Wildlife Rabies Research Articles

Estimates of small Indian mongoose densities: Implications for rabies management

ABSTRACTThe small Indian mongoose (Herpestes auropunctatus) is an invasive species and rabies reservoir in Puerto Rico. In the continental United States, terrestrial wildlife rabies is primarily managed by the National Rabies Management Program (NRMP) of the United States Department of Agriculture through oral rabies vaccination (ORV); the distribution of the vaccine baits is influenced by the population density of the target species. The NRMP uses a density index for estimating raccoon (Procyon lotor) population density to guide bait distribution. In Puerto Rico, a wildlife rabies vaccination program does not exist and vaccination of domestic animals is limited and not compulsory. To acquire information on density and other population dynamics, we compared a mongoose density index (MDI) adapted from the NRMP raccoon density index (RDI) to 3 other methods (2 types of capture–mark–recapture [CAPTURE and MARK] and spatially explicit capture–recapture [SECR]) for estimating density that incorporate modeling procedures on detection probabilities, and examined the spatial distribution of mongooses within our study plots. We used the RDI trapping protocol modified for mongooses to livetrap mongooses in El Yunque National Forest (El Yunque) and Cabo Rojo National Wildlife Refuge (Cabo Rojo) in fall of 2011 and spring of 2012 resulting in 4 trapping sessions. The MDI estimates were consistently less than those from other methods for estimating mongoose densities. The MDI detected a greater mongoose density during the wet season (0.55 mongooses/ha) than the dry season (0.34 mongooses/ha) at Cabo Rojo, consistent with all 3 other density estimation methods. Overall, the correlation coefficient between MDI and the other calculation methods was ≥0.68. When we examined known locations of mongooses and travel distances, we detected more mongooses in a smaller area within the study plot at Cabo Rojo than at El Yunque. The MDI provided information on the spatial distribution of mongooses, which will be needed to implement an ORV program to target mongooses in Puerto Rico. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Update on oral vaccination of foxes and raccoon dogs against rabies

An assessment of a report issued by the European Commission in 2002 is presented about the oral vaccination of foxes against rabies, as well as additional topics such as the rabies aetiology and its occurrence in Europe, the target species for oral vaccination, i.e. foxes and raccoon dogs, the oral vaccines available and their thermostability, rabies surveillance and monitoring, and the recent international guidelines for rabies surveillance are discussed. Foxes are the only known reservoir for rabies in Europe, and raccoon dogs are important transmitters, while other carnivores play a less important epidemiological role. The demographic expansion of raccoon dogs and their movements after hibernation are risk factors for rabies recurrence. The combined densities of foxes and raccoon dogs, which often share the same habitats, could allow rabies epizootics to persist. The epidemiological role and the pathogenesis of rabies in raccoon dogs and other carnivores must still be clarified. Four vaccines are authorised in the EU and their effectiveness is proven to successfully contribute to rabies elimination. Experimental and field evidence shows that climatic and weather conditions may impact on bait casings and vaccine stability. Data on the stability of vaccine baits under different field conditions should be provided. It is recommended that bait should keep its integrity at the release point. Because of bait stability issues, the season most appropriate for implementing oral rabies vaccination or a heat-stable vaccine should be considered. Rabies surveillance and monitoring of vaccination, based on assessment of bait uptake and seroconversion in host species, are important tools for the evaluation and adjustment of vaccination campaigns, although alternatives to tetracyclines as biomarkers should be developed. Oral immunisation by vaccine baits has proven to be successful in eliminating terrestrial wildlife rabies, but long-term strategy, temporal continuity of vaccination and cross-border cooperation are needed and recommended.

Cattle rabies vaccination—A longitudinal study of rabies antibody titres in an Israeli dairy herd

In contrast to many regions of the world where rabies is endemic in terrestrial wildlife species, wildlife rabies has been controlled in Israel by oral rabies vaccination programs, but canine rabies is re-emerging in the northern area of the Golan Heights. From 2009 to 2014 there were 208 animal rabies cases in Israel; 96 (46%) were considered introduced primary cases in dogs, triggering 112 secondary cases. One third (37/112) of the secondary cases were in cattle. Rabies vaccination is voluntary for cattle in Israel, except those on public exhibit. Rabies vaccination schedules for cattle vary based on farm practices and perception of risk. In this study 59 cattle from a dairy farm which routinely vaccinates against rabies were assigned into six groups according to age and vaccination histories. Four groups contained adult cows which had received one previous rabies vaccination, one group of adults had received two previous vaccinations, and one group was unvaccinated calves. Serum samples were collected and the cows were vaccinated with a commercial rabies vaccine. Sera were again collected 39 days later and the calf group re-vaccinated and re-sampled 18 days later. Sera were analyzed for the presence of rabies virus neutralizing antibodies using the rapid immunofluorescent antibody test. Cattle with antibody titres ≥0.5IU/ml were considered to be protected against rabies. Twenty-six of 27 adult cattle (96%) vaccinated once at less than five months old did not have protective titres. Sixty percent (6/10) cattle vaccinated once at around six months of age did have adequate titres. Cattle previously vaccinated twice (n=10; 100%) with an 18 month interval between inoculations, had protective titres and protective antibody titres following booster vaccination (n=51; 100%). The anamnestic response of cattle to a killed rabies vaccine was not affected by the time interval between vaccinations, which ranged from 12 to 36 months. These results suggest that calves from vaccinated cows should not be vaccinated before six months old to avoid maternal antibody interference. Whilst most cattle older than six months old will be protected after a single inoculation, a second inoculation ensures a higher antibody levels for improved protection. Cattle receiving an effective priming dose responded well to a booster up to 36 months later. Such results demonstrate the effectiveness of rabies vaccination in cattle and the added value of a second dose to ensure a prolonged immune response against rabies.

Genetic characterisation of the rabies virus vaccine strains used for oral immunization of foxes in Poland to estimate the effectiveness of vaccination.

The main reservoir of rabies virus in Poland has been the red fox. To control rabies in wildlife, oral immunization of foxes was introduced in 1993. The vaccine is effective when it confers immunity against the virus circulating in the environment. To assess the above issue, a study of the molecular characteristics of 570-bp fragments of the N and G genes of vaccine strains SAD B19 and SAD Bern against street virus strains was performed. The results confirmed the similarity of the vaccine strains and rabies virus strains circulating in the environment and also demonstrate the genetic stability of vaccine strains that have been distributed in Poland for 20 years.

Evaluation of 6 ONRAB Ultralite bait flavor matrices delivered to coyotes (Canis latrans): Implications for oral rabies vaccination

The spread of rabies in terrestrial wildlife throughout the United States is primarily controlled through oral rabies vaccination. Relatively low bait acceptance and seroconversion rates by some target species have prompted investigation into an alternative to the RABORAL V-RG bait currently used. In Canada, ONRAB Ultralite baits are used to vaccinate raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). Comparative studies between RABORAL V-RG and ONRAB found higher seroconversion rates among raccoons that ingested ONRAB, suggesting that it may be a suitable alternative. However, ONRAB has not been evaluated in many rabies reservoir species, including coyotes (Canis latrans). Vaccination of coyotes is a critical element in preventing reemergence of canine strain of rabies in the United States. We evaluated flavor preference of ONRAB Ultralite oral rabies vaccine baits by coyotes. Preferences among bait types differed (Friedman c 2 ¼ 13.28; df ¼ 5; P ¼ 0.02). Of the 6 bait flavors evaluated, cheese ranked the highest, followed by fish, chicken, sugar-vanilla, egg, and bacon flavors. Pairwise trials among the top 3 flavors (cheese, fish, and chicken) showed no difference (Friedman c 2 ¼ 3.00; df ¼ 2; P ¼ 0.22). Our

Oral vaccination and protection of striped skunks (Mephitis mephitis) against rabies using ONRAB®

Skunks are one of the most important rabies vector species in North America due to their wide geographic distribution, high susceptibility to the rabies virus, and tendency to inhabit areas around human dwellings and domestic animals. Oral vaccination is a cost-effective, socially acceptable technique often used to control rabies in terrestrial wildlife; however, control of rabies in skunks has proven especially challenging due to the lack of a vaccine effective by the oral route in this species. In this study, we examined the antibody response of captive striped skunks (Mephitis mephitis) to ONRAB® and tested the protection afforded by the vaccine against rabies virus. Thirty-one skunks were each offered one ONRAB® vaccine bait, 25 skunks were administered ONRAB® via direct instillation into the oral cavity (DIOC) and ten controls received no vaccine. A blood sample was collected from controls and vaccinates 6 weeks prior to treatment, and then 5 and 7 weeks post-vaccination (PV). A competitive ELISA was used to detect rabies antibody (RAb). Pre-vaccination sera for all skunks, and sera for all controls throughout the serology study, were negative for RAb. Fifty-eight percent (18/31) of skunks in the bait group and 100% (25/25) of skunks that received ONRAB® DIOC had detectable RAb by 7 week PV. All 10 controls succumbed to experimental rabies infection. In the group of skunks administered ONRAB® DIOC, 100% (23/23) survived challenge 247 days PV. Survival of skunks presented ONRAB® baits was 81% (25/31). In the bait group, all 18 skunks that had detectable RAb by 7 week PV survived challenge. Seven additional skunks without detectable RAb prior to week 7 PV also survived. Lack of any remarkable pathology in study animals, together with positive serology and challenge results, supports that ONRAB® is a safe and effective oral rabies vaccine for use in skunks.

Experimental Oral Immunization of Ferret Badgers (Melogale moschata) with a Recombinant Canine Adenovirus Vaccine CAV-2-E3Δ-RGP and an Attenuated Rabies Virus SRV9

Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

Costs of raccoon rabies incidents in cattle herds in Hampshire County, West Virginia, and Guernsey County, Ohio

To determine direct and indirect costs associated with raccoon rabies incidents involving cattle herds in Hampshire County, WV, in 2008 and Guernsey County, Ohio, in 2010. Ex post cost analysis. 1 cattle herd in Hampshire County, WV, in 2008 and 1 cattle herd in Guernsey County, Ohio, in 2010. Data were collected for each incident through telephone and email interviews with 16 federal, state, and county agency personnel involved in the case investigations and coordinated responses for rabies in the cattle herds. To characterize the economic impact associated with rabies in the 2 cattle herds, cost analysis was conducted with 7 cost variables (salary and benefits for personnel involved in the response, human postexposure prophylaxis, indirect patient costs, rabies diagnostic testing, cattle carcass disposal, market value of euthanized cattle, and enhanced rabies surveillance). Estimates of direct costs were determined on the basis of agency records and other relevant data obtained from notes and reports made by agency staff at the time of the incident and from a review of the literature. Primary costs included the market value of euthanized cattle ($51,461 in West Virginia; $12,561 in Ohio), human postexposure prophylaxis ($17,959 in West Virginia; $11,297 in Ohio), and salary and benefits for personnel involved in the response ($19,792 in West Virginia; $14,496 in Ohio). These results should provide a basis for better characterization of the economic impact of wildlife rabies in cattle in the United States.

The introduction of fox rabies into Italy (2008–2011) was due to two viral genetic groups with distinct phylogeographic patterns

Fox rabies re-emerged in north-eastern Italy at the end of 2008 and circulated until early 2011. As with previous rabies epidemics, the Italian cases were linked to the epidemiological situation in adjacent regions. To obtain a comprehensive picture of the dynamics of the recent Italian epidemic, we performed a detailed evolutionary analysis of RABVs circulating in north-eastern Italy. Sequences were obtained for the hyper-variable region of the nucleoprotein gene, the complete glycoprotein gene, and the intergenic region G-L from 113 selected fox rabies cases. We identified two viral genetic groups, here referred to as Italy-1 and Italy-2. Phylogenetic and phylogeographic analyses revealed that both groups had been circulating in the Western Balkans and Slovenia in previous years and were only later introduced into Italy (into the Friuli Venezia Giulia region-FVG), occupying different areas of the Italian territories. Notably, viruses belonging to the Italy-1 group remained confined to the region of introduction and their spread was minimised by the implementation of oral fox vaccination campaigns. In contrast, Italy-2 viruses spread westward over a territory of 100km from their first identification in FVG, likely crossing the northern territories where surveillance was inadequate. A genetic sub-group (Italy-2A), characterised by a unique amino acid mutation (D106A) in the N gene, was also observed to occupy a distinct geographic cluster. This molecular epidemiological analysis of the 2008–2011 fox rabies epidemic will contribute to future control programmes both at national and regional levels. In particular, our findings highlight the weaknesses of the national surveillance strategy in the period preceding rabies re-emergence, and of control plans implemented immediately after rabies notification, and underline the need of a coordinated approach at the regional level for both the surveillance and control of wildlife rabies.

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.

世界の野生動物狂犬病の現状と日本の対応策

Rabies situation in different parts of the world is reviewed with emphasis on wildlife rabies. Measures required for the prevention and control of wildlife rabies are listed, and it is stressed that the Ministry of Environment should play a major role in planning and implementing programs related to surveillance and control of wildlife rabies. It is also suggested that veterinary schools and the wildlife research institutes in Japan could form a group to carry out various research and investigations on the subjects related to the surveillance and control of wildlife rabies both in Japan and in the neighboring countries.

Rabies transmission by Marmoset (Callithrix jacchus) in Ceará state, Brazil. A review

A Raiva é uma grave zoonose causada por um vírus pertencente à família Rhabdoviridae, gênero Lyssavirus . A doença é caracterizada por uma encefalite aguda e letal e a transmissão ocorre pela inoculação do vírus rábico, presente na saliva de mamíferos infectados, através de mordedura, arranhadura ou lambedura de mucosas. De acordo com o seu mecanismo de transmissão e seu ciclo epidemiológico, a doença pode ser classificada em: urbana, rural, silvestre aérea e silvestre terrestre. A Raiva envolvendo animais silvestres é um grave perigo para animais domésticos, assim como para os seres humanos. Dentre os principais reservatórios da Raiva silvestre no Brasil, encontram-se os saguis de tufo branco ( Callithrix jacchus ). No Ceará, a manutenção do ciclo de Raiva entre os saguis tem sido um tema importante para as autoridades de saúde pública. Este trabalho teve como objetivo fazer uma breve abordagem epidemiológica da transmissão da Raiva por Saguis no Estado do Ceará, Brasil, visto que o histórico do número de casos de raiva em C. jacchus , confirma a sua importância epidemiológica e reforça a necessidade crescente de vigilância em saúde pública no Ceará.

The WHO Rabies Bulletin europe: a key source of information on rabies and a pivotal tool for surveillance and epidemiology

Rabies is one of the most, if not the most, prominent and feared zoonotic diseases in the world and the World Health Organization (WHO) estimates that 55,000 people die of the disease every year. Most of these deaths occur in Asia and Africa and are usually the result of dog-mediated rabies. In Europe, the red fox is considered the main reservoir species for wildlife rabies caused by the rabies virus. Besides foxes, bats have also been identified as a reservoir for European bat lyssaviruses in many European countries. Here, the authors present the rabies surveillance data for Europe in recent years, as reported to the WHO Rabies Bulletin Europe. This journal has evolved into a web-based platform for rabies information (including an online accessible database) that on average receives more than 60,000 visitors each year.

Rabies stateside

Rabies kills an estimated 55,000 people every year and while a disproportionate number occur in sub-Saharan Africa many developed nations struggle to control the disease too. John Bonner talks to Richard Chipman, head of US wildlife rabies control.

Mucosal Adjuvants to Improve Wildlife Rabies Vaccination

RABORAL V-RG(®)a is a recombinant vaccine used in oral rabies vaccination (ORV) programs for wildlife in the United States. Vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. Research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. We evaluated the possibility of using two benign compounds, chitosan and N,N,N-trimethylated chitosan (TMC), to increase the viscosity of the vaccine and potentially act as adjuvants to improve the immune response in raccoons (Procyon lotor). Forty mildly sedated raccoons were orally vaccinated via needleless syringe with either RABORAL V-RG (n = 12), chitosan+RABORAL V-RG (n = 12), TMC+ RABORAL V-RG (n = 12), or no vaccine (n = 4), on day 0 and again on day 90. We collected sera every 2-4 wk for 4 mo and evaluated rabies virus-neutralizing antibodies (rVNA). Raccoons were considered responders if rVNA titers were ≥ 0.1 IU/mL. Eleven of 12 raccoons vaccinated with TMC+RABORAL V-RG responded after one dose of vaccine, as did eight of 12 vaccinated with RABORAL V-RG, and three of 12 vaccinated with chitosan+ RABORAL V-RG. Our results suggest that the inclusion of an adjuvant, such as TMC, could increase vaccine efficacy to aid in controlling rabies virus spread in wildlife reservoirs.

Uptake of buried baits by badgers: Implications for rabies control in Great Britain and the delivery of an oral TB vaccine

AbstractThe British Government's contingency plan for the control of wildlife rabies is based on oral vaccination around a focal outbreak, with the option of the targeted lethal control of foxes (Vulpes vulpes) and badgers (Meles meles) using buried poisoned bait. We investigated uptake by badgers of nonpoison meat‐based baits buried along transects for 10 consecutive days in 1995. The original aim was to evaluate the likely effectiveness of this contingency option. However, the results are also pertinent to the development of an oral tuberculosis (TB) vaccine baiting strategy for badgers, for which research has primarily been carried out since this study was completed. Bait disappearance steadily increased over time, reaching an asymptote after 7 days. By incorporating iophenoxic acid biomarkers into baits, we showed that about 51% of subsequently captured badgers had consumed bait, the majority of which did so during the first 7 days. Bait uptake was significantly higher among adults. Rates of uptake by badgers of baits buried along transects could be increased by shortening the prebaiting period or extending the baiting period. However, considerably higher levels of uptake by adults and cubs are likely to be achieved by targeting bait deployment at badger setts, and this is now included in Britain's rabies contingency plan. Although meat‐based baits cannot be used for TB control, the relevance of these results to the delivery of an oral TB vaccine bait to badgers is discussed. © 2012 Crown copyright

SURVIS: a fully-automated aerial baiting system for the distribution of vaccine baits for wildlife.

Large-scale oral vaccination of wildlife against rabies using aerial bait distribution has been successfully used to control terrestrial wildlife rabies in Europe and North America. A technical milestone to large-scale oral rabies vaccination campaigns in Europe was the development of fully-automated, computer-supported and cost-efficient technology for aerial distribution of baits like the SURVIS -system. Each bait released is recorded by the control unit through a sensor, with the exact location, time and date of release and subsequently the collected data can be evaluated, e.g. in GIS programmes. Thus, bait delivery systems like SURVIS are an important management tool for flight services and the responsible authorities for the optimization and evaluation of oral vaccination campaigns of wildlife against rabies or the control of other relevant wildlife diseases targeted by oral baits.

Process optimization and scale-up for production of rabies vaccine live adenovirus vector (AdRG1.3)

Rabies virus is an important causative agent of disease resulting in an acute infection of the nervous system and death. Although curable if treated in a timely manner, rabies remains a serious public health issue in developing countries, and the indigenous threat of rabies continues in developed countries because of wildlife reservoirs. Control of rabies in wildlife is still an important challenge for governmental authorities. There are a number of rabies vaccines commercially available for control of wildlife rabies infection. However, the vaccines currently distributed to wildlife do not effectively immunize all at-risk species, particularly skunks. A replication competent recombinant adenovirus expressing rabies glycoprotein (AdRG1.3) has shown the most promising results in laboratory trials. The adenovirus vectored vaccine is manufactured using HEK 293 cells. This study describes the successful scale-up of AdRG1.3 adenovirus production from 1 to 500 L and the manufacturing of large quantities of bulk material required for field trials to demonstrate efficacy of this new candidate vaccine. The production process was streamlined by eliminating a medium replacement step prior to infection and the culture titer was increased by over 2 fold through optimization of cell culture medium. These improvements produced a more robust and cost-effective process that facilitates industrialization and commercialization. Over 17,000 L of AdRG1.3 adenovirus cultures were manufactured to support extensive field trials. AdRG1.3 adenovirus is formulated and packaged into baits by Artemis Technologies Inc. using proprietary technology. Field trials of AdRG1.3 rabies vaccine baits have been conducted in several Canadian provinces including Ontario, Quebec and New Brunswick. The results from field trials over the period 2006-2009 demonstrated superiority of the new vaccine over other licensed vaccines in immunizing wild animals that were previously difficult to vaccinate.

First report of rabies infection in bats, Molossus molossus, Molossops neglectus and Myotis riparius in the city of São Paulo, State of São Paulo, southeastern Brazil

This paper presents the first report of rabies in three bat species, Molossus molossus, Molossops neglectus and Myotis riparius in the city of São Paulo, Brazil. Bats were diagnosed as positive for rabies using the fluorescent antibody test and mouse inoculation test. The isolates were characterized antigenically using a panel of eight monoclonal antibodies. The samples were also genetically analyzed by partial sequencing of the portion of nucleoprotein gene between positions 1157 and 1445 nt. Analysis of the results verified that the sample isolated from the species M. molossus presented antigenic variant 6, while the other two samples showed a different profile from that established in the panel, one not previously reported in the literature. The results of genetic analysis revealed that the M. molossus sample segregated with Lasiurus sp. isolates, M. neglectus segregated with a subgroup of Eptesicus furinalis isolates and the Myotis riparius sample segregated with Myotis sp. isolates. The cases reported in this paper emphasize the need for clarification of the circumstances in which cases of rabies in wildlife occur, principally in urban areas.

Update on rabies.

Human rabies is almost invariably fatal, and globally it remains an important public health problem. Our knowledge of rabies pathogenesis has been learned mainly from studies performed in experimental animal models, and a number of unresolved issues remain. In contrast with the neural pathway of spread, there is still no credible evidence that hematogenous spread of rabies virus to the central nervous system plays a significant role in rabies pathogenesis. Although neuronal dysfunction has been thought to explain the neurological disease in rabies, recent evidence indicates that structural changes involving neuronal processes may explain the severe clinical disease and fatal outcome. Endemic dog rabies results in an ongoing risk to humans in many resource-limited and resource-poor countries, whereas rabies in wildlife is important in North America and Europe. In human cases in North America, transmission from bats is most common, but there is usually no history of a bat bite and there may be no history of contact with bats. Physicians may not recognize typical features of rabies in North America and Europe. Laboratory diagnostic evaluation for rabies includes rabies serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Methods of postexposure rabies prophylaxis, including wound cleansing and administration of rabies vaccine and human rabies immune globulin, are highly effective after recognized exposure. Although there have been rare survivors of human rabies, no effective therapy is presently available. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (known as the "Milwaukee protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. New therapeutic approaches for human rabies need to be developed. A better understanding of basic mechanisms involved in rabies pathogenesis may be helpful in the development of potential new therapies for the future.