattle and poultry as a source of human illness needs to be further assessed. In this narrative review, we present the current knowledge about toxinotypes C, D, C/D, and D/C in cattle and poultry with, amongst various other aspects, their epidemiological cycles. We also discuss the zoonotic potential of these toxinotypes and some possible ways of risk mitigation. An adapted and effective management of botulism outbreaks in livestock also requires a better understanding of these less common and known toxinotypes.

[Role of vaccination in the collective fight against infectious animal diseases]. / Rôle de la vaccination dans la lutte collective contre les maladies infectieuses animales.

"Role of vaccination in the collective fight against infectious animal diseases The part of vaccinations in collective fight against contagious animal diseases depends on objectives selected according to their impact on human health as well as on animal health and production, their prevalence and their epidemiological characteristics. In association with sanitary measures (biosecurity), the systematic vaccination, when vaccines are available, is often the first step indispensable to control the diseases and reduce their impact t an acceptable level, in particular if prevalence of infected animals is high. But vaccination is often insufficient to allow infectious agents eradicating. Now, for the more important diseases, eradication is an objective often required in order to obtain a free status. When the prevalence is very low, subsequent steps can include vaccination ban and adoption of program based only on a test and slaughter policy. Following successful eradication, emergency vaccination should be also implemented in order to prevent or contain spread of infection in unaffected areas."

"Rôle de la vaccination dans la lutte collective contre les maladies infectieuses animales Le rôle de la vaccination dans la lutte collective contre les maladies infectieuses des animaux dépend des objectifs retenus en fonction de leur impact sur la santé humaine et/ou sur la santé animale et la production, de leur prévalence et leurs caractéristiques épidémiologiques. En association avec les mesures sanitaires (biosécurité), la vaccination systématique, lorsque des vaccins sont disponibles, est souvent la première étape indispensable pour contrôler les maladies et réduire leur impact à un niveau acceptable, notamment en situation de prévalence élevée. Mais la vaccination est souvent insuffisante pour permettre l'élimination des agents infectieux. Or, pour les maladies animales les plus importantes, l'éradication est un objectif souvent recherché pour obtenir un statut indemne. Lorsque la prévalence est devenue très faible, il est alors préférable d'interdire la vaccination et d'adopter des mesures uniquement fondées sur le dépistage et l'élimination des animaux infectés. Une fois l'éradication atteinte, la vaccination d'urgence peut être encore mise en oeuvre pour prévenir ou contenir la propagation de l'infection en zone indemne."

[Risk of zoonoses by animal bites and scratches]. / Risque de zoonoses par morsures et griffures animales.

Risk of zoonoses by animal bites and scratches. The objectives of this study are to identify zoonosis risks related to animal bites and scratches in France. Pet-transmitted zoonoses, as pasteurellosis, cat scratches disease and various specific bacterial infections, are predominant, resulting usually in localized infections or, sometimes, in serious systemic infections (as those caused by Capnocytophaga canimorsus) in immunocompromised patients. On the other hand, the rat bite fever due to Strepto bacillus monoliformis is rarely diagnosed in humans. Because the France is a country free from rabies in non-flying mammals, exposure risk is limited to patients in contact with animals (predominantly non-vaccinated dogs or cats) illicitly imported from rabies enzootic areas. But, population may be exposed to infections by lyssaviruses isolated from bats, as European bat lyssaviruses type 1 (EBLV-1) transmitted by serotine bats (happily insectivorous and having little contact with humans), and more seriously in French Guyana, rabies virus transmitted by vampire bats. Lastly, exposure risk to Asian macaque monkeys infected by herpesvirus B present in some zoological parks in France is negligible for general population.

Risque de zoonoses par morsures et griffures animales. Les objectifs de cet article sont d'identifier les risques zoonotiques associés à des morsures et griffures animales en France. Les zoonoses transmises par des animaux de compagnie, comme la pasteurellose d'inoculation, la maladie des griffes du chat et diverses infections bactériennes spécifiques sont prédominantes, provoquant habituellement des infections localisées, parfois des infections systémiques sévères (comme celles causées par Capnocytophaga canimorsus) chez des patients immunodéprimés. En revanche, la « fièvre de la morsure du rat ¼ due à Streptobacillus monoliformis est rarement diagnostiquée chez les humains. La France étant indemne de rage des mammifères non volants, le risque d'exposition est limité à des contacts avec des animaux (surtout des chiens et des chats non vaccinés) illicitement introduits de zones d'enzootie rabique. La population reste néanmoins exposée à des infections par des lyssavirus isolés chez des chiroptères, comme le lyssavirus de la chauve-souris européenne de type 1 (EBLV-1) transmis par des sérotines (heureusement insectivores et n'ayant que peu de contact avec l'homme) et, plus gravement en Guyane, le virus rabique transmis par des chauves-souris vampires.Enfin, le risque d'exposition à des singes macaques asiatiques infectés par l'herpèsvirus B découverts dans certains parcs zoologiques en France peut être qualifié de négligeable pour la population générale.

A simple method to estimate the number of doses to include in a bank of vaccines. The case of Lumpy Skin Disease in France.

A simple method to estimate the size of the vaccine bank needed to control an epidemic of an exotic infectious disease in case of introduction into a country is presented. The method was applied to the case of a Lumpy Skin disease (LSD) epidemic in France. The size of the stock of vaccines needed was calculated based on a series of simple equations that use some trigonometric functions and take into account the spread of the disease, the time required to obtain good vaccination coverage and the cattle density in the affected region. Assuming a 7-weeks period to vaccinate all the animals and a spread of the disease of 7.3 km/week, the vaccination of 740 716 cattle would be enough to control an epidemic of LSD in France in 90% of the simulations (608 196 cattle would cover 75% of the simulations). The results of this simple method were then validated using a dynamic simulation model, which served as reference for the calculation of the vaccine stock required. The differences between both models in different scenarios, related with the time needed to vaccinate the animals, ranged from 7% to 10.5% more vaccines using the simple method to cover 90% of the simulations, and from 9.0% to 13.8% for 75% of the simulations. The model is easy to use and may be adapted for the control of different diseases in different countries, just by using some simple formulas and few input data.

Risk of introduction of Lumpy Skin Disease into France through imports of cattle.

The lumpy skin disease (LSD) virus belongs to the genus Capripoxvirus and causes a disease in cattle with economic impacts. In November 2014, the disease was first reported in Europe (in Cyprus); it was then reported in Greece (in August 2015) and has spread through different Balkan countries since 2016. Although vector transmission is predominant in at-risk areas, long-distance transmission usually occurs through movements of infected cattle. In order to estimate the threat for France, a quantitative import risk analysis (QIRA) model was developed to assess the risk of LSD being introduced into France by imports of cattle. Based on available information and using a stochastic model, the probability of a first outbreak of LSD in France following the import of batches of infected live cattle for breeding or fattening was estimated to be 5.4 × 10-4 (95% probability interval [PI]: 0.4 × 10-4 ; 28.7 × 10-4 ) in summer months (during high vector activity) and 1.8 × 10-4 (95% PI: 0.14 × 10-4 ; 15 × 10-4 ) in winter months. The development of a stochastic QIRA made it possible to quantify the risk of LSD being introduced into France through imports of live cattle. This tool is of prime importance because the LSD situation in the Balkans is continuously changing. Indeed, this model can be updated to process new information on the changing health situation in addition to new data from the TRAde Control and Expert System (TRACES, EU database). This model is easy to adapt to different countries and to other diseases.

Risk of introduction of lumpy skin disease in France by the import of vectors in animal trucks.

BACKGROUND: The lumpy skin disease virus (LSDV) is a dsDNA virus belonging to the Poxviridae family and the Capripoxvirus genus. Lumpy skin diseases (LSD) is a highly contagious transboundary disease in cattle producing major economic losses. In 2014, the disease was first reported in the European Union (in Cyprus); it was then reported in 2015 (in Greece) and has spread through different Balkan countries in 2016. Indirect vector transmission is predominant at small distances, but transmission between distant herds and between countries usually occurs through movements of infected cattle or through vectors found mainly in animal trucks. METHODS AND PRINCIPAL FINDINGS: In order to estimate the threat for France due to the introduction of vectors found in animal trucks (cattle or horses) from at-risk countries (Balkans and neighbours), a quantitative import risk analysis (QIRA) model was developed according to the international standard. Using stochastic QIRA modelling and combining experimental/field data and expert opinion, the yearly risk of LSDV being introduced by stable flies (Stomoxys calcitrans), that travel in trucks transporting animals was between 6 x 10-5 and 5.93 x 10-3 with a median value of 89.9 x 10-5; it was mainly due to the risk related to insects entering farms in France from vehicles transporting cattle from the at-risk area. The risk related to the transport of cattle going to slaughterhouses or the transport of horses was much lower (between 2 x 10-7 and 3.73 x 10-5 and between 5 x 10-10 and 3.95 x 10-8 for cattle and horses, respectively). The disinsectisation of trucks transporting live animals was important to reduce this risk. CONCLUSION AND SIGNIFICANCE: The development of a stochastic QIRA made it possible to quantify the risk of LSD being introduced in France through the import of vectors that travel in trucks transporting animals. This tool is of prime importance because the LSD situation in the Balkans is continuously changing. Indeed, this model can be updated to process new information on vectors and the changing health situation, in addition to new data from the TRAde Control and Expert System (TRACES, EU database). This model is easy to adapt to different countries and to other vectors and diseases.

Complete sequence of the floR-carrying multiresistance plasmid pAB5S9 from freshwater Aeromonas bestiarum.

OBJECTIVES: A multiresistant Aeromonas bestiarum strain, shown to be persistent and spreading in a freshwater stream, was investigated for the presence, location and organization of antimicrobial resistance genes. METHODS: The plasmid pAB5S9 was transferred by electroporation into Escherichia coli TG1. The resistance phenotype mediated by pAB5S9 was determined. Moreover, the plasmid was sequenced completely and analysed for its structure and organization of reading frames. RESULTS: Plasmid pAB5S9 mediated resistances to phenicols, sulphonamides, streptomycin and tetracycline. The analysis of the 24.7 kb sequence revealed the presence of 20 predicted coding sequences (CDSs), which included the floR, sul2 and strA-strB resistance genes and a tetR-tet(Y) determinant. Approximately 7.5 kb of pAB5S9 showed 100% nucleotide sequence identity to three non-contiguous segments of the SXT element of Vibrio cholerae. Regions identical to SXT comprised the floR gene, flanked upstream by a complete and downstream by a truncated ISCR2 element, and the region of the sul2 and strA-strB genes. Other CDSs of pAB5S9 related to plasmid replication and partitioning, metabolic and gene regulation functions as well as conjugative transfer showed homology to sequences from diverse bacterial species, indicating a mosaic structure. CONCLUSIONS: This study provides the first report of a floR-carrying plasmid in the genus Aeromonas and the first description of a tetR-tet(Y) determinant. The analysis of the multiresistant A. bestiarum strain indicates that strains of this species, some of which are opportunistic pathogens for fish, might also act as a resistance gene reservoir in the freshwater environment.

In vitro antimicrobial activity of orbifloxacin against Staphylococcus intermedius isolates from canine skin and ear infections.

The objective of the study was to evaluate the in vitro activity of orbifloxacin against Staphylococcus intermedius strains isolated in France from canine skin and ear infections. The minimum inhibitory concentrations (MICs) of orbifloxacin against 240 field S. intermedius isolates (69 skin and 171 ear isolates) ranged from 0.016 to 8 mg l(-1), with MIC50 and MIC90 equal to 0.5 and 1 mg l(-1), respectively. Only one strain, a pyoderma isolate was resistant (MIC=8 mg l(-1)). Orbifloxacin was tested at different concentrations for killing rate against five isolates obtained from pyoderma cases and against a reference strain (Staphylococcus aureus ATCC 29213). Orbifloxacin expressed a concentration-dependent bactericidal activity against the S. aureus reference strain, but a time-dependent bactericidal activity against S. intermedius. Orbifloxacin induced bactericidal effect against the S. intermedius strains tested with concentrations equal to or two times MIC.

Myxomatosis of the Depilated Angora rabbit. A Preliminary Study.

Abstract- A nodular eruption occurring on the skin of depilated Angora rabbits was studied at 47 rabbit farms in 1988. Virus isolation, electron microscopy, transmission experiments and comparison with experimental infection using recognised strains of myxoma virus confirmed that the disease was myxomatosis. The disease occurred particularly in July and August in rabbits vaccinated in March or April with the heterologous vaccine. Morbidity on farms where lesions occurred only on depilated skin was much lower than on those where generalised forms occurred. In experimental intradermal infections of unvaccinated New Zealand White rabbits, both primary and secondary myxomas occurred earlier in inoculated animals depilated up to five days before or on the day of inoculation; but after six days development of lesions in the depilated area was not observed. The authors advance the hypotheses that the nature ot the spontaneous disease in rabbitries is dependant on the residual level of post-vaccinal immunity. Where this is high, myxomatosis does not occur. Where it is low classical myxomatosis, with numerous lesions on the depilated skin, occurs. Intermediate levels of immunity are able to restrict the development of myxomas to the depilated area. Résumé- Des nodules cutanés, se développant exclusivement sur le dos de quelques animaux récemment épilés, ont été observés en 1988 dans 47 élevages de lapins angora. L'isolement viral, la microscopie électronique, la transmission expérimentale et la comparaison avec l'infection expérimentale par des souches de virus myxomateux ont permis de montrer qu'il s'agissait d'une forme particulière de myxomatose. La maladie était principalement observée en juillet et août sur des lapins vaccinés en mars et avril avec un vaccin hétérologue. La morbidité dans les élevages atteins était significativement inférieure à celle constatée dans les élevages affectés par des formes classiques de myxomatose. L'infection expérimentale de lapins néo-zélandais non vaccinés a montré que le développement des myxomes était plus précoce lorsque les animaux étaient épilés cinq jours avant ou le jour de l'inoculation; mais aucune lésion ne fut observée dans la zone épilée lorsque l'épilation avait lieu plus de six jours après l'inoculation. Les auteurs émettent l'hypothèse que l'aspect de la maladie dépend du niveau résiduel de l'immunité post-vaccinale. Si ce niveau est élevé, la maladie n'apparaît pas. S'il est insuffisant, on observe une forme classique de myxomatose, avec en plus de nombreux myxomes dans la zone cutanée épilée. Une immunité intermédiaire limite le développement des myxomes aux zones cutanées épilées. Zusammenfassung- Das Auftreten von Nodula auf der Haut von enthaarten Angorakaninchen wurde 1988 in 47 Kaninchenfarmen untersucht. Durch Virusisolierung, elektronenmikroskopische Untersuchungen, Übertragungsversuche und den Vergleich mit experimentellen Infektionen mit bekannten Myxomavirusstämmen konnte bestätigt werden, daß es sich bei der Erkrankung urn Myxomatose handelte. Die Ekrankung trat vor allem im Juli und August bei Kaninchen auf, die im März oder April mit heterologen Vakzinen geimpft worden waren. Die Morbidität in Betrieben, wo die Veränderungen nur auf enthaarter Haut auftraten, war viel niedriger als bei denen, wo generalisierte Formen auftraten. Bei experimentellen intradermalen Infektionen nicht geimpfter Weiße Neuseeland-Kaninchen traten sowohl primäre wie sekundäre Myxome früher auf bei den inokulierten Tieren, die bis zu fünf Tage vor der Inokulation depiliert worden waren; 6 Tage danach jedoch wurde keine Entwicklung von Veränderungen im depilierton Bereich festgestellt. Die Autoren stellen die Hypothese auf, daß der Grad der natürlichen Erkrankung in Kaninchenhaltungen von dom residualen Spiegel der durch Impfung erzeugten Immunität abhängt. Wo dieser Spiegel hoch ist, tritt die Myxomatose nicht auf. Wo er niedrig ist, kommt es zu der klassischen Myxomatose mit zahlreichen Veränderungen auf der enthaarten Haut. Mittlere Immunitätsspiegel können die Entwicklung der Myxome of enthaarte Gebiete beschränken. Resumen Una erupción nodular producida en la piel de conejos de Angora depilados fue estudiada en 47 granjas de conejos en 1988. El aislamiento de virus, microscopía electrónica, experimentos de transmisión y la comparación con infecciones experimentales usando cultivos conocidos del virus myxoma, confirmaron que la enfermedad era myxomatosis. La enfermedad ocurrió especialmente en julio y agosto en conejos vacunados en marzo o abril con la vacuna heteróloga. En infecciones experimentales intradérmicas de conejos no vacunados New Zealand y Blancos, ambos myxomas, primario y secundario ocurrieron más pronto en animales inoculados depilados hasta unos cinco dias antes o en el día de la inoculacion; pero después de seis días no se observó desarrollo de lesiones en el area depilada. Los autores avanzaron la hipotesis de que la naturaleza de la enfermedad espontánea en rabbitrios es dependiente del nivel residual de inmunidad post-vacunal. Dónde este es elevado no se produce myxomatosis. Dónde es bajo, se produce la clásica myxomatosis con numerosas lesiones en la piel depilada. Niveles intermedios de inmunidad son capaces de restringir el desarrollo de myxomas en el area depilada.