Extension of the known distribution of a novel clade C betacoronavirus in a wildlife host.

Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green® real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.

Antigenic site changes in the rabies virus glycoprotein dictates functionality and neutralizing capability against divergent lyssaviruses.

Lyssavirus infection has a near 100 % case fatality rate following the onset of clinical disease, and current rabies vaccines confer protection against all reported phylogroup I lyssaviruses. However, there is little or no protection against more divergent lyssaviruses and so investigation into epitopes within the glycoprotein (G) that dictate a neutralizing response against divergent lyssaviruses is warranted. Importantly, the facilities required to work with these pathogens, including wild-type and mutated forms of different lyssaviruses, are scarcely available and, as such, this type of study is inherently difficult to perform. The relevance of proposed immunogenic antigenic sites within the lyssavirus glycoprotein was assessed by swapping sites between phylogroup-I and -II glycoproteins. Demonstrable intra- but limited inter-phylogroup cross-neutralization was observed. Pseudotype viruses (PTVs) presenting a phylogroup-I glycoprotein containing phylogroup-II antigenic sites (I, II III or IV) were neutralized by antibodies raised against phylogroup-II PTV with the site II (IIb, aa 34-42 and IIa, aa 198-200)-swapped PTVs being efficiently neutralized, whilst site IV-swapped PTV was poorly neutralized. Specific antibodies raised against PTV-containing antigenic site swaps between phylogroup-I and -II glycoproteins neutralized phylogroup-I PTVs efficiently, indicating an immunodominance of antigenic site II. Live lyssaviruses containing antigenic site-swapped glycoproteins were generated and indicated that specific residues within the lyssavirus glycoprotein dictate functionality and enable differential neutralizing antibody responses to lyssaviruses.

Assessing the impact of public education on a preventable zoonotic disease: rabies.

Effective methods to increase awareness of preventable infectious diseases are key components of successful control programmes. Rabies is an example of a disease with significant impact, where public awareness is variable. A recent awareness campaign in a rabies endemic region of Azerbaijan provided a unique opportunity to assess the efficacy of such campaigns. A cluster cross-sectional survey concerning rabies was undertaken following the awareness campaign in 600 households in 38 randomly selected towns, in districts covered by the campaign and matched control regions. This survey demonstrated that the relatively simple awareness campaign was effective at improving knowledge of rabies symptoms and vaccination schedules. Crucially, those in the awareness campaign group were also 1·4 times more likely to report that they had vaccinated their pets, an essential component of human rabies prevention. In addition, low knowledge of appropriate post-exposure treatment and animal sources of rabies provide information useful for future public awareness campaigns in the region and other similar areas.

Introduction History of rabies control by vaccination. / Introduction History of rabies control by vaccination.

Since antiquity, rabies has remained one of the deadliest infectious diseases known to humankind, with a case fatality rate approaching 100% following the onset of clinical disease. It is present on all continents where terrestrial mammals exist, with the majority of animal and human cases being reported in the resourcelimited countries of Africa and Asia, with thousands of human rabies deaths being recorded annually. It is likely, however, that the global figure of approximately 59,000 annual human rabies fatalities is an underestimate. The impact of the disease has been reduced substantially across vast regions of the globe since the development of effective rabies vaccines. The success of different vaccines and vaccination policies in the defined 'at risk' populations has been born out of scientific innovation. Mass vaccination campaigns of animals, using parenteral vaccines to immunise companion animals, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several regions worldwide, including Western Europe and much of North America. In addition, human vaccines, largely used for post-exposure treatments, have reduced the burden of rabies in endemic areas.

La rage est depuis l'Antiquité l'une des maladies infectieuses faisant le plus de victimes humaines, avec un taux de létalité atteignant 100 % une fois les signes cliniques déclarés. La rage est présente sur tous les continents où existent des mammifères terrestres. La majorité des cas animaux et humains surviennent dans les pays à faibles revenus d'Afrique et d'Asie et des milliers de décès humains dus à la rage sont enregistrés chaque année dans le monde. Il est toutefois probable que les estimations mondiales d'environ 59 000 décès humains dus à la rage soient en-deçà de la réalité. L'impact de la maladie a fortement diminué dans de vastes régions du globe depuis la mise au point de vaccins efficaces. L'innovation scientifique a permis de développer plusieurs vaccins et d'appliquer avec succès des politiques de vaccination ciblant les populations définies comme « à risque ¼. Les campagnes de vaccination massive d'animaux par voie parentérale pour immuniser les animaux de compagnie et les progrès de la vaccination orale des animaux sauvages ont permis d'éliminer la rage chez les carnivores terrestres dans plusieurs régions du monde, dont l'Europe occidentale et une grande partie de l'Amérique du Nord. En outre, l'emploi systématique de vaccins humains pour les traitements post-exposition a allégé le fardeau de la rage dans les zones d'endémie.

La rabia ha sido desde tiempos antiguos, y sigue siendo aún hoy, una de las enfermedades infecciosas más mortíferas que ha conocido la humanidad, con una tasa de letalidad cercana al 100% una vez que ha entrado en su fase clínica. Está presente en todos los continentes que albergan mamíferos terrestres, si bien la mayoría de los casos de rabia humana y animal se declaran en países africanos y asiáticos con escasos recursos, donde la rabia mata cada año a miles de personas. Es probable, sin embargo, que el cálculo a escala mundial de unos 59 000 fallecimientos anuales por rabia humana esté por debajo de las cifras reales. Desde que existen vacunas antirrábicas eficaces, el impacto de la enfermedad ha menguado sensiblemente en vastas regiones del globo. El éxito obtenido con diferentes vacunas y políticas de vacunación en las poblaciones consideradas «expuestas¼ es deudor de la innovación científica. Las campañas de vacunación masiva de animales de compañía por vía parenteral y los avances en la vacunación oral de la fauna silvestre han servido para acabar con la rabia en las poblaciones de carnívoros terrestres de varias regiones del mundo, en particular Europa Occidental y gran parte de América del Norte. Además, las vacunas humanas, utilizadas principalmente como tratamiento tras la exposición, han reducido la carga de rabia en las zonas donde la enfermedad es endémica.

High prevalence of Seoul hantavirus in a breeding colony of pet rats.

As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.

Passive surveillance of United Kingdom bats for lyssaviruses (2005-2015).

Passive surveillance for lyssaviruses in UK bats has been ongoing since 1987 and has identified 13 cases of EBLV-2 from a single species; Myotis daubentonii. No other lyssavirus species has been detected. Between 2005 and 2015, 10 656 bats were submitted, representing 18 species, creating a spatially and temporally uneven sample of British bat fauna. Uniquely, three UK cases originate from a roost at Stokesay Castle in Shropshire, England, where daily checks for grounded and dead bats are undertaken and bat carcasses have been submitted for testing since 2007. Twenty per cent of Daubenton's bats submitted from Stokesay Castle since surveillance began, have tested positive for EBLV-2. Phylogenetic analysis reveals geographical clustering of UK viruses. Isolates from Stokesay Castle are more closely related to one another than to viruses from other regions. Daubenton's bats from Stokesay Castle represent a unique opportunity to study a natural population that appears to maintain EBLV-2 infection and may represent endemic infection at this site. Although the risk to public health from EBLV-2 is low, consequences of infection are severe and effective communication on the need for prompt post-exposure prophylaxis for anyone that has been bitten by a bat is essential.

Pathobiological investigation of naturally infected canine rabies cases from Sri Lanka.

BACKGROUND: The recommended screening of rabies in 'suspect' animal cases involves testing fresh brain tissue. The preservation of fresh tissue however can be difficult under field conditions and formalin fixation provides a simple alternative that may allow a confirmatory diagnosis. The occurrence and location of histopathological changes and immunohistochemical (IHC) labelling for rabies in formalin fixed paraffin embedded (FFPE) canine brain is described in samples from 57 rabies suspect cases from Sri-Lanka. The presence of Negri bodies and immunohistochemical detection of rabies virus antigen were evaluated in the cortex, hippocampus, cerebellum and brainstem. The effect of autolysis and artefactual degeneration of the tissue was also assessed. RESULTS: Rabies was confirmed in 53 of 57 (93%) cases by IHC. IHC labelling was statistically more abundant in the brainstem. Negri bodies were observed in 32 of 53 (60.4%) of the positive cases. Although tissue degradation had no effect on IHC diagnosis, it was associated with an inability to detect Negri bodies. In 13 cases, a confirmatory Polymerase chain reaction (PCR) testing for rabies virus RNA was undertaken by extracting RNA from fresh frozen tissue, and also attempted using FFPE samples. PCR detection using fresh frozen samples was in agreement with the IHC results. The PCR method from FFPE tissues was suitable for control material but unsuccessful in our field cases. CONCLUSIONS: Histopathological examination of the brain is essential to define the differential diagnoses of behaviour modifying conditions in rabies virus negative cases, but it is unreliable as the sole method for rabies diagnosis, particularly where artefactual change has occurred. Formalin fixation and paraffin embedding does not prevent detection of rabies virus via IHC labelling even where artefactual degeneration has occurred. This could represent a pragmatic secondary assay for rabies diagnosis in the field because formalin fixation can prevent sample degeneration. The brain stem was shown to be the site with most viral immunoreactivity; supporting recommended sampling protocols in favour of improved necropsy safety in the field. PCR testing of formalin fixed tissue may be successful in certain circumstances as an alternative test.

United Nations Secretary-General's Mechanism.

The credibility and legitimacy of the United Nations Secretary-General's Mechanism (UNSGM) for investigating the alleged use of biological weapons relies in part on qualified experts trained to undertake fact-finding missions using an empirical scientific approach. As observed in the 2013 investigation into the alleged use of chemical weapons in the Syrian Arab Republic, this mechanism can be an effective tool in the verification of and as a deterrent against the use of chemical and biological weapons. The World Organisation for Animal Health (OIE) has a memorandum of understanding with the United Nations Office for Disarmament Affairs, supporting the UNSGM and providing experts for its roster for missions. As the majority of biological agents are of animal origin, the expertise of the OIE in this area, and its involvement in the UNSGM, are of paramount importance. Since 2014, experts from the OIE have participated in relevant training and are available for deployment to investigate any alleged use of a biological weapon anywhere in the world if the UNSGM were triggered.

La crédibilité et la légitimité du Mécanisme du Secrétaire général des Nations Unies visant à enquêter rapidement sur les allégations relatives à l'emploi possible d'armes biologiques reposent en partie sur le travail d'experts qualifiés et formés aux enquêtes d'établissement des faits, qui font appel à une méthode scientifique empirique. Comme cela a été constaté lors de l'enquête de 2013 concernant l'emploi allégué d'armes chimiques en République arabe syrienne, ce mécanisme peut constituer un outil efficace de vérification et de dissuasion en matière d'utilisation d'armes chimiques et biologiques. L'Organisation mondiale de la santé animale (OIE) a conclu un Mémorandum d'accord avec le Bureau des affaires de désarmement des Nations Unies, par lequel l'OIE s'engage à soutenir le Mécanisme du Secrétaire général et à mettre à disposition des experts pour participer aux missions. Les agents biologiques étant majoritairement d'origine animale, les compétences de l'OIE dans ce domaine et sa contribution au Mécanisme du Secrétaire général des Nations Unies sont d'une importance capitale. Depuis 2014, les experts de l'OIE ont participé aux formations requises ; en cas d'activation du mécanisme, ils sont donc opérationnels pour prendre part aux missions d'enquête sur l'emploi allégué d'armes biologiques partout dans le monde.

La credibilidad y legitimidad del Mecanismo del Secretario General de las Naciones Unidas para la Investigación del Presunto Empleo de Armas Químicas, Biológicas o Toxínicas reposa en parte en la participación de expertos cualificados y formados para llevar a cabo misiones de esclarecimiento de los hechos empleando métodos científicos experimentales. Como dejó patente la investigación sobre el presunto uso de armas químicas en la República Árabe Siria realizada en 2013, este mecanismo puede constituir una eficaz herramienta de verificación y un factor disuasorio del uso de armas químicas o biológicas. La Organización Mundial de Sanidad Animal (OIE) tiene suscrito con la Oficina de Asuntos de Desarme de las Naciones Unidas un memorando de entendimiento en virtud del cual presta apoyo al Mecanismo del Secretario General y proporciona expertos que figuran en la lista de especialistas llamados a participar en sus misiones. Toda vez que la mayoría de los agentes biológicos son de origen animal, la competencia técnica de la OIE en este ámbito, así como su participación en el Mecanismo, revisten una importancia capital. Desde 2014, expertos de la OIE han participado en actividades de formación sobre el tema y están disponibles para desplegarse en cualquier lugar del mundo e investigar todo caso de presunta utilización de un arma biológica en cuanto se active el Mecanismo del Secretario General.

Production and calibration of the second batch of OIE anti-rabies positive reference serum.

The Biological Standards Commission of the World Organisation for Animal Health (OIE) oversees the preparation and validation of OIE-approved International Reference Standards for use in serological assays for detecting infectious diseases of animals or the adequacy of their immune response following vaccination against those diseases. The principal use of OIE-approved International Reference Standards is to harmonise serological testing and to promote the mutual recognition of test results for international trade. In the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, the organisation recommends the use of the OIE anti-rabies positive reference serum of dog origin to titrate serum samples in international units (IU)/ml for use in rabies serological tests. The first batch of OIE reference serum of dog origin was produced in1991 and was used internationally until the beginning of 2010. The preparation of the new batch began in 2012 and, in contrast to the previous batch, three commercial inactivated rabies vaccines based on the most frequently used vaccine strains (Pasteur Virus and Flury Low Egg Passage) were selected for the immunisation of dogs in accordance with OIE guidelines. In 2013, calibration was completed through an inter-laboratory test involving five OIE Reference Laboratories for Rabies with the Second World Health Organization (WHO) International Standard for Anti-Rabies Immunoglobulin being used as a reference standard in this calibration. After statistical analysis of the results, the consensus titre was established as 5.59 IU/ml. The technical and statistical data were submitted to the OIE for assessment. In February 2014, the OIE Biological Standards Commission adopted this serum as an OIE-approved standard reagent for rabies serology.

La Commission des normes biologiques de l'Organisation mondiale de la santé animale (OIE) supervise la préparation et la validation de réactifs internationaux de référence approuvés par l'OIE et destinés aux épreuves sérologiques ayant pour objet le diagnostic des maladies infectieuses des animaux ou le suivi de l'effet protecteur obtenu par la vaccination contre ces maladies. Les réactifs internationaux de référence approuvés par l'OIE sont principalement utilisés pour harmoniser les tests sérologiques et permettre la reconnaissance mutuelle des résultats des tests dans le cadre des échanges internationaux. Le Manuel des tests de diagnostic et des vaccins pour les animaux terrestres de l'OIE recommande d'utiliser le sérum de référence antirabique positif d'origine canine de l'OIE pour exprimer le titre des échantillons de sérum analysés en unités internationales (UI)/ml lors des épreuves sérologiques. Le premier lot de sérum de référence d'origine canine de l'OIE, produit en 1991, a été utilisé à l'échelle internationale jusqu'au début de l'année 2010. La préparation d'un nouveau lot a commencé en 2012 et, contrairement au lot précédent, trois vaccins antirabiques inactivés disponibles dans le commerce, basés sur les souches vaccinales les plus utilisées dans le monde (souche Pasteur et souche Flury Low Egg Passage) ont été choisis pour l'immunisation des chiens, conformément aux lignes directrices de l'OIE. L'étalonnage s'est achevé en 2013 lors d'un essai inter-laboratoires auquel ont participé cinq Laboratoires de référence de l'OIE pour la rage ; le second étalon international pour l'immunoglobuline antirabique de l'Organisation mondiale de la santé (OMS) a été utilisé en tant que réactif de référence pour cet étalonnage. Après analyse statistique des résultats, le titre consensuel obtenu est de 5,59 UI/ml. Les données techniques et statistiques ont été soumises à l'OIE pour évaluation. En février 2014, la Commission des normes biologiques de l'OIE a adopté ce sérum en tant qu'étalon de référence approuvé par l'OIE pour la sérologie de la rage.

La Comisión de Normas Biológicas de la Organización Mundial de Sanidad Animal (OIE) supervisa la preparación y validación de patrones de referencia internacional aprobados por la OIE para su utilización en ensayos serológicos destinados a detectar enfermedades animales infecciosas o a valorar la idoneidad de la respuesta inmunitaria de un animal al ser vacunado contra una u otra enfermedad. Dichos patrones sirven sobre todo para armonizar la realización de pruebas serológicas y promover el reconocimiento mutuo de los resultados de las pruebas con fines de comercio internacional. En su Manual de las Pruebas de Diagnóstico y de las Vacunas para los Animales Terrestres, la OIE recomienda el empleo del suero positivo antirrábico de referencia de la OIE, de origen canino, para titular muestras de suero en unidades internacionales (UI)/ml y utilizarlas en pruebas serológicas de detección de la rabia. El primer lote de suero de referencia de la OIE procedente de perros fue elaborado en 1991 y estuvo en uso a nivel internacional hasta principios de 2010. La preparación del nuevo lote dio comienzo en 2012 y, a diferencia del lote anterior, para la inmunización del perro se seleccionaron tres vacunas inactivadas comerciales basadas en las cepas vacunales utilizadas con más frecuencia (virus Pasteur y cepa Flury Low Egg Passage), de conformidad con las directrices de la OIE. En 2013 culminó el proceso de calibración con una prueba interlaboratorios en la que intervinieron cinco Laboratorios de Referencia de la OIE para la rabia. En esta calibración se utilizó como patrón de referencia el segundo patrón internacional de inmunoglobulina antirrábica de la Organización Mundial de la Salud (OMS). Tras el análisis estadístico de los resultados, el título de consenso quedó fijado en 5,59 UI/ml. Los datos técnicos y estadísticos fueron sometidos a la valoración de la OIE, cuya Comisión de Normas Biológicas, en febrero de 2014, aprobó este suero como reactivo de referencia aprobado por la OIE para pruebas serológicas de detección de la rabia.

The challenge of using experimental infectivity data in risk assessment for Ebola virus: why ecology may be important.

Analysis of published data shows that experimental passaging of Zaire ebolavirus (EBOV) in guinea pigs changes the risk of infection per plaque-forming unit (PFU), increasing infectivity to some species while decreasing infectivity to others. Thus, a PFU of monkey-adapted EBOV is 10(7) -fold more lethal to mice than a PFU adapted to guinea pigs. The first conclusion is that the infectivity of EBOV to humans may depend on the identity of the donor species itself and, on the basis of limited epidemiological data, the question is raised as to whether bat-adapted EBOV is less infectious to humans than nonhuman primate (NHP)-adapted EBOV. Wildlife species such as bats, duikers and NHPs are naturally infected by EBOV through different species giving rise to EBOV with different wildlife species-passage histories (heritages). Based on the ecology of these wildlife species, three broad 'types' of EBOV-infected bushmeat are postulated reflecting differences in the number of passages within a given species, and hence the degree of adaptation of the EBOV present. The second conclusion is that the prior species-transmission chain may affect the infectivity to humans per PFU for EBOV from individuals of the same species. This is supported by the finding that the related Marburg marburgvirus requires ten passages in mice to fully adapt. It is even possible that the evolutionary trajectory of EBOV could vary in individuals of the same species giving rise to variants which are more or less virulent to humans and that the probability of a given trajectory is related to the heritage. Overall the ecology of the donor species (e.g. dog or bushmeat species) at the level of the individual animal itself may determine the risk of infection per PFU to humans reflecting the heritage of the virus and may contribute to the sporadic nature of EBOV outbreaks.

Evaluation of a temperate climate mosquito, Ochlerotatus detritus (=Aedes detritus), as a potential vector of Japanese encephalitis virus.

The U.K. has not yet experienced a confirmed outbreak of mosquito-borne virus transmission to people or livestock despite numerous autochthonous epizootic and human outbreaks of mosquito-borne diseases on the European mainland. Indeed, whether or not British mosquitoes are competent to transmit arboviruses has not been established. Therefore, the competence of a local (temperate) British mosquito species, Ochlerotatus detritus (=Aedes detritus) (Diptera: Culicidae) for transmission of a member of the genus Flavivirus, Japanese encephalitis virus (JEV) as a model for mosquito-borne virus transmission was assessed. The JEV competence in a laboratory strain of Culex quinquefasciatus (Diptera: Culicidae), a previously incriminated JEV vector, was also evaluated as a positive control. Ochlerotatus detritus adults were reared from field-collected juvenile stages. In oral infection bioassays, adult females developed disseminated infections and were able to transmit virus as determined by the isolation of virus in saliva secretions. When pooled at 7-21 days post-infection, 13% and 25% of O. detritus were able to transmit JEV when held at 23 °C and 28 °C, respectively. Similar results were obtained for C. quinquefasciatus. To our knowledge, this study is the first to demonstrate that a British mosquito species, O. detritus, is a potential vector of an exotic flavivirus.

Louping ill virus: an endemic tick-borne disease of Great Britain.

In Europe and Asia, Ixodid ticks transmit tick-borne encephalitis virus (TBEV), a flavivirus that causes severe encephalitis in humans but appears to show no virulence for livestock and wildlife. In the British Isles, where TBEV is absent, a closely related tick-borne flavivirus, named louping ill virus (LIV), is present. However, unlike TBEV, LIV causes a febrile illness in sheep, cattle, grouse and some other species, that can progress to fatal encephalitis. The disease is detected predominantly in animals from upland areas of the UK and Ireland. This distribution is closely associated with the presence of its arthropod vector, the hard tick Ixodes ricinus. The virus is a positive-strand RNA virus belonging to the genus Flavivirus, exhibiting a high degree of genetic homology to TBEV and other mammalian tick-borne viruses. In addition to causing acute encephalomyelitis in sheep, other mammals and some avian species, the virus is recognized as a zoonotic agent with occasional reports of seropositive individuals, particularly those whose occupation involves contact with sheep. Preventative vaccination in sheep is effective although there is no treatment for disease. Surveillance for LIV in Great Britain is limited despite an increased awareness of emerging arthropod-borne diseases and potential changes in distribution and epidemiology. This review provides an overview of LIV and highlights areas where further effort is needed to control this disease.

Bovine rabies in Turkey: patterns of infection and implications for costs and control.

The incidence of rabies in livestock is an important factor for estimating the economic impact of the disease, but obtaining reliable data is hindered by inadequate surveillance. In order to understand the contribution of livestock rabies to the overall burden of disease, the rabies incidence in cattle was investigated in detail for Turkey between 2008 and 2011. Data were compiled on cattle numbers, samples submitted for rabies diagnosis, vaccinated animals and positive rabies cases in animals for seven regions in Turkey. Rabies incidence in cattle fluctuated annually and differed between regions from 0·10 to 3·87 cases/100 000 animals. The positive influence of compensation schemes was observed. Livestock losses were conservatively estimated at around $250 000 international dollars per annum, although in areas where compensation schemes are not operating this could be an underestimate of the economic burden. Vaccination of cattle remains an option for disease prevention, although oral rabies vaccination through aerially distributed baits should be implemented to prevent the further spread of fox-mediated rabies, which could result in much greater economic costs.

Epidemiological perspectives on West Nile virus surveillance in wild birds in Great Britain.

West Nile virus (WNV) is a zoonotic arthropod-borne pathogen with continued geographical expansion in Europe. We present and evaluate data on the temporal, spatial and bird species focus of the WNV surveillance programme in dead wild birds in Great Britain (2002-2009). During this period all bird samples tested negative for WNV. Eighty-two per cent of the 2072 submissions occurred during the peak period of vector activity with 53% tested during April-July before human and equine infection would be expected. Samples were received from every county, but there was significant geographical clustering (nearest neighbour index=0·23, P<0·001). Over 240 species were represented, with surveillance more likely to detect WNV in resident bird species (92% of submissions) than migrants (8%). Evidence indicates that widespread avian mortality is not generally a reported feature of WNV in Europe and hence additional activities other than dead bird surveillance may maximize the ability to detect WNV circulation before the onset of human and equine infections.

Developments in rabies vaccines.

The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection.

Pathology associated with a human case of rabies in the United Kingdom caused by European bat lyssavirus type-2.

Human infection with the rabies-related virus European bat lyssavirus type-2 (EBLV-2) has only been reported on two occasions. Here we report the pathology observed within spinal cord and visceral tissues associated with EBLV-2 infection for the first time. Neuronal labelling with an anti-rabies nucleocapsid monoclonal antibody was observed and appeared indistinguishable from the labelling reported from human infection with rabies virus.

Endemic Lagos bat virus infection in Eidolon helvum.

Phylogenetic analyses suggest lyssaviruses, including Rabies virus, originated from bats. However, the role of bats in the maintenance, transmission and evolution of lyssaviruses is poorly understood. A number of genetically diverse lyssaviruses are present in Africa, including Lagos bat virus (LBV). A high seroprevalence of antibodies against LBV was detected in Eidolon helvum bats. Longitudinal seroprevalence and age-specific seroprevalence data were analysed and capture-mark-recapture (CMR) analysis used to follow 98 bats over 18 months. These data demonstrate endemic infection, with evidence of horizontal transmission, and force of infection was estimated for differing age categories. The CMR analysis found survival probabilities of seronegative and seropositive bats were not significantly different. The lack of increased mortality in seropositive animals suggests infection is not causing disease after extended incubation. These key findings point towards acute transmission of bat lyssaviruses in adapted bat hosts that occurs at a far higher rate than the occurrence of disease.

A quantitative release assessment for the noncommercial movement of companion animals: risk of rabies reintroduction to the United kingdom.

In 2004, the European Union (EU) implemented a pet movement policy (referred to here as the EUPMP) under EU regulation 998/2003. The United Kingdom (UK) was granted a temporary derogation from the policy until December 2011 and instead has in place its own Pet Movement Policy (Pet Travel Scheme (PETS)). A quantitative risk assessment (QRA) was developed to estimate the risk of rabies introduction to the UK under both schemes to quantify any change in the risk of rabies introduction should the UK harmonize with the EU policy. Assuming 100 % compliance with the regulations, moving to the EUPMP was predicted to increase the annual risk of rabies introduction to the UK by approximately 60-fold, from 7.79 × 10(-5) (5.90 × 10(-5), 1.06 × 10(-4)) under the current scheme to 4.79 × 10(-3) (4.05 × 10(-3), 5.65 × 10(-3)) under the EUPMP. This corresponds to a decrease from 13,272 (9,408, 16,940) to 211 (177, 247) years between rabies introductions. The risks associated with both the schemes were predicted to increase when less than 100 % compliance was assumed, with the current scheme of PETS and quarantine being shown to be particularly sensitive to noncompliance. The results of this risk assessment, along with other evidence, formed a scientific evidence base to inform policy decision with respect to companion animal movement.

Molecular diversity and evolutionary history of rabies virus strains circulating in the Balkans.

Molecular studies of European classical rabies viruses (RABV) have revealed a number of geographically clustered lineages. To study the diversity of Balkan RABV, partial nucleoprotein (N) gene sequences were analysed from a unique panel of isolates (n = 210), collected from various hosts between 1972 and 2006. All of the Balkan isolates grouped within the European/Middle East Lineage, with the majority most closely related to East European strains. A number of RABV from Bosnia & Herzegovina and Montenegro, collected between 1986 and 2006, grouped with the West European strains, believed to be responsible for the rabies epizootic that spread throughout Europe in the latter half of the 20th Century. In contrast, no Serbian RABV belonged to this sublineage. However, a distinct group of Serbian fox RABV provided further evidence for the southwards wildlife-mediated movement of rabies from Hungary, Romania and Serbia into Bulgaria. To determine the optimal region for evolutionary analysis, partial, full and concatenated N-gene and glycoprotein (G) gene sequences were compared. Whilst both the divergence times and evolutionary rates were similar irrespective of genomic region, the 95 % highest probability density (HPD) limits were significantly reduced for full N-gene and concatenated NG-gene sequences compared with partial gene sequences. Bayesian coalescent analysis estimated the date of the most common recent ancestor of the Balkan RABV to be 1885 (95 % HPD, 1852-1913), and skyline plots suggested an expansion of the local viral population in 1980-1990, which coincides with the observed emergence of fox rabies in the region.