Dog Rabies Virus Research Articles

Developments in human rabies prophylaxis.

Rabies is entirely preventable. All deaths are the result of failed prophylaxis. Rabies encephalomyelitis has never been reported in anyone who received both pre-exposure vaccination and a post-exposure booster. Awareness of the risk of contact with rabid animals is crucial. A lack of basic knowledge and the inaccessibility of expensive rabies vaccines can discourage patients bitten by suspected rabid animals from seeking prompt post-exposure prophylaxis. Similarly, people working with mammals, residents of areas where dog rabies is endemic, travellers, and others at risk often fail to take advantage of pre-exposure prophylaxis. However, since human infection by a dog rabies virus has always proved fatal in unvaccinated patients, there is understandable reluctance to accept any change in vaccine protocols. The intramuscular route of delivery is wasteful and the current, low-dose intradermal (ID) regimen is not always economical or universally trusted. A new, one-week ID regimen, using less vaccine, injected at multiple sites, and involving two clinic visits, could increase the accessibility of highly immunogenic prophylaxis and reduce the prohibitive cost. The recent 2018 World Health Organization recommendations for rabies prophylaxis are included.

Landscape attributes governing local transmission of an endemic zoonosis: Rabies virus in domestic dogs.

Landscape heterogeneity plays an important role in disease spread and persistence, but quantifying landscape influences and their scale dependence is challenging. Studies have focused on how environmental features or global transport networks influence pathogen invasion and spread, but their influence on local transmission dynamics that underpin the persistence of endemic diseases remains unexplored. Bayesian phylogeographic frameworks that incorporate spatial heterogeneities are promising tools for analysing linked epidemiological, environmental and genetic data. Here, we extend these methodological approaches to decipher the relative contribution and scale‐dependent effects of landscape influences on the transmission of endemic rabies virus in Serengeti district, Tanzania (area ~4,900 km2). Utilizing detailed epidemiological data and 152 complete viral genomes collected between 2004 and 2013, we show that the localized presence of dogs but not their density is the most important determinant of diffusion, implying that culling will be ineffective for rabies control. Rivers and roads acted as barriers and facilitators to viral spread, respectively, and vaccination impeded diffusion despite variable annual coverage. Notably, we found that landscape effects were scale‐dependent: rivers were barriers and roads facilitators on larger scales, whereas the distribution of dogs was important for rabies dispersal across multiple scales. This nuanced understanding of the spatial processes that underpin rabies transmission can be exploited for targeted control at the scale where it will have the greatest impact. Moreover, this research demonstrates how current phylogeographic frameworks can be adapted to improve our understanding of endemic disease dynamics at different spatial scales.

Antibodies against rabies virus in dogs with and without history of vaccination in Santa Maria - RS - Brazil

ABSTRACT: The present study investigated the frequency and magnitude of neutralizing antibodies to rabies virus (RABV) in dogs with and without historic of vaccination in Santa Maria/RS. Group A included serum samples from 440 dogs with recent historic of vaccination against rabies, obtained during the 2015 rabies vaccination campaign. Group B included 300 serum samples from dogs submitted to the Veterinary Hospital of the Universidade Federal de Santa Maria in 2015, whose historic of rabies vaccination was unknown. Serum samples were submitted to the rapid fluorescent focus inhibition test (RFFIT) to detect neutralizing antibodies against RABV. In group A, 70.6% (310/440) of the samples had neutralizing antibody titers ≥0.5 international units per milliliter (IU mL-1), considered an indicative of protection against rabies by the World Health Organization. However, approximately 30% of the dogs did not contain antibodies in adequate levels. In group B, 42.3% (127/300) of the samples contained neutralizing antibody titers ≥0.5IU mL-1 and 57.7% (173/300) were negative or contained titers below of the value considered immunized. These results demonstrate that an important proportion of vaccinated dogs (~30%) did not develop adequate antibody levels, mainly those receiving a single vaccine dose. Serologic testing of animals with unknown historic of vaccination revealed relatively low vaccine coverage in the general dog population. Thus, reformulation of immunization strategies - especially the recommendation of a boost vaccination 30 days after the primary dose - and extension of vaccination campaigns are necessary to reach adequate levels and coverage of immunity against RABV in the canine population.

Genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host.

Host shift events play an important role in epizootics as adaptation to new hosts can profoundly affect the spread of the disease and the measures needed to control it. During the late 1990s, an epizootic in Turkey resulted in a sustained maintenance of rabies virus (RABV) within the fox population. We used Bayesian inferences to investigate whole genome sequences from fox and dog brain tissues from Turkey to demonstrate that the epizootic occurred in 1997 (±1 year). Furthermore, these data indicated that the epizootic was most likely due to a host shift from locally infected domestic dogs, rather than an incursion of a novel fox or dog RABV. No evidence was observed for genetic adaptation to foxes at consensus sequence level and dN/dS analysis suggested purifying selection. Therefore, the deep sequence data were analysed to investigate the sub-viral population during a host shift event. Viral heterogeneity was measured in all RABV samples; viruses from the early period after the host shift exhibited greater sequence variation in comparison to those from the later stage, and to those not involved in the host shift event, possibly indicating a role in establishing transmission within a new host. The transient increase in variation observed in the new host species may represent virus replication within a new environment, perhaps due to increased replication within the CNS, resulting in a larger population of viruses, or due to the lack of host constraints present in the new host reservoir.

Elimination of Dog-Mediated Human Rabies Deaths by 2030: Needs Assessment and Alternatives for Progress Based on Dog Vaccination.

Rabies imposes a substantial burden to about half of the world population. The World Health Organization (WHO), World Organization for Animal Health, and the Food and Agriculture Organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. This could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. Here, we focused on the resources needed for the elimination of dog rabies virus by 2030. Drawing from multiple datasets, including national dog vaccination campaigns, rabies literature, and expert opinion, we developed a model considering country-specific current dog vaccination capacity to estimate the years and resources required to achieve dog rabies elimination by 2030. Resources were determined based on four factors: (a) country development status, (b) dog vaccination costs, (c) dog rabies vaccine availability, and (d) existing animal health workers. Our calculations were based on the WHO's estimate that vaccinating 70% of the dog population for seven consecutive years would eliminate rabies. If dog rabies vaccine production remains at 2015 levels, we estimate that there will be a cumulative shortage of about 7.5 billion doses to meet expected demand to achieve dog rabies elimination. We estimated a present cost of $6,300 million to eliminate dog rabies in all endemic countries, equivalent to a $3,900 million gap compared to current spending. To eliminate dog rabies, the vaccination workforce may suffice if all public health veterinarians in endemic countries were to dedicate 3 months each year to dog rabies vaccination. We discuss implications of potential technology improvements, including population management, vaccine price reduction, and increases in dog-vaccinating capacities. Our results highlight the resources needed to achieve elimination of dog-mediated human rabies deaths by 2030. As exemplified by multiple successful disease elimination efforts, one size does not fit all. We suggest pragmatic and feasible options toward global dog rabies elimination by 2030, while identifying several benefits and drawbacks of specific approaches. We hope that these results help stimulate and inform a necessary discussion on global and regional strategic planning, resource mobilization, and continuous execution of rabies virus elimination.

Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts.

The natural evolution of rabies virus (RABV) provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. Using 321 genome sequences spanning an unprecedented diversity of RABV, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. Two major phylogenetic groups, bat-related RABV and dog-related RABV, experiencing markedly different evolutionary dynamics were identified. While no correlation between time and genetic divergence was found in bat-related RABV, the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. Subsequent molecular clock dating indicated that dog-related RABV likely underwent a rapid global spread following the intensification of intercontinental trade starting in the 15th century. Strikingly, although dog RABV has jumped to various wildlife species from the order Carnivora, we found no clear evidence that these host-jumping events involved adaptive evolution, with RABV instead characterized by strong purifying selection, suggesting that ecological processes also play an important role in shaping patterns of emergence. However, specific amino acid changes were associated with the parallel emergence of RABV in ferret-badgers in Asia, and some host shifts were associated with increases in evolutionary rate, particularly in the ferret-badger and mongoose, implying that changes in host species can have important impacts on evolutionary dynamics.

Revealing the Micro-scale Signature of Endemic Zoonotic Disease Transmission in an African Urban Setting.

The development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. Taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the National Reference Centre for Rabies of Bangui, the capital city of Central African Republic, we used a combination of mathematical modeling and phylogenetic analysis to determine the spatiotemporal dynamics of rabies in domestic dogs as well as the frequency of extinction and introduction events in an African city. We show that although dog rabies virus (RABV) appears to be endemic in Bangui, its epidemiology is in fact shaped by the regular extinction of local chains of transmission coupled with the introduction of new lineages, generating successive waves of spread. Notably, the effective reproduction number during each wave was rarely above the critical value of 1, such that rabies is not self-sustaining in Bangui. In turn, this suggests that rabies at local geographic scales is driven by human-mediated dispersal of RABV among sparsely connected peri-urban and rural areas as opposed to dispersion in a relatively large homogenous urban dog population. This combined epidemiological and genomic approach enables development of a comprehensive framework for understanding disease persistence and informing control measures, indicating that control measures are probably best targeted towards areas neighbouring the city that appear as the source of frequent incursions seeding outbreaks in Bangui.

Genetic Mapping of Rabies Virus in Dogs as a Basis for Disease Control

The purpose of this study was to determine the genetic characteristics of rabies virus based on phylogenetic relationship among rabies virus in various regions in Indonesia. The amino acid sequence of the nucleoprotein gene of rabies virus isolate from Banten (RV/Banten01/dog/2007),Makasar (RV/MKS-26/dog/2010), Bukit Tinggi (RV/BKT-52/dog/2009 and RV/BKT-58/dog/2009), Medan (RV/Medan27/dog/2007)andBali(RV/Bali-1/dog/2009;RV/Bali-2/dog/2009;RV/Bali-3/dog/2009),Indonesiawasdetermined.TheseisolatesshowedahighdegreeofhomologyamongIndonesianisolateswhichreached100%.Meanwhile,thelevelofhomologybetweenrabiesvirusisolatesfromcatsrabiesvirusisolatesfromdogsreached97%.ResultsofphylogeneticanalysisusingtheaminoacidsequencesoftheNgenesshowedthatallofIndonesianrabiesvirusisolateswerecloselyrelatedtorabiesvirusesfromChinathanthosefromThailand,Laos,Burma,andVietnamwhichgeograficallycloser to Indonesia. Data obtained from the phylogenetic analysis is expected to trace the source of rabies spread and thepossibility to create a vaccines which more suitable with rabies virus that spreads in Indonesia. Based on the phylogenetic relationship analysisusing the amino acid sequence of the rabies virus N protein gene showed that all of rabies virus isolated from Indonesian regions share a highhomology with others ranging from 97-100%..Key words: sequencing, rabies, nucleoprotein gene (N), homology

Molecular genetic characterization of rabies virus glycoprotein gene sequences from rabid dogs in Bangkok and neighboring provinces in Thailand, 2013-2014.

Because of its association with dogs, rabies virus (RABV) is still endemic in Thailand, where it is a serious public health problem. The genetic characterization of RABV in Thailand is limited. Therefore, in this study, we investigated the molecular epidemiology and genetic diversity of RABV in the endemic area. Viral RNA from 48 brain specimens from rabid dogs, collected in Bangkok and seven neighboring provinces in 2013-2014, was extracted and sequenced. The complete rabies glycoprotein (G) gene sequences (1575 nt) were aligned, and a phylogenetic analysis was performed using the maximum-likelihood method. All of the Thai rabies virus isolates belonged to lyssavirus genotype 1 and clustered in the same lineage as isolates from South East Asia (SEA) and China. The Thai rabies virus isolates formed two distinct clades, THA-1 and THA-2. Clade THA-1 was the predominant clade and could be divided into two subclades, THA-1A and THA-1B. Clade THA-2 was closely associated with human Thai isolates collected in a previous study. The overall mean rate of evolution based on the G gene was approximately 1.56 × 10(-4) substitutions/site/year. The genetic identities among the isolates from Thailand and other SEA countries were >88.4 % at the nucleotide sequence level and 95 % at the amino acid sequence level. The deduced amino acid sequences of the G proteins of the RABV isolates were compared. A single amino acid change (N194T) in subclade THA-1A distinguished the Thai RABV isolates from other RABV isolates. Our results suggest that these Thai dog RABV isolates share a common ancestor with the RABV isolates circulating in the endemic regions of SEA countries and China. Furthermore, there were strong genetic relationship to RABV from Cambodia, Vietnam and Laos. These data extend our understanding of the relatedness and genetic variation of RABV in Thailand.

Safety and immunogenicity of recombinant rabies virus (ERAGS) in mice and raccoon dogs.

PurposeThe development of a genetically modified live rabies vaccine applicable to wild raccoon dogs is necessary for the eradication of rabies in Korea. Thus, we constructed a recombinant rabies virus (RABV) called the ERAGS strain, using a reverse genetic system and evaluated its safety and efficacy in mice and its safety and immunogenicity in raccoon dogs.Materials and MethodsERAGS, which has Asn194Ser and Arg333Glu substitutions in the glycoprotein, was constructed using site-directed mutagenesis. Mice were inoculated with the ERAGS strain (either 105.0 or 107.0 FAID50/mL) via intramuscular (IM) or intracranial injections and then challenged with a virulent RABV. Raccoon dogs were administered the ERAGS strain (108.0 FAID50/mL) either orally or via the IM route and the immunogenicity of the strain was evaluated using fluorescent antibody virus neutralization tests.ResultsThe ERAGS strain inoculated into murine neuroblastoma cells reached 107.8 FAID50/mL at 96-hour post-inoculation. The virus was not pathogenic and induced complete protection from virulent RABV in immunized 4- and 6-week-old mice. Korean raccoon dogs immunized with the ERAGS strain via IM or oral route were also safe from the virus and developed high titer levels (26.4-32.8 IU/mL) of virus-neutralizing antibody (VNA) at 4 weeks post-inoculation.ConclusionThe ERAGS RABV strain was effectively protective against rabies in mice and produced a high VNA titer in raccoon dogs.

Evidence of two distinct phylogenetic lineages of dog rabies virus circulating in Cambodia

This first extensive retrospective study of the molecular epidemiology of dog rabies in Cambodia included 149 rabies virus (RABV) entire nucleoprotein sequences obtained from 1998–2011. The sequences were analyzed in conjunction with RABVs from other Asian countries. Phylogenetic reconstruction confirmed the South-East Asian phylogenetic clade comprising viruses from Cambodia, Vietnam, Thailand, Laos and Myanmar. The present study represents the first attempt to classify the phylogenetic lineages inside this clade, resulting in the confirmation that all the Cambodian viruses belonged to the South-East Asian (SEA) clade. Three distinct phylogenetic lineages in the region were established with the majority of viruses from Cambodia closely related to viruses from Thailand, Laos and Vietnam, forming the geographically widespread phylogenetic lineage SEA1. A South-East Asian lineage SEA2 comprised two viruses from Cambodia was identified, which shared a common ancestor with RABVs originating from Laos. Viruses from Myanmar formed separate phylogenetic lineages within the major SEA clade. Bayesian molecular clock analysis suggested that the time to most recent common ancestor (TMRCA) of all Cambodian RABVs dated to around 1950. The TMRCA of the Cambodian SEA1 lineage was around 1964 and that of the SEA2 lineage was around 1953. The results identified three phylogenetically distinct and geographically separated lineages inside the earlier identified major SEA clade, covering at least five countries in the region. A greater understanding of the molecular epidemiology of rabies in South-East Asia is an important step to monitor progress on the efforts to control canine rabies in the region.

The establishment of immune protection against a CNS viral challenge (VIR1P.1157)

Abstract The neuroinvasive rabies virus (RABV) requires CD4 T and B cell infiltration into CNS tissue and local production of virus neutralizing antibody (VNA) in order to be successfully cleared. This occurs during attenuated but not in wild-type dog RABV infection. Effective protection against a CNS challenge with dog RABV is only established by a vaccination regimen that delivers RABV-specific immune effectors to the CNS. Mice that recover from an attenuated RABV of the CNS are protected long term against subsequent CNS challenge by pathogenic dog RABV, whereas long term protection is not seen in mice that received attenuated RABV in the gastrocnemius. This difference is likely to be due to the increased formation of memory like cells which remain in the brain following a direct CNS vaccination, resulting in a more robust and effective response during CNS challenge. Since the blood-brain barrier (BBB) evidently remains intact during dog RABV infection, it is likely that immune memory cells capable of reactivating to produce VNA upon challenge must be resident in the CNS rather than enter from the periphery. In support of this concept, adoptive transfer of RABV immune cells fails to protect against a dog RABV infection of the CNS. A robust CNS immune response during initial vaccination appears to be the only effective way to establish long term protection against a pathogenic RABV infection that reaches the CNS.

Factors Impacting the Control of Rabies.

Rabies is a classical zoonosis that has been known to man for ages. The disease can be caused by several viral species in the Lyssavirus genus, but the type species, rabies virus (RABV), is by far the most important from a zoonosis perspective. The extreme neurotropism of RABV and the evolutionarily conserved elements and structures of the mammalian brain suggest that this virus evolved an ultimate niche for replication, simultaneously exploiting classical social behavior of a wide diversity of hosts among the chiropters and carnivores. There is substantial evidence that RABV originated in bats and later switched hosts to yield globally disseminated canine rabies. Following the revolutionary work of Louis Pasteur, control and elimination of dog rabies was achieved in Europe, but widespread colonial introduction of European strains of dog RABV to other parts of the world occurred. Thus, dog rabies spread rapidly in the 1900s, and today the vast majority of the tens of thousands of annual human rabies cases stem from dog rabies, which has become endemic in the entire developing world. The fact that human rabies is preventable, through control in the dog reservoir on one hand and through effective prophylaxis in cases of exposure on the other hand, is an indictment of public health strategies and practices. This article discusses some of the drivers that have contributed to the recurrent neglect of rabies in the modern world, as well as evolving One Health-based rabies control partnerships and initiatives that have been progressive, productive, and promising of true global benefits.

Presence of Virus Neutralizing Antibodies in Cerebral Spinal Fluid Correlates with Non-Lethal Rabies in Dogs

BackgroundRabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Methodology/Principal FindingsNon-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico) correlates with the presence of high level of virus neutralizing antibodies (VNA) in the cerebral spinal fluid (CSF) and mild immune cell accumulation in the central nervous system (CNS). By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Conclusions/SignificanceNon-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

Raccoons (Procyon lotor) in Germany as potential reservoir species for Lyssaviruses

Raccoons can be found almost everywhere in Germany since their first successful introduction in 1934. Although the animal is a well-known reservoir species for rabies in the USA, during the last European fox rabies epizootic, only a few rabid raccoons were reported from Germany. In recent years, the raccoon population density has increased tremendously, especially in (semi) urban settings. Presently, Germany is free of terrestrial wildlife rabies. To assess the potential risk that the raccoon population in Germany could act as a reservoir species upon reemergence of rabies, the susceptibility of the local raccoon population was investigated. Wild-caught animals were inoculated with the most likely lyssavirus variants to infect the local population. It was shown that the raccoons were fully susceptible for a dog and raccoon rabies virus isolate. Also, five of six raccoons inoculated with a fox rabies virus isolate showed clinical signs. However, none of the raccoons infected with European Bat Lyssavirus type 1 succumbed to rabies; meanwhile, all these raccoons seroconverted. It is concluded that the highest risk for the raccoon population in Germany to become infected with lyssaviruses is through the importation of rabies infected dogs.

Serologic Survey of Rabies Virus, Canine Distemper Virus and Parvovirus in Wild Raccoon Dogs (Nyctereutes procyonoides koreensis) in Korea

Oral rabies vaccination (ORV) program for the wild animals in rabies risk regions of Korea has been conducted since 2000. Evaluation of ORV program under field condition and information concerning the incidence of exposure to canine distemper and canine parvovirus (CPV) are needed in wild raccoon dogs (Nyctereutes procyonoides koreensis). Ninety four sera of wild raccoon dogs were screened for antibodies against rabies, canine distemper virus (CDV) and CPV in Korea. The overall prevalence of antibodies against rabies virus (RABV), CDV and CPV in wild raccoon dogs was 35.1%, 89.4% and 24.5%, respectively. Comparisons of sero-prevalences of RABV, CDV and CPV were assayed in two regions (Gyeonggi-do and Gangwon-do). The Gyeonggi-do (36.4%) showed higher sero-positive rate against CPV than Gangwon-do (20.8%). In contrast, Gangwon-do (41.7% and 97.2%) showed higher sero-positive rates against RABV and CDV than Gyeonggi-do (13.6% and 63.6%). These results indicate that there was severe circulation of CDV and CPV among wild raccoon dogs in the two regions of Korea. Furthermore, raccoon dogs showing a protective antibody titer (0.5 IU/ml) were 15.9%, suggesting that new rabies control program such as trap-vaccination-release (TVR) should be launched urgently in rabies risk regions.

Dog rabies in Africa: genetic analysis, geographic structure and dynamics

This work illustrates the studies that have provided a better understanding of the genetic and geographic structure of dog rabies virus and the dynamics of rabies in domestic dogs in Africa, the second largest continent most affected by this disease. These investigations are a key element to control the disease and identify effective strategies for eliminating rabies locally, nationally as well as internationally and could drastically reduce human deaths caused by this disease. They also allow for the first time the investigation of the role of humans in the canine rabies virus spreading.

Newcastle disease virus-vectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats.

Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10⁹·⁸ 50% egg infective doses (EID₅₀)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10⁸·³ EID₅₀ completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.

Phylodynamics and Human-Mediated Dispersal of a Zoonotic Virus

Understanding the role of humans in the dispersal of predominately animal pathogens is essential for their control. We used newly developed Bayesian phylogeographic methods to unravel the dynamics and determinants of the spread of dog rabies virus (RABV) in North Africa. Each of the countries studied exhibited largely disconnected spatial dynamics with major geo-political boundaries acting as barriers to gene flow. Road distances proved to be better predictors of the movement of dog RABV than accessibility or raw geographical distance, with occasional long distance and rapid spread within each of these countries. Using simulations that bridge phylodynamics and spatial epidemiology, we demonstrate that the contemporary viral distribution extends beyond that expected for RABV transmission in African dog populations. These results are strongly supportive of human-mediated dispersal, and demonstrate how an integrated phylogeographic approach will turn viral genetic data into a powerful asset for characterizing, predicting, and potentially controlling the spatial spread of pathogens.

Evolutionary history of dog rabies in Brazil

Although dogs are considered to be the principal transmitter of rabies in Brazil, dog rabies had never been recorded in South America before European colonization. In order to investigate the evolutionary history of dog rabies virus (RABV) in Brazil, we performed a phylogenetic analysis of carnivore RABV isolates from around the world and estimated the divergence times for dog RABV in Brazil. Our estimate for the time of introduction of dog RABV into Brazil was the late-19th to early-20th century, which was later than the colonization period but corresponded to a period of increased immigration from Europe to Brazil. In addition, dog RABVs appeared to have spread to indigenous animals in Brazil during the latter half of the 20th century, when the development and urbanization of Brazil occurred. These results suggest that the movement of rabid dogs, along with human activities since the 19th century, promoted the introduction and expansion of dog RABV in Brazil.