Risk-based cost modelling of oral rabies vaccine interventions for raccoon rabies

Distribution of oral rabies vaccine (ORV) is an effective but costly strategy to control raccoon rabies. Because of high costs, ORV for raccoon rabies in the U.S. has been limited primarily to epizootic areas, leaving extensive raccoon rabies regions without any ORV intervention. Several cost scenarios for ORV application in raccoon rabies enzootic and epizootic regions were modelled in New York State to obtain estimated costs of ORV baits per scenario and potential savings compared with a uniform ORV baiting strategy. These cost scenarios modelled at the census tract, level the application of ORV baits at different densities according to levels of risk defined by the observed number of raccoon rabies cases per km2 and the expected number of cases per km2 estimated with a Poisson regression model. Bait purchase costs were lower using the modelled cost scenarios than a uniform baiting strategy, for both the NYS enzootic region and the Long Island epizootic zone. The proportion of savings for the NYS enzootic region was 29.57%, and the proportion of savings for the Long Island epizootic zone was 38.9%. Use of these cost scenarios to determine bait distribution by rabies risk level should be considered to maximize efficacy and reduce costs of ORV interventions.     

Stability of attenuated live virus rabies vaccine in baits targeted to wild foxes under operational conditions

The viability of an attenuated live virus rabies vaccine in a bait targeted to red foxes was examined under various operational conditions in a series of experiments in Ontario. The virus was relatively stable over a 28-day period in the field, losing a mean 0.5, s = 0.2 log10 of virus titer. The micro-environment into which the bait was placed (open cultivated field, grassy meadow, wooded grove, sun or shade) did not make an appreciable difference in the viability of the virus. There was no significant difference (P < or = 0.05) between mean ambient temperatures and the temperature of fluids in blister packs of baits placed in sun or shade. Sixty-three percent of foxes fed baits exposed to sun and shade conditions for 21 days (titer 10(6.2) tissue culture infective doses per 1 mL) developed rabies virus-neutralizing antibodies. Storage of vaccine baits at -30 degrees C prior to bait distribution was important in maintaining virus viability.     

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

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

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.     

Stability of vaccinia-vectored recombinant oral rabies vaccine under field conditions: a 3-year study

Rabies is an incurable zoonotic disease caused by rabies virus, a member of the rhabdovirus family. It is transmitted through the bite of an infected animal. Control methods, including oral rabies vaccination (ORV) programs, have led to a reduction in the spread and prevalence of the disease in wildlife. This study evaluated the stability of RABORAL, a recombinant vaccinia virus vaccine that is used in oral rabies vaccination programs. The vaccine was studied in various field microenvironments in order to describe its viability and facilitate effective baiting strategies. Field microenvironments influenced the stability of this vaccine in this study. This study emphasizes the importance of understanding how vaccines perform under varying field conditions in order to plan effective baiting strategies.     

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.     

A baiting system suitable for the delivery of oral rabies vaccine to dog populations in Zimbabwe

A baiting system suitable for the delivery of oral rabies vaccine to dog populations in developing countries was studied in Zimbabwe. In a field trial, 369 sponge baits containing a placebo liquid, rhodamine B as a biomarker and a pungent attractant were distributed over an area of 60 sq km in a communal land in Manicaland with a dog population of over 500. Twenty-four hours later 21 per cent of the baits were recovered and 79 per cent of these had been significantly bitten or chewed. Twenty-five per cent of the dogs examined showed evidence of superficial staining by rhodamine B indicating that they had chewed baits or ingested their contents. It was concluded that the system would deliver an oral vaccine to dog populations more efficiently than had been the case in comparable studies in wildlife populations, but that the number of baits per unit area should in future studies be increased.     

Influence of different factors on the costs and benefits of oral vaccination of foxes against rabies

The oral rabies vaccination (ORV) programme is the most widespread vaccination programme that is implemented in the European Union and targets wildlife diseases. The size of the project requires significant financial resources, so a cost–benefit analysis is necessary to establish the economic value of the project. We summarized all ORV costs during the period 2011–2016 in Croatia, calculated all established benefits and presented the cost–benefit ratio (CBR). Additionally, we analysed all components included in the ORV and rabies control programme (surveillance, preventive human treatment and vaccination of dogs) to find possibilities to increase the benefits. According to our results, in the period 2011–2016, the CBR was only 0.05, and the majority of the cost was derived from the preventive vaccination of dogs (72.3%). With the implementation of 2‐ or 3‐year vaccination intervals, the CBR can be increased to 1.46 or 1.92, respectively, confirming positive economic value. This study shows the importance of analysing all rabies control and eradication components based on the specific characteristics of a particular country to determine the factors that can be modified to potentially improve the benefits of ORV.     

不同诱剂配方对柑橘小实蝇的引诱作用

测试了不同诱剂配方对柑橘小实蝇成虫的诱杀效果,试验结果表明,引诱效果最好的是甲基丁香酚 水解蛋白 红糖 敌百虫,7d内对柑橘小实蝇的引诱数量为:15.3333?6.514头/瓶,雌虫率占总虫量的18.9 %;其次为乙酸乙酯 甲基丁香酚,7d内引诱数量为:11.9667?7.4597头/瓶;另外,添加一定量的红糖、乙酸乙酯可显著提高引诱率,猎蝇、异丁香酚诱瓶诱杀效果不理想。     

Evaluation of baits for oral vaccination of European wild boar piglets

The objective of this study was to develop and evaluate new baits for the oral delivery of vaccine preparations to 2–4 month-old wild boar piglets. Baits were prepared using a matrix composed of wild boar feed, wheat flour, paraffin, sacarose and cinnamon-truffle powder attractant with polyethylene capsules dipped into the matrix to introduce vaccine formulation. Physical stability studies demonstrated that baits were stable for at least three days at temperatures as high as 42 °C. Recombinant Escherichia coli expressing the membrane-displayed BM95-MSP1a fusion protein were used to test bacterial viability in the baits and the antibody response in orally immunized wild boar. The E. coli viability was not significantly affected after bait incubation at 25 and 37 °C for 96 h. Bait acceptance studies using artificial feeders in the field showed that baits were accepted by 2–3 month-old animals, the preferred age for vaccination. Orally immunized wild boar piglets excreted recombinant E. coli in the feces and developed antibody titers to recombinant BM95-MSP1a protein, thus confirming that vaccine composition was released and reached the wild boar gastrointestinal track. The results of these experiments support the use of these baits for oral delivery of vaccine formulations to 2–4 month-old wild boar piglets.     

浑善达克沙地不同沙丘类型土壤种子库时空动态

以浑善达克沙地为研究对象,分析了自然状态下不同沙丘类型土壤种子库的时空变化规律.结果表明,在整个生长季节,土壤中保留一定数量有活力的种子.随着生长季的结束,土壤种子库中的种子量明显增加.土壤种子库的水平分布呈现斑块的特点;不同沙丘类型土壤种子库的垂直分布呈现不同的规律.     

Vaccination of Tunisian dogs with the lyophilised SAG2 oral rabies vaccine incorporated into the DBL2 dog bait

The protective effect of the lyophilised SAG2 oral vaccine bait DBL2, already demonstrated on laboratory dogs, needed to be verified on common Tunisian dogs. Seven Tunisian dogs consumed totally or partially one DBL2 bait containing 10(8.3) TCID50 of the highly attenuated rabies vaccine strain, SAG2. Five of the seven vaccinated animals survived a challenge administered 33 days later with a Tunisian canine street rabies virus to which five of the six controls that were not vaccinated and had no specific antibodies succumbed. The partial or total consumption of a single DBL2 bait thus conferred a protective immune response similar to that observed in laboratory dogs to dogs of poor health status. The sero-antibody response was, however, weak: only two vaccinated dogs exhibited a significant neutralising antibody response after vaccination and before the challenge, and four after the challenge.     

Testing for immunogenic and protective properties of vaccine against tissue-inactivated rabies

The immunogenic and protective potency was tested of vaccine against inactivated tissue rabies developed from the Vnukovo-32 strain, and produced in the Bioveta state corporation at Ivanovice in Haná. In 21 days after an i. m. application of 3 cm3 of vaccine, the average titre of virus-neutralizing antibodies was found to be 1:47. In this period the animals were revaccinated in the same way. The average titre of virus-neutralizing antibodies was 1:99 three months after revaccination, 1:57 in six months and 1:24 in nine months. In this period a challenge test was performed in a dog using the dose of 10(5) MICLD50 of street rabies virus. This dose was implanted i. m. into masticatory muscles. Another dog was infected experimentally 18 months after immunization. The experiment has proved the good immunogenic potency of vaccine against inactivated tissue rabies and its ability to induce the protection of vaccinated dogs from the strees infection with street rabies virus. The control rabies vaccine of foreign make RABISIN was tested in a similar way.     

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 rabies vaccination of foxes with one or two delayed distributions of SAG2 baits during the spring

During the spring of 1997, various protocols of rabies vaccine bait (SAG2) distribution for foxes were compared: in the first test zone, a first distribution was organised at the end of April, followed by a second distribution two weeks later; in the second test zone, there was a first distribution at the same period as for the previous zone, followed by a second distribution four weeks later, at the end of May. In two control zones, a classical single bait distribution was organised during the same periods as for the second distribution in the respective test zones. No statistical differences were observed for adult foxes or fox cubs sampled in the test and control zones neither for baits uptake nor for seroconversion rate. However, seroconversion rates observed in fox cubs population were significantly higher (P < 0.01) in areas vaccinated at the end of May (43 and 56%) compared with those vaccinated at mid-May (24 and 20%). The vaccinal efficacy of baits was also significantly (P < 0.05) increased for the fox cubs in the areas vaccinated at the end of May (46 and 57%) compared with those vaccinated at mid-May (24 and 25%). This increase in immunological response by fox cubs when vaccinating in late spring must be related to their development. In the early spring, fox cubs are generally too young to have access to baits or to be vaccinated when eating them. For most of these fox cubs, a second distribution will not constitute a booster. Therefore, in order to increase the efficient access of fox cubs to vaccine baits, Spring distribution of baits should preferably be organised during May or June rather than in April.