In 2002, the former Scientific Committee on Animal Health and Animal Welfare of the European Commission (EC) issued a scientific report on the oral vaccination of foxes against rabies, covering the type of vaccines and baits, the methods of release of vaccine baits, the density of baits and distribution patterns, and the seasonal pattern of releases.
In accordance with the present mandate, the EC asks the European Food Safety Authority (EFSA) i) to update the above-mentioned report and, in particular, to consider if the conclusions and recommendations are still valid; ii) to assess the additional following topics: the new target species (e.g. raccoon dogs), the availability of a new vaccine in the European Union market, the thermostability of the bait casing and the possible impact on stability of the virus strain, and the recent European and international guidelines for rabies surveillance and oral vaccination monitoring.
The following topics are presented and discussed in the present opinion: (i) the rabies aetiology and an update on the phylogeny of the rabies virus and related diagnostic tests; (ii) an update of the occurrence of rabies in animals and humans in Europe up to 2014; (iii) a description of the potential reservoir and transmitter species for sylvatic rabies; (iv) an update on the ecology of foxes and raccoon dogs and the rabies epidemiology in these species, including the interaction dynamics of these two populations; (v) the characteristics of the vaccines available; (vi) the thermostability of the bait casing stability of the virus strain, confirmed by providing the results of experimental studies and the prescriptions of the new version of the European Pharmacopoeia; and (vii) a description of the criteria for rabies surveillance, monitoring of oral vaccination campaigns and the vaccination strategy, in line with the new EC ‘Guidelines to design an EU co-financed programme on eradication and control of rabies in wildlife’.
The recent European and international guidelines for rabies surveillance, as requested in the Terms of Reference have been used as a source of data and information for the current work. This includes documents issued by the EC, the EU task force on the eradication of animal disease (subgroup rabies), the World Health Organization (WHO), the World Organisation for Animal Health (OIE) and the European Pharmacopoeia. In particular, the most recent guidelines for rabies surveillance and oral vaccination are the EC guidance document issued in 2015 about the design and implementation of an EU co-financed programme on the elimination and control of rabies in wildlife; the update of the European Pharmacopoeia ‘Rabies vaccine (live, oral) for foxes and raccoon dogs’ issued in 2014, which includes raccoon dogs as target species; chapter 2.1.13, about rabies, of the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (Terrestrial Manual), updated in 2014; and the EFSA external scientific report ‘Development of harmonised schemes for monitoring and reporting of rabies in animals in the European Union’ issued in 2010, which provides recommendations for improving and harmonising rabies surveillance and reporting in animals in Europe. Scientific literature has been also screened, and the databases from Rabies Bulletin Europe and the Animal Disease Notification System (ADNS) has been used to provide updated information on the occurrence of rabies in Europe, both in Member States (MSs) and in neighbouring countries.
The conclusions and recommendations from the previous report issued by the EC in 2002 were comparatively assessed for their validity.
With regard to the host species, it is concluded that foxes are the only known reservoir for rabies in Europe, whereas raccoon dogs are not known to be reservoirs, but they are considered as important transmitters. Other carnivores may be infected by rabies, although their role as virus transmitters is generally less important. Ecological patterns of raccoon dogs may be important in rabies epidemiology, such as their rapid demographic expansion, as a risk factor for rabies recurrence, and the movements of adult raccoon dogs after hibernation in spring and the dispersal of juveniles. If winters are mild, depending on the latitude (e.g. in western Europe), raccoon dogs do not usually hibernate. As regards the interaction of host species, it is concluded that foxes and raccoon dogs often share the same habitats and their home ranges overlap making contacts between species likely. Moreover, their combined densities could lay above the threshold density values for rabies transmission, thus allowing rabies epizootics to persist in a certain area. Epidemiological studies and surveillance systems are needed to clarify the role of raccoon dogs and other carnivores in rabies epidemiology and pathogenesis.
With regard to the vaccines available in the EU, there are currently four vaccines authorised, all of which comply with the prescriptions of the European Pharmacopoeia for efficacy and safety. Each vaccine batch should be tested and approved for titre and stability by an acknowledged quality control scheme in accordance with OIE standards and WHO recommendations. Laboratories involved in the monitoring and evaluation of rabies programmes are advised to monitor the virus titre of batches of rabies vaccine baits before and during release into the field. The effectiveness of the four marketed oral vaccines is proven in the field and epidemiological data demonstrate that the existing vaccines have contributed to the success of rabies control and elimination in several European countries.
As regards the thermostability of bait casings and vaccines, there is experimental and field evidence that weather conditions may have a negative impact on the bait casings and vaccine virus stability; however, conditions are often different from those tested by the producers under laboratory conditions. Therefore, data on the stability of bait under different field conditions of landscape and temperatures, and on the related melting point, should be provided. In relation to thermostability of baits and vaccines, the countries implementing oral rabies vaccination (ORV), in particular those in southern Europe, should conduct vaccination campaigns in seasons when temperatures and/or climatic conditions do not compromise bait and vaccine stability, or should use a heat-stable vaccines. It is recommended that bait casing should keep its integrity when released into the environment, so that it does not melt and the capsule of the vaccine is still fully covered by the casing.
With regard to vaccination strategy and distribution patterns, the recent EC guidelines issued in 2015 provide clear and exhaustive information about bait distribution methods, and the current document is in line with the information provided there. Oral vaccination campaigns should be conducted on a biannual basis, in spring and autumn, taking climatic conditions into account. Autumn vaccination should generally be performed in September or October. Spring distribution should be carried out taking into account the birth time of fox and raccoon dog cubs, and also the possible hibernation of raccoon dogs, in order to increase the efficient access of fox and raccoon dog cubs to baits. Vaccinations at den entrances are recognised as costly and time-consuming, thus they should be applied only after a careful cost–benefit evaluation.
The minimum distributed bait density should not be less than 20 baits/km2. An increased bait density of up to 25–30 baits/km2 in combination with reduced flight-line distance (e.g. 300 m) should be considered in cases of setbacks and persisting residual foci.
In cases of reintroduction of rabies from infected neighbouring regions, buffer vaccination zones should be established, taking into account natural barriers. This belt should be at least 50 km beyond the front of a rabies endemic zone, unless natural barriers are present, then it could be reduced to a width of 20 km. In cases of rabies re-emergence in a previously rabies-free area, emergency vaccination needs to be conducted immediately. An emergency vaccination area with a radius of at least 50 km around the outbreak should be established. Manual distribution of baits can be used as a complementary method to aerial distribution, and managed using a case-by-case approach. In general, wherever the distribution system allows flexibility, the pattern of habitat use of host species should be considered.
Rabies surveillance and monitoring of the vaccination effectiveness are important tools for the assessment and adjustment of vaccination campaigns. Harmonised surveillance and monitoring methods should be sought in order to facilitate comparison of results and international cooperation.
Rabies surveillance should include examination of all wild and domestic mammals suspected of being infected by rabies, those found dead, including road kills, as well as those at the origin of human exposure. The viruses isolated from all positive cases in the vaccinated areas should be typed with the currently available molecular methods, in order to distinguish field rabies virus from vaccine associated cases.
Monitoring of vaccination programmes includes assessment of bait uptake through biomarker testing and of seroconversion in host species during vaccination campaigns. The need for a biomarker in vaccine baits and related testing for bait uptake could be reconsidered after the first few years, e.g. after the first two or three years, of ORV campaign implementation, according to the rabies situation in each country and to the overall control strategy in place. Moreover, the use of tetracyclines as biomarkers could potentially give rise to safety issues related to ecotoxicity and antimicrobial resistance, although no risk assessment has ever been performed on these aspects. Therefore, it is recommended that risk assessments are performed on this topic, and alternatives to tetracyclines as biomarkers should be developed. Also, the vaccine capsules inside the baits should be made of biodegradable material, so to avoid environmental contamination.
As a general conclusion, it was confirmed that oral immunisation against rabies by means of vaccine baits has been found to be successful in eliminating terrestrial wildlife rabies in most cases, both in foxes and raccoon dogs, although it requires a long-term strategy, temporal continuity of implementation of the vaccination campaigns and cross-border cooperation. The latter conditions are recommended for the success of the campaigns. For example, several MSs (the Czech Republic, Germany, Italy, Austria, Estonia, Latvia and Lithuania) have acquired or re-acquired the status of rabies-free country since 2003, thanks to oral vaccination against rabies.