Spatial extent of ORV areas in Europe ever covered with a single vaccine bait of particular oral vaccine strains against rabies during 1978 and 2014.

<p>(A) SAG1 (orange), Vnukovo 32 (brown) and RV-97 (magenta), and (B) SAD VA1 (green), KMIEV-94 (blue) and ERA G333 (yellow).</p

Size of ORV areas in European countries in km² vaccinated with three or more different oral vaccine strains against rabies over the entire time span of ORV.

<p>Size of ORV areas in European countries in km² vaccinated with three or more different oral vaccine strains against rabies over the entire time span of ORV.</p

Size of ORV areas in European countries in km² exclusively vaccinated with one particular oral vaccine strain against rabies over the entire time span of ORV.

<p>Size of ORV areas in European countries in km² exclusively vaccinated with one particular oral vaccine strain against rabies over the entire time span of ORV.</p

Size of ORV areas in European countries in km² vaccinated with two different oral vaccine strains against rabies over the entire time span of ORV.

<p>Size of ORV areas in European countries in km² vaccinated with two different oral vaccine strains against rabies over the entire time span of ORV.</p

Number of individual vaccine doses disseminated in ORV programmes in Europe between 1978 and 2014.

<p>Approximate calculation of the numbers of vaccine doses of different oral vaccine strains against rabies over the past four decades (x axis) based on the cumulative area ever vaccinated with a single vaccine bait (y axis) and an assumed average bait density of 20 baits/km².</p

Implementation of ORV programmes in Europe (1978–2014).

<p>The year of (re-) implementation, duration and the year of cessation of ORV programmes including early field trials in several European countries is depicted. Red coloured bars show countries which achieved a rabies free status due to ORV and blue coloured bars represent countries in which ORV programmes are still implemented.</p

ORV effort and oral vaccine strains against rabies.

<p>Spatial extent of ORV area showing the spatial distribution of different oral vaccine strains against rabies used between 1978 and 2014. Deviating colours from those assigned to certain vaccines indicate overlapping regions.</p

Isolates and viruses used in the study including details of their respective characteristics, year of isolation, host and origin.

<p>Isolates and viruses used in the study including details of their respective characteristics, year of isolation, host and origin.</p

Comparative analysis of European bat lyssavirus 1 pathogenicity in the mouse model

<div><p>European bat lyssavirus 1 is responsible for most bat rabies cases in Europe. Although EBLV-1 isolates display a high degree of sequence identity, different sublineages exist. In individual isolates various insertions and deletions have been identified, with unknown impact on viral replication and pathogenicity. In order to assess whether different genetic features of EBLV-1 isolates correlate with phenotypic changes, different EBLV-1 variants were compared for pathogenicity in the mouse model. Groups of three mice were infected intracranially (i.c.) with 10² TCID50/ml and groups of six mice were infected intramuscularly (i.m.) with 10⁵ TCID50/ml and 10² TCID50/ml as well as intranasally (i.n.) with 10² TCID50/ml. Significant differences in survival following i.m. inoculation with low doses as well as i.n. inoculation were observed. Also, striking variations in incubation periods following i.c. inoculation and i.m. inoculation with high doses were seen. Hereby, the clinical picture differed between general symptoms, spasms and aggressiveness depending on the inoculation route. Immunohistochemistry of mouse brains showed that the virus distribution in the brain depended on the inoculation route. In conclusion, different EBLV-1 isolates differ in pathogenicity indicating variation which is not reflected in studies of single isolates.</p></div

Diagnostic results of South African field samples.

<p>Diagnostic results of South African field samples.</p