The economic implications of sylvatic rabies eradication in Italy

After more than 10 years of absence, sylvatic rabies re‐appeared in Italy in 2008. To prevent disease spread, three oral rabies vaccination (ORV) campaigns targeting red foxes were performed through manual distribution of vaccine baits between January and September 2009. As these campaigns proved unsuccessful, at the end of December 2009, baits started being distributed using helicopters, allowing uniform coverage of larger areas in a shorter time period. From winter 2009 to autumn 2016, a total of 15 ORV campaigns (four emergency, four regular and seven preventive ORV) were implemented through aerial distribution of baits. In this study, we assessed the costs of the aerial ORV campaigns, which were aimed at eradicating the disease and reobtaining the rabies‐free status. Cumulative costs per km² were estimated at €59.45 during emergency campaigns and ranged between €51.94 and €65.67 in the regular vaccinations. The main portion of costs for ORV programmes were related to baits supply and distribution: €49.24 (82.83%) in emergency campaigns and from €40.33 to € 43.35 in regular ORVs (71.97% and 66.02%, respectively). At the end of each ORV campaign, the efficacy of vaccination activities was estimated by assessing the proportion of foxes testing positive for tetracycline biomarker in jawbone, indicating bait intake. Results revealed that the proportion of foxes that ingested baits varied between 70.97% and 95.51%. Statistical analysis indicated that reducing the density of dropped baits could potentially lead to a cost‐saving of 22.81%, still maintaining a satisfactory level of bait intake by the fox population.     

Oral vaccination against rabies and the behavioural ecology of the red fox (Vulpes vulpes)

As a result of oral vaccination of foxes (Vulpes vulpes) against rabies, this virus disease has almost been completely eradicated from West- and Central Europe. In most countries, vaccine baits were distributed twice a year: during spring (March to May) and autumn (September to October). This strategy has shown to be able to control and eventually eradicate rabies. However, it remains to be clarified if this is the most cost-effective strategy. Astonishingly, the behavioural ecology of the target species, the red fox, did receive only limited attention selecting the periods when baits should be distributed. Considering the behavioural ecology and rabies epidemiology of foxes, territory owners seem to play a key role in the spread and maintenance of rabies. Thus, oral vaccination campaigns should be targeted primarily at these animals. It is suggested that the optimal timing for bait distribution in Europe is late autumn (November) or early winter (December), depending on the prevailing climatic conditions. Additional campaigns, when financially feasible, can be implemented in order to maintain a high vaccination coverage during the remaining year. Furthermore, different baiting strategies can be selected in case of re-infection or persistent residual foci.     

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.     

The spatial and temporal disappearance of different oral rabies vaccine baits

Bait disappearance can give valuable information for the assessment of oral vaccination campaigns of foxes against rabies. In this study, the spatial and temporal disappearance of three different vaccine baits under almost identical conditions was investigated. In the study area, 350 baits were placed at previously marked positions during two different periods; late autumn and early spring. The distribution of baits was in accordance with the method as recommended by the European Union; a density of 20 baits per km2 along flight lines 500m apart. Bait disappearance was checked 1, 3, 5 and 7 days after distribution. At least 80% of the baits had disappeared within one week after distribution. No difference in bait disappearance was observed between the two selected periods. However, a significant higher bait disappearance was observed in forested areas when compared to open agricultural areas. Furthermore, the differences in bait disappearance between the three type of baits tested were relatively small and not significant.     

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.     

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.     

Acceptance and palatability for domestic and wildlife hosts of baits designed to deliver a tuberculosis vaccine to wild boar piglets

Tuberculosis (TB) caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex, is an important health problem worldwide. The control of TB through vaccination of wildlife reservoirs may potentially have advantages over other management strategies. The most practical approach to deliver vaccines to wildlife is using oral baits that are stable under field conditions and effective in reaching the target species. Baits were developed in our laboratory to deliver oral vaccines to wild boar piglets. However, these baits were well accepted by other wild species. Therefore, bait consumption by different M. bovis hosts was evaluated herein. The results showed that the baits were well accepted by cattle, feral pigs, and adult red deer whereas small mammals like badgers and possums showed varying bait acceptance. Bait acceptance by different species has the advantage of targeting more than one wildlife reservoir when they coexist in the same area and need to be vaccinated for TB control. However, bait delivery methods such as the use of selective feeders to target the desired species should be developed to avoid bait consumption by other species.     

The potential of oral vaccines for disease control in wildlife species

Numerous infectious diseases caused by bacteria or viruses persist in developed and developing countries due to ongoing transmission among wildlife reservoir species. Such diseases become the target of control and management programmes in cases where they represent a threat to public health (for example rabies, sylvatic plague, Lyme disease), or livestock production (for example bovine tuberculosis, brucellosis, pseudorabies), or where they threaten the survival of endangered animal populations. In the majority of cases, lethal control operations are neither economically feasible nor publicly supported as a practical means for disease management. Prophylactic vaccination has emerged over the last 15 years as an alternative control strategy for wildlife diseases, mainly driven by the success of widescale oral rabies vaccination programmes for meso-carnivores in North America and Northern Europe. Different methods have been trialled for the effective delivery of wildlife vaccines in the field, however oral vaccination remains the most widely used approach. Successful implementation of an oral wildlife vaccine is dependent on a combination of three components: an efficacious immunogen, a suitable delivery vehicle, and a species-specific bait. This review outlines the major wildlife disease problems for which oral vaccination is currently under consideration as a disease management tool, and also focuses on the technological challenges that face wildlife vaccine development. The major conclusion is that attenuated or recombinant live microbes represent the most widely-used vaccines that can be delivered by the oral route; this in turn places major emphasis on effective delivery systems (to maintain vaccine viability), and on selective baiting systems, as the keys to wildlife vaccine success. Oral vaccination is a valuable adjunct or alternative strategy to culling for the control of diseases which persist in wildlife reservoirs.     

Evaluation of 6 ONRAB Ultralite bait flavor matrices delivered to coyotes (Canis latrans): Implications for oral rabies vaccination

The spread of rabies in terrestrial wildlife throughout the United States is primarily controlled through oral rabies vaccination. Relatively low bait acceptance and seroconversion rates by some target species have prompted investigation into an alternative to the RABORAL V-RG bait currently used. In Canada, ONRAB Ultralite baits are used to vaccinate raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). Comparative studies between RABORAL V-RG and ONRAB found higher seroconversion rates among raccoons that ingested ONRAB, suggesting that it may be a suitable alternative. However, ONRAB has not been evaluated in many rabies reservoir species, including coyotes (Canis latrans). Vaccination of coyotes is a critical element in preventing reemergence of canine strain of rabies in the United States. We evaluated flavor preference of ONRAB Ultralite oral rabies vaccine baits by coyotes. Preferences among bait types differed (Friedman χ² = 13.28; df = 5; P = 0.02). Of the 6 bait flavors evaluated, cheese ranked the highest, followed by fish, chicken, sugar-vanilla, egg, and bacon flavors. Pairwise trials among the top 3 flavors (cheese, fish, and chicken) showed no difference (Friedman χ² = 3.00; df = 2; P = 0.22). Our research suggests that among the bait flavors we evaluated, cheese, fish, or chicken-flavored baits may be an appropriate flavor for delivery of ONRAB Ultralite baits to coyotes.     

Terrestrial rabies control in the European Union: Historical achievements and challenges ahead

Due to the implementation of oral rabies vaccination (ORV) programmes, the European Union (EU) is becoming progressively free of red fox (Vulpes vulpes)-mediated rabies. Over the past three decades, the incidence of rabies had decreased substantially and vast areas of Western and Central Europe have been freed from rabies using this method of controlling an infectious disease in wildlife. Since rabies control is a top priority in the EU, the disease is expected to be eliminated from the animal source in the near future. While responsible authorities may consider the mission of eliminating fox rabies from the EU almost accomplished, there are still issues to be dealt with and challenges to be met that have not yet been in the focus of attention, but could jeopardise the ultimate goal. Among them are increasing illegal movements of animals, maintaining funding support for vaccination campaigns, devising alternative vaccine strategies in neighbouring Eastern European countries and the expanding distribution range of several potential rabies reservoir species in Europe.     

The safety and efficacy of immunizing foxes (Vulpes vulpes) using bait containing attenuated rabies virus vaccine.

Foxes given ERA rabies vaccine baits were challenged at one, six, 12 and 24 months later and showed a resistance to challenge in 80%, 78%, 60% and 44% of individuals respectively. All animals showing seroconversion following vaccination, resisted challenge at 24 months, suggesting that successful vaccination by the oral route could confer a relatively long term duration of immunity. The trials showed that fox pups did not immunize as easily as adult foxes using ERA rabies vaccine baits. Back-passage studies and the consumption of ERA injected mice by foxes failed to show any reversion of the vaccine virus to a virulent state. The fox and mouse are shown to be highly susceptible to rabies street virus, while the domestic species tested are consisderably more resistant. Monkeys were found to be intermediate in susceptibility to the virus. Safety tests carried out on various species of wildlife showed only the mouse to be susceptible to infection from ingesting the vaccine in the form of a bait. ERA rabies vaccine was shown to be safe in monkeys even when high titred virus was administered by the oral route.     

Cost-efficient vaccination of foxes (Vulpes vulpes) against rabies and the need for a new baiting strategy

In this study, ecological models, optimisation algorithms and threshold analysis were linked to develop oral-vaccination strategies against rabies in fox populations. It is important that such strategies are cost-efficient and resistant to environmental conditions which would lessen their success.The model validation shows that the ecological models used are suited to predict the proportion of tetracycline- (TC) marked foxes in the course of time. This figure indicates the proportion of foxes which had at least one contact to vaccine baits, and is based on the design of the vaccination strategy (i.e. the number and timing of vaccination campaigns and the number of baits used per square kilometre and campaign). The design of a vaccination strategy also determines the costs.It is the combination of ecological models and optimisation algorithms that helped us to design a vaccination strategy which is capable of achieving a continuous rate of >70% of TC-marked foxes within an analytical horizon of 3 years at low costs. Compared to the standard strategy (baseline comparator), the improved strategy incurs just over half of the cost while almost doubling the number of weeks during which the proportion of TC-marked foxes is >70%.In the improved strategy, June is recommended as the time for bait distribution. The standard strategy, however, avoids summer months (because high temperatures reduce the durability of the baits) which again leads to a reduction of the bait intake by the foxes. Using threshold analysis, we examined the effect of a reduced durability of the baits on the design of the improved vaccination strategy. We concluded that distribution of baits in June was optimal given that the durability of baits is above a threshold of 7 days.     

Cost of distributing oral raccoon-variant rabies vaccine in Ohio: 1997-2000

OBJECTIVE: Analysis of the cost of 8 distributions of oral rabies vaccine (ORV) with strains known to infect raccoons in Ohio between 1997 and 2000. DESIGN: Original study. PROCEDURE: Fishmeal bait containing ORV was distributed on foot, by vehicle, and by helicopter and fixed-wing aircraft. The cost of personnel, vehicles, and helicopter and aircraft use and other associated expenses were obtained from field records and interviews with personnel and agencies involved in the ORV program. RESULTS: Each bait distribution lasted approximately 1 week. Areas baited ranged from 1,701 km2 to 6,497 km2. Density varied for each distribution, with means of 79 baits/km2 for ground baiting and 93 baits/km2 for aerial baiting. Typically, 72 people participated in the ground portion of each distribution and 32 in the aerial portion. The cost of ground baiting (mean +/- SD, 19.24 dollars/km2 +/- 6.35 dollars/km2) was consistently less than that for air baiting (mean +/- SD, 24.71 dollars/km2 +/- 4.65 dollars/kml) for each distribution. The total cost of distribution varied from 30,568 dollars to 145,842 dollars (mean, 96,791 dollars), and bait cost varied from 150,714 dollars to 1,029,423 dollars (mean, 543,839 dollars). The total cost of ORV distributions ranged from 102 dollars/km2 to 261 dollars/km2 (mean, 153 dollars/km2). CONCLUSIONS: In the United States, rabies strains that infect raccoons have been responsible for the largest increase in rabies in animals in the past 3 decades. Use of ORV is a promising new tool that can be used to control rabies in raccoons. Documenting the estimated cost of implementing an ORV program may lead to more efficient use of resources to control and limit the spread of rabies. In addition, accurately measured distribution costs can be used to perform an economic cost-benefit analysis for an ORV program.     

Twenty year experience of the oral rabies vaccine SAG2 in wildlife: a global review

The SAG2 vaccine (RABIGEN® SAG2) is a modified live attenuated rabies virus vaccine, selected from the SAD Bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. The strain is genetically stable and does not spread in vivo or induce a persistent infection. Its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. The efficacy of SAG2 baits was demonstrated according to the EU requirements for the red fox and raccoon dog. The use of safe and potent rabies vaccines such as SAG2 largely contributed to the elimination of rabies in Estonia, France, Italy and Switzerland. Importantly, these countries were declared free of rabies after few years of oral vaccination campaigns with SAG2 baits distributed with an appropriate strategy. The excellent tolerance of the SAG2 vaccine has been confirmed in the field since its first use in 1993. No safety issues have been reported, and in particular no vaccine-induced rabies cases were diagnosed, after the distribution of more than 20 million SAG2 baits in Europe.     

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.     

The raccoon (Procyon lotor) as potential rabies reservoir species in Germany: a risk assessment

Terrestrial wildlife rabies has been successfully eliminated from Germany predominantly as a result of the distribution of oral rabies vaccine baits. In case that wildlife rabies would re-emerge among its known reservoir species in Germany, swift action based on previous experiences could spatially and temporally limit and subsequently control such an outbreak. However, if rabies emerged in the raccoon population in Germany (Procyon lotor), there are no tools or local experience available to cope with this situation. This is especially worrisome for urban areas like Kassel (Hesse) due to the extremely high raccoon population density. A rabies outbreak among this potential reservoir host species in these urban settings could have a significant impact on public and animal health.     

First Report on the Efficiency of Oral Vaccination of Foxes against Rabies in Serbia

Rabies is one of the oldest known zoonotic diseases that has significant impact on public health, but still remains neglected in Serbia. Rabies virus can infect humans and other mammals and causes inflammation of the brain associated with encephalomyelitis and neurological symptoms. In 2010, Veterinary Directorate (national Competent Authority for animal health in Serbia) has started multi‐annual project of oral rabies vaccination of foxes and other wild carnivores (e.g. jackals), as support of long‐term programme of eradication of rabies in Serbia, co‐funded by EU (financed by Instrument for Pre‐Accession Assistance). Monitoring of the effectiveness of oral vaccination campaigns has been carried out in continuation from 2011 and was based on: (i) post‐mortem laboratory examination of brain tissue of target animals (foxes, jackals and other carnivores) by fluorescent antibody test (FAT), (ii) detection of antibodies against rabies virus in serum samples by ELISA and (iii) detection of tetracycline biomarker in the mandibles for the evaluation of vaccine bait uptake. From September 2011 to May 2014, the total number of 4943 brain tissue samples, 4241 sera and 4971 mandibles were analysed. Confirmed rabies‐positive brains decreased from 10 in 2011/2012 to 6 in 2012/2013 and eventually to 1 positive case in 2013/2014. The seroconversion rate increased from 10.48% (133/1269) in 2011/2012 to 20.11% (362/1800) in 2012/2013 and 42.23% (495/1172) in 2013/2014. Along with the seroconversion, the number of detected tetracycline‐positive mandibles demonstrated an increasing tendency in the same period, being 49.67% (682/1373) in 2011/2012, 62.60% (1294/2067) in 2012/2013 and 90.33% (1383/1531) in the monitoring programme carried out in 2013/2014. Presented results confirmed that ORV of foxes and other wildlife in Serbia against rabies was successful and characterized by steady increase of vaccine baits uptake and immunization of animals.     

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.     

Antibody response to Raboral VR-G® oral rabies vaccine in captive and free-ranging black-backed jackals (Canis mesomelas)

Rabies is a zoonotic disease that remains endemic in large parts of southern Africa because of its persistence in wildlife and domestic dog vectors. The black-backed jackals (Canis mesomelas) is primarily the wildlife vector responsible for rabies outbreaks in northern parts of South Africa. Two trials were carried out to investigate antibody responses to the oral rabies vaccine Raboral V-RG® in black-backed jackals under captive and free-ranging conditions. In captive jackals 10/12 (83%; 95% confidence interval [CI]: 52% – 98%), seroconverted after single oral vaccination. Nine captive jackals had protective antibody titres (> 0.5 IU/mL) at 4 weeks (median: 2.1 IU/mL; inter quartile range [IQR]: 0.6–5.7) and 10 jackals had at 12 weeks (median: 3.5 IU/mL; IQR: 1.5–8.3) and three maintained antibody titres for up to 48 weeks (median: 3.4 IU/mL; IQR: 2.0–6.3). Four sites were baited with Raboral V-RG® vaccine for wild jackals, using fishmeal polymer and chicken heads. Baits were distributed by hand or from vehicle at three sites in north-eastern South Africa, with an average baiting density of 4.4 baits/km² and at one site in central South Africa, at 0.12 baits/km². This resulted in protective antibody titres in 3/11 jackals (27%; 95% Cl: 6–61) trapped between 3 and 12 months after baiting in north-eastern South Africa, compared with 4/7 jackals (57%; 95% Cl: 18–90) trapped after 3–18 months in central South Africa. This study shows the potential utility of oral rabies vaccination for the control of wildlife-associated rabies in north-eastern and central South Africa, but extensive studies with wider distribution of bait are needed to assess its potential impact on rabies control in wild jackals.     

Oral immunization against rabies: afterthoughts and foresight

The article contains personal views on some issues that are frequently addressed in discussions about rabies control, and on some related topics that are often overlooked. The first field applications of oral wildlife rabies immunization in the Swiss Rhone Valley were preceded by many years of international cooperative studies on efficacy and safety. They were significant "faits accomplis" that facilitated similar endeavors in other countries. Some aspects of the residual pathogenicity of oral rabies vaccines are discussed. The field efficacy of oral wildlife immunization is the outcome of complex interactions between vaccine and bait attributes, bait distribution procedures, and habitat properties. Significant difficulties hinder the interpretation of field observations on efficacy. Though oral wildlife immunization is not an animal welfare act and not a conservationist achievement, it is an attempt at zoonosis control intended to protect human health and prevent economic losses.