Surveillance of Human Rabies by National Authorities – A Global Survey

Effective prevention of deaths due to human rabies is currently hampered by a lack of understanding of the scale of the problem, and the distribution of both animal and human cases across countries, regions and continents. Unfortunately, despite the severity of the disease, accurate data on which to assess these questions and to prioritize and direct public health interventions are not available for many parts of the world. This survey sought to understand the current global situation regarding the surveillance of human rabies. Data were collected from 91 countries across all continents and all categories of human rabies risk, generating the most complete and representative global data set currently available. Respondents were asked key questions about whether human rabies was a notifiable disease, how the surveillance system for human rabies operated and whether the respondent considered that the surveillance system was working effectively. Across the 91 countries from which data were collated, human rabies was a notifiable disease in all but eight. Despite international guidance, surveillance systems were very varied. Even where rabies is a notifiable disease, many countries had surveillance system judged to be ineffective, almost all of these being high and moderate rabies risk countries in Africa and Asia. Overall, 41% of the population covered by this survey (around 2.5 billion people) live in countries where there is no or ineffective rabies surveillance. The lack of robust surveillance is hindering rabies control efforts. However, whilst worldwide rabies surveillance would be improved if rabies were notifiable in all countries, many other challenges to the implementation of effective global human rabies surveillance systems remain.     

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.     

Serodiagnosis of inapparent caseous lymphadenitis in goats and sheep, using the synergistic hemolysis-inhibition test

The synergistic hemolysis-inhibition (SHI) test, a serologic test for the detection of infection with Corynebacterium pseudotuberculosis, was applied to serum samples from 196 goats and 76 sheep, including animals both with and without C pseudotuberculosis abscesses. Fifty-one of 52 (98%) goats and 27 of 28 (96%) sheep with abscesses caused by C pseudotuberculosis had seropositive titers. Seropositivity continued on subsequent samplings, even after superficial lesions were completely healed. The SHI test may detect subclinically infected animals, as well as animals with clinically recognizable lesions. Of the animals without abscesses, 53 of 186 (28%) goats and 4 of 41 (10%) sheep were seropositive. Either the SHI test is lacking in specificity or these titers are a reflection of a past or a current infection without any grossly visible abscesses.     

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.     

Increased detection of rabies virus in bats in Ceará State (Northeast Brazil) after implementation of a passive surveillance programme

The intensification of dog, cat and livestock vaccination campaigns significantly reduced rabies cases in humans and domestic animals in Ceará State, Brazil. However, sylvatic animals—bats (order Chiroptera), wild canids, raccoons and non‐human primates— remain as reservoirs for the virus. Our hypothesis is that surveillance and monitoring of rabies virus in bats, especially passive surveillance, is of fundamental importance, besides the implementation of health education and strengthening of surveillance actions in humans exposed to aggressions. Thus, we assessed the occurrence of rabies virus in animals focusing on bats, before and after launching of the Sylvatic Rabies Surveillance Program in 2010. Surveillance data from the 184 municipalities of Ceará State were analysed, collected during the periods 2003–2010 (active surveillance) and 2011–2016 (passive surveillance), respectively. A total of 13,543 mammalian samples were received for rabies diagnosis from 2003 to 2016. Of these, 10,960 were from dogs or cats (80.9%), 1,180 from bats (8.7%), 806 from other sylvatic animals (foxes, marmosets, raccoons; 6.0%) and 597 from herbivores (cattle, goats, sheep, equines, pigs; 4.4%). A total of 588 (4.3%) samples were positive for rabies. About 8.4% (99/1,180) of the bat samples were infected with rabies virus, 92 (92.9%) of these were from non‐haematophagous bat species and 7 (7.1%) from haematophagous species. The number of bat samples received and infection rates increased considerably, after a shift from active surveillance (9/355 [2.5%] samples positive), to passive surveillance (90/825 [10.9%] samples positive). Surveillance of rabies virus in bats is fundamental for human and domestic animal health in Ceará State. Bats have to be considered as targets in surveillance and control programmes. Virus lineages should be characterized to increase knowledge on transmission dynamics of sylvatic rabies virus to domestic animals and the human population, and to provide additional evidence for planning and implementation of improved control measures.     

Rabies surveillance in the United States during 1990.

In 1990, the United States and its territories reported 4,881 cases of rabies in animals to the Centers for Disease Control, a 1.5% increase from 1989. Of these, 553 were domestic animals, 4,327 were wild animals, and one was a human being. Pennsylvania reported the highest number (611) of rabies cases in animals in 1990. For the first time since surveillance of rabies in wild animals was begun in the 1950s, the number of cases of rabies in raccoons exceeded that in skunks. Particularly large increases of cases of rabies in wild and domestic animals were reported in New Jersey (469 cases in 1990 compared with 50 cases in 1989, an increase of 838% from 1989) and New York (242 cases in 1990 compared with 54 cases in 1989, an increase of 348%). The 1,821 cases of rabies in raccoons represented a 17.9% increase over those reported in 1989 and 24.5% over those in 1988. This increase was largely attributable to the larger number of rabid raccoons in New Jersey and New York. Other states that reported an increased number of rabies cases in animals in 1990 included Utah (77.8%), Louisiana (64.7%), North Dakota (60.3%), Arizona (28.6%), Oklahoma (27.5%), Delaware (22.2%), and Maryland (20.6%). Thirty states reported a decrease in the number of cases of rabies in animals.     

The application of medical informatics to the veterinary management programs at companion animal practices in Alberta,Canada: A case study

Companion animals closely share their domestic environment with people and have the potential to, act as sources of zoonotic diseases. They also have the potential to be sentinels of infectious and noninfectious, diseases. With the exception of rabies, there has been minimal ongoing surveillance of, companion animals in Canada. We developed customized data extraction software, the University of, Calgary Data Extraction Program (UCDEP), to automatically extract and warehouse the electronic, medical records (EMR) from participating private veterinary practices to make them available for, disease surveillance and knowledge creation for evidence-based practice. It was not possible to build, generic data extraction software; the UCDEP required customization to meet the specific software, capabilities of the veterinary practices. The UCDEP, tailored to the participating veterinary practices’, management software, was capable of extracting data from the EMR with greater than 99%, completeness and accuracy. The experiences of the people developing and using the UCDEP and the, quality of the extracted data were evaluated. The electronic medical record data stored in the data, warehouse may be a valuable resource for surveillance and evidence-based medical research.     

The raccoon (Procyon lotor) as potential rabies reservoir species in Germany: a risk assessment

Terrestrial wildlife rabies has been successfully eliminated from Germany predominantly as a result of the distribution of oral rabies vaccine baits. In case that wildlife rabies would re-emerge among its known reservoir species in Germany, swift action based on previous experiences could spatially and temporally limit and subsequently control such an outbreak. However, if rabies emerged in the raccoon population in Germany (Procyon lotor), there are no tools or local experience available to cope with this situation. This is especially worrisome for urban areas like Kassel (Hesse) due to the extremely high raccoon population density. A rabies outbreak among this potential reservoir host species in these urban settings could have a significant impact on public and animal health.     

Review of Rabies Epidemiology and Control in South,South East and East Asia: Past,Present and Prospects for Elimination

Rabies is a serious public health problem in Asia. It causes substantial animal welfare, economic and human health impacts, with approximately 39 000 human deaths each year. Domestic dogs are the main reservoir and source of rabies in Asia. Common constraints for the control of rabies in the countries of Asia include inadequate resources; lack of political commitment to control programs; lack of consensus on strategy; weak intersectoral coordination and inadequate management structure; insensitive surveillance systems; limited accessibility to modern rabies vaccine and supply problems; lack of public awareness and public cooperation; and the existence of myths and religious issues. In this review, we summarize the epidemiology of rabies in both human and animals in each South and South East Asian country, the past and current approaches to control and the prospect for rabies elimination. We conclude that defining the cost of rabies to society and communicating this to decision‐makers might be the key to achieving such an advance.     

Protection of dogs against death from experimental rabies by postexposure administration of rabies vaccine and hyperimmune globulin (human).

Two experiments on simulated postexposure treatment were carried out in dogs using human rabies immunoglobulin (RIGH) and human diploid cell vaccine for human use. In one experiment, when animals were challenged by injecting street virus into the masseter muscle and treated with a combination of RIGH and vaccine, 50% of the animals were protected from rabies. In the other trial, in which animals were challenged by injecting the virus into the femoral muscle, treatment with RIGH and vaccine protected all the animals against rabies. To our knowledge this is the highest rate of postexposure survival in animals reported to date. In addition, five out of eight (62.5%) dogs that received RIGH alone after the virus challenge were protected, while none of the animals receiving vaccine alone were protected from rabies. These trials suggest that animals can be protected from rabies by postexposure treatment. The route of exposure and timing of the administration of vaccine and hyperimmune serum would seem to be important.     

Re‐emergence of rabies virus maintained by canid populations in Paraguay

Paraguay has registered no human cases of rabies since 2004, and the last case in dogs, reported in 2009, was due to a variant maintained in the common vampire bat “Desmodus rotundus”. In 2014, a dog was diagnosed as positive for rabies with aggression towards a boy and all required measures of control were successfully adopted. Epidemiological investigation revealed that the dog was not vaccinated and had been attacked by a crab‐eating fox, “zorro” (Cerdocyon thous). The sample was diagnosed by the Official Veterinary Service of the Country and sent to the Center on Rabies Research from the University of São Paulo, Brazil, for antigenic and genetic characterization. A second sample from a dog positive for rabies in the same region in 2015 and 11 samples from a rabies outbreak from Asuncion in 1996 were also characterized. The antigenic profile of the samples, AgV2, was compatible with one of the variants maintained by dogs in Latin America. In genetic characterization, the samples segregated in the canine (domestic and wild species)‐related group in an independent subgroup that also included samples from Argentina. These results and the epidemiology of the case indicate that even with the control of rabies in domestic animals, the virus can still circulate in wildlife and may be transmitted to domestic animals and humans, demonstrating the importance of continuous and improved surveillance and control of rabies, including in wild species, to prevent outbreaks in controlled areas.     

Assessment of naturally acquired neutralizing antibodies against rabies Lyssavirus in a subset of Nunavik’s Inuit population considered most at risk of being exposed to rabid animals

Contact with infected saliva through the bite of a rabid animal is the main route of infection with the rabies Lyssavirus in humans. Although a few individuals have survived the infection, rabies remains the most lethal zoonotic infection worldwide. Over the last century, the dogma that rabies is invariably fatal has been challenged by the survival and recovery of infected animals. In humans, 11 studies have found rabies virus‐specific antibodies in unvaccinated individuals exposed to rabies virus reservoir species, suggesting the possibility of asymptomatic rabies virus infection, contact with non‐infectious virus or exposure to the virus without viral replication. Two of these studies were conducted in Arctic hunters. Considering the extensive exposure of Nunavik's Inuit to potentially infected animals through hunting, trapping, skinning and the preparation of Arctic carnivores, we analysed archived serum samples from the 2004 Nunavik Inuit Health Survey for the presence of rabies virus‐neutralizing antibodies (rVNA) in this sub‐population. A total of 196 participants who were considered at highest risk for exposure to rabies virus were targeted. Serum samples were tested for the presence of rVNA using a variation of the fluorescent antibody virus neutralization test, an assay recommended for the quantification of neutralizing antibody titres following vaccination. Our study identified two seropositive individuals among the 196 participants but a review of their medical record and a phone interview revealed previous vaccination. Our results do not provide evidence for naturally acquired rVNA in Nunavik's Inuit population.     

Trends in national surveillance for rabies among bats in the United States (1993-2000)

OBJECTIVE: To describe surveillance trends and epidemiologic features of rabies in bats in the United States, focusing on 3 bat species primarily associated with variants of the rabies virus that affect humans. DESIGN: Retrospective study. ANIMALS: 31,380 bats. PROCEDURE: Data on rabies for bats identified to species and reported by state laboratories from 1993 to 2000 were analyzed, focusing on silver-haired, eastern pipistrelle, and Brazilian free-tailed bats. Categoric variables were derived from other provided information. RESULTS: Data were reported from 37 states during the study interval; complete species-specific data were not reported by any state for the entire interval. Bats primarily associated with rabies virus variants affecting humans were more likely to yield positive test results for rabies (22.7%), compared with all other bats (5.5%) in most seasons and from most regions of the United States. However, certain other bat species had higher percentages of positive results. Risk of positive results was highest in the fall and highest among bats originating in the southwestern United States. CONCLUSIONS AND CLINICAL RELEVANCE: Increased risk of rabies among certain groups of bat species was consistently found across seasons and most geographic regions of the United States. Results were in general agreement with those of previous studies conducted within smaller geographic regions. There are ongoing efforts to improve surveillance of rabies in bats, although surveillance is incomplete in some regions.     

狂犬病病毒流行病学特征与实验室诊断技术的研究进展

狂犬病是由狂犬病病毒引起的以中枢神经系统感染为特征的一种人兽共患病。狂犬病病毒具有嗜神经性,能在人和多种哺乳动物中引起致死性感染,病死率几乎为100%。除常规的临床诊断外,狂犬病的确诊依赖于实验室诊断方法,方法主要有病原学诊断、血清学诊断和分子生物学诊断方法等。狂犬病作为一种人兽共患烈性传染病,呈全球分布的态势,中国每年因狂犬病病毒感染而导致死亡的人数居全球第2位。因此,加强对该病的病原学、流行病学特征的认识、加快实验室诊断方法的研究对其综合防控工作具有十分重要的意义。作者主要介绍了目前国内外狂犬病流行病学特征和诊断方法的研究进展,并比较了各种方法的优点和缺点,为狂犬病的临床快速诊断和深入研究提供科学依据。     

A simulation model of intraherd transmission of foot and mouth disease with reference to disease spread before and after clinical diagnosis.

Intraherd transmission of foot and mouth disease virus (FMDV) was examined using a simulation model for a hypothetical 1,000-cow dairy, assuming clinical diagnosis was made when at least 1% (10 cows) or 5% (50 cows) had clinical signs of FMD, I index case cow, and transition state distributions for the latent, subclinically infectious, and clinically infectious periods of FMD calculated from published data. Estimates assumed for the number of animal-to-animal contacts (k) adequate for transmission ranged from 0.6 to 9.0 per hour (13.7-216.0 per day). A total of 40,000 iterations (5,000 for each scenario, assessing 4 adequate contact rates and 2 detection criteria) were run. The model predicted that FMD would not be diagnosed in the herd until 10.0-13.5 days after the index case cow had become infected, at which time between 65% and 97% of the cows (646-967 cows) to nearly 100% (978-996 cows) would already have become infected with the virus, if the number of cows showing clinical signs of FMD at the time of diagnosis were 10 or 50, respectively. At the time of diagnosis, the simulated number of infectious cattle varied substantially from 82-472 to 476-537 cows, depending on adequate contact rate and whether the diagnosis was made when 10 or 50 animals were showing clinical signs, respectively. The simulated number of infectious cows increased rapidly during the first few days after diagnosis. In the scenario where at least 10 cows showing clinical signs was necessary before a clinical diagnosis was made, each day after diagnosis, the number of infectious animals increased by nearly 100 to more than 200 cases per day up to day 5, assuming 0.57-9.0 animal-to-animal contacts per hour, respectively. Results obtained when it was assumed that at least 50 clinical cases were present at the time of diagnosis showed smaller relative increases because nearly one-half of the herd was projected to be infected at the time of diagnosis. From these results, it is clear that once an individual in a herd becomes infected with FMDV, herd infectivity is not static, rather it accelerates as would be expected as long as there are sufficient susceptible animals to sustain the increasing transmission rate, after which time the rate at which new infections occurs will diminish. Results indicate that biosecurity strategies aimed at minimizing both intraherd and interherd contact will be critical in minimizing the spread of FMD before the initial diagnosis is made. In addition, simulations suggest that very early clinical diagnosis of FMD and effective isolation or depopulation and disposal will be critical in limiting the number of infectious animals capable of transmitting the virus to other herds and thus in timely control of an epidemic. Early diagnosis will rely on early virus detection from animals in the preclinical phase of infection, rather than waiting for clinical signs to manifest in sufficient numbers to be noticed and to warrant investigation.     

Elimination of terrestrial rabies in Germany using oral vaccination of foxes

Oral rabies vaccination (ORV) has become the method of choice in fox rabies control in Europe. During the past three decades fox-mediated rabies virtually disappeared from Western and Central Europe. Following Switzerland, Germany was the second European country to launch ORV field trials on its territory in 1983. This paper provides a historical overview on the emergence of fox rabies in Germany; describing the basic principles and milestones of the German rabies eradication programme and presenting results of two decades of efforts to control the disease in foxes. Also, setbacks as well as country-specific differences and particularities on Germany's long way to rabies elimination in comparison to other European countries are addressed. Since the first field trials in Germany the number of rabies cases steadily decreased from 10 484 in 1983 to three cases recorded in 2006. On February 3rd 2006 the last case of terrestrial rabies in Germany was detected in a fox near the town of Mainz, Rhineland-Palatinate. In 2008, ORV ceased after 25 years and Germany was officially declared as free from terrestrial rabies. The German rabies eradication programme did cost approximately 100 million euro of which 37 million euro were covered by the EU. For the future, efforts should focus on maintaining a rabies free status by implementing measures to prevent reintroduction of terrestrial rabies from endemic countries.     

狂犬病疫苗研究进展

狂犬病是感染中枢神经系统的一种人兽共患的急性接触性传染病,由狂犬病病毒(Rabies virus,RV)引起,病毒粒子聚集形成胞浆内包含体,只在神经细胞胞浆和蒲肯野氏细胞里存在.RV可分成4个血清型和2个尚待定型的病毒株.随着RV血清型变异,目前人用和动物用狂犬病疫苗毒株已不能提供针对所有种类RV的有效保护,为了对狂犬病及其研究进展有一个全面的认识,该文主要对RV病原以及狂犬病疫苗等方面的研究进展进行了综述.     

The Epidemiological Importance of Bats in the Transmission of Rabies to Dogs and Cats in the State of São Paulo,Brazil, Between 2005 and 2014

In Brazil, rabies control in dogs and cats was pioneered by the state of São Paulo with the adoption of the Pan American Health Organization recommendations for prophylaxis and control, which led to a reduction in rabies cases from 1994 onwards. As a result of these measures, the rabies virus (RABV) genetic lineage associated with dogs has not been found in the state since 1998, and all the cases in domestic animals reported since then have been caused by bat‐associated lineages of RABV. In the light of this, this study sought to investigate rabies cases in dogs and cats in the state of São Paulo between 2005 and 2014 and identify the associated transmission cycles by characterizing the RABV lineages responsible for these cases. Nine samples from dogs (n = 5) and from cats (n = 4) were collected between 2005 and 2014. The tenth animal, a rabid cat, was analysed by a different laboratory. The N gene nucleotide sequences obtained were analysed with the neighbor‐joining algorithm and Kimura 2‐parameter model using the MEGA 6 program. Phylogenetic analysis revealed that the genetic lineages identified in all the samples were those circulating in Brazilian bats. The findings of this study demonstrate that bats play an important role in the transmission of rabies to domestic animals in São Paulo state and that emphasis should be placed on the implementation of public policies to support surveillance of chiropterans for rabies.     

Epizootic of rabies in raccoons in Maryland from 1981 to 1987.

The epizootic of rabies in raccoons entered Maryland in 1981 and systematically moved through the state affecting raccoons in all counties except those of the lower Eastern Shore. A precoded surveillance form was provided to all county and city health departments and data were requested for each animal head submitted for testing for the year 1985. The disease persisted and, in 1987, all counties previously reporting rabies in raccoons also had documented cases in other species. The incidence of rabies in raccoons increased in late winter and peaked in March. Most human exposures occurred during daylight hours and in private yards. Agricultural areas were similarly affected by rabid animals. Analysis of vaccination status of animals exposed to rabid animals gave estimations of statewide vaccination rates for dogs (70%) and cats (28%). The danger of rabies in cats was emphasized by the large number of animals exposed by each rabid cat. The spillover of rabies in raccoons to other species persisted in all jurisdiction through 1992, with periodic upsurges of disease at 3- to 4-year intervals as the raccoon population is replenished. Rabies was not diagnosed in any human beings.