The role of a mechanistic host in maintaining arctic rabies variant distributions: Assessment of functional genetic diversity in Alaskan red fox (Vulpes vulpes).

Populations are exposed to different types and strains of pathogens across heterogeneous landscapes, where local interactions between host and pathogen may present reciprocal selective forces leading to correlated patterns of spatial genetic structure. Understanding these coevolutionary patterns provides insight into mechanisms of disease spread and maintenance. Arctic rabies (AR) is a lethal disease with viral variants that occupy distinct geographic distributions across North America and Europe. Red fox (Vulpes vulpes) are a highly susceptible AR host, whose range overlaps both geographically distinct AR strains and regions where AR is absent. It is unclear if genetic structure exists among red fox populations relative to the presence/absence of AR or the spatial distribution of AR variants. Acquiring these data may enhance our understanding of the role of red fox in AR maintenance/spread and inform disease control strategies. Using a genotyping-by-sequencing assay targeting 116 genomic regions of immunogenetic relevance, we screened for sequence variation among red fox populations from Alaska and an outgroup from Ontario, including areas with different AR variants, and regions where the disease was absent. Presumed neutral SNP data from the assay found negligible levels of neutral genetic structure among Alaskan populations. The immunogenetically-associated data identified 30 outlier SNPs supporting weak to moderate genetic structure between regions with and without AR in Alaska. The outliers included SNPs with the potential to cause missense mutations within several toll-like receptor genes that have been associated with AR outcome. In contrast, there was a lack of genetic structure between regions with different AR variants. Combined, we interpret these data to suggest red fox populations respond differently to the presence of AR, but not AR variants. This research increases our understanding of AR dynamics in the Arctic, where host/disease patterns are undergoing flux in a rapidly changing Arctic landscape, including the continued northward expansion of red fox into regions previously predominated by the arctic fox (Vulpes lagopus).

Epidemiological scenarios for human rabies exposure notified in Colombia during ten years: A challenge to implement surveillance actions with a differential approach on vulnerable populations.

Based on notified cases of human rabies exposure and human deaths by rabies to Colombia public health surveillance system between 2007 and 2016, we conducted a spatiotemporal analysis to identify epidemiological scenarios of high human rabies exposure due to dogs, cats, bats, or farm animals (n = 666,411 cases). The incidence rate of human rabies exposures was analyzed by using geographical information system (spatiotemporal distribution and Cluster and Outlier Analysis (Anselin Local Moran's I)) data for all Colombian cities. The incidence rate of human rabies exposures due to dogs and cats showed an increasing trend, while aggression due bats and farm animals fluctuated throughout the analyzed period. Human deaths by rabies transmitted by cat and bat occurred in the Andean and Orinoquia regions, which had urban and rural scenarios. The urban scenario showed the highest exposure to human rabies due to cats and dogs in cities characterized with high human population density and greater economic development. In contrary, the highest human rabies exposure in the rural scenario was observed due to contact of mucosa or injured skin with the infected saliva of farm animals with the rabies virus, principally among workers in the agroforestry area. The inequality scenario showed some outlier cities with high human rabies exposure due to farm animals principally in the Pacific region (characterized by the highest poverty rates in Colombia), being Afro-descendant and indigenous population the most exposed. The highest exposure due to bats bite was observed among indigenous people residing in cities of the Amazon region as a dispersed population (Amazonian scenario). None of the high exposure scenarios were related to human deaths by rabies due to dogs aggression. The identified scenarios can help develop better surveillance systems with a differential approach to the vulnerable population and strengthening them in areas with rabies viral circulation.

Moving from rabies research to rabies control: lessons from India.

BACKGROUND: Despite the availability of effective interventions and public recognition of the severity of the problem, rabies continues to suffer neglect by programme planners in India and other low and middle income countries. We investigate whether this state of 'policy impasse' is due to, at least in part, the research community not catering to the information needs of the policy makers. METHODS #ENTITYSTARTX00026; FINDINGS: Our objective was to review the research output on rabies from India and examine its alignment with national policy priorities. A systematic literature review of all rabies research articles published from India between 2001 and 2011 was conducted. The distribution of conducted research was compared to the findings of an earlier research prioritization exercise. It was found that a total of 93 research articles were published from India since 2001, out of which 61% consisted of laboratory based studies focussing on rabies virus. Animals were the least studied group, comprising only 8% of the research output. One third of the articles were published in three journals focussing on vaccines and infectious disease epidemiology and the top 4 institutions (2 each from the animal and human health sectors) collectively produced 49% of the national research output. Biomedical research related to development of new interventions dominated the total output as opposed to the identified priority domains of socio-politic-economic research, basic epidemiological research and research to improve existing interventions. CONCLUSION: The paper highlights the gaps between rabies research and policy needs, and makes the case for developing a strategic research agenda that focusses on rabies control as an expected outcome.

Rabies research in resource-poor countries.

Many cost-benefit/effective rabies research projects need to be carried out in less-developed canine-endemic regions. Among these are educational approaches directed at the public and governments. They would address effective primary wound care, availability, and proper use of vaccines and immunoglobulins, better reporting of rabies, final elimination of dangerous nerve tissue-derived vaccines, and the recognition that rabies is still expanding its geographic range. Such efforts could also reduce deaths in victims who had received no or less than adequate postexposure prophylaxis. There is a need for new technology in canine population control and sustainable vaccination. We have virtually no workable plans on how to control bat rabies, particularly that from hematophagous bats. Preexposure vaccination of villagers in vampire rabies-endemic regions may be one temporary solution. Current efforts to reduce further the time required and vaccine dose required for effective postexposure vaccination need to be encouraged. We still have incomplete understanding of the transport channels from inoculation site to rabies virus antibody generating cells. The minimum antigen dose required to achieve a consistently protective and lasting immune response has been established for intramuscular vaccine administration, but is only estimated for intradermal use. Greater knowledge may have clinical benefits, particularly in the application of intradermal reduced dose vaccination methods. Curing human rabies is still an unattained goal that challenges new innovative researchers.

Host phylogeny constrains cross-species emergence and establishment of rabies virus in bats.

For RNA viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. Using a data set of hundreds of rabies viruses sampled from 23 North American bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data. These estimates demonstrate diminishing frequencies of both cross-species transmission and host shifts with increasing phylogenetic distance between bat species. Evolutionary constraints on viral host range indicate that host species barriers may trump the intrinsic mutability of RNA viruses in determining the fate of emerging host-virus interactions.

Elimination of terrestrial rabies in Western European countries.

Since the late 1930s, the red fox (Vulpes vulpes) has been the main vector of rabies in Europe. Practically, decimation of fox population did not prevent the spread of the disease. The only efficient method to control wildlife rabies consisted in using oral vaccination by depositing vaccine baits containing a capsule or a plastic sachet filled with an attenuated anti-rabies liquid vaccine throughout fox habitats. Several live virus vaccines have been and are currently being used: the SAD B19 and SAD P5/88 are rabies strains attenuated in cell culture, the SAG1 and SAG2 strains are apathogenic mutants of an already attenuated rabies strain, and the VRG vaccine is an attenuated vaccinia virus recombinant coding for the rabies glycoprotein gene. These vaccines have different residual pathogenicity. SAG1 and SAG2 are pathogenic only for suckling mice inoculated by intracerebral and oral routes. VRG presents absolutely no rabies risk to humans and the environment and the residual pathogenicity of the vaccinia vector virus is very low even for humans. Other parameters such as the thermostability of the vaccine and the melting point of the bait casing are of utmost importance to guarantee the success of oral vaccination campaigns. Additionally, VRG is the only vaccine that did not interfere with maternal immunity in fox cubs, an important issue for spring campaigns. Successes and failure of national programmes confirm that whatever the ecological conditions, the same rules must be strictly followed to ensure the success of rabies elimination programmes: (i) considering the strategy, any rabies vaccination programme must be organised with the support of a national scientific team specially designated for the task that will have to apply the only methods that have already been proved successful elsewhere in Europe, including rabies surveillance, bait distribution calendar and pattern, and monitoring of this distribution; (ii) vaccination must be pursued for at least two years after the last reported case of rabies in the area; (iii) the choice of a low cost but poorly efficient and poorly stable vaccine does not prove to be cost-beneficial for successful elimination of rabies. Several European countries have become rabies-free: Belgium, Luxembourg, France, Italy, Switzerland, Finland and the Netherlands. Since the European Union is going comprise 25 countries from May 2004, all the scientific knowledge is available for establishing efficient and adapted oral programmes aimed at eliminating terrestrial rabies from this area.

[Comparative assessment of the neurovirulence of vaccinal strains of the rabies virus]. / Sravnitel'naia otsenka neirovirulentnosti vaktsinnykh shtammov virusa beshenstva.

Neurovirulence of three vaccine strains of rabies virus ("Moscow", "Vnukovo-32", and "MIVP-74") was studied in mice using pathomorphology data. After intracerebral inoculations changes in the CNS were similar. The presence and the degree of the involvement of the Ammon horn is the main indicator of the infectious activity of the strain. The disease and death of the animals after inoculation with an attenuated strain may be due to the damage of intermediate neurons of descending projection tracts of the brain stem and cerebellum. Differences between strains in neurovirulence were most clearly observed after peripheral inoculation, when the "MIVP-74" strain, unlike the other two, proved to be apathogenic. Neurovirulent properties should be evaluated by characteristics of the CNS pathomorphology after intracerebral and peripheral inoculations.