FIELD TRIALS OF ONTARIO RABIES VACCINE BAIT IN THE NORTHEASTERN USA, 2012-14.

In the US, rabies virus (RV) has been enzootic in raccoons ( Procyon lotor) since the late 1940s. Oral rabies vaccination (ORV) was implemented in the 1990s to halt the spread of raccoon RV and continues to be used as a wildlife management tool. Our objective was to evaluate a recombinant human adenovirus-rabies virus glycoprotein vaccine in northern New York, Vermont, and New Hampshire over a 3-yr period, using changes in RV neutralizing antibody (RVNA) seroprevalence in raccoon populations as an immunologic index of ORV impact. Vaccine baits were distributed at 75 baits/km2 and 750-m flight-line spacing in the study area. Animal sampling occurred during 10-d intervals pre- and post-ORV during 2012-14 within eight study cells: four northern cells had a history of ORV with a different vaccine for 3 or more years prior and four southern cells were ORV naive. Baseline raccoon RVNA seroprevalence was 27.3% ( n=1,079, 95% confidence interval [CI]: 24.8-30.1) before ORV in 2012. Raccoon RVNA seroprevalence averaged 68.5% ( n=1,551, 95% CI: 66.2-70.8) post-ORV during the 3-yr study. The RVNA seroprevalence levels in this study were considered to be adequate for stopping raccoon RV transmission and supported and expanded the results from a West Virginia field trial, as well as earlier evaluations along the Canada-US border.

Cost and Relative Value of Road Kill Surveys for Enhanced Rabies Surveillance in Raccoon Rabies Management.

Oral rabies vaccination (ORV) requires knowledge of the spatial-temporal distribution of rabies virus variants targeted for control. Rabies-exposure based public health surveillance alone may not provide a sound basis for ORV decisions. The value and cost of road kill surveys was evaluated for the late spring⁻early fall 2005⁻2007 as a part of enhanced rabies surveillance in northern New York, where raccoon rabies is enzootic and ORV has occurred since the late 1990s. Structured surveys were conducted to collect raccoons and other meso-carnivores for rabies testing at the New York State Rabies Laboratory. Of the 209 meso-carnivore heads collected and submitted for testing, 175 were testable by direct fluorescent antibody; none was rabid. Rabies was also not reported through public health surveillance in survey zones during 2005⁻2007. Overall, survey costs were $37,118 (2016 USD). Salaries and benefits accounted for 61% of costs, followed by fuel (22%), vehicle depreciation (14%), and sample shipping (3%). Mean daily distance driven was 303 ± 37 km and 381 ± 28 km for total road kills and raccoons, respectively. Costs/road kill collected and submitted was $176/all species and $224/raccoon. This study provides costs for planning road kill surveys and underscores the need to continually improve enhanced rabies surveillance approaches to support ORV decision making.

Enhanced Rabies Surveillance to Support Effective Oral Rabies Vaccination of Raccoons in the Eastern United States.

Enhanced rabies surveillance (ERS) is essential for sound oral rabies vaccination (ORV) decisions to prevent the spread of specific rabies virus variants in meso-carnivores and to achieve disease elimination. Use of a direct rapid immunohistochemistry test (dRIT) in North America for timely, accurate rabies diagnosis in the field has facilitated greater ERS emphasis since 2005. ERS used in tandem with exposure-based public health surveillance provides a comprehensive understanding of the geographic distribution of rabies as an aid to formulate effective management strategies for raccoons and other meso-carnivores. In 2015, best management practices were implemented for improving, reinvigorating, and standardizing ERS. A point system for weighing ERS sample categories was evaluated, to determine whether sampling emphasis should be focused upon ill or strange-acting animals, the highest quality category. During 2016, 70.7% of rabid animals detected through ERS in raccoon rabies management states were obtained from strange-acting animals, followed by animals found dead (14.1%), road kills (9.1%), and nuisance-collected specimens (6.1%). Sample category weights may be adjusted based on additional evaluation to ensure continued emphasis on the highest value samples. High quality ERS, in conjunction with serologic evidence of population-based immunity, form the backbone for ORV decisions in the elimination of raccoon rabies.

Progress towards Bait Station Integration into Oral Rabies Vaccination Programs in the United States: Field Trials in Massachusetts and Florida.

Bait stations for distribution of oral rabies vaccine baits are designed for rabies management in highly-developed areas where traditional distribution of oral rabies vaccine baits may be difficult. As part of national efforts to contain and eliminate the raccoon (Procyon lotor) variant of the rabies virus (raccoon rabies) in the eastern United States, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services program, distributed vaccine baits by bait stations experimentally and operationally in Massachusetts during 2006-present, and in Florida during 2009⁻2015. In Massachusetts, a rabies virus-neutralizing antibody (RVNA) response of 42.1% for raccoons captured in areas baited with high density bait stations during 2011⁻2015 was achieved, compared with 46.2% in areas baited by hand, suggesting the continuation of this as a strategy for the oral rabies vaccination (ORV) program there, and for similar locations. Non-target competition for vaccine baits is problematic, regardless of distribution method. In Massachusetts, bait station visitation rates for targeted raccoons and non-target opossums (Didelphis virginiana) were similar (1.18:1) during 2006⁻2009 (p > 0.05). Bait station modifications for reducing non-target uptake were tested, and in Massachusetts, reduced non-target bait access was achieved with two design alternatives (p < 0.001). However, no difference was noted between the control and these two alternative designs in Florida. Due to ongoing trials of new vaccines and baits, the bait station performance of an adenovirus rabies glycoprotein recombinant vaccine bait, ONRAB® bait (Artemis Technologies, Guelph, ON, Canada) and a vaccinia-rabies glycoprotein recombinant vaccine bait, RABORAL V-RG®bait (Merial Limited, Athens, GA, USA), was compared. While uptake of the ONRAB bait was greater in Massachusetts (p < 0.001) in this limited trial, both types performed equally well in Florida. Since bait station tampering or theft as well as potential human bait contacts has been problematic, performance of camouflaged versus unpainted white bait stations was analyzed in terms of internal temperatures and maintaining a stable bait storage environment. In Massachusetts, camouflaged bait station interiors did not reach higher average temperatures than plain white bait stations in partially- or fully-shaded locations, while in Florida, camouflaged bait stations were significantly warmer in light exposure categories (p < 0.05). As ORV operations expand into more heavily-urbanized areas, bait stations will be increasingly important for vaccine bait distribution, and continued refinements in the strategy will be key to that success.

Evaluation of Bait Station Density for Oral Rabies Vaccination of Raccoons in Urban and Rural Habitats in Florida.

Efforts to eliminate the raccoon variant of the rabies virus (raccoon rabies) in the eastern United States by USDA, APHIS, Wildlife Services and cooperators have included the distribution of oral rabies vaccine baits from polyvinyl chloride (PVC) bait stations in west-central Florida from 2009 to 2015. Achieving sufficient vaccine bait uptake among urban raccoons is problematic, given limitations on aerial and vehicle-based bait distribution for safety and other reasons. One or three bait stations/km² were deployed across four 9-km² sites within rural and urban sites in Pasco and Pinellas Counties, Florida. Based on tetracycline biomarker analysis, bait uptake was only significantly different among the urban (Pinellas County) high and low bait station densities in 2012 (p = 0.0133). Significant differences in RVNA were found between the two bait station densities for both urban 2011 and 2012 samples (p = 0.0054 and p = 0.0031). Landscape differences in terms of urban structure and human population density may modify raccoon travel routes and behavior enough for these differences to emerge in highly urbanized Pinellas County, but not in rural Pasco County. The results suggest that, in urban settings, bait stations deployed at densities of >1/km² are likely to achieve higher seroprevalence as an index of population immunity critical to successful raccoon rabies control.

Modeling Raccoon (Procyon lotor) Habitat Connectivity to Identify Potential Corridors for Rabies Spread.

The United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Wildlife Services National Rabies Management Program has conducted cooperative oral rabies vaccination (ORV) programs since 1997. Understanding the eco-epidemiology of raccoon (Procyon lotor) variant rabies (raccoon rabies) is critical to successful management. Pine (Pinus spp.)-dominated landscapes generally support low relative raccoon densities that may inhibit rabies spread. However, confounding landscape features, such as wetlands and human development, represent potentially elevated risk corridors for rabies spread, possibly imperiling enhanced rabies surveillance and ORV planning. Raccoon habitat suitability in pine-dominated landscapes in Massachusetts, Florida, and Alabama was modeled by the maximum entropy (Maxent) procedure using raccoon presence, and landscape and environmental data. Replicated (n = 100/state) bootstrapped Maxent models based on raccoon sampling locations from 2012⁻2014 indicated that soil type was the most influential variable in Alabama (permutation importance PI = 38.3), which, based on its relation to landcover type and resource distribution and abundance, was unsurprising. Precipitation (PI = 46.9) and temperature (PI = 52.1) were the most important variables in Massachusetts and Florida, but these possibly spurious results require further investigation. The Alabama Maxent probability surface map was ingested into Circuitscape for conductance visualizations of potential areas of habitat connectivity. Incorporating these and future results into raccoon rabies containment and elimination strategies could result in significant cost-savings for rabies management here and elsewhere.

Safety and immunogenicity of Ontario Rabies Vaccine Bait (ONRAB) in the first us field trial in raccoons (Procyon lotor).

In 2011, we conducted a field trial in rural West Virginia, USA to evaluate the safety and immunogenicity of a live, recombinant human adenovirus (AdRG1.3) rabies virus glycoprotein vaccine (Ontario Rabies Vaccine Bait; ONRAB) in wild raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). We selected ONRAB for evaluation because of its effectiveness in raccoon rabies management in Ontario and Quebec, Canada, and significantly higher antibody prevalence rates in raccoons compared with a recombinant vaccinia-rabies glycoprotein (V-RG) vaccine, Raboral V-RG®, in US-Canada border studies. Raccoon rabies was enzootic and oral rabies vaccination (ORV) had never been used in the study area. We distributed 79,027 ONRAB baits at 75 baits/km(2) mostly by fixed-wing aircraft along parallel flight lines at 750-m intervals. Antibody prevalence was significantly higher at 49.2% (n=262) in raccoons after ONRAB was distributed than the 9.6% (n=395) before ORV. This was the highest antibody prevalence observed in raccoons by US Department of Agriculture Wildlife Services for areas with similar management histories evaluated before and after an initial ORV campaign at 75 baits/km(2) with Raboral V-RG. Tetracycline biomarker (TTCC) was significantly higher among antibody-positive raccoons after ONRAB baiting and was similar among raccoons before ORV had been conducted, an indication of vaccine-induced rabies virus-neutralizing antibody production following consumption of bait containing TTCC. Skunk sample size was inadequate to assess ONRAB effects. Safety and immunogenicity results supported replication of this field trial and led to a recommendation for expanded field trials in 2012 to evaluate safety and immunogenicity of ground-distributed ONRAB at 150 baits/km(2) in residential and commercial habitats in Ohio, USA and aerially distributed ONRAB at 75 baits/km(2) in rural habitats along US-Quebec border.

Costs of raccoon rabies incidents in cattle herds in Hampshire County, West Virginia, and Guernsey County, Ohio.

OBJECTIVE: To determine direct and indirect costs associated with raccoon rabies incidents involving cattle herds in Hampshire County, WV, in 2008 and Guernsey County, Ohio, in 2010. DESIGN: Ex post cost analysis. ANIMALS: 1 cattle herd in Hampshire County, WV, in 2008 and 1 cattle herd in Guernsey County, Ohio, in 2010. PROCEDURES: Data were collected for each incident through telephone and email interviews with 16 federal, state, and county agency personnel involved in the case investigations and coordinated responses for rabies in the cattle herds. To characterize the economic impact associated with rabies in the 2 cattle herds, cost analysis was conducted with 7 cost variables (salary and benefits for personnel involved in the response, human postexposure prophylaxis, indirect patient costs, rabies diagnostic testing, cattle carcass disposal, market value of euthanized cattle, and enhanced rabies surveillance). Estimates of direct costs were determined on the basis of agency records and other relevant data obtained from notes and reports made by agency staff at the time of the incident and from a review of the literature. RESULTS: Primary costs included the market value of euthanized cattle ($51,461 in West Virginia; $12,561 in Ohio), human postexposure prophylaxis ($17,959 in West Virginia; $11,297 in Ohio), and salary and benefits for personnel involved in the response ($19,792 in West Virginia; $14,496 in Ohio). CONCLUSIONS AND CLINICAL RELEVANCE: These results should provide a basis for better characterization of the economic impact of wildlife rabies in cattle in the United States.

Oral rabies vaccination variation in tetracycline biomarking among Ohio raccoons.

Oral rabies vaccination (ORV) programs have traditionally relied on tetracycline marking as an index to bait uptake. Whether tetracycline serves well in this capacity depends on its deposition affinity and ability to be detected consistently among tissues selected for analysis from target species. We evaluated samples from 760 hunter-harvested raccoons (Procyon lotor) from areas in Ohio where ORV had been conducted during 1998, 1999, and 2001. Tetracycline marking was evaluated within and among first premolar (PM1), second premolar (PM2), and canine (CN) teeth, and mandibular bone (MB) by side (left versus right); and by tissue type. Tetracycline detection ranged from 6.5% in PM1 in 1998 to 56.3% in right-side MB in 2001. PM1 teeth were less frequently marked (21.7%) than PM2 (27.7%), CN (33.0%), or MB (42.0%). Tetracycline detection was similar in left and right PM1, PM2, and CN teeth, but differed in MB. Tetracycline marking was significantly different among all tissue types.

Oral rabies vaccination in north america: opportunities, complexities, and challenges.

Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues toward the development and testing of new bait-vaccine combinations that increase the chance for improved delivery and performance in the diverse meso-carnivore rabies reservoir complex in the US.

Influence of oral rabies vaccine bait density on rabies seroprevalence in wild raccoons.

The effect of different oral rabies vaccine (ORV) bait densities (75, 150, and 300 baits/km(2)) on the seroprevalence of rabies virus neutralizing antibodies (RVNAs) in raccoons (Procyon lotor) was assessed at a 15% seroprevalence difference threshold in rural areas of northeast Ohio. Results (n=588 raccoons) indicated that seropositivity for RVNAs was associated with both bait density and bait campaign frequency. Associations were not detected for raccoon gender, age, or macro-habitat. The odds of being seropositive were greater for raccoons originating from 300 bait/km(2) treatment areas relative to those coming from the 75 bait/km(2) areas (odds ratio [OR]=4.4, probability [P]<0.001, 95% confidence interval [CI]=2.4-7.9), while accounting for cumulative ORV campaigns. No statistical advantage in seroprevalence was detected when comparing 150-75 baits/km(2). These results indicate that a relatively extreme bait density when evenly distributed may be necessary to obtain a significant increase in seroprevalence. Higher bait densities may be more appropriate and less costly to address focused outbreaks than labor intensive trap-vaccinate-release and local population reduction campaigns. Finally, dramatic increases in seroprevalence of RVNA were not observed in raccoons between sequential, semi-annual campaigns, yet cumulative ORV campaigns were associated with gradual increases in seroprevalence.