Canine Rabies in Australia: A Review of Preparedness and Research Needs

Australia is unique as a populated continent in that canine rabies is exotic, with only one likely incursion in 1867. This is despite the presence of a widespread free‐ranging dog population, which includes the naturalized dingo, feral domestic dogs and dingo‐dog cross‐breeds. To Australia's immediate north, rabies has recently spread within the Indonesian archipelago, with outbreaks occurring in historically free islands to the east including Bali, Flores, Ambon and the Tanimbar Islands. Australia depends on strict quarantine protocols to prevent importation of a rabid animal, but the risk of illegal animal movements by fishing and recreational vessels circumventing quarantine remains. Predicting where rabies will enter Australia is important, but understanding dog population dynamics and interactions, including contact rates in and around human populations, is essential for rabies preparedness. The interactions among and between Australia's large populations of wild, free‐roaming and restrained domestic dogs require quantification for rabies incursions to be detected and controlled. The imminent risk of rabies breaching Australian borders makes the development of disease spread models that will assist in the deployment of cost‐effective surveillance, improve preventive strategies and guide disease management protocols vitally important. Here, we critically review Australia's preparedness for rabies, discuss prevailing assumptions and models, identify knowledge deficits in free‐roaming dog ecology relating to rabies maintenance and speculate on the likely consequences of endemic rabies for Australia.     

Dogs Entering the United States from Rabies‐Endemic Countries, 2011–2012

International dog imports pose a risk because of the potential movement of disease agents, including the canine rabies virus variant which has been eliminated from the United States since 2007. US regulations require a rabies vaccination certificate for dogs arriving from rabies‐endemic countries, but permit the importation of dogs that have not been adequately immunized against rabies, provided that the dogs are confined under conditions that restrict their contact with humans and other animals until they have been immunized. CDC Form 75.37, ‘Notice to Owners and Importers of Dogs’, explains the confinement requirements and serves as a binding confinement agreement with the importer. In this evaluation, we describe the characteristics of unimmunized dogs imported into the United States over a 1‐year period based upon dog confinement agreements recorded at the Centers for Disease Control and Prevention (CDC) quarantine stations. Confinement agreements were issued for nearly 2800 unimmunized dogs that entered the United States during 1 June 2011–31 May 2012, the majority of which travelled to the United States by air and without any seasonal pattern in import volume. Over 60% of these animals were puppies <3 months of age and included a wide variety of breeds. The dogs arrived from 81 countries, with the majority arriving from North America or Europe. Dogs placed on confinement agreements had final destinations in 49 states. California, New York, Texas, Washington and Florida received the largest number of dogs on confinement agreements. These results (which do not reflect human travel or US dog ownership data) suggest that a large portion of unimmunized dogs arrive from rabies‐endemic countries for commercial, shelter and rescue purposes. Further evaluation and key stakeholder involvement are needed to assess whether the current dog importation regulations are an adequate compromise between the benefits and risks of dog importation.     

Impact of Rabies Vaccination History on Attainment of an Adequate Antibody Titre Among Dogs Tested for International Travel Certification,Israel – 2010–2014

Rabies is endemic in wildlife or domestic carnivore populations globally. Infection of domestic dogs is of particular concern in many areas. In regions where domestic animals are at risk of exposure to rabies virus, dogs should be routinely vaccinated against rabies to protect both pet and human populations. Many countries require demonstration of an adequate level of serum rabies neutralizing antibodies to permit entry of dogs during international travel. We analysed rabies titres of dogs seeking travel certification in Israel to assess demographic and vaccine history factors associated with antibody titres below the acceptable threshold for travel certification. Having received only one previous rabies vaccination and a longer duration since the most recent vaccination was received were primary risk factors for not achieving an adequate rabies virus neutralizing antibody titre for travel certification. These risk factors had stronger effects in younger animals, but were consistent for dogs of all ages. In particular, these findings reiterate the importance of administering at least two rabies vaccinations (the primo vaccination and subsequent booster) to ensure population‐level protection against rabies in dogs globally.     

Fighting Rabies in Eastern Europe,the Middle East and Central Asia ‐ Experts Call for a Regional Initiative for Rabies Elimination

MEEREB is an informal network of rabies experts from the Middle East, Eastern Europe and Central Asia, seeking to eliminate rabies from the region. They met for the second time to review the current rabies situation, both globally and in their respective countries, highlighting current rabies control problems and potential solutions. Success stories in Latin America, in Western Europe, in some Asian countries, as well as in Croatia and Serbia prove that elimination of human rabies is achievable in the MEEREB region. It requires political willingness and cooperation of all stakeholders, including Ministries of Health and of Agriculture; adequate management of animal bites through post‐exposure prophylaxis; pre‐exposure prophylaxis for populations at high risk of rabies exposure, animal vaccination and humane control of stray dog populations. MEEREB members called for a regional initiative for rabies elimination in Eastern Europe and the Middle East. They are confident that the elimination of human rabies of canine origin can be achieved in the region through adopting a One Health approach, and that campaigns for rabies elimination will have significant benefit for public health, including strengthening the structure for control of other zoonoses.     

Exploring animal rabies endemicity to inform control programmes in Punjab,India

Previous studies estimate that one‐third of the annual global burden of rabies (~20,000 cases) occurs in India. Elimination of canine rabies is essential to reduce this burden. Surveillance of animal cases can assess both the risk to humans and the efficacy of control strategies. The objective of this study was to describe the spatial and temporal occurrence of reported confirmed cases of rabies in animals in Punjab, India, from 2004 to 2014. We analysed passive surveillance data on 556 samples submitted from 2004 to 2014 to GADVASU, Ludhiana, Punjab, India. Regression and time series analyses were conducted to understand seasonal and long‐term variation of cases and identify cross‐correlation of monthly cases between species. Spatio‐temporal analyses assessed spatial autocorrelation of date of reporting, mean geographic centres of disease occurrence and clustering of cases using Kulldorff's space‐time permutation statistic. The annual number of submissions and proportion of confirmed cases were consistent throughout 2004–2014. Most submissions (320; 57.6%) were confirmed rabies cases, including dogs (40.6%), buffalo (29.7%) and cattle (23.1%). Regression analysis of monthly cases in dogs showed seasonal variation with significant increases in cases in March and August. Monthly case numbers in buffalo decreased over time. Long‐term temporal trend was not detected in dog and cattle cases. Time‐series models identified significant cross‐correlation between dog and buffalo cases, suggesting that buffalo cases were spillover events from dogs. Significant spatio‐temporal variation or clusters of cases were not detected. These results indicate that rabies cases in animals—and therefore, the potential for exposure to humans—were temporally and spatially stable during 2004–2014 in Punjab, India. The endemic nature of rabies transmission in this region demands a coordinated, sustained control programme. This study provides baseline information for assessing the efficacy of rabies control measures and developing seasonally targeted dog vaccination and rabies awareness strategies.     

Meeting the urgent need for rabies education in Haiti

The highest rate of human rabies deaths reported in the Americas is in Haiti, and most of these deaths result from rabies virus infections that occur after individuals are bitten by infected dogs and do not receive rabies post‐exposure prophylaxis. One barrier to rabies prevention in Haiti is a lack of knowledge about this disease among healthcare professionals and community members. During the past 4 years, The US Centers for Disease Control and Prevention has collaborated with public health officials and partners to develop, test and refine educational materials aimed at filling this need for rabies education. This report summarizes the use of feedback from knowledge, attitudes and practises surveys; key informant interviews; and focus groups to develop culturally appropriate rabies prevention materials for community members, health officials, clinicians, laboratory professionals, veterinary professionals, government officials and national and local district leaders about ways to prevent rabies. These formative research methods were critically important in ensuring that the materials would be culturally appropriate and would stand the greatest likelihood of motivating Haitians to protect themselves from rabies. Centers for Disease Control and Prevention is using lessons learned in Haiti to develop and test materials in other countries with high rates of canine rabies.     

Prevention and Control of Rabies in an Age of Global Travel: A Review of Travel‐ and Trade‐Associated Rabies Events – United States, 1986–2012

Rabies prevention and control efforts have been successful in reducing or eliminating virus circulation regionally through vaccination of specific reservoir populations. A notable example of this success is the elimination of canine rabies virus variant from the United States and many other countries. However, increased international travel and trade can pose risks for rapid, long‐distance movements of ill or infected persons or animals. Such travel and trade can result in human exposures to rabies virus during travel or transit and could contribute to the re‐introduction of canine rabies variant or transmission of other viral variants among animal host populations. We present a review of travel‐ and trade‐associated rabies events that highlight international public health obligations and collaborative opportunities for rabies prevention and control in an age of global travel. Rabies is a fatal disease that warrants proactive coordination among international public health and travel industry partners (such as travel agents, tour companies and airlines) to protect human lives and to prevent the movement of viral variants among host populations.     

Rabies status in Zambia for the period 1985-2004

Rabies has been present in Zambia since the early years of the 20th century. It is a significant public health problem in Zambia. Domestic dogs accounted for 69.7% (1348/1935) of the samples received for rabies diagnosis for the period 1985-2004. Of the 1069 positive cases confirmed by the fluorescent antibody test, 747 (69.9%) were from domestic dogs, 139 (13.0%) from cattle and 98 (9.2%) from humans. Wildlife samples accounted for 4.5% (87/1935) of the samples tested with the jackal (Canis adustus) being the predominant species. Cases of rabies were highest in Lusaka Province followed by the Copperbelt, Southern and Central Provinces. The monthly distribution of canine rabies showed an average of 2.93 (95% CI 2.59-3.29) dog positive cases per month. The study confirms that rabies is endemic in Zambia and that the domestic dog is the principal maintenance host. The epidemiology and control measures currently used in Zambia are herein discussed highlighting their limitations and successes. Based on the findings obtained from this study we advocate for strengthening the delivery of public health services and that steps must taken to reduce the incidence of rabies in Zambia.     

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.     

Interleukin‐31: its role in canine pruritus and naturally occurring canine atopic dermatitis

Background – Interleukin‐31 (IL‐31) is a member of the gp130/interleukin‐6 cytokine family that is produced by cell types such as T helper 2 lymphocytes and cutaneous lymphocyte antigen positive skin homing T cells. When overexpressed in transgenic mice, IL‐31 induces severe pruritus, alopecia and skin lesions. In humans, IL‐31 serum levels correlate with the severity of atopic dermatitis in adults and children. Hypothesis/Objective – To determine the role of IL‐31 in canine pruritus and naturally occurring canine atopic dermatitis (AD). Animals – Purpose‐bred beagle dogs were used for laboratory studies. Serum samples were obtained from laboratory animals, nondiseased client‐owned dogs and client‐owned dogs diagnosed with naturally occurring AD. Methods – Purpose‐bred beagle dogs were administered canine interleukin‐31 (cIL‐31) via several routes (intravenous, subcutaneous or intradermal), and pruritic behaviour was observed/quantified via video monitoring. Quantitative immunoassay techniques were employed to measure serum levels of cIL‐31 in dogs. Results – Injection of cIL‐31 into laboratory beagle dogs caused transient episodes of pruritic behaviour regardless of the route of administration. When evaluated over a 2 h period, dogs receiving cIL‐31 exhibited a significant increase in pruritic behaviour compared with dogs that received placebo. In addition, cIL‐31 levels were detectable in 57% of dogs with naturally occurring AD (≥13 pg/mL) but were below limits of quantification (<13 pg/mL) in normal, nondiseased laboratory or client‐owned animals. Conclusions – Canine IL‐31 induced pruritic behaviours in dogs. Canine IL‐31 was detected in the majority of dogs with naturally occurring AD, suggesting that this cytokine may play an important role in pruritic allergic skin conditions, such as atopic dermatitis, in this species.     

The development and validation of an antibody-ELISA to detect Trypanosoma evansi infection in cattle in Australia and Papua New Guinea

Trypanosoma evansi is exotic to Australia and Papua New Guinea (PNG). However, it might have been introduced to Papua (Indonesia); thus, there is a risk of it entering PNG and thence Australia. Because of logistical difficulties in PNG and northern Australia, surveillance for T. evansi must rely on serological tests. The accuracy of an Ab-ELISA using a detergent extract of T. evansi and three antigen fractions purified from the detergent extract using stepwise precipitation with saturated ammonium sulphate (AS) were compared. The ELISA using the AS 40-50% fraction had greater discriminatory power compared to the ELISA using the other antigen fractions. This ELISA then was compared with two commercial tests: the Card Agglutination Test for trypanosomiasis/T. evansi (CATT) and Suratex. CATT/T. evansi at 1/4 serum dilution has higher sensitivity and the ELISA has higher specificity. There is no likely benefit in combining antibody detection tests to improve the accuracy of diagnosis. Furthermore, the combination of Suratex (which was independent of the antibody tests) with the CATT or the ELISA did not improve the sensitivity. None of the tests was sufficiently sensitive to be used confidently to determine freedom from infection in animals imported into Australia from countries where T. evansi infection is endemic.     

Canine vaccination--providing broader benefits for disease control

This paper reviews the broader benefits of canine vaccination to human and animal health and welfare with an emphasis on the impacts of mass dog vaccination against rabies in countries of the less-developed world. Domestic dogs are the source of infection for the vast majority (>95%) of cases of human rabies worldwide, and dogs remain the principal reservoir throughout Africa and Asia. Canine vaccination against rabies has been shown to dramatically reduce the number of cases in dogs, the incidence of human animal-bite injuries (and hence the demand for costly post-exposure prophylaxis) and the likely number of human cases, primarily in children. Further benefits include the mitigation of the psychological consequences of rabies in a community, improved attitudes towards animals and animal welfare and reduced livestock losses from canine rabies. Mass vaccination has recently been used in the conservation management of wild carnivore populations threatened by transmission of rabies and canine distemper virus from domestic dog populations. Vaccination of wildlife hosts directly may also provide an option for mitigating infectious disease threats. The development of integrated control measures involving public health, veterinary, wildlife conservation and animal welfare agencies is needed to ensure that control of canine diseases becomes a reality in Africa and Asia. The tools and delivery systems are all available--all that is needed is the political will to free the world from the ongoing tragedy of these diseases.     

Importation of dogs into the United States: risks from rabies and other zoonotic diseases

The importation of dogs into the United States poses a risk for the introduction of rabies and other zoonotic diseases. Federal regulations (42 CFR 71.51) currently require proof of valid rabies vaccination for imported dogs, but allow the importation of some unvaccinated dogs, including dogs less than 3 months of age, provided certain requirements for confinement are met until the dog is vaccinated. Although there are no accurate surveillance data on the number of dogs imported each year, it is estimated based on extrapolated data that over 287,000 dogs were imported into the United States during 2006. Of these, approximately 25% were either too young to be vaccinated or lacked proof of valid rabies vaccination. Import trends suggest that an increasing number of unvaccinated puppies are being imported into the United States, many through commercial resale or rescue operations. Since 2004, foreign canine rabies virus variants have been documented in at least two imported puppies. Federal regulations are currently being reviewed by the Centers for Disease Control and Prevention to determine if they can be updated to address current import trends and disease risks, such as requiring a health screen and valid rabies vaccinations for all dogs prior to entry.     

Exposure of free-ranging maned wolves (Chrysocyon brachyurus) to infectious and parasitic disease agents in the No?l Kempff Mercado National Park, Bolivia.

Maned wolves (Chrysocyon brachyurus) are neotropic mammals, listed as a CITES Appendix II species, with a distribution south of the Amazon forest from Bolivia, through northern Argentina and Paraguay and into eastern Brazil and northern Uruguay. Primary threats to the survival of free-ranging maned wolves include habitat loss, road kills, and shooting by farmers. An additional threat to the conservation of maned wolves is the risk of morbidity and mortality due to infectious and parasitic diseases. Captive maned wolves are susceptible to, and die from, common infectious diseases of domestic dogs (Canis familiaris) including canine distemper virus (CDV), canine parvovirus (CPV), rabies virus, and canine adenovirus (CAV). Results from this study show that free-ranging maned wolves in a remote area of Bolivia have been exposed to multiple infectious and parasitic agents of domestic carnivores, including CAV, CDV, CPV, canine coronavirus, rabies virus, Leptospira interrogans spp., Toxoplasma gondii, and Dirofilaria immitis, and may be at increased risk for disease due to these agents.     

Estimation of roaming dog populations in Timor Leste

The continued spread of rabies through the eastern islands of Indonesia poses a risk of rabies introduction to Timor Leste. To prepare for such an incursion and to undertake surveillance activities, the size and distribution of the roaming dog population needs to be estimated. We present the results of the first such surveys ever undertaken in Timor Leste.     

Use of Aspiration Method for Collecting Brain Samples for Rabies Diagnosis in Small Wild Animals

In developing countries such as Brazil, where canine rabies is still a considerable problem, samples from wildlife species are infrequently collected and submitted for screening for rabies. A collaborative study was established involving environmental biologists and veterinarians for rabies epidemiological research in a specific ecological area located at the Sao Paulo State, Brazil. The wild animals’ brains are required to be collected without skull damage because the skull’s measurements are important in the identification of the captured animal species. For this purpose, samples from bats and small mammals were collected using an aspiration method by inserting a plastic pipette into the brain through the magnum foramen. While there is a progressive increase in the use of the plastic pipette technique in various studies undertaken, it is also appreciated that this method could foster collaborative research between wildlife scientists and rabies epidemiologists thus improving rabies surveillance.     

Phylogenetic characterization of rabies virus isolates from Carnivora in Brazil

The incidence of canine rabies has been widely reported in Brazil, and new rabies virus (RV) variants, genetically similar to canine RV, have recently been isolated from foxes. In order to derive the epidemiological characteristics of Brazilian Carnivora RV, Brazilian RVs isolated from dogs, cats, and foxes were genetically analyzed. Brazilian Carnivora RV isolates were divided into 2 main lineages. The predominant lineage was found in dogs and cats, which included the Argentinean and Bolivian Carnivora RV isolates, and was extensively distributed throughout Brazil and surrounding countries. The other lineage consisted of three sublineages containing Brazilian dog and fox RV isolates, with the dog sublineages located on an internal branch of 2 fox sublineages, suggesting that RV transmission events might have occurred between foxes and dogs in the past. These results suggest that contact between dogs and wildlife has the potential to generate new rabies variants and that it is important to control RV infection cycles in both dogs and wildlife to prevent spread of rabies infection.     

Immunofluorescence Study of Wild Rabies Virus and Antibody

A concentrate of wild rabies antibody was prepared from hyperimmune serums of three dogs refractory to wild rabies. The animals resisted repeated intramuscular injections of large doses of wild rabies virus in emulsions of whole brain, in emulsions of submaxillary salivary glands, and in emulsified mixtures of brain and submaxillary glands taken from naturally rabid dogs.

The antibody was conjugated with fluorochrome and then absorbed by a procedure that gave “cell-free” working solutions of fluorescent antibody. The procedure entailed parallel absorption steps with minced pathological canine submaxillary glands from (1) naturally rabid dogs (these glands contained specific, undegraded, natural antigens of live wild rabies virus plus nonspecific substances and antigens) and (2) nonrabid dogs from a rabies endemic region (these glands contained nonspecific substances and antigens).

Extracts from submaxillary glands of the three naturally rabid dogs and one nonrabid dog were stained with a cell-free solution of the fluorescent antibody. The glands of the rabid dogs contained fluorescent aggregates of intense green spherical and filamentous particles. When nonfluorescent canine hyperimmune serum was incubated with rabies-containing submaxillary extract, the rabies antigens were quenched. When nonfluorescent equine fixed virus antiserum was incubated with such extracts, the aggregates still retained bright fluorescence.