Oral Rabies Vaccination Research Articles

Serological methods used for rabies post vaccination surveys: An analysis

The assessment of fox immunity following oral rabies vaccination (ORV) is commonly applied to assess the efficacy of an ORV campaign in the field. Several ELISA kits have been developed and validated for their use for rabies serology in wildlife as an alternative to neutralizing techniques (NT), such as the fluorescent antibody virus neutralization test (FAVN) and the rapid fluorescent foci inhibition test (RFFIT). At a European level, NT and ELISA tests are used interchangeably and on different types of samples collected for vaccination follow-up. This has resulted in a difficulty in comparing the results generated with different diagnostic tools. We have evaluated (a) the effect of two different matrices commonly used for serology in red foxes on the results of the FAVN and (b) the performance of two commercially available ELISAs in comparison with the FAVN, as a gold standard, using a panel of over 700 field fox samples. Moderate agreement was observed when comparing results from different matrices. We found a very low level of agreement and low values of relative sensitivity and specificity of the ELISAs tested in comparison with the FAVN. Our findings confirm, using a vast collection of field samples obtained during post-vaccination surveillance campaigns in Italy, the need for improved reliability of certain serological tests.

Bioeconomic Modelling of Raccoon Rabies Spread Management Impacts in Quebec, Canada

Beginning in 2006, point infection control operations and aerial distribution of oral rabies vaccines along the US border were performed in Quebec, Canada, to control the potential spread of raccoon rabies. A benefit-cost analysis assessed the economic efficiency of this rabies control programme into the future. In this study, a mathematical simulation model was used to determine the potential spread of raccoon rabies from the 2006 index case, and incidence rates of human post-exposure prophylaxis (PEP), animal testing and human exposure investigations were calculated. Benefits were calculated as the potential savings from reduced numbers of human PEP, animal testing and human exposure investigations owing to control, which ranged from $47 million to $53 million. Programme cost scenarios were based on projections of total expenditures, which ranged from $33 million to $49 million. Economic efficiency was indicated for approximately half of the modelled scenarios, with the greatest benefit-cost ratios resulting from reduced future programme costs.

Elimination of terrestrial rabies in Germany using oral vaccination of foxes.

Oral rabies vaccination (ORV) has become the method of choice in fox rabies control in Europe. During the past three decades fox-mediated rabies virtually disappeared from Western and Central Europe. Following Switzerland, Germany was the second European country to launch ORV field trials on its territory in 1983. This paper provides a historical overview on the emergence of fox rabies in Germany; describing the basic principles and milestones of the German rabies eradication programme and presenting results of two decades of efforts to control the disease in foxes. Also, setbacks as well as country-specific differences and particularities on Germany's long way to rabies elimination in comparison to other European countries are addressed. Since the first field trials in Germany the number of rabies cases steadily decreased from 10 484 in 1983 to three cases recorded in 2006. On February 3rd 2006 the last case of terrestrial rabies in Germany was detected in a fox near the town of Mainz, Rhineland-Palatinate. In 2008, ORV ceased after 25 years and Germany was officially declared as free from terrestrial rabies. The German rabies eradication programme did cost approximately 100 million euro of which 37 million euro were covered by the EU. For the future, efforts should focus on maintaining a rabies free status by implementing measures to prevent reintroduction of terrestrial rabies from endemic countries.

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.

SURVIS: a fully-automated aerial baiting system for the distribution of vaccine baits for wildlife.

Large-scale oral vaccination of wildlife against rabies using aerial bait distribution has been successfully used to control terrestrial wildlife rabies in Europe and North America. A technical milestone to large-scale oral rabies vaccination campaigns in Europe was the development of fully-automated, computer-supported and cost-efficient technology for aerial distribution of baits like the SURVIS -system. Each bait released is recorded by the control unit through a sensor, with the exact location, time and date of release and subsequently the collected data can be evaluated, e.g. in GIS programmes. Thus, bait delivery systems like SURVIS are an important management tool for flight services and the responsible authorities for the optimization and evaluation of oral vaccination campaigns of wildlife against rabies or the control of other relevant wildlife diseases targeted by oral baits.

Short-term interval baiting to combat the re-emergence of fox rabies in Rhineland Palatinate (Germany) in 2005.

In 2005, the final phase of terrestrial rabies eradication in Germany was put at risk by a severe setback due to re-introduction of the disease in Rhineland-Palatinate from neighbouring Hesse after seven years of absence. The rapid westward spread of the disease prompted veterinary authorities to react swiftly and apply a new yet unproven vaccination strategy to rapidly increase herd immunity in an almost unprotected fox population to stop the epidemic. The cornerstones of this emergency oral rabies vaccination strategy, i. e. vaccination intervals, identification of high risk spots, real time epidemiological assessment, capable to eliminate rabies within 13 months after incursion are described here. This strategy may be used as a template to tackle similar emergency situations in Europe in the future.

National surveillance for human and pet contact with oral rabies vaccine baits, 2001–2009

To determine the rate and absolute number of human and pet exposures to oral rabies vaccine (ORV) bait containing liquid vaccinia rabies glycoprotein recombinant vaccine and to evaluate factors that might affect human contact with bait to modify the program and reduce human exposure to the vaccine. Retrospective analysis of surveillance data (2001 to 2009). Reports on human and pet contact with ORV baits in states with ORV surveillance programs. Data were collected from passive, multistate ORV surveillance systems in Alabama, Arizona, Florida, Georgia, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Texas, Vermont, Virginia, and West Virginia. Data collected included the nature of human or pet contact with bait and vaccine, the caller's knowledge of the ORV bait program, local human population density, and other relevant demographic data. All 18 states participated in the surveillance program for at least 1 year, for a combined 68 years of observation. One thousand four hundred thirty-six calls were reported, representing 3,076 found baits (6.89/100,000 baits dropped); 296 (20%) calls were related to human contact with ruptured bait, and 550 (38%) involved pet contact with the bait. Six adverse events in humans were reported, one of which required hospitalization. Fifty-nine adverse events in pets were noted, all of which were nonserious. Findings from surveillance activities have been used to improve baiting strategies and minimize human and pet contact with ORV baits. Overall, human and pet contact with ORV baits was infrequent. Surveillance has led to early identification of persons exposed to ORV and rapid intervention.

COMPARING ONRAB® AND RABORAL V-RG® ORAL RABIES VACCINE FIELD PERFORMANCE IN RACCOONS AND STRIPED SKUNKS, NEW BRUNSWICK, CANADA, AND MAINE, USA

Control of rabies in mesocarnivore reservoirs through oral rabies vaccination (ORV) requires an effective vaccine bait. Oral rabies vaccine performance in the field may be affected by a variety of factors, including vaccine bait density and distribution pattern, habitat, target species population density, and the availability of competing foods. A field study in which these covariates were restricted as much as possible was conducted along the international border of the state of Maine (ME), USA, and the province of New Brunswick (NB), Canada, to compare the performance of two oral rabies vaccines in raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). RABORAL V-RG(®) (vaccinia-rabies glycoprotein recombinant oral vaccine in fishmeal-coated sachet) or ONRAB(®) (adenovirus-rabies glycoprotein recombinant oral vaccine in Ultralite bait matrix) were distributed in ME and NB, respectively, by fixed-wing aircraft at a density of 75 baits/km(2) along parallel flight lines spaced 1.0 km apart. Sera were collected from live-trapped raccoons and skunks 5-7 wk post-ORV and assayed to determine antibody prevalence in each area. Duplicate serum samples were provided blind to two different laboratories for analyses by rabies virus serum neutralization assays (at both laboratories) and a competitive enzyme-linked immunosorbent assay (at one laboratory). There was no significant difference in the proportion of antibody-positive animals determined by the three serologic methods, nor was there a significant difference between ONRAB and RABORAL V-RG in the proportion of antibody-positive striped skunks observed post-ORV. In contrast, the proportion of antibody-positive raccoons was significantly higher in the ONRAB- versus the RABORAL V-RG-baited areas (74% vs. 30%; χ(2)=89.977, df=5, P<0.0001). These data support that ONRAB may serve as an effective tool for raccoon rabies control.

Risk Assessment of Oral Rabies Vaccine Released

Risk Assessment of Oral Rabies Vaccine Released

A Spatial Model to Forecast Raccoon Rabies Emergence

Although raccoons are widely distributed throughout North America, the raccoon rabies virus variant is enzootic only in the eastern United States, based on current surveillance data. This variant of rabies virus is now responsible for >60% of all cases of animal rabies reported in the United States each year. Ongoing national efforts via an oral rabies vaccination (ORV) program are aimed at preventing the spread of raccoon rabies. However, from an epidemiologic perspective, the relative susceptibility of naïve geographic localities, adjacent to defined enzootic areas, to support an outbreak, is unknown. In the current study, we tested the ability of a spatial risk model to forecast raccoon rabies spread in presumably rabies-free and enzootic areas. Demographic, environmental, and geographical features of three adjacent states (Ohio, West Virginia, and Pennsylvania), which include distinct raccoon rabies free, as well as enzootic areas, were modeled by using a Poisson Regression Model, which had been developed from previous studies of enzootic raccoon rabies in New York State. We estimated susceptibility to raccoon rabies emergence at the census tract level and compared the results with historical surveillance data. Approximately 70% of the disease-free region had moderate to very high susceptibility, compared with 23% in the enzootic region. Areas of high susceptibility for raccoon rabies lie west of current ORV intervention areas, especially in southern Ohio and western West Virginia. Predicted high susceptibility areas matched historical surveillance data. We discuss model implications to the spatial dynamics and spread of raccoon rabies, and its application for designing more efficient disease control interventions.

Preliminary Evaluation of Raboral V-RG&amp;reg; Oral Rabies Vaccine in Arctic Foxes (Vulpes lagopus)

We tested the Raboral V-RG® recombinant oral rabies vaccine for its response in Arctic foxes (Vulpes lagopus), the reservoir of rabies virus in the circumpolar North. The vaccine, which is currently the only licensed oral rabies vaccine in the United States, induced a strong antibody response and protected foxes against a challenge of 500,000 mouse intracerebral lethal dose 50% of an Arctic rabies virus variant. However, one unvaccinated control fox survived challenge with rabies virus, either indicating a high resistance of Arctic foxes to rabies infection or a previous exposure that induced immunity. This preliminary study suggested that Raboral V-RG vaccine may be efficacious in Arctic foxes.

Emergency oral rabies vaccination of foxes in Italy in 2009–2010: identification of residual rabies foci at higher altitudes in the Alps

Following a resurgence of fox rabies in northeastern Italy in 2008-2009, two emergency oral rabies vaccination (ORV) campaigns were performed in the Alpine mountain ranges in 2009 and 2010 using aerial distribution to prevent the disease from spreading further inland. Vaccine baits were distributed only below the freezing point altitude, 1000 m above sea level (a.s.l.) in December 2009-January 2010 and 1500 m a.s.l. in April-May 2010, to avoid repeated freeze-thaw cycles. Spatial analysis unexpectedly identified fox rabies hotspots above the threshold altitudes, probably representing local residual rabies foci which may have contributed to maintaining the infectious cycle in areas not vaccinated at higher altitudes. Based on the results obtained, in May 2010, the second ORV campaign was extended to include threshold altitudes of up to 2300 m a.s.l. to eliminate residual foci. The observations made may help in the formulation of ORV strategies in countries sharing similar topographical features.

High-Density Baiting with ONRAB® Rabies Vaccine Baits to Control Arctic-Variant Rabies in Striped Skunks in Ontario, Canada

The Arctic variant of rabies virus has been maintained in striped skunks in small foci in southwestern Ontario, Canada, despite the control of the disease in red foxes. To control the disease in skunks, high-density baiting with ONRAB(®) oral rabies vaccine baits was conducted by air and by hand distribution of baits in the vicinity of skunk cases. During 2009, antibody prevalences in skunks were higher in areas baited at a density of 300 baits/km(2) and flight-line spacing of 0.25 km than at 0.5-km spacing. Once an area containing Arctic-variant cases was treated with high densities of ONRAB baits, the disease did not reoccur in skunks in those areas. During 2009, only eight skunks were diagnosed with the Arctic variant of rabies virus in Ontario.

Could recombinant technology facilitate the realisation of a fertility-control vaccine for possums?

While lethal control remains the primary tool for possum control in New Zealand, there has been substantial research effort over the last decade into controlling possum populations by reducing the animals’ breeding potential. In particular, the potential of immunological control to reduce fertility has been investigated, whereby the possums’ immune system is induced to react against its reproductive system, in order to block or destroy key components of the reproductive process. Two of the most targeted key components have been the blocking of circulating hormones (e.g. gonadotrophin-releasing hormone) and the inhibition of functional egg surface proteins (e.g. zona pellucida). While some success has been achieved for each approach, three main obstacles remain to the development of a working fertility-control vaccine for possums: first, ensuring that the vaccine remains efficacious in oral-delivery formulation; second, ensuring sufficient levels of fertility reduction; and third, ensuring that the induced immune response is sustained for a duration sufficient for long-term suppression of reproduction. The use of a genetically modified recombinant organism (parasite, bacterium or virus) to deliver a fertility-control vaccine could satisfy these requirements. A strong precedent for this approach has been set already in wildlife biology, namely the oral rabies vaccine, which is based on a recombinant vaccinia virus and which has been used successfully for the last 25 years as a disease-eliminating vaccine in mesocarnivores in Europe and North America. This review outlines the different forms and examples of recombinant organisms with potential for engineering into recombinant fertility-control vaccines to reduce possum reproduction; non-transmissible agents or fully-transmissible vectors are discussed, with shortcomings and benefits outlined for each.

Optimal vaccine distribution in a spatiotemporal epidemic model with an application to rabies and raccoons

We formulate an S–I–R (Susceptible, Infected, Immune) spatiotemporal epidemic model as a system of coupled parabolic partial differential equations with no-flux boundary conditions. Immunity is gained through vaccination with the vaccine distribution considered a control variable. The objective is to characterize an optimal control, a vaccine program which minimizes the number of infected individuals and the costs associated with vaccination over a finite space and time domain. We prove existence of solutions to the state system and existence of an optimal control, as well as derive corresponding sensitivity and adjoint equations. Techniques of optimal control theory are then employed to obtain the optimal control characterization in terms of state and adjoint functions. To illustrate solutions, parameter values are chosen to model the spread of rabies in raccoons. Optimal distributions of oral rabies vaccine baits for homogeneous and heterogeneous spatial domains are compared. Numerical results reveal that natural land features affecting raccoon movement and the relocation of raccoons by humans can considerably alter the design of a cost-effective vaccination regime. We show that the use of optimal control theory in mathematical models can yield immediate insight as to when, where, and what degree control measures should be implemented.

IMMUNOGENICITY AND EFFICACY OF TWO RABIES VACCINES IN WILD-CAUGHT, CAPTIVE RACCOONS

The immunogenicity and efficacy of two rabies vaccines in wild-caught, captive raccoons (Procyon lotor) were investigated. Raccoons were fed Ontario Slim (OS) baits containing a recombinant vaccinia virus-rabies glycoprotein (VRG) oral rabies vaccine, or they were given an intramuscular (IM) injection of IMRAB(®) 3 rabies vaccine. Blood samples collected before treatment and from weeks 1 to 16 posttreatment were assessed for the presence of rabies virus antibody (RVA). There were significantly more positive responders in the group that received an IM injection of IMRAB 3 (18/27) than in the group that consumed VRG in OS baits (VRG-OS; 4/ 26). There were no significant associations among age, sex, and seroconversion. Of those animals that mounted a humoral immune response to vaccination, RVA was first detected between weeks 1 and 5, with the majority of initial seroconversions detectable at week 2. A subsample of 50 raccoons (19 VRG-OS, 18 IMRAB 3, and 13 controls) from the longitudinal serology study was challenged with live raccoon variant rabies virus 442 days after initial treatment. There were significantly more survivors in the group that received IMRAB 3 (13/18) than in the VRG-OS (5/19) or control (2/13) groups. All 15 raccoons that demonstrated a serologic response survived challenge regardless of treatment. Of the 35 raccoons with no detectable serologic response, 30 (86%) succumbed to rabies virus infection (14/15 VRG-OS, 5/7 IMRAB 3, and 11/13 controls).

Evaluation of rhodamine B as a biomarker for raccoons

The USDA/APHIS/Wildlife Services (WS) oral rabies vaccination program uses tetracycline, a broad-spectrum antibiotic and relatively reliable biomarker, to quantify vaccine- bait uptake by raccoons (Procyon lotor). However, obtaining samples (e.g., bone or teeth) to assess tetracycline uptake is highly invasive, and sample preparation can be expensive. By contrast, rhodamine B, a commercially available dye, is absorbed systemically in growing tissues, including hair and whiskers, and can be observed under ultraviolet (UV) light as fluorescent orange bands. Our goal was to evaluate whether rhodamine B can be used as a biomarker to monitor bait uptake by raccoons. We began by orally administering a solution containing 100 mg, 150 mg, or 200 mg of rhodamine B to captive raccoons. We monitored whisker and hair samples for fluorescence using a hand-held UV lamp and a fluorescent microscope for 13-weeks post-treatment. All raccoons that were administered rhodamine B exhibited fluorescence in their whisker and hair samples during the course of the study. Our ability to detect fluorescing whiskers varied based on the method of detection and time interval, but not with rhodamine B dosage level. We detected rhodamine B in 81% of marked individuals using the fluorescent microscope and 58% of marked subjects using the UV lamp. We were able to detect rhodamine B when doses as low as 1 mg/kg were given. Raccoons did not exhibit a taste aversion to baits containing ≤3% rhodamine B. We believe that rhodamine B can be a useful biomarker for raccoons and has potential as an application to monitor the uptake of oral rabies vaccine.

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.

Impact of emergency oral rabies vaccination of foxes in northeastern Italy, 28 December 2009–20 January 2010: preliminary evaluation

Fox rabies re-emerged in northeastern Italy in 2008, in an area bordering Slovenia. In 2009, the infection spread westward to Veneto region and in 2010 to the provinces of Trento and Bolzano. Aerial emergency oral fox vaccination was implemented in the winter 2009-10. Since this vaccination was performed at altitudes below the freezing level, a statistical analysis was conducted to evaluate its impact. Of the foxes sampled following the vaccination campaign, 77% showed a rabies antibody titre of >or=0.5 IU/ml.

Response of Captive Skunks to Microencapsulated Tetracycline

A captive striped skunk (Mephitis mephitis) study was conducted between February and June 2004 at the United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services National Wildlife Research Center, Fort Collins, Colorado, USA. The main objective was to determine the percentage of adult striped skunks that were marked after consuming placebo oral rabies vaccine (ORV) baits containing 100 mg of an experimental microencapsulated (coated microparticle) tetracycline hydrochloride biomarker. Biomarkers were identified in the canine teeth and mandibles of five of five skunks that consumed an ORV bait. A second objective was to determine if the microencapsulated tetracycline was resistant to photochemical conversion from tetracycline to epitetracycline. After 15 days of exposure, conversion from tetracycline to epitetracycline concentration in the microencapsulated product (mean 1.9% conversion, SD=1.24) was significantly less (P=0.006) than the pure-grade tetracycline powder (mean 7.5% conversion, SD=1.37). Results support the use of microencapsulated tetracycline hydrochloride as a biomarker in circumstances where the use of conventional powdered tetracycline hydrochloride is not feasible due to ORV bait design constraints.