The European Union (EU) aims to eliminate foxmediated rabies from its territory by 2020. At first sight, this seems a rather ambitious goal considering that this horrifying disease has tormented humans and animals in Europe since ancient times. However, Dr Conrad Freuling (WHO), Dr Ad Vos (Ceva) and Dr Thomas Müller (WHO) are confident that collecting and sharing rabies surveillance data through the RBE will safeguard the unprecedented success in rabies control achieved in Europe.
Rabies has always been a disease that has attracted the attention of the public eye. Due to the high case fatality rate of infected humans and animals, government authorities have always invested resources for its control and prevention. It is necessary to keep a close watch for outbreaks of the virus, to ensure rapid implementation of control measures and reassess disease epidemiology. This article's intention is to give an updated assessment of the status of rabies in Europe, focusing on distribution, risk, diagnosis and prevention.
At the beginning of the 21st century, rabies, the oldest known zoonosis to mankind, is still a notoriously underreported and neglected disease in many parts of the world causing tens of thousands of human deaths annually. Together with WHO and FAO, the OIE has taken a leadership role in reducing the public health and economic burden of rabies by controlling and eliminating the disease at the animal source and by identifying the current epidemiological situation in the OIE Regions as well as by identifying the control measures and the challenges faced by the Veterinary Services of Member Countries in implementing the OIE guidelines and standards. During the 83rd General Session of the OIE World Assembly of Delegates held in Paris in May 2015, the OIE Regional Commission for Europe adopted 'Control and elimination of rabies in Europe: Challenges and strategies for a rabies-free Europe' as the Technical Item 1 (with questionnaire) to be presented during the 27th Conference of the OIE Regional Commission for Europe to be held in Lisbon, Portugal, from 19 to 23 September 2016. The questionnaire developed to address Technical Item 1 was sent to all Member Countries of the Region and resulted in 49 of 53 Member Countries responding (92% response rate). This response rate, being the highest from this OIE Region on a questionnaire related to a Technical Item to be presented in a Conference of the OIE Regional Commission for Europe, indicates a high level of interest in this topic by the Member Countries. There was a range of responses across a variety of topics including epidemiological situation, rabies surveillance, diagnostic capacities and capabilities, reporting, legislation, use of guideline and standards, host reservoir, targeted rabies control programmes and related issues, stray dog population management, cross-border collaboration, intersectorial collaboration and the challenges ahead related to this disease. The variability of responses reflects differences in epidemiological situations in the Region ranging from freedom of disease (51%) to endemic occurrence in either wildlife- or in both dog- and wildlifemediated rabies (49%). In addition, the variability of responses demonstrates differences in challenges associated with disease surveillance and control, including public awareness and communication. Although 34% of endemic countries envisage elimination of rabies within the next five years, one third of responders (32%) indicated the desire for OIE to be more proactive and to provide guidance to Member Countries that would support Competent Authorities and Veterinary Services in their efforts of eliminating rabies form their countries. The greatest emphasis was placed on rabies surveillance, standardised and efficient rabies control measures (including training and facilitation of cross border activities), as well as adequate support in the design, financing, implementation and monitoring of stray dog population management programmes.
Following the implementation of oral rabies vaccination of foxes (ORV) in Western Europe, a continuous decrease in rabies incidence was reported, and eventually rabies was eliminated. Once fox rabies is eliminated in a given area, re-infection from neighbouring infected countries is a permanent threat. As a result, countries need to maintain a vaccination belt along common borders until rabies is also eliminated in sufficiently large border regions of neighbouring infected countries. In a theoretical approach EU member states were taken as a prime example, assuming that they were rabies-free but that neighbouring countries were still infected. Using GIS, a 50 km deep vaccination belt beyond the front of the rabies endemic zone was installed in countries bordering those regions. The annual cost for the prevention of re-infection of the EU territory was calculated considering current EU recommendations (vaccination twice per year, aerial and complementary hand distribution, bait density of 30 baits per km2). Minimum and maximum prices for commercial available oral rabies vaccine baits, aircraft and rabies surveillance were considered for the calculation of costs. The total vaccination area which needed to be established was about 251,000 km2. Using mainly fixed-wing aircraft, the annual cost for ORV including rabies surveillance varied between a minimum of 10 and a maximum of 16M Euro, depending on the cost of vaccine bait. If helicopters were used exclusively, the maximum cost increased to about 32M Euro. Depending on the length of the border to infected regions, countries will have to pay up to 25% of the total cost. Countries which need to install a vaccination belt will never have a rabies-free status because of the likely occurrence of rabies cases in border zones.
Infectious diseases are often transmitted through local interactions. Yet, both surveillance and control measures are implemented within administrative units. Capturing local transmission processes and spatial coupling between regions from aggregate level data is therefore a technical challenge that can shed light on both theoretical questions and practical decisions. Fox rabies has been eliminated from much of Europe through oral rabies vaccination (ORV) programmes. The European Union (EU) co-finances ORV to maintain rabies freedom in EU member and border states via a cordon sanitaire. Models to capture local transmission dynamics and spatial coupling have immediate application to the planning of these ORV campaigns and to other parts of the world considering oral vaccination. We fitted a hierarchical Bayesian state-space model to data on three decades of fox rabies cases and ORV campaigns from Eastern Germany. Specifically, we find that (i) combining regional spatial coupling and heterogeneous local transmission allows us to capture regional rabies dynamics; (ii) incursions from other regions account for less than 1% of cases, but allow for re-emergence of disease; (iii) herd immunity achieved through bi-annual vaccination campaigns is short-lived due to population turnover. Together, these findings highlight the need for regular and sustained vaccination efforts and our modelling approach can be used to provide strategic guidance for ORV delivery. Moreover, we show that biological understanding can be gained from inference from partially observed data on wildlife disease.
Infectious diseases are often transmitted through local interactions. Yet, both surveillance and control measures are implemented within administrative units. Capturing local transmission processes and spatial coupling between regions from aggregate level data is therefore a technical challenge that can shed light on both theoretical questions and practical decisions. Fox rabies has been eliminated from much of Europe through oral rabies vaccination (ORV) programmes. The European Union (EU) co-finances ORV to maintain rabies freedom in EU member and border states via a cordon sanitaire. Models to capture local transmission dynamics and spatial coupling have immediate application to the planning of these ORV campaigns and to other parts of the world considering oral vaccination. We fitted a hierarchical Bayesian state-space model to data on three decades of fox rabies cases and ORV campaigns from Eastern Germany. Specifically, we find that (i) combining regional spatial coupling and heterogeneous local transmission allows us to capture regional rabies dynamics; (ii) incursions from other regions account for less than 1% of cases, but allow for re-emergence of disease; (iii) herd immunity achieved through bi-annual vaccination campaigns is short-lived due to population turnover. Together, these findings highlight the need for regular and sustained vaccination efforts and our modelling approach can be used to provide strategic guidance for ORV delivery. Moreover, we show that biological understanding can be gained from inference from partially observed data on wildlife disease.
Infectious diseases are often transmitted through local interactions. Yet, both surveillance and control measures are implemented within administrative units. Capturing local transmission processes and spatial coupling between regions from aggregate level data is therefore a technical challenge that can shed light on both theoretical questions and practical decisions. Fox rabies has been eliminated from much of Europe through oral rabies vaccination (ORV) programmes. The European Union (EU) co-finances ORV to maintain rabies freedom in EU member and border states via a cordon sanitaire. Models to capture local transmission dynamics and spatial coupling have immediate application to the planning of these ORV campaigns and to other parts of the world considering oral vaccination. We fitted a hierarchical Bayesian state-space model to data on three decades of fox rabies cases and ORV campaigns from Eastern Germany. Specifically, we find that (i) combining regional spatial coupling and heterogeneous local transmission allows us to capture regional rabies dynamics; (ii) incursions from other regions account for less than 1% of cases, but allow for re-emergence of disease; (iii) herd immunity achieved through bi-annual vaccination campaigns is short-lived due to population turnover. Together, these findings highlight the need for regular and sustained vaccination efforts and our modelling approach can be used to provide strategic guidance for ORV delivery. Moreover, we show that biological understanding can be gained from inference from partially observed data on wildlife disease.
Rabies was eradicated from the UK in 1922 through strict controls of dog movement and investigation of every incident of disease. Amendments were made to the UK quarantine laws and the Pet Travel Scheme (PETS) was subsequently introduced in 2000 for animals entering the UK from qualifying listed countries. European Regulation 998/2003 on the non-commercial movement of pet animals initiated the European Union Pet Movement Policy (EUPMP) in July 2004. The introduction of EUPMP harmonized the movement of pet animals within the EU (EUPMPlisted) but raised the possibility of domestic animals entering the UK from a non-EU state where rabies is endemic (EUPMPunlisted). A quantitative risk assessment was developed to estimate the risk of rabies entering the UK from Turkey via companion animals that are incubating the disease and enter through PETS or EUPMP compared to quarantine. Specifically, the risk was assessed by estimating the annual probability of rabies entering the UK and the number of years between rabies entries for each scheme. The model identified that the probability of rabies entering the UK via the three schemes is highly dependent on compliance. If 100% compliance is assumed, PETS and EUPMPunlisted (at the current level of importation) present a lower risk than quarantine, i.e. the number of years between rabies entry is more than 170 721 years for PETS and 60 163 years for EUPMPunlisted compared to 41 851 years for quarantine (with 95% certainty). If less than 100% compliance is assumed, PETS and EUPMPunlisted (at the current level of importation) present a higher risk. In addition, EUPMPlisted and EUPMPunlisted (at an increased level of importation) present a higher risk than quarantine or PETS at 100% compliance and at an uncertain level of compliance.
EU Regulation 998/2003 requires the serological testing of rabies-vaccinated dogs and cats in approved laboratories using serum neutralization tests prior to movement of pet animals between certain EU member states and before pet animals are imported from unlisted third countries. Serum neutralisation tests are also used for measuring the efficacy of oral rabies vaccination programmes conducted in wild carnivore populations. In this study we evaluated an OIElisted commercial ELISA as a potential replacement for serum neutralization assays under routine conditions as a diagnostic tool for both the serological testing of dog and cat sera as part of pet travel schemes and for follow-up investigations as part of oral vaccination campaigns. When dog and cat sera were analyzed by ELISA, a sensitivity compared to the standard serological test of 36.9-82.0% and 44.4-88.9%, respectively, was calculated depending on the method used. For fox field samples from oral vaccination areas the sensitivity compared to the Rapid Fluorescent Focus Inhibition Test (RFFIT) was 32.4% (95% CI 24.8-40.0%).In its present format, the ELISA cannot replace standard serological assays neither in the pet travel scheme nor in follow-up investigations of oral vaccination campaigns. The results obtained resemble those of other rabies ELISAs recently evaluated for the same purpose and may therefore exemplify a general misconception (binding versus neutralization) in rabies serology rather than a failure of this ELISA test per se. Also, problems with technical and legislative issues associated with the serological testing of dog and cat sera for non-commercial movement and related to the outcome of this study are addressed.
Due to the implementation of oral rabies vaccination (ORV) programmes, the European Union (EU) is becoming progressively free of red fox (Vulpes vulpes)-mediated rabies. Over the past three decades, the incidence of rabies had decreased substantially and vast areas of Western and Central Europe have been freed from rabies using this method of controlling an infectious disease in wildlife. Since rabies control is a top priority in the EU, the disease is expected to be eliminated at the animal source in the near future. Whilst responsible authorities may consider the mission of eliminating fox rabies from the EU almost accomplished, there are still issues to be dealt with and challenges to be met that have not yet been the focus of attention, but could jeopardise the ultimate goal. Among these are increasing illegal movements of animals, maintaining funding support for vaccination campaigns, devising alternative vaccine strategies in neighbouring Eastern European countries and the expanding distribution range of several potential rabies reservoir species in Europe.
In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec), are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.
Following a sustained spill-over event from dogs to foxes, fox rabies spread rapidly in the Aegean region, Turkey. In order to control the outbreak a program of oral vaccination of foxes against rabies was introduced. In the selected vaccination area three annual campaigns between 2008 and 2010 were undertaken during the winter months whereby the vaccine baits were distributed exclusively by plane using a density of 18 baits per km². Subsequently, fox rabies cases were reported only from locations bordering the non-vaccinated areas. Hence, it was shown that fox rabies control by means of oral rabies vaccination is feasible in Turkey. However, for the progress towards the elimination of fox-mediated rabies in Turkey to be maintained, it is necessary that political and financial support is secured to extend oral vaccination where infected foxes remain.
In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec), are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.
Rabies is one of the oldest known zoonoses. Recognized etiological agents consist of at least 15 proposed species of lyssaviruses with primary reservoirs residing in the Orders Carnivora and Chiroptera. A plethora of viral variants, maintained by a diverse set of abundant hosts, presents a formidable challenge to a strict concept of true disease eradication. Despite the availability of affordable and efficacious animal and human vaccines, today however dog rabies continues to escalate unabated across much of Asia and Africa, causing millions of suspect human exposures and tens of thousands of human rabies deaths annually. By identifying what hampers global human rabies elimination this chapter emphasizes that, given the global epidemiology of rabies, the "One Health" concept is key to solving the problem. Next to state of the art human rabies prevention, immunization and experimental therapy, it is obvious that human rabies can only be eliminated through rabies control at the animal source. This 'paradigm shift', however, needs new grassroot initiatives as well as political will and the closing of ranks of all stakeholders in the near future.
Pathogen discovery contributes to our knowledge of bat-borne viruses and is linked to the heightened interest globally in bats as recognised reservoirs of zoonotic agents. The transmission of lyssaviruses from bats-to-humans, domestic animals, or other wildlife species is uncommon, but interest in these pathogens remains due to their ability to cause an acute, progressive, invariably fatal encephalitis in humans. Consequently, the detection and characterisation of bat lyssaviruses continues to expand our knowledge of their phylogroup definition, viral diversity, host species association, geographical distribution, evolution, mechanisms for perpetuation, and the potential routes of transmission. Although the opportunity for lyssavirus cross-species transmission seems rare, adaptation in a new host and the possibility of onward transmission to humans requires continued investigation. Considering the limited efficacy of available rabies biologicals it is important to further our understanding of protective immunity to minimize the threat from these pathogens to public health. Hence, in addition to increased surveillance, the development of a niche pan-lyssavirus vaccine or therapeutic biologics for post-exposure prophylaxis for use against genetically divergent lyssaviruses should be an international priority as these emerging lyssaviruses remain a concern for global public health. ; Defra, the Scottish Government and Welsh Government; European Union's Horizon 2020 research and innovation program; South African Research Chair Initiative (of the Department of Science and Innovation administered by the National Research Foundation of South Africa. ; http://www.mdpi.com/journal/viruses ; pm2021 ; Medical Virology
