The role of a mechanistic host in maintaining arctic rabies variant distributions: Assessment of functional genetic diversity in Alaskan red fox (Vulpes vulpes).

Populations are exposed to different types and strains of pathogens across heterogeneous landscapes, where local interactions between host and pathogen may present reciprocal selective forces leading to correlated patterns of spatial genetic structure. Understanding these coevolutionary patterns provides insight into mechanisms of disease spread and maintenance. Arctic rabies (AR) is a lethal disease with viral variants that occupy distinct geographic distributions across North America and Europe. Red fox (Vulpes vulpes) are a highly susceptible AR host, whose range overlaps both geographically distinct AR strains and regions where AR is absent. It is unclear if genetic structure exists among red fox populations relative to the presence/absence of AR or the spatial distribution of AR variants. Acquiring these data may enhance our understanding of the role of red fox in AR maintenance/spread and inform disease control strategies. Using a genotyping-by-sequencing assay targeting 116 genomic regions of immunogenetic relevance, we screened for sequence variation among red fox populations from Alaska and an outgroup from Ontario, including areas with different AR variants, and regions where the disease was absent. Presumed neutral SNP data from the assay found negligible levels of neutral genetic structure among Alaskan populations. The immunogenetically-associated data identified 30 outlier SNPs supporting weak to moderate genetic structure between regions with and without AR in Alaska. The outliers included SNPs with the potential to cause missense mutations within several toll-like receptor genes that have been associated with AR outcome. In contrast, there was a lack of genetic structure between regions with different AR variants. Combined, we interpret these data to suggest red fox populations respond differently to the presence of AR, but not AR variants. This research increases our understanding of AR dynamics in the Arctic, where host/disease patterns are undergoing flux in a rapidly changing Arctic landscape, including the continued northward expansion of red fox into regions previously predominated by the arctic fox (Vulpes lagopus).

Influence of different factors on the costs and benefits of oral vaccination of foxes against rabies.

The oral rabies vaccination (ORV) programme is the most widespread vaccination programme that is implemented in the European Union and targets wildlife diseases. The size of the project requires significant financial resources, so a cost-benefit analysis is necessary to establish the economic value of the project. We summarized all ORV costs during the period 2011-2016 in Croatia, calculated all established benefits and presented the cost-benefit ratio (CBR). Additionally, we analysed all components included in the ORV and rabies control programme (surveillance, preventive human treatment and vaccination of dogs) to find possibilities to increase the benefits. According to our results, in the period 2011-2016, the CBR was only 0.05, and the majority of the cost was derived from the preventive vaccination of dogs (72.3%). With the implementation of 2- or 3-year vaccination intervals, the CBR can be increased to 1.46 or 1.92, respectively, confirming positive economic value. This study shows the importance of analysing all rabies control and eradication components based on the specific characteristics of a particular country to determine the factors that can be modified to potentially improve the benefits of ORV.

First four Oral Rabies Vaccination campaigns of the red foxes in Greece: Evaluating factors and assessment.

Following the last animal rabies outbreak in Greece in 2012, Oral Rabies Vaccination (ORV) campaigns of red foxes (Vulpes vulpes) were conducted in order to halt the spread of the disease, as widely and effectively have also been implemented in other countries. The present study aims to report the main outcomes following the first Greek ORV campaigns during autumn 2013, 2014, 2015 and spring 2016, to assess their effectiveness and to investigate factors potentially related to their success. Blood samples, mandible bones and teeth, derived by 452 foxes, were tested for rabies antibody titration, animal age determination and tetracycline (TTC) detection. The laboratory results obtained were statistically analyzed. High seroprevalence and TTC detection rates were obtained following the autumn campaigns studied, while these rates were significantly reduced following the spring campaign. The year or the season of the vaccination campaign, the estimated age group of the animal and the geographical Regional Unit (RU), where the animal was hunted, were identified as important factors. On the contrary, no significance could be ascertained for TTC detection based on exclusively previous uptake, use of filter paper, blood sample type and quality, as well as sex of animal. Based on the monitoring results achieved, the first ORV campaigns conducted in the country can be generally considered to be satisfactory. No positives cases were detected since May 2014. Seasonal, geographical parameters and factors related to fox ecology may interfere with monitoring results and should be always considered when planning future ORV programs.

Rabid fox bites and human rabies in a village community in southern India: epidemiological and laboratory investigations, management and follow-up.

Human rabies transmitted from wild animals is rarely reported in endemic countries like India, where nearly 95% deaths occur due to bites from rabid dogs. In this paper, we report an incidence of rabid fox bites in a village in southern part of India involving 18 individuals, including 4 children. All people had category III exposures, including bites on the face and neck. The attacking fox was killed by the forest department and buried immediately. The victims of the fox bite did not receive appropriate and adequate postexposure treatment. Thirteen days after the bite, one of the bite victims developed typical symptoms of furious rabies and died 2 days later in a local hospital. His brain tissue, obtained at autopsy, was strongly positive for rabies by fluorescent antibody technique (FAT) and virus isolation. Panic prevailed in the community and the rest of the 17 cases were referred to our institute for advice and further management. Only 35% of them had protective levels of rabies virus neutralizing antibodies (RVNA). All of the patients were administered with an 8-site intradermal regimen with purified chick embryo cell (PCEC) vaccine and were followed up regularly. All of them developed adequate titers (>0.5 IU/mL) of RVNA 7 days later. They were under regular follow-up and after nearly 2 years none have developed rabies. The partial Nucleoprotein (N) gene sequencing of the virus isolate from the patient who died of rabies had close homology with species I (prototype rabies) sequences available in GenBank and our own past isolates from dogs and humans, thus confirming that virus spillover from wildlife to domestic dogs continues to occur. This episode should prompt health authorities to focus more attention on training rural medical practitioners in state-of-the-art modern prophylactic measures.

A retrospective economic analysis of the Ontario red fox oral rabies vaccination programme.

Ontario initiated a red fox (Vulpes vulpes) oral rabies vaccination (ORV) programme in 1989. This study utilized a benefit-cost analysis to determine if this ORV programme was economically worthwhile. Between 1979 and 1989, prior to ORV baiting, the average annual human post-exposure treatments, positive red fox rabies diagnostic tests and indemnity payments for livestock lost to rabies were 2248, 1861 and $246,809, respectively. After baiting, from 1990 to 2000, a 35%, 66% and 41% decrease in post-exposure treatments, animal rabies tests and indemnity payments was observed, respectively. These reductions were viewed as benefits of the ORV programme, whereas total costs were those associated with ORV baiting. Multiple techniques were used to estimate four different benefit streams and the total estimated benefits ranged from $35,486,316 to $98,413,217. The annual mean ORV programme cost was $6,447,720, with total programme costs of $77,372,637. The average benefit-cost ratios over the analysis period were .49, 1.06, 1.27 and 1.36, indicating overall programme efficiency in three of the four conservative scenarios.

Scenario-analysis evaluating semergency strategies after rabies re-introduction.

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.

Elimination of terrestrial rabies in Western European countries.

Since the late 1930s, the red fox (Vulpes vulpes) has been the main vector of rabies in Europe. Practically, decimation of fox population did not prevent the spread of the disease. The only efficient method to control wildlife rabies consisted in using oral vaccination by depositing vaccine baits containing a capsule or a plastic sachet filled with an attenuated anti-rabies liquid vaccine throughout fox habitats. Several live virus vaccines have been and are currently being used: the SAD B19 and SAD P5/88 are rabies strains attenuated in cell culture, the SAG1 and SAG2 strains are apathogenic mutants of an already attenuated rabies strain, and the VRG vaccine is an attenuated vaccinia virus recombinant coding for the rabies glycoprotein gene. These vaccines have different residual pathogenicity. SAG1 and SAG2 are pathogenic only for suckling mice inoculated by intracerebral and oral routes. VRG presents absolutely no rabies risk to humans and the environment and the residual pathogenicity of the vaccinia vector virus is very low even for humans. Other parameters such as the thermostability of the vaccine and the melting point of the bait casing are of utmost importance to guarantee the success of oral vaccination campaigns. Additionally, VRG is the only vaccine that did not interfere with maternal immunity in fox cubs, an important issue for spring campaigns. Successes and failure of national programmes confirm that whatever the ecological conditions, the same rules must be strictly followed to ensure the success of rabies elimination programmes: (i) considering the strategy, any rabies vaccination programme must be organised with the support of a national scientific team specially designated for the task that will have to apply the only methods that have already been proved successful elsewhere in Europe, including rabies surveillance, bait distribution calendar and pattern, and monitoring of this distribution; (ii) vaccination must be pursued for at least two years after the last reported case of rabies in the area; (iii) the choice of a low cost but poorly efficient and poorly stable vaccine does not prove to be cost-beneficial for successful elimination of rabies. Several European countries have become rabies-free: Belgium, Luxembourg, France, Italy, Switzerland, Finland and the Netherlands. Since the European Union is going comprise 25 countries from May 2004, all the scientific knowledge is available for establishing efficient and adapted oral programmes aimed at eliminating terrestrial rabies from this area.

Bat-eared fox behavioural ecology and the incidence of rabies in the Serengeti National Park.

This paper provides a brief introduction into some aspects of bat-eared fox biology and social organization that is important to understanding rabies transmission and disease management in susceptible wildlife species (Macdonald 1980; 1993). A detailed description of the effects of two rabies outbreaks on a population of known individuals in the Serengeti National Park is given, Inter- and intrasexual differences in adult mortality rates are reported and discussed.