Documenting Freedom From Disease and Re-Establishing a Free Status After a Breakdown Rabies

Rabies reappeared in Finland in the spring of 1988 after a 29-year absence. This time rabies occurred in sylvatic form and the major species involved was the raccoon dog. During the outbreak 1988–89 66 animals were diagnosed rabid. Vaccination of cats, cattle and horses was strongly recommended and vaccination of dogs was compulsory in the outbreak area. A field trial was started on oral immunisation of raccoon dogs and foxes against rabies using baits containing rabies vaccine strain. The outbreak area and a wide buffer zone were baited three times. Finland was declared free of rabies again in 1991. Oral vaccination campaign with vaccine baits has been organised along the southeastern border once a year since the beginning of 90s. Continuous surveillance and epidemiological screening is necessary to detect any new outbreaks of rabies at an early stage.     

An Epidemic of Sylvatic Rabies in Finland

When rabies reappeared in Finland in April 1988, the country had been rabies free since 1959. Soon a picture of sylvatic rabies become evident, its main vector and victim being the raccoon dog (Nyctereutes procyonoides). Between 8 April 1988 and 16 February 1989, 66 virologically verified cases were recorded (48 raccoon dogs, 12 red foxes, 2 badgers, 2 cats, l dog and 1 dairy bull) in an area estimated at 1700 km2 in south-eastern Finland. The greatest distance between recorded cases was 67 km. A positive reaction with monoclonal antibody p-41 indicated that the virus was an arctic-type strain. A field trial on oral immunization of small predators was initiated in September 1988 using Tübingen fox baits according to the Bavarian model of bait distribution. Each bait contained 5*107 TCID50/ml modified live rabies virus (SAD-B19). The 6 months’ surveillance indicate a seroconversion rate of 72% (N=126) in the raccoon dog population, 67% (N=56) in the red foxes and 13% (N=16) in the badgers, when titers ≥1.0 IU/ml are considered seropositive. In the whole follow-up period, no statistically significant difference could be detected between the raccoon dogs and red foxes in the rate of seroconversion or in the uptake of tetracycline from the baits. Notably high antibody levels were recorded in both raccoon dogs and red foxes within 4–5 months after vaccination. Of the seropositive animals, the proportion of animals with titers 3.0 IU/ml or greater was higher in raccoon dogs (73%) than in red foxes (51%) (x2= 5.29, p< 0.05). The trial shows that raccoon dogs can be immunized against rabies in the field with vaccine baits originally developed for controlling sylvatic rabies in foxes.     

The Italian experience in the control of rabies. III. Laboratory studies on SADB19 Tü vaccine used in the fox vaccination campaign

Results of laboratory investigations on the SADB19 Tü vaccine used for oral vaccination of fox show: 1) the need to check the vaccine efficacy before its application in the field; 2) the importance of monoclonal antibodies to distinguish sylvatic from vaccinal virus strains in the diagnosis of rabies during the vaccination campaigns; 3) the relevance of a careful evaluation of the epidemiological risk encountered when releasing baits containing activated vaccine.     

Oral vaccination in the control of feral rabies

The authors briefly report the results of laboratory and epidemiological investigations on living modified and inactivated antirabies vaccines, started in 1975 and carried out in collaboration with public health authorities and scientific institutions. The antirabies oral vaccination of foxes, using a live and modified vaccine (SADB19 Tüb.) began in Brescia province (Val Camonica) in 1984 and was extended in 1985 to Bolzano and Trento provinces. Since July 1986 no more cases of rabies have been observed in Italy. The problems related to the distribution in the territory of live and modified antirabies vaccines, the immunological value of inactivated vaccines, the connections between sylvatic rabies and bat rabies (or pseudorabies), are discussed.     

Oral rabies vaccine contact by raccoons and nontarget species in a field trial in Florida

Rabies is enzootic in raccoons (Procyon lotor) in the eastern United States. Oral vaccination of free-ranging raccoons against rabies has the potential to control the disease in a principal reservoir and reduce the risk of rabies exposure among domestic animals and humans. Free-ranging animal contact with baits containing a vaccinia virus recombinant vaccine expressing the rabies glycoprotein gene (V-RG) was monitored in Pinellas County (Florida, USA) from February through May 1997. Bait contact was assessed with 423 tracking plate nights; conducted in four land use zones: single residential, multiple residential, industrial-commercial, and undeveloped. The undeveloped land use zone was further described by six vegetation communities: mangrove swamp, red maple swamp, beach dune, pine forest, mixed oak hammock, and cabbage palm hammock. Seven animal taxa contacted the baited tracking plates across the four land use zones: raccoons, opossums (Didelphis virginiana), cats (Felis catus), dogs (Canis familiaris), rabbits (Sylvilagus sp.), unidentified rodents, and birds. A total of 252/413 (61%) of the baits was contacted by animals; 95 (38%) of these were specifically by the raccoon, the target species. Overall bait contact by all animals was significantly different among the four land use zones, being highest in the undeveloped zone (82%) and lowest in the industrial-commercial zone (34%). Bait contact by raccoons also was significantly different among the undeveloped and pooled urban zones. Among the six vegetation communities, bait contact by all animals was significantly different ranging from 95% in the mangrove to 50% in the cabbage palm hammock. Among the four vegetation communities tested, bait contact by raccoons also was significantly different.     

Vaccination of small Asian mongoose (Herpestes javanicus) against rabies

Oral vaccination of free-ranging wildlife is a promising technique in rabies control. The small Asian mongoose (Herpestes javanicus) is an important reservoir of rabies on several Caribbean islands, but no vaccines have been evaluated for this species. Captive mongooses were used to test the safety and efficacy of the commercially licensed vaccinia-rabies glycoprotein (V-RG) recombinant vaccine and a newly developed genetically engineered oral rabies virus vaccine (SPBNGA-S). In one study using V-RG, no vaccinated animals developed detectable rabies virus-neutralizing antibodies, and all but one died after experimental challenge with rabies virus. In contrast, all animals given SPBNGA-S demonstrated seroconversion within 7 to 14 days after vaccination and survived rabies virus challenge. On the basis of these preliminary results indicating the greater efficacy of SPBNGA-S vs. V-RG vaccine, additional investigations will be necessary to determine the optimal dose and duration of vaccination, as well as incorporation of the SPBNGA-S vaccine into edible bait.     

Subcutaneous rabies vaccination of pigtail macaques

Abstract: Nonhuman primates housed in outside cages in rabies enzootic areas should be vaccinated against rabies because of the risk of exposure to rabid wildlife. This article reports that vaccination with an inactivated rabies vaccine for domestic animals induced levels of neutralizing antibodies against rabies in pigtail macaques (Macaca nemestrina) without causing adverse reactions.     

Emergency response to raccoon rabies introduction into Ontario

During 15 July to 4 October, 1999, rabies control programs were implemented with the objective being to contain the first three confirmed cases of raccoon rabies in Canada. The strategy, called point infection control (PIC) involved the use of three tactics: population reduction (PR), trap-vaccinate-release (TVR) and oral rabies vaccination with baits (ORV), to control the spread of raccoon rabies. A total of 1,202 raccoons (Procyon lotor) and 337 skunks (Mephitis mephitis) were captured and euthanized using 24,719 trap-nights in the three PR zones around the location of the three rabies cases, near Brockville, Ontario. That represented an 83% to 91% reduction in the raccoon populations in an approximate 225 km2 area around the three rabies cases. Raccoon density in the PR zones declined from 5.1-7.1/km2 to 0.6-1.1/km2 following control. All tested specimens were negative for rabies by the fluorescent antibody test (FAT). In addition, 1,759 raccoons and 377 skunks were intramuscularly vaccinated against rabies and released using 27,956 trap-nights in an approximate 485 km2 TVR zone implemented outside of the PR zones. A total of 856 cats from both PR and TVR areas were also captured, vaccinated and released. Cost for the three PIC operations was $363,000.00 Cdn or about $500.00 Cdn/km2. To further contain the outbreak, about 81,300 baits containing Raboral V-RG oral rabies vaccine were aerially distributed on 8 and 27 September 1999, to create an 8 to 15 km wide buffer zone (1,200 km2 area) of vaccinated raccoons immediately beyond the PR and TVR zones. This was the first time that V-RG was used in Canada to orally vaccinate free ranging raccoons against rabies. Baiting costs were $241,000.00 Cdn or about $200.00 Cdn/km2 including post baiting assessment costs. As of 31 August, 2000, thirty-five additional cases (38 in total) of raccoon rabies have occurred in the control and vaccination zones. This number is far below the level of rabies prevalence in USA jurisdictions where raccoon rabies was epizootic. In the future, PIC methodologies will continue to be used in Ontario to contain isolated cases of raccoon rabies.     

Eliminating rabies in Estonia

The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV) campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania.     

Domestic dog demographics and estimates of canine vaccination coverage in a rural area of Zambia for the elimination of rabies

BackgroundAn estimated 75% or more of the human rabies cases in Africa occur in rural settings, which underscores the importance of rabies control in these areas. Understanding dog demographics can help design strategies for rabies control and plan and conduct canine mass vaccination campaigns effectively in African countries.Methodology/Principal findingsA cross-sectional survey was conducted to investigate domestic dog demographics in Kalambabakali, in the rural Mazabuka District of Zambia. The population of ownerless dogs and the total achievable vaccination coverage among the total dog population was estimated using the capture-recapture-based Bayesian model by conducting a canine mass vaccination campaign. This study revealed that 29% of the domestic dog population was under one year old, and 57.7% of those were under three months old and thus were not eligible for the canine rabies vaccination in Zambia. The population growth was estimated at 15% per annum based on the cross-sectional household survey. The population of ownerless dogs was estimated to be small, with an ownerless-to-owned-dog ratio of 0.01–0.06 in the target zones. The achieved overall vaccination coverage from the first mass vaccination was estimated 19.8–51.6%. This low coverage was principally attributed to the owners’ lack of information, unavailability, and dog-handling difficulties. The follow-up mass vaccination campaign achieved an overall coverage of 54.8–76.2%.Conclusions/SignificanceThis paper indicates the potential for controlling canine rabies through mass vaccination in rural Zambia. Rabies education and responsible dog ownership are required to achieve high and sustainable vaccination coverage. Our findings also propose including puppies below three months old in the target population for rabies vaccination and emphasize that securing an annual enforcement of canine mass vaccination that reaches 70% coverage in the dog population is necessary to maintain protective herd immunity.     

Control of rabies in Slovenia

Red foxes (Vulpes vulpes) are the main reservoir of rabies in Slovenia, whereas cases of rabies in other wildlife species occur sporadically. In 1995, a program of oral vaccination of wildlife in Slovenia was initiated; baits with oral vaccine were distributed by air at a density of 20 baits/km(2). During 1995, when the oral vaccination program was started, 1,089 cases of rabies (including both wild and domestic animals) were reported. Five years later (1999), only six positive animals were detected among 1,195 tested (0.5%). Despite an increase in bait density (25 baits/km(2)) during the years 2000 and 2001, reported rabies cases increased to 115 and 135, respectively. In 2003, following initiation of a new bait-dropping strategy, which incorporated perpendicular rather than parallel flight lines, the number of rabies cases decreased to eight.     

Sylvatic Plague Vaccine: A New Tool for Conservation of Threatened and Endangered Species?

Plague, a disease caused by Yersinia pestis introduced into North America about 100?years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.     

Progression in studies on pathogenesis of rabies virus

Rabies virus causes lethal neurological symptoms in humans and animals. Rabies epidemics have continued to occur throughout the world, despite the fact that rabies can be effectively prevented by vaccination. The development of inexpensive and safe attenuated live vaccines and the establishment of cures are the keys to control rabies. To achieve these objectives, it is important to elucidate mechanism by which rabies virus causes disease. Here, previous studies on the pathogenesis of rabies virus are reviewed and ways to apply previous findings to rabies control are also discussed.     

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.     

The influence of homologous vs. heterologous challenge virus strains on the serological test results of rabies virus neutralizing assays

The effect that the relatedness of the viral seed strain used to produce rabies vaccines has to the strain of challenge virus used to measure rabies virus neutralizing antibodies after vaccination was evaluated. Serum samples from 173 subjects vaccinated with either purified Vero cell rabies vaccine (PVRV), produced from the Pittman Moore (PM) seed strain of rabies virus, or purified chick embryo cell rabies vaccine (PCECV), produced from the Flury low egg passage (Flury-LEP) seed strain of rabies virus, were tested in parallel assays by RFFIT using a homologous and a heterologous testing system. In the homologous system, CVS-11 was used as the challenge virus in the assay to evaluate the humoral immune response in subjects vaccinated with PVRV and Flury-LEP was used for subjects vaccinated with PCECV. In the heterologous system, CVS-11 was used as the challenge virus in the assay to evaluate subjects vaccinated with PCECV and Flury-LEP was used for subjects vaccinated with PVRV. Although the difference in G protein homology between the CVS-11 and Flury-LEP rabies virus strains has been reported to be only 5.8%, the use of a homologous testing system resulted in approximately 30% higher titers for nearly two-thirds of the samples from both vaccine groups compared to a heterologous testing system. The evaluation of equivalence of the immune response after vaccination with the two different vaccines was dependent upon the type of testing system, homologous or heterologous, used to evaluate the level of rabies virus neutralizing antibodies. Equivalence between the vaccines was achieved when a homologous testing system was used but not when a heterologous testing system was used. The results of this study indicate that the strain of virus used in the biological assays to measure the level of rabies virus neutralizing antibodies after vaccination could profoundly influence the evaluation of rabies vaccines.     

Exhaustive Exercise Does Not Affect Humoral Immunity and Protection after Rabies Vaccination in a Mouse Model

Rabies is one of the most dangerous and widespread zoonosis and is characterized by severe neurological signs and a high case-mortality rate of nearly 100%. Vaccination is the most effective way to prevent rabies in humans and animals. In this study, the relationship between exhaustive exercise and the humoral immune response after immunization with inactivated rabies vaccine was investigated in a mouse model with one-time exhaustive exercise. It was found that compared with the mice with no exercise after vaccination, no significant differences were found in those with exhaustive exercise after vaccination on body-weight changes, virus-neutralizing antibody (VNA) titers, antibody subtypes and survivor ratio after lethal rabies virus (RABV) challenge. This study indicated that exhaustive exercise does not reduce the effects of the rabies inactivated vaccine.     

The efficacy of a cultured rabies vaccine studied in guinea pigs preliminarily infected with a fixed rabies virus]

In experiments of curative vaccination, carried out with the use of an experimental model similar to the current practice of treatment with antirabies preparations, the advantages of using tissue-culture rabies vaccine with immunogenic potency equal to 1.3 international units (I. U.) were shown. In these experiments the vaccine was introduced into guinea pigs infected with fixed rabies virus, the course of vaccination consisting of 14 daily injections. No correlation between the induction of virus-neutralizing antibodies and the immunogenic potency of tissue-culture rabies vaccine was established: the use of the vaccine with immunogenic potency equal to 0,3 and 1,3 I.U. had no essential influence on the level of antibody formation in the animals.     

Factors associated with the success of rabies vaccination of dogs in Sweden

Background  

United Kingdom, Ireland, Malta and Sweden maintain their national provisions for a transitional period regarding rules concerning rabies vaccination and individual serological test for rabies neutralizing antibodies. The purpose of vaccinating dogs against rabies is to establish pre-exposure immunity and protect individual animals from contracting rabies.     

Trap-vaccinate-release and oral vaccination for rabies control in urban skunks, raccoons and foxes.

Two rabies control tactics, trap-vaccinate-release (T-V-R) and oral vaccination were used for the control of rabies in skunks (Mephitis mephitis), raccoons (Procyon lotor), and foxes (Vulpes vulpes) in metropolitan Toronto, Canada. Using T-V-R, a mean of 45% to 72% (95% confidence limits of 40% to 81%) of the skunks and a mean of 17% to 68% (95% confidence limits of 14% to 76%) of the raccoons in a 60 km2 area of Toronto were vaccinated against rabies between 1987 and 1991. The area has been free of skunk rabies from May 1989 to April 1992. Forty-five rabies cases were diagnosed during 1980 to 1986. In contrast, only three skunk cases have been reported since the vaccination program began in July 1987. The T-V-R area also remained rabies free during an epizootic of skunk rabies in metropolitan Toronto during 1991. Following distribution of rabies vaccine-baits throughout the ravines of metropolitan Toronto, June 1989 to December 1991, 46% to 80% of the Toronto fox population was immunized during 1989, 1990 and 1991. Only one case of fox rabies was reported in metropolitan Toronto since vaccination began, compared to 80 cases reported between 1982 and 1988. The area has been free of reported fox rabies from October 1990 to April 1992.     

Application of the GARC Data Logger—a custom-developed data collection device—to capture and monitor mass dog vaccination campaigns in Namibia

Domestic dogs are responsible for 99% of all cases of human rabies and thus, mass dog vaccination has been demonstrated to be the most effective approach towards the elimination of dog-mediated human rabies. Namibia demonstrated the feasibility of this approach by applying government-led strategic rabies vaccination campaigns to reduce both human and dog rabies incidences in the Northern Communal Areas of Namibia since 2016. The lessons learnt using paper-based form for data capturing and management of mass dog vaccination campaign during the pilot and roll out phase of the project (2016–2018) led to the implementation of a simple and accurate data collection tool in the second phase (2019–2022) of the rabies elimination program. In this paper, we describe the implementation of such custom-developed vaccination tracking device, i.e. the Global Alliance for Rabies Control (GARC) Data Logger (GDL), and the integration of the collected data into a website-based rabies surveillance system (Rabies Epidemiological Bulletin—REB) during 2019 and 2020 campaigns. A total of 10,037 dogs and 520 cats were vaccinated during the 2019 campaign and 13,219 dogs and 1,044 cats during the 2020 campaign. The vaccination data were recorded with the GDL and visualized via REB. Subsequent GIS-analysis using gridded population data revealed a suboptimal vaccination coverage in the great majority of grid cells (82%) with a vaccination coverage below 50%. Spatial regression analysis identified the number of schools, estimated human density, and adult dog population were associated with the vaccination performance. However, there was an inverse correlation to human densities. Nonetheless, the use of the GDL improved data capturing and monitoring capacity of the campaign, enabling the Namibian government to improve strategies for the vaccination of at-risk areas towards achieving adequate vaccination coverage which would effectively break the transmission of rabies.