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Over the last fifteen years or so, classical rabies in terrestrial wildlife has been eliminated from large areas of Western Europe. Over the next few years, terrestrial rabies is likely to occur only east of a line from the Baltic Sea to the Black Sea; the overall aim is to eliminate terrestrial rabies from the whole European Union. Elimination of rabies from the less rich countries of Eastern Europe, and the protection of Europe against a resurgence of rabies in the longer term requires modifications to existing OIE and WHO strategies. Here we discuss the options available to eliminate rabies in wildlife while taking account of financial cost, and how to maintain a 'cordon sanitaire' along the eastern boundary of the EU in order to protect the rabies-free areas from rabies incursion. Minimising financial costs at the national level is obviously essential, considering the competing priorities for development and health. This could be achieved either by increasing external funding (for example by the EU) and/or by changing the currently agreed vaccination strategy to reduce costs; any such change must not substantially reduce the chances of rabies elimination. A cordon sanitaire might be placed outside the economic area of the EU, to protect the whole of the EU, or it might be placed within the easternmost countries to ensure logistical consistency of vaccination. Policy must also anticipate an emergency due to rabies breaking out in a previously freed region. Strategic planning may be complicated by the increasing range and abundance of the raccoon dog, an introduced species that is increasingly important as a host for fox rabies. It is argued here that models help to evaluate altemative strategies, exploring options for optimising costs by minimising bait density and frequency or by reducing the vaccination area.

Germany has reported one of the highest levels of EBLV cases in bats in Europe. So far, all isolates originating from Germany have been identified as EBLV-1, using monoclonal antibodies, and a preliminary epidemiological study has indicated that there is a distinct geographical distribution of EBLV-1 in Germany. To further investigate the spatial and temporal distribution of EBLV-1 variants in Germany and their impact on molecular epidemiology, isolates were selected using a random grid sampling procedure based on GIS. Agrid layer 30 km long over the entire area of Germany was applied to 120 geo-referenced isolates and one isolate of each grid cell containing EBLV isolates was randomly chosen. Once selected, the nucleoprotein (N) plus parts of the phosphoprotein (P) gene of each isolate were sequenced using direct cycle sequencing. Results of the subsequent phylogenetic analysis of the N-gene confirmed previous studies on European EBLVs, showing a high sequence homology between German EBLV-1 isolates. Almost identical sequence homologies within certain geographical regions indicate genomic stability during the transmission cycle of EBLV-1, with little geographic spread or intermixing. Interestingly, a 6 bp insertion as well as a single nucleotide insertion, detected in the N-P intergenic region, has been found in EBLV-1 isolates from Germany.

Now that the elimination of rabies in Western Europe is nearly complete, thanks to the oral mass vaccination of foxes (ORV) which took place over the last 25 years, it is necessary to prepare for emergency situations due to the re-introduction of rabies from still infected areas. Such emergency strategies should aim at minimizing the risk of falling back to large-scale vaccination, in a cost efficient manner. An approved spatially-explicit simulation model of spread and control of rabies was adapted to the new problem of re-introduction of rabies into free areas. The logic of the model and options for local emergency vaccination (for example ring-vaccination vs. compact area treatment or heavily concentrated vs. thin extended control areas) were determined. Based on systematic simulation experiments the performance of strategic options was assessed. Key issues such as public health risk (i.e. number of rabies cases), failure risk (i.e. disease breakout from the control area), and budgetary risk (i.e. duration of the emergency program) were simultaneously considered. The results obtained reveal efficiency relations that contradict a priori derived management suggestions.

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.

For the first time, the effectiveness of oral rabies vaccines against European Bat Lyssaviruses Type 1 (EBLV-1) and Type 2 (EBLV-2) by means of cross-neutralization assays was investigated. Sera from orally vaccinated red foxes (Vulpes vulpes) and raccoon dogs (Nyctereutes procyonoides) with the Street Alabama Dufferin (SAD) B19 and SAD P5/88 live-modified vaccine viruses were used to study the cross reactive antigenicity against CVS-11 (genotype 1), EBLV-1 (genotype 5) and EBLV-2 (genotype 6). For comparison, similar crossneutralization assays with sera from EBLV-1 and EBLV-2 infected ferrets (Mustela putorius furo) and/or foxes were conducted. Sera from animals vaccinated with the two oral rabies vaccines were reactive against CVS-11 (homologous virus), EBLV-1 and EBLV-2 (heterologous virus). There was a positive relationship among the virus neutralising antibody titres (VNA); high VNA titres against CVS-11 also resulted in high VNA titres against each EBLV, whereas in general, the VNA-titres obtained with homologous virus were statistically higher than those with the heterologous virus except for SAD P5/88 vaccinated raccoon dogs. No significant difference was found between EBLV-1 and EBLV-2 VNA titres. A similar trend was observed when the results of the cross-neutralization data of the foxes and ferrets inoculated i.m. with EBLV-1 and/or EBLV-2 was analysed. Based on the similarity of the EBLV-VNA titres obtained in our study questions were raised on whether the genetic distance of genotype 5 & 6 within phylogroup 1 really does reflect their antigenetic characteristics or whether this is a feature of attenuated live vaccine viruses. This broad cross protection, however, demonstrated that the representatives of attenuated SAD strains of oral rabies vaccines currently used in Germany are most likely able to protect the reservoir species, red fox and raccoon dog, against EBLV-1 and EBLV-2 infection.

Despite a long history of oral vaccination of foxes (OVF) against rabies, in a few restricted areas of Germany rabies is still endemic, posing a continuous risk of re-introduction of rabies into adjacent, rabies-free areas. The endemic area is characterized by a high density population. It is hypothesized that the degree of urbanization in the area under consideration influences the number of rabies cases via the mode of bait distribution. In urban areas vaccine baits are distributed by hand, whereas in non-urban areas baits can be distributed aerially with the help of fixed-winged aircraft. Statistical analysis of the effect of the mode of bait distribution upon the number of rabies cases shows a significant influence. In areas where baits are distributed by hand the number of rabies cases is significantly higher than the expected number. This finding forces managers to reassess the procedure of bait distribution by hand in urban areas, taking into account the ecologically and biologically different dynamics of urban fox populations. If the oral vaccination of foxes in urban areas can be refined, rabies eradication in Germany is expected to succeed in due course.