Transmission Of Canine Distemper Virus Research Articles

The First Report and Phylogenetic Analysis of Canine Distemper Virus in Cerdocyon thous from Colombia.

Simple SummaryCanine distemper virus (CDV) is the etiological agent of a highly frequent viral disease of domestic and wild carnivores. It poses a threat for the conservation of endangered species. Our aim was to assess the presence and phylogenetic characterization of CDV from naturally infected Crab-eating Fox (Cerdocyon thous) from Colombia. We confirm for the first time the circulation of CDV South America/North America-4 Lineage in Crab-eating Fox. Our results are crucial for the understanding of the interspecies transmission of CDV in the domestic/wild interface and for the prevention and control of such an important multi-host pathogen.Canine distemper virus (CDV) is the etiological agent of a highly prevalent viral infectious disease of domestic and wild carnivores. This virus poses a conservation threat to endangered species worldwide due to its ability to jump between multiple species and produce a disease, which is most often fatal. Although CDV infection has been regularly diagnosed in Colombian wildlife, to date the molecular identity of circulating CDV lineages is currently unknown. Our aim was to evaluate the presence and phylogenetic characterization of CDV detected in samples from naturally infected Cerdocyon thous from Colombia. We sequenced for the first time the CDV infecting wildlife in Colombia and demonstrated the presence of South America/North America-4 Lineage with a higher relationship to sequences previously reported from domestic and wild fauna belonging to the United States of America. Our results are crucial for the understanding of the interspecies transmission of CDV in the domestic/wild interface and for the prevention and control of such an important multi-host pathogen.

Multiple Receptors Involved in Invasion and Neuropathogenicity of Canine Distemper Virus: A Review.

The canine distemper virus (CDV) is a morbillivirus that infects a broad range of terrestrial carnivores, predominantly canines, and is associated with high mortality. Similar to another morbillivirus, measles virus, which infects humans and nonhuman primates, CDV transmission from an infected host to a naïve host depends on two cellular receptors, namely, the signaling lymphocyte activation molecule (SLAM or CD150) and the adherens junction protein nectin-4 (also known as PVRL4). CDV can also invade the central nervous system by anterograde spread through olfactory nerves or in infected lymphocytes through the circulation, thus causing chronic progressive or relapsing demyelination of the brain. However, the absence of the two receptors in the white matter, primary cultured astrocytes, and neurons in the brain was recently demonstrated. Furthermore, a SLAM/nectin-4-blind recombinant CDV exhibits full cell-to-cell transmission in primary astrocytes. This strongly suggests the existence of a third CDV receptor expressed in neural cells, possibly glial cells. In this review, we summarize the recent progress in the study of CDV receptors, highlighting the unidentified glial receptor and its contribution to pathogenicity in the host nervous system. The reviewed studies focus on CDV neuropathogenesis, and neural receptors may provide promising directions for the treatment of neurological diseases caused by CDV. We also present an overview of other neurotropic viruses to promote further research and identification of CDV neural receptors.

Drivers of canine distemper virus exposure in dogs at a wildlife interface in Janos, Mexico.

BackgroundHuman population expansion has increased the contact between domestic animals and wildlife, thereby increasing the transmission of infectious diseases including canine distemper virus (CDV). Here, we investigated the risk factors associated with CDV exposure in domestic and wild carnivores from the Janos Biosphere Reserve (JBR), Mexico.MethodsA cross‐sectional household questionnaire study was performed in four rural towns to investigate the risk factors associated with the presence of CDV in domestic and wild carnivores from the JBR, Mexico. In addition, we tested serum samples from 70 dogs and three wild carnivores, including one bobcat (Lynx rufus), one striped skunk (Mephitis mephitis) and one gray fox (Urocyon cinereoargenteus) for CDV antibodies using immunochromatographic and viral neutralization assays.ResultsOverall, 62% of domestic dogs were seropositive for CDV, and the presence of antibodies was significantly higher in free‐roaming owned dogs than dogs with restricted movement. Among the wild carnivores, only the bobcat was seropositive. The rate of vaccination against CDV in dogs was low (7%), and there was a high rate of direct interactions between domestic dogs and wild carnivores.ConclusionOur serological assays show that CDV is circulating in both domestic dogs and wild carnivores, suggesting cross‐species transmission. Our finding of low vaccination rates, high number of unrestrained owned dogs and direct interactions between wildlife and domestic animals reported in the region may be perpetuating the high prevalence of the virus and increasing the risk of CDV transmission between wild and domestic carnivores. Therefore, long‐term longitudinal studies are recommended in order to monitor infectious diseases at the domestic‐wildlife interface in this highly biodiverse region.

Canine distemper in Nepal's Annapurna Conservation Area - Implications of dog husbandry and human behaviour for wildlife disease.

Dogs are often commensal with human settlements. In areas where settlements are adjacent to wildlife habitat, the management of dogs can affect risk of spillover of disease to wildlife. We assess dog husbandry practices, and measure the prevalence of Canine Distemper Virus (CDV) in dogs, in 10 villages in Nepal's Annapurna Conservation Area (ACA), an important region for Himalayan wildlife. A high proportion (58%) of owned dogs were allowed by their owners to roam freely, and many village dogs originated from urban areas outside the region. CDV antibodies, indicating past exposure, were detected in 70% of dogs, and 13% were positive for P-gene, suggesting current circulation of CDV. This is the first detection of canine distemper virus in a National Park in Nepal Himalaya. Dogs were generally in good condition, and none exhibited clinical signs of CDV infection, which suggests that infections were asymptomatic. CDV exposure varied with village location and age of dogs, but this variation was minor, consistent with high rates of movement of dogs across the region maintaining high seroprevalence. Residents reported the occurrence of several species of wild carnivores in or close to villages. These results suggest a high potential for transmission of CDV from village dogs to wild carnivores in ACA. We suggest that control of dog immigration, along with vaccination and neutering of dogs could mitigate the risk of CDV spillover into wild carnivore populations.

Evolution and Interspecies Transmission of Canine Distemper Virus-An Outlook of the Diverse Evolutionary Landscapes of a Multi-Host Virus.

Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus Morbillivirus within the Paramyxoviridae family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of mammals. Due to the high morbidity and mortality rates and broad host range, understanding the epidemiology of CDV is not only important for its control in domestic animals, but also for the development of reliable wildlife conservation strategies. The present review aims to give an outlook of the multiple evolutionary landscapes and factors involved in the transmission of CDV by including epidemiological data from multiple species in urban, wild and peri-urban settings, not only in domestic animal populations but at the wildlife interface. It is clear that different epidemiological scenarios can lead to the presence of CDV in wildlife even in the absence of infection in domestic populations, highlighting the role of CDV in different domestic or wild species without clinical signs of disease mainly acting as reservoirs (peridomestic and mesocarnivores) that are often found in peridomestic habits triggering CDV epidemics. Another scenario is driven by mutations, which generate genetic variation on which random drift and natural selection can act, shaping the genetic structure of CDV populations leading to some fitness compensations between hosts and driving the evolution of specialist and generalist traits in CDV populations. In this scenario, the highly variable protein hemagglutinin (H) determines the cellular and host tropism by binding to signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors of the host; however, the multiple evolutionary events that may have facilitated CDV adaptation to different hosts must be evaluated by complete genome sequencing. This review is focused on the study of CDV interspecies transmission by examining molecular and epidemiological reports based on sequences of the hemagglutinin gene and the growing body of studies of the complete genome; emphasizing the importance of long-term multidisciplinary research that tracks CDV in the presence or absence of clinical signs in wild species, and helping to implement strategies to mitigate the infection. Integrated research incorporating the experience of wildlife managers, behavioral and conservation biologists, veterinarians, virologists, and immunologists (among other scientific areas) and the inclusion of several wild and domestic species is essential for understanding the intricate epidemiological dynamics of CDV in its multiple host infections.

Landscape Structures Affect Risk of Canine Distemper in Urban Wildlife

Urbanization rapidly changes landscape structure worldwide, thereby enlarging the human-wildlife interface. The emerging urban structures should have a key influence on the spread and distribution of wildlife diseases such as canine distemper, by shaping density, distribution and movements of wildlife. However, little is known about the role of urban structures as proxies for disease prevalence. To guide management, especially in densely populated cities, assessing the role of landscape structures in hampering or promoting disease prevalence is thus of paramount importance. Between 2008 and 2013, two epidemic waves of canine distemper hit the urban red fox (Vulpes vulpes) population of Berlin, Germany. The directly transmitted canine distemper virus (CDV) causes a virulent disease infecting a range of mammals with high host mortality, particularly in juveniles. We extracted information about CDV serological state (seropositive or seronegative), sex and age for 778 urban fox carcasses collected by the state laboratory Berlin Brandenburg. To assess the impact of urban landscape structure heterogeneity (e.g. richness) and shares of green and grey infrastructures at different spatial resolutions (areal of 28 ha, 78 ha, 314 ha) on seroprevalence we used Generalized Linear Mixed-Effects Models with binomial distributions. Our results indicated that predictors derived at a 28 ha resolution were most informative for describing landscape structures effects (AUC = 0.92). The probability to be seropositive decreased by 66% (0.6 to 0.2) with an increasing share of grey infrastructure (40 % to 80 %), suggesting that urbanization might hamper CDV spread in urban areas, owing to a decrease in host density (e.g. less foxes or raccoons) or an absence of wildlife movement corridors in strongly urbanized areas. However, less strongly transformed patches such as close-to-nature areas in direct proximity to water bodies were identified as high risk areas for CDV transmission. Therefore, surveillance and disease control actions targeting urban wildlife or human-wildlife interactions should focus on such areas. The possible underlying mechanisms may be increased isolation, the absence of alternative hosts or an abiotic environment, all impairing the ability of CDV to persist without a host.

Isolation and phylogenetic analysis of canine distemper virus among domestic dogs in Vietnam.

Canine distemper virus (CDV) is one of the most serious pathogens found in many species of carnivores, including domestic dogs. In this study, hemagglutinin (H) genes were detected in five domestic Vietnamese dogs with diarrhea, and two CDVs were successfully isolated from dogs positive for H genes. The complete genome of one isolate, CDV/dog/HCM/33/140816, was determined. Phylogenetic analysis showed that all Vietnamese CDVs belonged to the Asia-1 genotype. In addition, the H proteins of Vietnamese CDV strains were the most homologous to those of Chinese CDVs (98.4% to 99.3% identity). These results indicated that the Asia-1 genotype of CDV was the predominant genotype circulating among the domestic dog population in Vietnam and that transboundary transmission of CDV has occurred between Vietnam and China.

Serosurvey of canine distemper virus and canine parvovirus in wild canids and domestic dogs at the rural interface in the Coquimbo Region, Chile

Our goal was to investigate demographic and ecological factors influencing canine distemper virus (CDV) and canine parvovirus (CPV) infection in domestic dogs to wild canids (foxes) in rural areas of the Coquimbo Region, Chile. Cross-sectional dog and fox serological sampling was conducted in seven rural sites from 2005 to 2006. Additionally, the relative abundance of each fox species was determined using a scent-station method. Overall, 249 dog-owning households were interviewed across the seven sites, and blood samples collected and analysed from a total of 267 domestic dogs and 33 wild foxes. CDV seroprevalences were similar in dogs (51 %) and foxes (42 %), whilst dogs had a higher CPV seroprevalence than foxes (77 and 49 %, respectively). Foxes were more abundant in the lowlands in areas where CDV prevalence was highest in domestic dogs. We hypothesise that cross-species transmission of CDV is likely to be occurring most frequently in lowland areas, and that wildlife in these areas may be at risk from spillover transmission from domestic dogs.

A model-based approach for investigation and mitigation of disease spillover risks to wildlife: Dogs, foxes and canine distemper in central India

Multi-host pathogens can pose a serious conservation threat when free-ranging domestic animal populations occur alongside susceptible populations of wild species. An example is canine distemper virus (CDV), which can occur at high prevalence in domestic dog (Canis familiaris) populations from which it may be transmitted (spillover) into wild carnivore populations. Effective management of such disease threats is hindered by our limited understanding of the the dynamics of interspecific CDV transmission in natural settings. We used a modeling approach to better understand CDV spillover threats to wild Indian foxes (Vulpes bengalensis) occurring in a protected grassland habitat in central India. An agent-based stochastic simulation model was built, and parameterized with data from ecological and epidemiological studies. Based on the sensitivity analyses of the model, the CDV incidence rate in dogs was most influenced by the proportion of roamer dogs in the dog population. The CDV incidence rate in dogs was also sensitive to the CDV introduction frequency in the dog population. The proportion of roamer dogs in the dog population also influenced the number of CDV spillover events. The basic reproductive number (R0) for CDV in the model fox population was 0.85, indicating that CDV could not be independently sustained in the fox population. We used the model to explore potential management strategies to mitigate the risk of CDV spillover. Vaccination of local dog populations was an ineffective disease control strategy, while fox vaccination was highly effective. Interventions potentially resulting in lower contact rates between dogs and foxes, like reduction in village dog density and restricting dog movements in fox habitat, implemented in a sustained and integrated manner would be most effective in mitigating disease threats to foxes. Such modeling approaches can be used to better understand disease threats for other species of management concern, and to contrast potential management interventions.

Invasive American Mink: Linking Pathogen Risk Between Domestic and Endangered Carnivores

Infectious diseases, in particular canine distemper virus (CDV), are an important threat to the viability of wild carnivore populations. CDV is thought to be transmitted by direct contact between individuals; therefore, the study of species interactions plays a pivotal role in understanding CDV transmission dynamics. However, CDV often appears to move between populations that are ecologically isolated, possibly through bridge hosts that interact with both species. This study investigated how an introduced species could alter multihost interactions and act as a bridge host in a novel carnivore assemblage of domestic dogs (Canis familiaris), invasive American mink (Neovison vison), and threatened river otters (Lontra provocax) in southern Chile. We found that rural dogs interact with mink near farms whereas in riparian habitats, minks and river otters shared the same latrines with both species visiting sites frequently within time intervals well within CDV environmental persistence. No interactions were observed between dogs and otters at either location. Both dog and mink populations were serologically positive for CDV, making the pathogen transfer risk to otters a conservation concern. Altogether, introduced mink in this ecosystem have the potential to act as bridge hosts between domestic dogs and endangered carnivores.

Wildlife Reservoirs of Canine Distemper Virus Resulted in a Major Outbreak in Danish Farmed Mink (Neovison vison)

A major outbreak of canine distemper virus (CDV) in Danish farmed mink (Neovison vison) started in the late summer period of 2012. At the same time, a high number of diseased and dead wildlife species such as foxes, raccoon dogs, and ferrets were observed. To track the origin of the outbreak virus full-length sequencing of the receptor binding surface protein hemagglutinin (H) was performed on 26 CDV's collected from mink and 10 CDV's collected from wildlife species. Subsequent phylogenetic analyses showed that the virus circulating in the mink farms and wildlife were highly identical with an identity at the nucleotide level of 99.45% to 100%. The sequences could be grouped by single nucleotide polymorphisms according to geographical distribution of mink farms and wildlife. The signaling lymphocytic activation molecule (SLAM) receptor binding region in most viruses from both mink and wildlife contained G at position 530 and Y at position 549; however, three mink viruses had an Y549H substitution. The outbreak viruses clustered phylogenetically in the European lineage and were highly identical to wildlife viruses from Germany and Hungary (99.29% – 99.62%). The study furthermore revealed that fleas (Ceratophyllus sciurorum) contained CDV and that vertical transmission of CDV occurred in a wild ferret. The study provides evidence that wildlife species, such as foxes, play an important role in the transmission of CDV to farmed mink and that the virus may be maintained in the wild animal reservoir between outbreaks.

The effect of protected areas on pathogen exposure in endangered African wild dog (Lycaon pictus) populations

Infectious diseases impact African wild dogs (Lycaon pictus), but the nature and magnitude of this threat likely varies among populations according to different factors, such as the presence and prevalence of pathogens and land-use characteristics. We systematically evaluated these factors to assist development of locally appropriate strategies to mitigate disease risk. Wild dogs from 16 sites representing five unconnected populations were examined for rabies virus, canine distemper virus (CDV), canine parvovirus, canine coronavirus, and Babesia spp. exposure. Analyses revealed widespread exposure to viral pathogens, but Babesia was never detected. Exposure to CDV was associated with unprotected and protected-unfenced areas where wild dogs likely have a high probability of domestic dog contact and, in the case of protected-unfenced areas, likely reside amongst high wildlife densities. Our findings also suggest that domestic dog contact may increase rabies and coronavirus exposure risk. Therefore, domestic dogs may be a source of CDV, rabies and coronavirus, while wildlife may also play an important role in CDV transmission dynamics. Relatively high parvovirus seroprevalence across land-use types suggests that it might persist in the absence of spillover from domestic dogs. Should intervention be needed to control pathogens in wild dogs, efforts to prevent rabies and coronavirus exposure might be directed at reducing infection in the presumed domestic dog reservoir through vaccination. If prevention of CDV and parvovirus infections were deemed a management necessity, control of disease in domestic dogs may be insufficient to reduce transmission risks, and vaccination of wild dogs themselves may be the optimal strategy.

An Outbreak of Canine Distemper Virus in Tigers (<i>Panthera tigris</i>): Possible Transmission from Wild Animals to Zoo Animals

Canine distemper virus (CDV), a morbillivirus that causes one of the most contagious and lethal viral diseases known in canids, has an expanding host range, including wild animals. Since December 2009, several dead or dying wild raccoon dogs (Nyctereutes procyonoides) were found in and around one safari-style zoo in Japan, and CDV was isolated from four of these animals. In the subsequent months (January to February 2010), 12 tigers (Panthera tigris) in the zoo developed respiratory and gastrointestinal diseases, and CDV RNA was detected in fecal samples of the examined tigers. In March 2010, one of the tigers developed a neurological disorder and died; CDV was isolated from the lung of this animal. Sequence analysis of the complete hemagglutinin (H) gene and the signal peptide region of the fusion (F) gene showed high homology among these isolates (99.8-100%), indicating that CDV might have been transmitted from raccoon dog to tiger. In addition, these isolates belonged to genotype Asia-1 and had lower homology (<90%) to the vaccine strain (Onderstepoort). Seropositivity of lions (Panthera leo) in the zoo and wild bears (Ursus thibetanus) captured around this area supported the theory that a CDV epidemic had occurred in many mammal species in and around the zoo. These results indicate a risk of CDV transmission among many animal species, including large felids and endangered species.

Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, “outrunning” the host’s immune response in demyelinating plaques, thus continuously eliciting new lesions.

Epizootiological investigations of canine distemper virus in free-ranging carnivores from Germany

Canine distemper virus (CDV) infects a broad range of carnivores. To assess whether wild carnivores may play a role in the epidemiology of CDV in domestic dogs in Germany, the seroprevalence of CDV was determined. In sera from red foxes (30 of 591 (5%)) and stone martens (2 of 10 (20%)) antiviral antibodies were detected using a neutralization assay, whereas sera of raccoons, two mink, one pine marten and one raccoon dog were negative. In foxes, there was a significantly higher prevalence in urban and suburban compared to rural regions. When testing lung and spleen tissue samples (fox, badger, stone marten, polecat, raccoon dog) 13 of 253 (5.1%) foxes, 2 of 13 (15.4%) stone martens and 2 of 6 (33%) badgers were virus positive using RT-PCR. Phylogenetic analysis based on partial sequences of the F gene revealed a distinct relatedness to canine CDV isolates. Together, the data support the concept of transmission of CDV between domestic dogs and wild carnivores.