Enzootic Rabies Research Articles

Large-scale phylogenetic analysis reveals genetic diversity and geographic distribution of rabies virus in South-East and South Asia.

South-East Asia (SEA) and South Asia (SA) are two important geographic regions with the most severe enzootic rabies in the world. In these regions, phylogenetic analysis of rabies virus (RABV) has been conducted only at a country level; the results obtained from different countries are scattered and unequal, with a non-uniform system to name RABV genotypes. Therefore, it is difficult to undertake origin-tracking and compare inter-country RABV evolution and transmission. To avoid the confusion in understanding and to generate a panoramic picture of RABV genetic diversity, distribution, and transmission in SEA and SA, the present study conducted a systematic phylogenetic analysis by combining all sequences representing 2368 RABV strains submitted to GenBank by 14 rabies endemic SEA and SA countries. The results showed that RABVs circulating in two regions were classified into four major clades and many subclades: the Asia clade is circulating only in SEA, the Indian subcontinent, and Arctic-like clades only in SA, while the Cosmopolitan clade has been detected in both regions. The results also showed a wide range of hosts were infected by divergent RABV subclades, with dogs being the major transmission source. However, wildlife rabies was also found to be an important issue with 6 wild carnivore species identified as potential sources of spillover risk for sylvatic rabies to humans, domestic animals, and other wild animals. Current findings indicate that the two regions have separate virus clades circulating thus indicating the absence of cross-transmission between the regions. The study emphasizes the importance of phylogenetic analysis in the regions using uniform genotyping and naming systems for rabies surveillance, to coordinate actions of member countries to eliminate dog-mediated human rabies by 2030.

A country classification system to inform rabies prevention guidelines and regulations.

Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies. CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high. A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk. We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.

Historical, current and expected future occurrence of rabies in enzootic regions.

Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.

Ecological niche modeling of rabies in the changing Arctic of Alaska

BackgroundRabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions.ResultsHere we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate.ConclusionsOur results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic.

Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe.

In 2015, countries in western Europe were declared free of rabies in nonflying mammals. Surveillance data for 2001–2013 indicate that risk for residual rabies is not 0 because of pet importation from countries with enzootic rabies. However, the risk is so low (7.52 × 10−10) that it probably can be considered negligible.

A preliminary study of recombinant human interferon-α-2a activity against rabies virus in murine model.

Rabies remains an important public health problem in the world due to uncontrolled enzootic rabies. Although rabies associated fatalities may be prevented with timely immunoprophylaxis, but till date a therapeutic molecule has remained elusive. We investigated the role of rhuIFN α-2a in murine model challenged with rabies virus. Titre of 10(4.25) LD50/0.03 ml of 10% w/v RV CVS stock suspension were obtained. Based on 1LD50 titre, challenge dose of 50 LD 50 was administered along with rhuIFN α-2a with pre-exposure (primed) and post-exposure with the rabies virus. Both showed increased survival time as compared with the virus controls. These findings suggest that the rhuIFN α-2a might have some anti-viral activity, which can be used for the treatment of rabies infection. Further research on the efficacy of interferon along with anti-viral drugs for the treatment will be helpful in designing combination therapy against the disease.

English

Rabies remains an important public health problem in the world due to uncontrolled enzootic rabies, lack of safe efficient vaccines and poor information on the risk of contracting rabies post animal exposure. The lethality and mutagenic potential of challenge virus standard (CVS) was evaluated in mice. Mice were intracerebrally infected (MIC) with low, medium and high viral LD50 (MICLD50). Mice were subjected to immunomodulation using interferon (IFN
-2a) pre- infection. The infected groups pretreated with IFN-
2a showed a higher survival rate than the infected group. Statistically significant increase in structural and numerical chromosomal aberrations and a decreased mitotic activity of mice bone marrow cells was observed post infection. Pretreatment of the infected groups with IFN
-2a showed a marked and significant reduction of these cytogenetic changes. The increased survival rate and reduced cytogenetic changes suggest that protection induced by interferon against rabies virus activity could be, at least partially, attributable to blockage of the replication of CVS strain of rabies virus. It could be concluded that interferon can be used as an immune enhancer to the application of vaccine administration.

Enzootic Rabies Elimination from Dogs and Reemergence in Wild Terrestrial Carnivores, United States

To provide molecular and virologic evidence that domestic dog rabies is no longer enzootic to the United States and to identify putative relatives of dog-related rabies viruses (RVs) circulating in other carnivores, we studied RVs associated with recent and historic dog rabies enzootics worldwide. Molecular, phylogenetic, and epizootiologic evidence shows that domestic dog rabies is no longer enzootic to the United States. Nonetheless, our data suggest that independent rabies enzootics are now established in wild terrestrial carnivores (skunks in California and north-central United States, gray foxes in Texas and Arizona, and mongooses in Puerto Rico), as a consequence of different spillover events from long-term rabies enzootics associated with dogs. These preliminary results highlight the key role of dog RVs and human-dog demographics as operative factors for host shifts and disease reemergence into other important carnivore populations and highlight the need for the elimination of dog-related RVs worldwide.

Molecular Diversity of Rabies Viruses Associated with Bats in Mexico and Other Countries of the Americas

Bat rabies and its transmission to humans and other species in Mexico were investigated. Eighty-nine samples obtained from rabid livestock, cats, dogs, and humans in Mexico were studied by antigenic typing and partial sequence analysis. Samples were further compared with enzootic rabies associated with different species of bats in the Americas. Patterns of nucleotide variation allowed the definition of at least 20 monophyletic clusters associated with 9 or more different bat species. Several lineages associated with distinctive antigenic patterns were found in rabies viruses related to rabies in vampire bats in Mexico. Vampire bat rabies virus lineages associated with antigenic variant 3 are widely spread from Mexico to South America, suggesting these lineages as the most likely ancestors of vampire bat rabies and the ones that have been moved by vampire bat populations throughout the Americas. Rabies viruses related to Lasiurus cinereus, Histiotus montanus, and some other not yet identified species of the genus Lasiurus were found circulating in Mexico. Long-range dissemination patterns of rabies are not necessarily associated with migratory bat species, as in the case of rabies in Desmodus rotundus and Histiotus montanus. Human rabies was associated with vampire bat transmission in most cases, and in one case, rabies transmission from free-tailed bats was inferred. The occurrence of rabies spillover from bats to domestic animals was also demonstrated. Genetic typing of rabies viruses allowed us to distinguish trends of disease dissemination and to address, in a preliminary fashion, aspects of the complex evolution of rabies viruses in different host-reservoir species.

Rabies surveillance in the United States during 2003

During 2003, 49 states and Puerto Rico reported 7,170 cases of rabies in nonhuman animals and 3 cases in human beings to the CDC. This represents a 10% decrease from the 7,967 cases in nonhuman animals and 3 cases in human beings reported in 2002. More than 91 (n = 6,556) were in wild animals, and 8.6% (614) were in domestic species (compared with 92.5% in wild animals and 74% in domestic species in 2002). The relative contributions of the major groups of animals were as follows: 2,635 raccoons (36.7%), 2,112 skunks (29.4%), 1,212 bats (16.9%), 456 foxes (6.4%), 321 cats (4.5%), 117 dogs (1.6%), and 98 cattle (1.4%). Compared with cases reported in 2002, the number of cases reported in 2003 decreased among all reporting groups with the exception of cats, dogs, equids, and swine. Ten of the 19 states with enzootic rabies in raccoons, the District of Columbia, and New York City reported decreases in the numbers of rabid raccoons during 2003. Tennessee reported 4 cases of indigenous rabies in raccoons during 2003, becoming the 20th state where rabies in raccoons is known to be enzootic. On a national level, the number of rabies cases in skunks during 2003 decreased by 13.2% from those reported in 2002. Texas again reported the greatest number (n = 620) of rabid skunks during 2003, as well as the greatest overall state total of rabies cases (909). As in 2002, Texas did not report any cases of rabies associated with the dog/coyote variant of the rabies virus, but did report 61 cases associated with the gray fox variant of the virus (compared with 65 cases in 2002). The 1,212 cases of rabies reported in bats during 2003 represented a decline of nearly 12% from the previous year's record high of 1,373 cases for this group of mammals. Cases of rabies reported in foxes.and raccoons declined 10.2% and 8.9%, respectively, during 2003. Rabies among sheep and goats decreased from 15 cases in 2002 to 12 cases in 2003, whereas cases reported in cats, dogs, and equids increased 74%, 18.2%, and 8.6%, respectively. In Puerto Rico, reported cases of rabies in mongooses and dogs decreased 26.9% and 35.7%, respectively, from those reported in 2002. Three cases of rabies in human beings were reported in California, Virginia, and Puerto Rico during 2003. The Virginia case was the first reported occurrence of rabies in a human being infected with the raccoon rabies virus variant; however, the exposure history was unknown. The California and Puerto Rico cases were the result of infections with bat and dog/mongoose rabies virus variants, respectively, and each patient had a history of a bite.

Rabies surveillance in the United States during 1999.

During 1999, 49 states, the District of Columbia, and Puerto Rico reported 7,067 cases of rabies in nonhuman animals to the Centers for Disease Control and Prevention, a decrease of 11.2% from 7,961 cases in nonhuman animals and 1 case in a human being reported in 1998. More than 91% (6,466 cases) were in wild animals, whereas 8.5% (601 cases) were in domestic species (compared with 92.4% in wild animals and 7.6% in domestic species in 1998). No cases of rabies were reported in human beings in 1999. Decreases were evident in all major species groups, with the exception of cattle, sheep/goats, and swine. The relative contributions of the major groups to the total reported were as follows: raccoons (41.0%; 2,872 cases), skunks (29.4%; 2,076), bats (14.0%; 989), foxes (5.4%; 384), cats (3.9%; 278), cattle (1.9%; 135), and dogs (1.6%; 111). Reported cases (6) associated with the epizootic of rabies in raccoons in Ohio declined from the 26 cases reported in 1998. Fifteen of the 19 states where the raccoon variant of the rabies virus is enzootic reported fewer cases of rabies during 1999. Massachusetts and Rhode Island, states with enzootic rabies in raccoons, each reported more rabid skunks than rabid raccoons for the third consecutive year. In Texas, cases associated with the enzootic canine variants of the rabies virus remained low (10 cases), whereas cases associated with the gray fox variant of the virus increased (66). Cases of rabies in skunks decreased by 8.6%, compared with those reported in 1998. Michigan reported the largest percentage increase in rabid skunks (950.0%; 2 cases in 1998 to 21 in 1999). Cases of rabies in horses and mules declined 21%, from 82 cases in 1998 to 65 in 1999. Cases of rabies reported in bats (989) were similar in number to those reported in 1998 (992) and represented almost 14.0% of the total number of rabid animals reported during 1999. Reported cases of rabies in cats (278) and dogs (111) decreased by 1.4% and 1.8%, respectively, whereas cases in cattle (135) increased by 16.4%, compared with those reported in 1998.

Molecular epidemiology of enzootic rabies in California.

Molecular characterization of rabies virus has been used to trace spillover transmission from reservoir species to non-reservoir animals and humans (molecular epidemiology), and to monitor emergence of specific strains of the virus into new species and geographic areas (molecular surveillance). To characterize the enzootic strains of rabies virus in California wildlife for epidemiological investigation of transmission to non-reservoir animals and humans. Molecular characterization was performed on rabies strains from 213 bats, 276 terrestrial animals and one human case, by RT-PCR amplification of the viral nucleocapsid (N) gene followed by Dde I digestion and restriction endonuclease analysis (REA). Brain material from 88 terrestrial animals and 74 bats was stained with a panel of 20 monoclonal antibodies (MABs) directed against the N protein. In order to characterize rabies from very small quantities of brain tissue a nested RT-PCR was developed and evaluated for sensitivity of rabies detection. Enzootic terrestrial rabies in California is confined to the Central Valley, the western slope of the Sierra Nevada, and the Central and Northern Pacific Coast Ranges. No terrestrial reservoirs were identified south of the Tehachapi Mountains or east of the Sierra Nevada. Bat strains accounted for rabies in terrestrial animals in these regions. Among terrestrial rabies strains REA identified ten genotypes that segregated geographically and were associated with skunk and fox populations from distinct locations. Co-circulation of three genotypes occurred in Placer County, which had the highest incidence of rabies in skunks. In regions with terrestrial enzootic rabies, the strain from that region accounted for 73% of spillover cases. Bat strains accounted for the remaining 27%. Among terrestrial animals MABs identified three predominant patterns. In rabies strains from bats REA identified ten major and two minor patterns primarily associated with genus and species of bat. Sharing of strains between species was observed. An additional sixteen unclassified REA bat patterns were observed in only one or two individuals of various species. MABs identified four major patterns in bats associated with genus and species of bat with considerable variability. The bat strains most frequently detected in spillover cases throughout California were from the California myotis (Myotis californicus) and Mexican free-tailed bat (Tadarida brasiliensis). Nested RT-PCR increased the detection level of rabies virus 100,000-fold, to 0.03 TCID50.

Skunk rabies.

In North America, the number of cases of rabies diagnosed in skunks generally exceeds that in either raccoons or foxes. Enzootic skunk rabies occurs mainly in four geographic regions: (1) southern Ontario and Quebec and upper New York State; (2) the north central United States and the Canadian provinces of Manitoba, Saskatchewan, and Alberta; (3) California; and (4) south central United States (Texas and several adjacent states). Rabies in these areas (in skunks and, to a large extent, in other terrestrial mammals) is caused mainly by three street virus variants, as determined by monoclonal antibody testing (one variant for areas 2 and 3 and separate variants for each of areas 1 and 4). Experimental studies suggest that the species specificity (e.g., raccoon vs. skunk) of enzootic rabies is due, at least partly, to differences in the pathogenicity of variants of rabies virus.

Monoclonal antibody studies of rabies in insectivorous bats of the United States.

Isolates of rabies virus from terrestrial animals in six geographically separate rabies enzootic areas of the United States were examined with a panel of monoclonal antibodies to the viral N protein. Characteristic differences in immunofluorescence reactions permitted the formation of five antigenically distinct reaction groups from the 328 isolates tested. Distinctive reaction patterns were also identified for isolates from four species of bats. These observations were used to determine the role of infected bats in 19 cases of rabies that had occurred in terrestrial animals living in areas free of enzootic rabies in terrestrial wildlife and to estimate the contribution of infected bats to rabies in cats and foxes in the United States. The findings suggest that monoclonal antibodies can be used to study the prevalence, distribution, and transmission of rabies among wildlife species.

The Raccoon an Emerging Rabies Host

The geographic distribution of enzootic rabies in raccoons is currently limited to Florida and Georgia. The enzootic area has steadily expanded northward into Georgia during the 1960's. An epizootic in a population of raccoons closely associated with the human residents of a small, off-shore island was investigated. Forty-seven raccoons from the island were confirmed rabies positive by the State Laboratory from January 22 to May 20, 1969. About 10 percent of the raccoons trapped during the peak of the epizootic were positive and all of these had high titers of virus in their salivary glands but were asymptomatic in behavior. Human exposure typically resulted from close approach to a "sick" raccoon. Similar outbreaks may occur elsewhere when humans live in close contact with a semi-domesticated raccoon population. Rabies vaccination of raccoons should be considered as an alternative to population reduction in such situations.

Enzootic rabies in rodents in Thailand.

RABIES virus has occasionally been isolated from feral rats1 and yet rodents are not considered to be a significant reservoir of sylvatic rabies2. These conclusions are based on negative results of surveys of small mammal species in areas in which rabies is endemic2,3. The isolation of rabies virus from a field rat, Bandicoota indicus, in the course of routine diagnostic procedures prompted a survey of several small mammals in Thailand, a country where rabies is endemic. When it was certain that the virus was present in a number of Bandicoota indicus, it then became important to determine whether overt disease occurred and if virus was being transmitted as an inapparent infection in the species. The results of the survey and preliminary data on the epidemiology of rabies in Bandicoota indicus are the subject of this report.