Optimising spring oral vaccination campaigns of foxes against rabies

To optimise spring vaccination campaigns the following set of data has been analysed; (i) population dynamics of the red fox, (ii) onset and progress of the reproductive season, and (iii) maternal immunity and the immune response of fox cubs to oral vaccination. The field data originated from foxes caught in Bavaria, Germany. The results of our analysis clearly demonstrate that certain periods during spring are less suitable for bait distribution. If the objective of a vaccination campaign is to reach only the adult foxes, it is suggested to conduct the campaign during the first half of March. If also young foxes are to be vaccinated, baits should not be distributed before the end of May in previously baited areas, because a large segment of the young fox population can not be vaccinated effectively before this date as a result of maternally transferred immunity. In areas vaccinated for the first time, baits can be distributed earlier, since 5 weeks old cubs are already immunocompetent.     

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.     

Effect of maternal immunity on the immune response to oral vaccination against rabies in young foxes.

OBJECTIVE: To determine effect of maternal antibodies on immune response to oral vaccination against rabies in young foxes. ANIMALS: 250 cubs from 48 vixens. PROCEDURE: Sera were obtained from cubs of 36 vaccinated (maternally vaccinated [MV+]) and 12 nonvaccinated (MV-) vixens between 23 and 71 days of age and tested for neutralizing antibodies. Seventy-one MV+ cubs and 33 MV-cubs were vaccinated orally with modified-live virus vaccine SAD B19. Geometric mean titer (GMT) was determined in these cubs approximately 21, 39, and 57 days after vaccination. In a subsequent experiment, 10 vaccinated MV+ cubs, 6 vaccinated MV- cubs, and 6 control cubs were challenge inoculated with virulent rabies virus approximately 100 days after vaccination. RESULTS: Serum GMT of nonvaccinated MV cubs (0.23 U/ml) was significantly greater than that of non-vaccinated MV- cubs (0.15 U/ml). The GMT of vaccinated MV+ cubs 21, 39, and 57 days after vaccination were 2.85, 2.11, and 0.79 U/ml, respectively, and were significantly less than those of vaccinated MV- cubs (12.19, 6.76, and 4.02 U/ml, respectively). All challenge-inoculated cubs with GMT < 0.5 U/ml succumbed to rabies. CONCLUSION AND CLINICAL RELEVANCE: Partially impaired immune response in cubs < 8 weeks old from vaccinated vixens causes insufficient protection against rabies. Inhibition of the immune response persists longer than the period during which maternal antibodies are detectable. Thus, oral vaccination campaigns for young foxes in areas where vaccination has been performed need to be reconsidered.     

Challenges to controlling rabies in skunk populations using oral rabies vaccination: A review

Controlling rabies in skunk populations is an important public health concern in many parts of the United States due to the potential for skunk rabies outbreaks in urban centres and the possible role for skunks in raccoon rabies variant circulation. Oral rabies vaccination (ORV) programmes have supported wildlife rabies control efforts globally but using ORV to control rabies in skunk populations has proven more challenging than with other target species, like foxes, coyotes and raccoons. A review of published studies found that some ORV constructs are immunogenic in skunks and protect against virulent rabies virus challenges, especially when delivered by direct installation into the oral cavity. However, in field ORV programmes using currently available vaccine‐bait formats and distribution methods targeting other rabies reservoir species, skunks often fail to seroconvert. Field effectiveness of ORV in skunks appears to be limited by poor bait uptake or inadequate ingestion of vaccine rather than from poor vaccine efficacy. Observations of captive skunks revealed vaccine spillage when handling and biting into baits such that modification of bait formats might improve field effectiveness. In addition, a dose–response relationship between bait distribution density and post‐baiting seroconversion among skunks was observed across the limited number of field studies. Additional research is needed to identify opportunities to modify ORV baits and distribution strategies to improve the viability of ORV as a rabies control strategy in skunks.     

Oral vaccination of foxes against rabies in Turkey between 2008 and 2010

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.     

Experiences with follow-up investigations of oral vaccination campaigns against rabies in foxes in Saxony with special emphasis on a standardised serology

An 8-year experience with organisation and standardisation of follow-up investigations within oral vaccination campaigns against rabies in foxes (OVF) in Saxony is summarised. With respect to OVF, the number of diagnostic tests performed during the years 1992-2000 on foxes amounts to a total of 52,226 Fluorescence antibody-(FAT), 7,551 marker-(TC) and 11,645 serological tests. The mean bait-uptake and the mean immunisation rate in foxes ranged between 78-86% and 60-89%, respectively. Based on the seroconversion rates of the years 1997-2000 observed in vaccination areas and in areas where vaccination was already finished, experience with a standardised serology under routine conditions is presented and discussed. Furthermore, recommendations concerning organisation and logistics of sampling are given.     

Immunogenicity and efficacy of the oral rabies vaccine SAD B19 in foxes

Studies on the immunogenicity and efficacy of SAD B19 attenuated rabies virus vaccine in foxes under laboratory conditions were conducted. Twenty-seven foxes (Vulpes vulpes) were offered a vaccine bait containing 10(6.3) FFU/ml SAD B19. Blood samples were collected 60, 110 and 190 days post-vaccination. On day 190 post vaccination the animals and 14 controls were challenged with a canid street rabies virus. Twenty-four of the 26 vaccinated foxes (92.3%) survived the challenge, whereas all the controls died from rabies. The two vaccinated foxes that did not survive the challenge did not show any detectable level of rabies neutralizing antibodies at any time after vaccination. The geometric mean titres (GMT) of foxes that seroconverted after vaccination were 43.5, 33.9 and 43.5 IU/ml 60, 110 and 190 days post-vaccination, respectively. Furthermore, to test the vaccine virus under sub-optimal conditions five naive and nine previously vaccinated vixens received 2 ml SAD B19 (10(6.7) FFU/ml) by direct administration of the vaccine virus into the oral cavity shortly before or during pregnancy. All vixens seroconverted above the threshold of 0.5 IU/ml. No booster effect was observed in the immune response of the previously vaccinated animals.     

The spatio-temporal dynamics of a post-vaccination resurgence of rabies in foxes and emergency vaccination planning

We used a simulation model to study the spatio-temporal dynamics of a potential rabies outbreak in an immunized fox population after the termination of a long-term, large-scale vaccination program with two campaigns per year one in spring and one in autumn. The 'worst-case' scenario of rabies resurgence occurs if rabies has persisted at a low prevalence despite control and has remained undetected by a customary surveillance program or if infected individuals invade to the control area. Even if the termination of a vaccination program entails such a risk of a subsequent new outbreak, prolonged vaccination of a wild host population is expensive and the declining cost-benefit ratio over time eventually makes it uneconomic. Based on the knowledge of the spatio-temporal dynamics of a potential new outbreak gained from our modelling study, we suggest "terminating but observing" to be an appropriate strategy. Simulating the decline of population immunity without revaccination, we found that a new outbreak of rabies should be detected by customary surveillance programs within two years after the termination of the control. The time until detection does not depend on whether vaccination was terminated within the fourth, fifth or sixth years of repeated biannual campaigns. But it is faster if the program was completed with an autumn campaign (because next-year dispersal then occurs after a noticeable decrease in population immunity). Finally, if a rabid fox is detected after terminating vaccination, we determine a rule for defining a circular hazard area based on the simulated spatial spread of rabies. The radius of this area should be increased with the time since the last vaccination campaign. The trade-off between the number of foxes potentially missed by the emergency treatment and the cost for the emergency measures in an enlarged hazard area was found.     

Use of vaccinia rabies recombinant for oral vaccination of wildlife

A vaccinia rabies recombinant virus was constructed and shown to induce the synthesis of rabies virus glycoprotein in infected cells and to induce rabies virus neutralizing antibodies and protection in susceptible animals. Active when orally administered, this recombinant is a good candidate for the development of vaccines for wild animal rabies vectors. This recombinant was found stable, safe for target and non-target animal species, and protective for most of the rabies vectors. After extensive experimental studies conducted under controlled conditions, it as used in limited field trials and in an extensive open field trial. The preliminary results confirmed its basic properties and potential for rabies eradication.     

Control of terrestrial animal rabies in Anne Arundel County, Maryland, after oral vaccination of raccoons (1998-2007)

Objective-To evaluate the effectiveness of an oral rabies vaccination (ORV) project conducted from 1998 through 2007 in Anne Arundel County, Md, for the control of rabies in terrestrial animals. Design-Retrospective analysis of surveillance data (1997 through 2007). Animals-Free-ranging raccoons (Procyon lotor) and other terrestrial mammals. Procedures-Vaccinia-rabies glycoprotein recombinant virus oral rabies vaccine-bait units were distributed annually by aircraft and ground teams targeting free-ranging raccoons. Approximately 2 to 4 weeks following the vaccine-bait placement, raccoons were live trapped, sedated, processed, and then released. Serologic samples were tested for the presence of rabies virus-neutralizing antibodies (RVNAs). Bait acceptance was estimated by analysis of tetracycline biomarking of sampled teeth. Rabies incidence was determined by the passive identification of rabid terrestrial animals. Results-The incidence of rabies in terrestrial animals decreased 92% between 1997 (the year prior to the start of the ORV project) and 2007. The mean RVNA prevalence across all years was 33% among trapped raccoons in areas baited with a fish meal polymer bait type, whereas the mean bait acceptance was 30%. Adult raccoons had a seropositivity rate twice that of juvenile raccoons, whereas the bait acceptance rate between adults and juveniles did not differ significantly. For areas baited with a coated sachet bait, adults and juveniles had the same seroprevalence. Juveniles had better seroprevalence when the annual campaign started in September and October, compared with August. Conclusions and Clinical Relevance-The ORV project contributed to a significant decrease in annual incidence of terrestrial animal rabies in Anne Arundel County, Md, during the 10-year project period. For fish meal polymer baits, juvenile raccoons accessed bait at the same rate as adult raccoons but had a significantly lower prevalence of RVNAs. For coated sachet baits, seroprevalence was the same in both age groups. The time of year the bait distribution occurred and the bait type used may be partial explanations for the difference in RVNA seroprevalence between adults and juvenile raccoons.     

The development of strategies for the field application of oral immunization of foxes against rabies

Preconditions for successful field application of the idea to orally immunize foxes against rabies were a) the development of an efficacious and safe vaccine and an attractive bait and b) a suitable strategy to reach a high proportion of the vector population with vaccine-ladden baits. A geographical and epidemiological concept on how to implement the vaccination strategy and how to achieve a sufficiently high level of surveillance were further cornerstones contributing to the success of the method. Finally, political decisions and a legal basis for the application of the method of oral immunization were required to eradicate fox rabies in Switzerland.     

Suitability of canine herpesvirus as a vector for oral bait vaccination of foxes

Studies were conducted to evaluate the feasibility of using canine herpesvirus (CHV) as a vaccine vector for bait-delivered oral vaccination of wild foxes. To test the viability of CHV in baits, CHV was freeze-dried, incorporated into different baits, stored, and the remaining viral infectivity tested in cell culture after varying periods of time at different storage temperatures. Experimental baits (mouse carcasses) and commercial baits (FOXOFF and PROBAIT) were prepared with either liquid or freeze-dried CHV and tested in two fox trials for their capacity to induce CHV-specific antibodies following oral baiting. Freeze-drying and storage temperatures below 0 degrees C had a stabilizing effect to virus infectivity. When stored at -20 degrees C, freeze-dried CHV retained its full infectivity for up to 3 months in PROBAIT baits, the remaining infectivity in FOXOFF baits was 100-fold less. Oral baiting with CHV induced antiviral serum antibodies in all vaccinated foxes (20/20). None of the vaccinated foxes became ill or shed infectious virus into the environment although viral DNA was detected in body secretions as evaluated by PCR. The results indicate that CHV can be freeze-dried and stored over extended periods of time without loosing much of its infectivity. This is the first report of CHV being used for oral bait vaccination of foxes. It appears that CHV is well suited for use as a recombinant vector for wild canids.     

Rabies oral vaccination of foxes during the summer with the VRG vaccine bait

The vaccination of foxes by distributing vaccine baits in the environment was initiated in France in 1986. Two campaigns per year were carried out: one in the spring and one in the autumn. After the spring campaigns, only 22-52% of fox cubs consumed vaccine baits compared to 75% of the adults and 70-80% of the adults or fox cubs after autumn campaigns. In order to reduce the period of time during which fox cubs do not have access to baits and are not immunised, a vaccination campaign was organised during the summer of 1992 over a contaminated area of 25,748 km2 where vaccines had never previously been given. Vaccine bait stability was assessed during the same summer in the field and their appetence tested on captive foxes. The efficacy of the campaign was evaluated by the relative decrease in rabies incidence and the rate of bait uptake by foxes compared to those from neighbouring areas vaccinated for the first time with the same vaccine during the spring or autumn. Summer vaccination significantly increased (P < 0.01) bait uptake by fox cubs (71%) compared with spring vaccination (39%), but no significant difference was observed for adult foxes. Moreover, the decrease in rabies incidence, measured during the 6-month period following the campaigns was less pronounced after summer vaccination (49% decrease) than when the first vaccination was carried out during the spring or autumn (79 and 72% decrease, respectively). Three campaigns led to an apparent elimination of rabies when the first campaign was performed in the spring or autumn, but only to a 76% decrease in rabies incidence density index when the first campaign was performed during the summer. The high thermostability of the Raboral VRG bait permits its use during the summer for an emergency campaign. For routine vaccination plans, however, the classical calendar of spring and autumn vaccination campaigns should continue to be preferred.