Rationale and support for a One Health program for canine vaccination as the most cost-effective means of controlling zoonotic rabies in endemic settings

Although dog vaccination has been demonstrated to reduce and eliminate rabies in humans, during meetings there are often calls for further pilot studies. The assembled data proves that a widespread approach is now required. While zoonotic rabies has a minimal presence in developed nations, it is endemic throughout most of Asia and Africa, where it is considered to be a neglected tropical disease. In these areas, rabies causes an estimated annual mortality of at least 55,000 human deaths. Worldwide rabid dogs are the source of the vast majority of human rabies exposures. The World Health Organization (WHO), the Food and Agriculture Organization (FAO) of the United Nations and the World Organization for Animal Health (OIE) advocate a collaborative One Health approach involving human public health and veterinary agencies, with mass canine vaccination programs in endemic areas being the mainstay of strategies to eliminate dog-mediated human rabies. While post-exposure prophylaxis (PEP) is effective in preventing deaths in people exposed to rabies, it is comparatively expensive and has little impact on the canine reservoir that is the primary source of zoonotic rabies. Indiscriminate culling of the dog population is expensive and there is little evidence that it is effective in controlling rabies in non-island locations. Mass canine vaccination programs using a One Health framework that achieves a minimum 70% vaccination coverage during annual campaigns have proven to be cost-effective in controlling zoonotic rabies in endemic, resource-poor regions. Case studies, such as in Tanzania and Bhutan, illustrate how an approach based on mass canine rabies vaccination has effectively reduced both canine and human rabies to minimal levels. The multiple benefits of mass canine rabies vaccination in these cases included eliminating rabies in the domestic dog reservoirs, eliminating human rabies cases, and decreasing the rabies economic burden by reducing expenditures on PEP.     

Costs and effectiveness of alternative dog vaccination strategies to improve dog population coverage in rural and urban settings during a rabies outbreak

Dog-rabies elimination programs have typically relied upon parenteral vaccination at central-point locations; however, dog-ownership practices, accessibility to hard-to-reach sub-populations, resource limitations, and logistics may impact a country’s ability to reach the 70% coverage goal recommended by the World Organization for Animal Health (OIE) and World Health Organization (WHO). Here we report the cost-effectiveness of different dog-vaccination strategies during a dog-rabies outbreak in urban and peri-urban sections of Croix-des-Bouquets commune of the West Department, Haiti, in 2016. Three strategies, mobile static point (MSP), mobile static point with capture-vaccinate-release (MSP + CVR), and door-to-door vaccination with oral vaccination (DDV + ORV), were applied at five randomly assigned sites and assessed for free-roaming dog vaccination coverage and total population coverage. A total of 7065 dogs were vaccinated against rabies during the vaccination campaign. Overall, free-roaming dog vaccination coverage was estimated at 52% (47%-56%) for MSP, 53% (47%-60%) for DDV + ORV, and 65% (61%-69%) for MSP + CVR (differences with MSP and DDV + ORV significant at p < 0.01). Total dog vaccination coverage was 33% (95% CI: 26%-43%) for MSP, 49% (95% CI: 40%-61%) for MSP + CVR and 78% (77%-80%) for DDV + ORV (differences significant at p < 0.001). Overall, the least expensive campaign was MSP, with an estimated cost of about $2039 per day ($4078 total), and the most expensive was DDV + ORV with a cost of $3246 per day ($6492 total). Despite the relative high cost of an ORV bait, combining DDV and ORV was the most cost-effective strategy in our study ($1.97 per vaccinated dog), largely due to increased efficiency of the vaccinators to target less accessible dogs. Costs per vaccinated dog were $2.20 for MSP and $2.28 for MSP + CVR. We hope the results from this study will support the design and implementation of effective dog vaccination campaigns to achieve the goal of eliminating dog-mediated human rabies deaths by 2030.     

Rabies in Thailand.

The prevalence of canine and human rabies in Thailand has decreased significantly during the last decade. This has been associated with an increasing number of human post-exposure treatments. Educational efforts, mass vaccination of dogs and cats and the use of safe and effective vaccines have all made an impact. The proportion of fluorescent antibody positive dogs, among those examined for rabies averaged 54% indicating that rabies is still a major public health threat. Canine rabies vaccination is not usually performed in animals < 3 months old. However, this study revealed that 14% of rabid dogs were < 3 months old and 42% were < or = 6 months old. This is the age group most likely to interact with humans and other dogs. Our study also supports the World Health Organization''s recommendation that observing suspected rabid dogs for 10 days is an adequate and safe practice.     

Rabies in a dog imported from Iraq--New Jersey, June 2008

Rabies vaccination and stray dog control have led to successful control of canine rabies in the United States. The number of rabid dogs reported decreased from approximately 5,000 in 1950 to 79 in 2006, when the canine rabies virus variant associated with dog-to-dog rabies transmission was declared eliminated in the United States. On June 18, 2008, a mixed-breed dog, recently shipped from Iraq into the United States, was confirmed to have rabies by the Public Health and Environmental Laboratories of the New Jersey Department of Health and Senior Services. A total of 24 additional animals in the shipment, all potentially exposed to the rabid dog, were distributed to 16 states. This report summarizes the epidemiologic investigation by the New Jersey Department of Health and Senior Services, Bergen County Department of Health, and CDC, and the ensuing public health response. These findings underscore the need for vigilance regarding rabies (and other zoonotic diseases) during animal importation to prevent the possible reintroduction and sustained transmission of canine rabies in U.S. dog populations.     

Rabies vaccine is associated with decreased all-cause mortality in dogs

Evidence suggests that rabies vaccine may have non-specific protective effects in animals and children. We analyzed four years of data (2012–2015) from an observational study of the health and demographics of a population of owned, free-roaming dogs in a low-income community in South Africa. The objective of this analysis was to assess the association between rabies vaccine and all-cause mortality in dogs, stratified by age group (0–3 months, 4–11 months, and 12 months and older), and controlling for the effects of sex and number of dogs in the residence. Rabies vaccination reduced the risk of death from any cause by 56% (95% CI = 16–77%) in dogs aged 0–3 months, by 44% (95% CI = 21–60%) in dogs aged 4–11 months and by 16% (95% CI = 0–29%) in dogs aged 12 months and older. We hypothesize that the protective association between rabies vaccination status and all-cause mortality is due to a protective effect of rabies vaccine against diseases other than rabies. Existence of a strong non-specific protective effect of rabies vaccine on mortality in dogs would have implications for the design of dog rabies control programs that aim to eliminate dog-mediated human rabies cases. Further, we propose that owned domestic dogs in high mortality settings provide a useful animal model to better understand any non-specific protective effect of rabies vaccine in children, due to dogs’ high numbers, high morbidity and mortality rates, relatively short lifespan, exposure to a variety of infectious and parasitic diseases, and shared environment with people.     

Public health response to a rabid dog in an animal shelter --- North Dakota and Minnesota, 2010

On March 31, 2010, the North Dakota Department of Health (NDDoH) was notified by a local public health department that a stray dog found in rural Minnesota and housed during March 9-20 in a North Dakota animal shelter had been found to have rabies. NDDoH, along with the local public health department, the North Dakota Board of Animal Health (BOAH), the Minnesota Board of Animal Health, and the Minnesota Department of Health, immediately began an investigation to identify persons requiring rabies postexposure prophylaxis (PEP) and to prevent further rabies transmission. This report summarizes the public health investigation, which used animal shelter records and public notification to identify possible human and animal contacts of the rabid dog. Among 32 persons who might have been exposed to the rabid dog at the shelter, 21 persons, including nine shelter employees and one volunteer, received PEP. In accordance with 2009 Compendium of Animal Rabies Prevention and Control guidance, the 25 dogs in the shelter with the rabid dog were euthanized. Among 25 other dogs without an up-to-date rabies vaccination that were adopted or claimed from the shelter and might have been exposed, 11 were euthanized, 13 were isolated for 6 months in their owners' homes, and one was unintentionally killed. No additional cases of rabies in dogs or humans had been identified as of December 2010. This event supports consideration of preexposure vaccination of animal shelter employees and highlights the continued importance of routine rabies vaccination of domestic animals.     

Canine rabies DNA vaccination: a single-dose intradermal injection into ear pinnae elicits elevated and persistent levels of neutralizing antibody

Rabid dog exposures cause >99% of human rabies deaths world-wide. In developing countries, where dogs are the viral reservoir, the 30-50% vaccination coverage of dog populations is insufficient to break the disease transmission cycle. In addition, many vaccines currently used in developing countries fail to maintain detectable levels of neutralizing antibody. The poor vaccination coverage with inadequate vaccines, in addition to the difficulty in locating dogs for booster vaccinations, suggest that an inexpensive vaccine that elicits long-term immunity after a single-dose vaccination could improve control of canine rabies in developing countries. One solution could be a DNA vaccine. This study was designed to evaluate in dogs the ability of different methods of a single-dose DNA vaccination to elicit enhanced levels of neutralizing antibody. Intradermal (i.d.) vaccination into ear pinnae elicited elevated and long-lasting levels of neutralizing antibody. Minimal or undetectable levels of neutralizing antibody were detected after vaccination into quadriceps muscle, gene gun vaccination into ear pinnae or i.d. vaccination into the neck. Intramuscular (i.m.) or gene gun vaccinations did not "immunologically prime" a majority of dogs vaccinated by these routes. The passive transfer of sera from dogs that had been vaccinated i.d. in ear pinnae protected mice against rabies virus challenge. A single-dose i.d. rabies DNA vaccination into ear pinnae could aid in the control of canine rabies in developing countries.     

Pivotal role of dogs in rabies transmission, China

The number of dog-mediated rabies cases in China has increased exponentially; the number of human deaths has been high, primarily in poor, rural communities. We review the incidence of rabies in China based on data from 1950 and 2004, obtained mainly from epidemiologic bulletins published by the Chinese Ministry of Health.     

Rabies postexposure prophylaxis, Marseille, France, 1994-2005

The administration of human rabies postexposure prophylaxis near Marseille (southern France) has changed since the eradication of terrestrial mammal rabies in 2001. Most injuries were associated with indigenous dogs; rabies vaccine was overprescribed. We suggest that the World Health Organization guidelines be adapted for countries free of terrestrial mammal rabies.     

Failure of rabies postexposure treatment in Thailand

Three failures of postexposure rabies treatment using imported purified duck embryo cell and Vero cell rabies vaccines are reported from Thailand. Reference is made to eight additional previously reported Thai patients, six of whom had received human diploid cell vaccine. An analysis of these cases reveals that there were serious flaws in management in all of these patients. It is stressed that 45% of human rabies deaths in Thailand occur within 20 days of being bitten and 71% are dead within 28 days. This short incubation period does not allow much time to start immunotherapy. Of Bangkok dogs found to have rabies at autopsy, approximately 8% have a rabies immunization history. Once a dog has bitten a patient immunotherapy should not be delayed in countries with a high incidence of dog rabies. Patients with chronic disease, alcoholics and drug addicts may have an impaired immune response to postexposure rabies vaccines.     

Operational performance and analysis of two rabies vaccination campaigns in N’Djamena,Chad

Transmission of rabies from animals to people continues despite availability of good vaccines for both human and animal use. The only effective strategy to achieve elimination of dog rabies and the related human exposure is to immunize dogs at high coverage levels. We present the analysis of two consecutive parenteral dog mass vaccination campaigns conducted in N’Djamena in 2012 and 2013 to advocate the feasibility and effectiveness for rabies control through proof of concept. The overall coverage reached by the intervention was >70% in both years. Monthly reported rabies cases in dogs decreased by more than 90% within one year. Key points were a cooperative collaboration between the three partner institutions involved in the control program, sufficient information and communication strategy to access local leaders and the public, careful planning of the practical implementation phase and the effective motivation of staff.The dynamic and semi to non-restricted nature of dog populations in most rabies endemic areas is often considered to be a major obstacle to achieve sufficient vaccination coverage. However, we show that feasibility of dog mass vaccination is highly dependent on human determinants of dog population accessibility and the disease awareness of dog owners. Consequently, prior evaluation of the human cultural and socio-economic context is an important prerequisite for planning dog rabies vaccination campaigns.     

Rabies control in South and Southeast Asia

We have the knowledge and tools to eliminate the threat of canine rabies but this disease, nevertheless, remains a public health threat in many parts of the world. Lack of motivation by governments, cultural issues and inadequate funding remain barriers. This is amazing since the number of human rabies deaths worldwide is greater than that from polio, meningococcal meningitis, Japanese encephalitis, yellow fever, SARS, bird flue and other scourges that attract more attention. Safe and effective vaccines are now widely available. Reduced dose effective and less expensive post-exposure vaccination regimens have helped eliminate nerve tissue vaccines in Thailand, Philippines and Sri Lanka. India and Pakistan, the major users of dangerous nerve tissue derived Semple type vaccine, are now considering following suite. Immediate wound care and prompt use of a potent vaccine will save a majority of infected persons. Rabies immunoglobulin, injected into and around bite wounds, provides added safety for the severely exposed. The high cost of rabies immunoglobulin and tissue culture vaccines are remaining barriers, but new manufacturers and the use of intradermal vaccination schedules can reduce costs. Ultimately, it is the need to control rabies in dogs that must occupy most of our attention. The tools are available, but attitudes must change before they can be applied. There have been many new developments since publication of the last WHO rabies expert committee report in 1992 (new version in print)] and we will address those that have practical applicability.     

2007～2008年高州市人狂犬病暴露与犬携带狂犬病病毒情况调查

[目的]了解高州市外观健康犬只狂犬病病毒携带情况和人群狂犬病暴露与处置情况,为提出狂犬病防制对策提供依据。[方法]收集2007年高州市犬只饲养与动物伤人资料,对2008年高州市某乡小学205名学生家长进行狂犬病知识与犬伤情况问卷调查,2008年7～9月在市场采集健康犬脑和及唾液腺检测狂犬病病毒。[结果]高州市2007年动物伤人12029例,其中被犬所伤者占80.46%。调查205人,85.37%听说过狂犬病,其中66.34%知道狂犬病是被动物伤所致;61.46%的家里养犬。检测200只犬的标本,均为狂犬病病毒阴性。[结论]高州市家养犬只数量多,犬伤暴露状况严峻,居民狂犬病相关知识知晓率不高,尚未发现携带狂犬病病毒的犬只。     

湘西自治州2008-2011年狂犬病监测分析

目的了解狂犬病暴露人群及狂犬病疫情流行特征,评价预防处置效果,为预防和控制狂犬病提供依据。方法对2008-2011年湘西自治州狂犬病暴露人群资料及狂犬病疫情资料进行分析。结果 2008-2011年狂犬病年度暴露数分别为15 509例、11 412例、9 845例、8 986例,暴露率分别为62.80/万、46.03/万、39.53/万、35.27/万,年均暴露率45.81/万。犬伤暴露占87.24%。2008-2011年湘西自治州狂犬病共报告发病48例,1例猫伤暴露,2例不详外,45例犬伤暴露。发病率分别为0.53/10万、0.20/10万、0.68/10万、0.51/10万,年均发病率为0.48/10万。Ⅰ级暴露占18.78%,Ⅱ级暴露占45.19%,Ⅲ级暴露占36.03%。Ⅱ、Ⅲ级暴露41例,占85.4%。门诊处理伤口3例,自行处理8例,未处理36例。接种疫苗2例,接种狂免1例,不详1例。结论消除或控制狂犬病发生的关键在于提高犬只免疫率。而研发新型兽用狂犬病疫苗,及时发现狂犬病暴露人群,加强狂犬病防治知识宣传,加强医务人员的培训,规范处理伤口,全程使用狂犬疫苗等举措,都将有利于控制狂犬疫情。     

Reemerging Rabies and Lack of Systemic Surveillance in People��s Republic of China

Rabies is a reemerging disease in China. The high incidence of rabies leads to numerous concerns: a potential carrier-dog phenomenon, undocumented transmission of rabies virus from wildlife to dogs, counterfeit vaccines, vaccine mismatching, and seroconversion testing in patients after their completion of postexposure prophylaxis (PEP). These concerns are all scientifically arguable given a modern understanding of rabies. Rabies reemerges periodically in China because of high dog population density and low vaccination coverage in dogs. Mass vaccination campaigns rather than depopulation of dogs should be a long-term goal for rabies control. Seroconversion testing after vaccination is not necessary in either humans or animals. Human PEP should be initiated on the basis of diagnosis of biting animals. Reliable national systemic surveillance of rabies-related human deaths and of animal rabies prevalence is urgently needed. A laboratory diagnosis–based epidemiologic surveillance system can provide substantial information about disease transmission and effective prevention strategies.     

Rabies intradermal post-exposure vaccination of humans using reconstituted and stored vaccine

Thailand's northern Petchabun province is endemic for canine rabies. There were 27 reported human rabies deaths between 1989 and 1998. A rabies control plan was formulated in 1997 between medical and veterinary public health officials. It started an intense education program and an ongoing dog vaccination campaign. Economic constraints and the high cost of biological were the main reasons for inadequate human post-exposure management (PET). It was therefore decided to use the economical Thai Red Cross Intradermal Vaccine Regimen (TRC-ID) throughout the province. The original TRC-ID method is only suitable for clinics that see more than one PET patient daily. TRC-ID was therefore modified by storing the reconstituted vaccine in a refrigerator for the same patient's next two visits. Data on a total of 8157 PET patients were collected. An additional modification of TRC-ID also eliminated the 90 day booster. There were no treatment failures and no human rabies deaths in 1999, 2000 and 2001. The modified TRC-ID method induces adequate levels of neutralizing antibodies, protects humans bitten by rabid dogs and results in significant savings in vaccine and travel costs.     

Evaluation of immune responses in dogs to oral rabies vaccine under field conditions

During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3–12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05 IU/mL), compared to 16/27 (59.3%, p < 0.01) dogs that received ORV or 21/27 (77.8%) as measured by ELISA (>40% blocking, p < 0.05). The fate of 291 oral vaccines was recorded; 283 dogs (97.2%) consumed the bait; 272 dogs (93.4%) were observed to puncture the blister, and only 14 blisters (4.8%) could not be retrieved by vaccinators and were potentially left in the environment. Pre-vaccination antibodies (RFFIT >0.05 IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the community.     

A dog rabies vaccination campaign in rural Africa: impact on the incidence of dog rabies and human dog-bite injuries

Despite the availability of safe and effective rabies vaccines, the incidence of dog rabies has been increasing throughout much of sub-Saharan Africa. Here we describe a vaccination strategy that has resulted in successful control of rabies in a rural dog population of Northwestern Tanzania. From October 1996 to February 2001, four central-point dog vaccination campaigns were conducted in villages within Serengeti District with a mean interval between campaigns of 338, 319 and 456 days. Vaccination coverage of the dog population was estimated from household questionnaires as 64.5, 61.1, 70.6 and 73.7% following each of the four campaigns, respectively. The incidence of dog rabies declined significantly in Serengeti District falling by 70% after the first campaign and by 97% after the second campaign. Over the same period, the incidence of dog rabies did not differ significantly in unvaccinated control villages of Musoma District. The incidence of human bite injuries from suspected rabid dogs declined significantly in Serengeti District after dog vaccination but not in adjacent unvaccinated districts. Vaccination of 60-70% of dogs has been sufficient to control dog rabies in this area and to significantly reduce demand for human post-exposure rabies treatment. Dog-bite injuries can provide a valuable and accessible source of data for surveillance in countries where case incidence data are difficult to obtain.     

An important date in rabies history

Rabies is estimated to cause 31,000 human deaths in Asia annually. Several recent events, including World Rabies Day have brought this neglected disease to the attention of the scientific community, governmental authorities, the media and the public. It is hoped that this will result in an increased collaboration between veterinary and human health authorities, and an involvement at all levels necessary for the control and elimination of rabies in dogs, the main reservoir and vector of rabies in Asia. Dog rabies elimination is considered as the most cost-effective solution to prevent rabies deaths in humans. Asian countries such as India and the Philippines have recently adopted the objective of eliminating rabies by 2020. To support World Rabies Day, the Asian Rabies Expert Bureau (AREB) had its 4th annual meeting from 5 to 7 September 2007, with the objective of debating strategies for lowering the human rabies toll. Human rabies deaths can already be prevented by improving the compliance to WHO post-exposure prophylaxis recommendations. In addition, in regions with a high incidence of canine rabies and where rabies control in dogs is not yet achieved or not effective, systematic pre-exposure vaccination of children who are the main victims of rabies, may prevent their premature deaths.     

Factors influencing the antibody response of dogs vaccinated against rabies

Since 2000, there has been a legal requirement in the UK that dogs and cats should have an effective rabies vaccination with demonstrable sero-conversion if their owners wish to avoid quarantine on re-entry to the UK. In 2002, 10,483 rabies titres were determined on dogs at the VLA. Statistical analyses assessed the efficacy of each vaccine within different dog breeds. Animal size, age, breed, sampling time and vaccine had significant effects on pass rates and median titres. Our data suggests that a general relationship between animal size and level of antibody response exists and smaller sized dogs elicited higher antibody levels than larger breeds of dog. It was not however, only the magnitude of response immediately following vaccination but also the duration of immunity that varied between breeds of dog. Another observation was that young animals, less than 1-year of age, generated a lower antibody response to rabies vaccination than adults. Considerably higher failure rates were also observed for different vaccines tested. Regression analysis revealed that two vaccines performed equally well, and significantly better than the others tested. The variation in antibody response relating to length of interval of sampling following vaccination is not unexpected and presumably relates to the response kinetics for primary vaccination. These data need to be placed in perspective in order to minimise the risk of rabies being re-introduced into a rabies-free country, especially in the consideration of removing the requirement for serological testing for rabies vaccinated dogs that participate in pet travel schemes.