Search

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention ‘very cost-effective’ by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.

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.La rage est l’une des plus anciennes maladies infectieuses enregistrées et la zoonose virale la plus largement représentée dans le monde. On présume que l’Antarctique est indemne de tout lyssavirus mais cette hypothèse n’est étayée par aucune surveillance basée sur des analyses de laboratoire. Il existe une menace de réintroduction de la maladie en Océanie, comme l’ont révélé le foyer historique survenu à Guam ainsi que l’arrivée de chauves-souris enragées à Hawaï. L’Australie est le seul continent habité où la rage ne sévit pas à l’état enzootique, le virus de la rage y étant absent. L’Europe et l’Amérique du Nord ont mis fin au cycle de la rage transmise par les chiens, dont il ne subsiste que quelques rares foyers de propagation en Amérique latine ; en revanche, la rage sylvatique reste prépondérante dans ces régions. Le fardeau le plus lourd est supporté par l’Ancien Monde. L’élimination de la rage humaine transmise par les chiens à l’horizon 2030 en Afrique, en Asie et au Moyen-Orient ne sera pas une tâche facile, rapide ni exempte de coûts mais elle peut réussir grâce aux outils disponibles partout dans le monde et aux enseignements tirés de l’expérience acquise tout au long du xxe siècle.La rabia, causada por uno de los patógenos más antiguos de los que hay constancia, presenta la distribución más amplia de cuantas zoonosis víricas se conocen. Se piensa que la Antártida está libre de todo tipo de lisavirus, pero no ha habido labores de vigilancia en laboratorio que prueben tal suposición. Oceanía está bajo la amenaza de reintroducción de la enfermedad, como demuestran el histórico brote registrado en Guam o el desplazamiento de murciélagos rabiosos a Hawái. Australia es el único continente habitado en el que no hay rabia enzoótica, esto es, en que el virus rábico no está presente. Europa y América del Norte han interrumpido el ciclo de la rabia transmitida por perros, de la que aún quedan contados focos en América Latina y el Caribe, aunque sigue prevaleciendo la rabia de la fauna silvestre. La carga más importante recae en el «Viejo Mundo». La eliminación de la rabia humana transmitida por perros para 2030 en África, Asia y el Oriente Medio no será sencilla, rápida ni barata, pero es factible si se emplean herramientas que ya están extendidas y se aplican las lecciones que hemos aprendido a lo largo del siglo XX.

Rabies is a major neglected zoonotic disease, despite the availability of highly sensitive diagnostic tests and efficacious human and animal vaccines. Perpetuation of rabies among multiple species of bats and wild carnivores, together with the presence of diverse lyssaviruses, remains a challenge for the prevention and control of this disease. However, most of the global burden may be reduced by mass vaccination of dogs, the major reservoir. Elimination of human rabies mediated by dogs may be feasible, based upon the elicitation of herd immunity, the application of sound health economic principles for appropriate disease management and technology transfer to those developing countries where rabies is hyper-endemic. Global canine rabies elimination has clear benefits for public health, veterinary medicine and conservation biology, so these sectors must collaborate using a transdisciplinary 'One Health' approach that allows the creation of long-term regional strategies for enhanced surveillance and practical intervention.La rage est une maladie zoonotique majeure, qui demeure négligée malgré l’existence de tests de diagnostic hautement sensibles et de vaccins efficaces chez l’homme comme chez l’animal. La persistance de la rage chez de nombreuses espèces de carnivores sauvages et de chauves-souris et la diversité des espèces de Lyssavirus continuent de poser des difficultés en termes de prévention et de lutte contre la maladie. Néanmoins, le fardeau mondial de la rage peut être considérablement réduit en pratiquant la vaccination massive des chiens, ces derniers constituant le principal réservoir. L’élimination de la rage transmise par les chiens est un objectif atteignable si l’on s’appuie sur des concepts solides en matière d’immunité à l’échelle des troupeaux, d’économie de la santé et de transfert technologique, tout en apportant des bénéfices mutuels accrus pour la santé publique, la médecine vétérinaire et la biologie de la conservation grâce à la mise en oeuvre d’une approche régionale pour la surveillance, les interventions, la certification et la collaboration pluridisciplinaire dans un contexte Une seule santé.La rabia es una importante enfermedad zoonótica desatendida, y ello pese a que existen pruebas de diagnóstico de gran sensibilidad y vacunas de contrastada eficacia en personas y animales. La perpetuación de la rabia en múltiples especies de carnívoros silvestres y murciélagos y la presencia de diversos lisavirus siguen dificultando el trabajo de prevención y control de la enfermedad. Con todo, cabe reducir buena parte de la carga mundial que impone la rabia mediante la vacunación masiva de perros, que son su principal reservorio. Si se aplican conceptos sólidos en materia de inmunidad de rebaño, economía de la salud y transferencia de tecnología, abordando las labores de vigilancia, intervención, certificación y colaboración multidisciplinar desde una lógica regional y desde los postulados de «Una sola salud», la eliminación de la rabia humana transmitida por perros puede ser un objetivo factible y muy beneficioso para la salud pública, la medicina veterinaria y la biología de la conservación.

Emerging infectious diseases represent a grave threat to animal and human populations in terms of their impact on global health, agriculture and the economy. Vaccines developed for emerging infections in animals can protect animal health and prevent transmission of zoonotic diseases to humans. Examples in this paper illustrate how industry and public health can collaborate to develop a vaccine to prevent an emerging disease in horses (West Nile virus vaccine), how poultry vaccination can protect animals and prevent transmission to people (avian influenza vaccine), how regulatory changes can pave the way for vaccines that will control the carrier state in animals and thus prevent infection in humans (Bartonella henselae vaccine in cats) and how novel technologies could be applied to vaccinate wildlife reservoir species for rabies. Stemming from the realisation that zoonotic diseases are the predominant source of human emerging infectious diseases, it behoves academic, public health, and animal health agencies to consider creative constructive approaches to combat serious public health challenges. Vaccination of vector/reservoir species, when efficacious vaccines are available, offers significant advantages to combating zoonotic human disease.

Zoonotic disease surveillance is typically initiated after an animal pathogen has caused disease in humans. Early detection of potentially high-risk pathogens within animal hosts may facilitate medical interventions to cope with an emerging disease. To effectively spillover to a novel host, a pathogen may undergo genetic changes resulting in varying transmission potential in the new host and potentially to humans. Rabies virus (RABV) is one model pathogen to consider for studying the dynamics of emerging infectious diseases under both laboratory and field conditions. The evolutionary history of RABV is characterized by regularly documented spillover infections and a series of notable host shifts. Within this context, enhanced field surveillance to improve detection of spillover infections will require validated techniques to non-invasively differentiate infected from non-infected individuals. In this study, we evaluate the use of infrared thermography to detect thermal changes associated with experimental RABV infection in big brown bats (Eptesicus fuscus) in a captive colony. Our results indicated that 62% of rabid bats had detectable facial temperature decreases (-4.6°C, SD ± 2.5) compared with pre-inoculation baseline values. These data suggest potential utility for discriminating rabid bats in natural field settings. In addition, focusing upon RABV circulating in the United States between 2008 and 2011, we confirmed spillover events of bat RABV among carnivores and identified cross-species transmission events caused by four lineages of RABV associated with insectivorous bats. Additionally, our analysis of RABV glycoprotein sequences identified substitutions in antigenic sites that may affect neutralizing activity associated with monoclonal antibodies proposed for use in human post-exposure prophylaxis. This study provides a glimpse into RABV pathobiology and spillover dynamics among and between bats and a variety of mesocarnivores.

A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented.

1 Anonymous: Outbreaks of diarrheal illness associated with cyanobacteria (blue-green algae)-like bodies-Chicago and Nepal, 1989 and 1990. Mortal Morbid Weekly Rep 40:325-327, I99 1 2 Chandler FW, Kaplan W, Ajello A: Protothecosis and infections caused by morphologically similar green algae. In: A Colour Atlas and Textbook of the Histopathology of Mycotic Disease, pp. 96-1 00. Wolfe Medical, London, England, 1980 3 Chandler FW, Kaplan W, Callaway CS: Differentiation between Prototheca and morphologically similar green algae in tissue. Arch Pathol Lab Med 102:353-356, 1978 4 Cordy DR: Chlorellosis in a lamb. Vet Pathol 10: 171176, 1973 5 Ivanov BG, Skalinskii EI: [Pathological changes in paratuberculosis of camels]. Tr Vses Inst Eksp Vet 20: 186206, 1957 6 Jones JW, McFadden HW, Chandler FW, Kaplan W, Connor DH: Green algal infections in a human. Am J Clin Pathol 80:102-107, 1983 7 Kaplan W, Chandler FW, Choudary C, Ramachandran PK: Disseminated unicellular green algal infection in two sheep in India. Am J Trop Med Hyg 32:405-411, 1983 8 Rogers RJ, Connole MD, Norton J, Thomas A, Ladds PW: Lymphadenitis ofcattle due to infection with green algae. J Comp Pathol90: 1-9, 1980 9 Sudman MS, Kaplan W: Identification of the Prototheca species by immunofluorescence. Appl Microbiol2598 1990, 1973 10 Zakia AM, Osheik AA, Halima MO: Ovine chlorellosis in the Sudan. Vet Rec 125:625-626, 1989

Canine adenovirus type 2 (CAV2) has been proposed for recombinant vaccines to control rabies in wild animals. To evaluate the suitability of CAV2 as a safe vector for the genetically engineered vaccines, seven wild-caught raccoons (three males and four females) were administered CAV2 per os. Two of the animals were euthanatized on each of post-infection days 3, 6, and 14, and one was euthanatized on day 21. Two other control raccoons (a male and a female) were also euthanatized on day 21. Microscopic pulmonary lesions of multifocal necrotizing bronchiolitis with basophilic intranuclear inclusions were seen in 3/4 raccoons euthanatized on post-infection days 3 and 6. Ultrastructural examination of lungs with pulmonary lesions revealed hexagonal viral particles characteristic of adenoviruses. CAV2 is potentially pathogenic for raccoons, and this susceptibility should be of concern to developers of recombinant vaccines who intend to use CAV2 as a vaccine vector.

In 2004, a teenager survived bat-associated rabies through the Milwaukee protocol (MP). This survivor and another patient with dog-associated rabies were found to have developed deficiencies of tetrahydrobiopterin (BH4) and associated neurotransmitters. BH4 is also essential for neuronal nitric oxide synthase (nNOS), so rabies is predicted to cause constriction of cerebral arteries. We assume that rabies virus, which almost exclusively targets neurons, would disproportionately affect cerebral over systemic perfusion by disrupting nNOS and lead to generalised cerebral artery spasm. Cranial artery vasospasm, therefore, was actively sought in two rabies patients, with the intention to specifically treat with BH4 and L-arginine when necessary. Flow velocities and resistive (RI) or pulsatility indices (PI) of middle cerebral arteries (MCA) were obtained by transcranial doppler ultrasound (TCD). A survival analysis of 8 attempts at the MP is presented. Of these, two cases are reported here. The first case is one child with bat-associated rabies who developed severe bilateral MCAspasm on hospital day (HD)-10 that responded to very low dose (0.2 mcg/kg/min) nitroprusside. The second case, a child with dog-associated rabies, developed spasm of MCA on HD-6 that responded to 6 mg/kg/day BH4. A second spasm with high RI (without cerebral oedema or increased intracranial pressure) responded to 20 mg/kg/day BH4 and 0.5 g/kg/dose L-arginine. Review of the TCD of the first child showed a similar second spasm seven days after first episode. Cerebral artery vasospasm occurred in the two children with rabies, but was clinically silent by standard monitoring. Spasm responded to drugs directed at the NOS pathway. Animal models for treatment of rabies are sorely needed to evaluate therapy.

Big brown bats (Eptesicus fuscus), either recently captured individuals or survivors from previous experimental infection with Irkut virus (IRKV), were inoculated with West Caucasian bat virus (WCBV), intramuscularly into the masseter (n=7) or neck (n=8) muscles, or orally (n=6). Three bats inoculated into the neck muscles developed rabies and died between days 10 and 18. Viral RNA was detected in a number of tissues but isolation was successful only from the brain. An oral swab of one of these bats was also PCR-positive, but the isolation attempt failed. Brains, salivary glands and swabs from the survivors (six months observation) were negative, as well as all blood pellets collected. Therefore, no suggestions for a carrier state or viremia were obtained. In four surviving bats inoculated in the masseter muscles, WCBV-neutralizing antibodies were detected up to the end of experiment. The absence of antibodies in the three rabid bats may be the result of shorter incubation periods. Bats infected orally neither died nor responded serologically. In the bats previously infected with IRKV, IRKV-neutralizing antibodies were detected as well, up to the end of observation (12 months after IRKV challenge), even if they were not boosted by WCBV inoculation.

Prior to 1977, raccoon (Procyon lotor) rabies was confined to the southeastern US. Translocations led to emergence of this rabies variant in the mid-Atlantic states, followed by spread northerly to northeast Ohio and Ontario, Quebec, and New Brunswick, Canada. Raccoon rabies is currently contiguous from southwest Alabama to southeastern Canada. Since 1998, state, federal, county and municipal as well as Canadian and Mexican experts have collaborated on goals and strategies to prevent raccoon rabies spread in North America. Coordinated programmes have been established from Maine to Alabama. Successes have been realized through strategies that rely heavily on oral vaccination. International coordination targeting raccoon rabies continues in eastern Canada, where contingency actions have led to elimination or near elimination in Ontario and New Brunswick. However, increasingly, focus in the US has been directed toward contingency actions to "hold-the-line" where raccoon rabies threatens to spread to new areas, rather than on raccoon rabies elimination. We report on the challenges of achieving enhanced rabies surveillance, containment of raccoon rabies, and local elimination of raccoon rabies, as well as the need for international coordination in meeting these challenges.

During development and subsequent field evaluation of an oral vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine, 53 adult porcupines ( Erethizon dorsatum; 38 females and 15 males) were examined. Microscopic examinations revealed the presence of giant epitheloid cells in various tissues (adrenal glands, spleen, liver, and lungs) of 4 (11%) female animals. These giant cells were approximately 20 times the size of the surrounding cells of the parenchyma. The cells were found singly and were not associated with any inflammatory cellular infiltrate and appeared to be located within vascular lumina. Morphologically these cells were typical of uterine epitheloid trophoblasts. This is the first record of the presence of trophoblast-like cells in nongenital tissues of porcupines.

Four rabies virus isolates from dogs that succumbed to rabies infection in Nigeria within one year of anti-rabies vaccination were characterised by monoclonal antibodies (MAbs). The samples were screened for rabies and rabies-related viral antigens by the indirect fluorescent antibody test, performed with MAb 502-2, which recognises the nucleocapsid (NC) protein of all known Lyssaviruses and with MAb 422-5 which identifies African rabies-related viruses. All four canine virus isolates displayed positive fluorescence with MAb 502-2 and were negative with MAb 422-5. In the anti-NC MAb characterisation with a panel of 34 additional MAbs, all isolates displayed positive staining with 32 of the MAbs, were negative with MAb 102-27 and all displayed poor immunofluorescence with MAb 377-7. On the basis of reactivity with a panel of 40 anti-glycoprotein (G) MAbs the isolates were separated into four distinct viral subtypes. None of these canine isolates was identified as the common attenuated Flury LEP rabies strain used for domestic animal vaccination and none resembled other previously characterised rabies viruses from Nigeria.

Rabies has a long history of occurrence throughout Africa, spanning hundreds of years. At least four distinct Lyssavirus species persist throughout the continent, among carnivores, bats and other mammals. Rabies virus is the most cosmopolitan member, with primary reservoirs within dogs and mongoose, but other wildlife vectors are important in viral maintenance, such as jackals. Besides a prominent toll on humans and domestic animals, the disease has an underappreciated role in conservation biology, especially for such highly endangered fauna as African wild dogs and Ethiopian wolves. Both Duvenhage and Lagos bat viruses are adapted to bats, but their epidemiology, together with Mokola virus, is poorly understood. Significantly, less than ideal cross-reactivity with modern biologicals used for veterinary and public health interventions is a major cause for concern among these emerging viral agents.

More than 3,000 bats were examined for lyssaviruses in the territory of the Former Soviet Union (FSU) over the past 41 years (1964-2004). European bat lyssavirus type 1 (EBLV-1) was registered in the Ukraine and the European part of Russia. Lyssaviruses Aravan (ARAV, Kyrgyzstan, 1991), Khujand (KHUV, Tajikistan, 2001), Irkut (IRKV, Irkutsk region, 2002) and West Caucasian Bat virus (WCBV, Krasnodar region, 2002) were proposed as new lyssavirus genotypes. All reports on rabies virus (RABV; serotype/genotype 1) isolation from bats to date are questionable and must be corroborated. Two human rabies cases of bat origin were registered in the town of Voroshilovgrad, the Ukraine (1977) and the town of Belgorod, Russia (1985). The second case was confirmed as EBLV-1, whereas the first case was not identified. At least five lyssaviruses, different from RABV and from each other, were recognized in the territory of the FSU, and their potential significance for veterinary and public health should not be underestimated.

Animal management is the keystone of any modern programme for the prevention and control of rabies. Historically, "animal control" for local elimination of disease was largely equated with population reduction. However, with relatively few exceptions, culling alone has not led to effective control of rabies. In most documented examples of effective control of rabies in the 20th century, an integrated management approach was used that included public education, responsible stewardship of animal populations, manipulation of the population carrying capacity of the local habitat, and vaccination strategies. Globally, the greatest burden on human health that is attributable to this zoonosis is caused by uncontrolled rabies in dogs. Where political willingness, biomedical infrastructure, and economic stability permit the sustained use of control measures (e.g. stray animal removal and mandatory parenteral vaccination), canine rabies has been significantly suppressed and even eliminated over large geographical areas. Examples include many island nations, most of North America, Europe, and increasingly in South America. Despite the effectiveness of such proven control techniques, however, their implementation in parts of Asia, Africa, and elsewhere has been limited, primarily because of a lack of dedicated resources and intersectoral cooperation, and also because of the burden of high-density populations of dogs. Implementation is often complicated by cultural and social factors, e.g. reluctance to cull apparently ownerless, nuisance animals that are suspected to have been exposed to rabies, partly on the basis of religious beliefs). Attempts to modify animal fertility (such as the encouragement of voluntary spay-neuter programmes or individual chemical contraception, and the extension of such actions to animals in the community) may provide ancillary support in line with other traditional methods of control of canine rabies. With the identification of complex situations in which wildlife rabies persists despite the elimination of canine rabies, e.g. in North America and Europe, cats can pose a significant public health risk requiring consideration of alternative approaches. In any model system, the threat of translocation of infected animals, unintentional or otherwise, provides a strong rationale for the creation of barriers to prevent reintroduction or exacerbation of the disease, and the maintenance of a minimum body of expertise related to surveillance, diagnosis, and the enactment of mitigating measures. While control activities have traditionally focused upon certain Carnivora species, bats represent another worldwide rabies reservoir. Indiscriminate killing of bats and destruction of roosts was once the norm, but such activities are not sanctioned by reputable organizations today. Even vampire bats, responsible for substantial effects on health and agricultural losses in the New World (Mexico to Argentina), should be targeted only by specific control applications, rather than by more widespread, unconventional, non-specific methodology. Bats should be excluded from human living quarters. Implementing measures to prevent bats from gaining access to homes should occur at an appropriate time when the bats are absent, especially to avoid sealing the non-flying young within a building. Although great progress has been made during the past four decades in the induction of herd immunity among free-ranging carnivores via oral vaccination against rabies, similar novel solutions have not been readily applied to bat populations. Given these challenges, new paradigm shifts are eagerly anticipated as additional biotechnological applications (including contraceptives and anticoagulants) are developed to deal with domestic animals and wildlife.

Microscopic vacuolar changes in neuronal perikaryon are described in two free-ranging raccoons ( Procyon lotor) from different geographic locations in the United States. Both animals were negative for rabies and scrapie-associated antigens. Microscopically, lesions were not seen in the neuropil. Neuronal vacuolations have previously been documented in brains of normal animals and in diseases such as rabies and prion-associated encephalopathies. Although experimental transmission of a spongiform mink encephalopathy has been documented in raccoons, a naturally occurring spongiform encephalopathy has not been described in this species. The presence of neuronal vacuolations in the raccoons is novel and requires further investigation to elucidate the mechanism of this phenomenon.

Rabies is an acute, progressive, fatal encephalitis caused by viruses in the Family Rhabdoviridae, Genus Lyssavirus. Rabies virus is the representative member of the group. Warm-blooded vertebrates are susceptible to experimental infection, but major primary hosts for disease perpetuation encompass bats and mammalian carnivores. The dog is the global reservoir, and important wild carnivores include foxes, raccoons, skunks, and mongoose, among others. Traditionally, reliance upon long-term, widespread, government-supported programmes aimed at population reduction of animals at risk has been unsuccessful as the sole means of rabies control, based in part upon economical, ecological and ethical grounds. In contrast, immunization of domestic dogs with traditional veterinary vaccines by the parenteral route led to the virtual extinction of canine-transmitted rabies in developed countries. Taken from this basic concept of applied herd immunity, the idea of wildlife vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of carnivores by the 1970s. The development of safe and effective rabies virus vaccines applied in attractive baits resulted in the first field trials in Switzerland in 1978. Thereafter, technical improvements occurred in vaccine quality and production, including the design of recombinant viruses, as well as in the ease of mass distribution of millions of edible baits over large geographical areas. Over the past few decades, extensive oral vaccination programmes focusing upon the red fox, using hand and aerial distribution of vaccine-laden baits, have resulted in the virtual disappearance of rabies in Western Europe. The same dramatic observation held true for southern Ontario. During the 1990s in the United States, oral vaccination programmes concentrated upon raccoons, grey foxes, and coyotes, with similar success. For example, raccoon rabies has not spread west of the current focus in the eastern states, grey fox rabies is contained in west central Texas, and no recent cases of rabies have been reported from coyotes away from the Mexican border for several years. Despite the progress observed and the absence of substantive adverse environmental or health effects, oral vaccination is not a panacea, and should be viewed as an important adjunct to traditional prevention and control techniques in human and veterinary medicine. Local outbreak suppression of rabies among free-ranging wildlife is documented, and regional elimination of particular virus variants among specific, targeted carnivore hosts is demonstrable, but true disease eradication is not achievable at the present time by current techniques. For example, no practical vaccination methods have been designed for bats. Although lyssaviruses appear in relative compartmentalization between the Chiroptera and Carnivora, major spillover events have been detected from bats to carnivores, and phylogenetic analyses suggest a historical basis for extant viral origins due to interactions between these taxa. Thus, bio-political considerations aside, the possibility for pathogen emergence resulting from transmission by rabid bats with subsequent perpetuation among other animals cannot be discounted easily on any continent, with the possible exception of Antarctica. Clearly, given their biodiversity, distribution, and abundance, novel methods would be necessary to consider meaningful control of rabies in these unique volant mammals. Newer approaches in biotechnology may be envisaged some day for eventual extension to bats, as well as more widespread application to global canine rabies remediation in developing countries.

Rabies virus variants associated with silver-haired bats (SHBRV) are responsible for most recent human rabies cases in the United States, which are not associated with a history of exposure. We compared their genotype and phenotype with those of dog rabies virus (DRV) variants, the classic cause of rabies in humans, to determine whether differences in these strains might have ramifications for therapeutic intervention, particularly vaccination.Eleven silver-haired bat and 8 dog rabies virus isolates were characterized by sequencing the glycoprotein gene, by assessing their ability to replicate in neuronal versus nonneuronal cultures at optimal and suboptimal temperatures, by assessing their pathogenicity in mice, and by determining the resistance of these viruses to therapeutic immunization with commercial vaccines.SHBRV isolates were less genetically diverse, less neuronal cell specific, more temperature sensitive, but as pathogenic, on average, as DRV isolates. Immune protection was equivalent for SHBRV and DRV strains of similar pathogenicity.SHBRV strains have unique characteristics that may explain their exceptional association with human rabies but have little bearing on their lethality in mice. The pathogenicity of a particular virus, rather than its antigenic makeup, determines the outcome of immunization.

A retrospective survey of 760 raccoons (Procyon lotor) revealed 9 animals with sarcocysts of Sarcocystis kirkpatricki in their brains. Six of the raccoons also had the organisms in their skeletal muscles, and 1 had them in the heart muscle. No age or gender predisposition was seen. Seven of the raccoons had concurrent viral diseases (canine distemper or rabies), suggesting that concurrent viral infections in raccoons may facilitate infection of brain tissue with S. kirkpatricki.

Four pairs of raccoons were treated orally with the following doses of lead acetate (mg/kg; 5 days/week, for 8 weeks): 0 (control), 1, 2 and 4. In the six experimental animals, this treatment produced dose-dependent increases in blood lead, without clinical signs or changes in haematological parameters. After 8 weeks, the liver and kidney of all lead-treated animals and the calvarium and radius of those receiving doses of 2 and 4 mg/kg contained elevated concentrations of lead. Acid-fast inclusions were observed by light and electron microscopy in the kidneys of all raccoons receiving the two highest doses and in one animal receiving the lowest dose. Hepatic acid-fast inclusions were seen in only one animal (dose 4 mg/kg). No inclusions were seen in osteoclasts of the radius. It is suggested that the findings, which support earlier observations that raccoons are fairly resistant to lead, may be of value in studying interactions between lead exposure and oral vaccination of wildlife against rabies.

In 1997, 49 states, the District of Columbia, and Puerto Rico reported 8,509 cases of rabies in nonhuman animals and 4 cases in human beings to the Centers for Disease Control and Prevention. Nearly 93% (7,899) were wild animals, whereas 7% (610) were domestic species. The total number of reported cases increased 19.4% from that of 1996 (7,128 cases). Increases were apparent in each of the major species groups, with the exception of cattle. The relative contributions of these groups to the total reported for 1997 were as follows: raccoons (50.5%; 4,300 cases), skunks (24.0%; 2,040), bats (11.3%; 958), foxes (5.3%; 448), cats (3.5%; 300), dogs (1.5%; 126), and cattle (1.4%; 122). The 958 cases of rabies reported in bats represented a 29.3% increase over the total reported for 1996 and the greatest number reported since 1984, with cases reported by 46 of the 48 contiguous states. The epizootic of rabies in raccoons expanded into Ohio in 1997 and now includes 19 states and the District of Columbia. Thirteen states, where rabies in raccoons is enzootic, reported increases over 1996 in total numbers of reported cases. New York (1,264 cases), North Carolina (879), Virginia (690), and Maryland (619) reported the greatest numbers of cases [corrected]. Five states reported increases that exceeded 50%, compared with cases reported in 1996: Ohio (673.3%; 15 cases in 1996 to 116 in 1997). Massachusetts (144.3%; 115 to 281), South Carolina (97.9%; 96 to 190), Connecticut (97.4%; 274 to 541), and Maine (86.3%; 131 to 244). Cases of rabies associated with foci of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas continued to decline, with this state reporting 78.3% fewer rabid foxes (13 cases), 26.7% fewer rabid dogs (11), and 63.2% fewer rabid coyotes (7) during 1997, compared with 1996. Reported cases of rabies in cats (300) and dogs (126) increased 12.8% and 13.5%, respectively, whereas cases in cattle (122) decreased by 6.9%. Thirty states, the District of Columbia, and Puerto Rico reported increases in rabies in animals during 1997, compared with decreases reported by 31 states and the District of Columbia in 1996. One state (Mississippi; 5 cases) remained unchanged. Hawaii was the only state that did not report a case of rabies in 1997. Four indigenously acquired cases of rabies reported in human beings were the result of infection with rabies virus variants associated with bats.

To determine susceptibility, incubation and morbidity periods, clinical signs of infection, serologic response, and excretion of virus in domestic ferrets inoculated with rabies virus of raccoon origin.54 domestic ferrets.5 groups of ferrets were inoculated IM with the rabies virus. Oral cavity swab specimens and saliva were obtained for virus isolation. Blood was obtained for virus-neutralizing antibody determination. If clinical signs were severe, ferrets were euthanatized immediately. Salivary gland and brain tissue was collected for virus isolation and rabies diagnosis, respectively.Of 51 inoculated ferrets, 19 (37%) were euthanatized with clinical signs of rabies. Mean incubation period was 28 days (range, 17 to 63 days). Clinical signs included ataxia, cachexia, inactivity, paresis, paraparesis, bladder atony, tremors, hypothermia, lethargy, constipation, paralysis, and anorexia. Two rabid ferrets manifested aggressive behavior. Mean morbidity period was 4 to 5 days (range, 1 to 8 days). Virus antigen was detected in brain tissue from all rabid ferrets (n = 19). Two rabid ferrets had detectable virus-neutralizing antibody. Of 32 ferrets that survived, only 1 seroconverted; survivors remained clinically normal throughout the observation period. Rabies virus was isolated from salivary glands of 12 of 19 (63%) rabid ferrets, and 9 (47%) shed virus in saliva. Initiation of virus excretion ranged from 2 days before onset of illness to 6 days after onset.Rabies should be considered in the differential diagnosis for ferrets that have acute onset of paralysis or behavioral changes and a condition that rapidly deteriorates despite intense medical intervention.

To evaluate the use of bait containing rabies vaccine to create a barrier of rabies-vaccinated raccoons in Massachusetts and to determine the effectiveness of various bait distribution strategies in halting the spread of rabies.Prospective study.Free-ranging raccoons.Baits were distributed twice yearly in a 207-km2 (80-mi2) area in the vicinity of the Cape Cod Canal. Bait density and distribution strategy varied among 3 treatment areas. Raccoons were caught in live traps after bait distribution and anesthetized; blood samples were obtained to measure serum antibody titers to rabies virus. Vaccination rates were determined by the percentage of captured raccoons with antibody titers to rabies virusor = 1:5. In addition, raccoons with clinical signs of illness inside the vaccination zone and adjacent areas were euthanatized and submitted for rabies testing.The percentage of vaccinated raccoons differed significantly among the following 3 areas with various bait densities: high-density area with uniform bait distribution (103 baits/km2 [267 baits/mi2]) = 37%; low-density area with additional targeted bait distribution (93 baits/km2 [240 baits/mi2]) = 67%; and, high-density area with additional targeted bait distribution (135 baits/km2 [350 baits/mi2]) = 77%. Nineteen animals with rabies (15 raccoons, 3 skunks, 1 cat) were reported in the area just outside of the vaccination zone, but only 1 raccoon with rabies was reported from inside the vaccination zone.In this suburban study area, an approximate vaccination rate of 63% was sufficient to halt the spread of rabies in free-ranging raccoons. Compared with uniform bait distribution, targeting raccoon habitats increased vaccination rates.

To document the number of human contacts with bait containing liquid vaccinia-rabies glycoprotein (V-RG) vaccine, to evaluate factors that might affect human contact with bait-vaccine units, and to summarize adverse reactions in people after contact with vaccine.Retrospective 4-year survey of directors of 6 oral rabies vaccination programs.Human residents in areas of vaccination programs.Data were collected from report forms and telephone conversations with directors of oral rabies vaccination programs in Florida, Massachusetts, New Jersey, Texas, and New York. Data collected included information regarding human contact with bait and vaccine, sex and age of person involved in contact, human population density, bait density, type of labeling used on bait, and other factors.Human contact with bait was more likely in areas where bait had white labels (vs lettering in black ink) and in areas with high human population densities. Directors of all programs reported that human contact with bait-vaccine units was minimal. Adverse reactions in exposed people were not reported. On the basis of these findings, concerns about V-RG vaccine posing a substantial public health risk remain unfounded.Directors of oral rabies vaccination programs should systematically collect information about exposures and potential factors affecting exposure of people to bait-vaccine units. People with substantial exposure to V-RG vaccine should be evaluated for immune status and any resulting symptoms should be documented and monitored.

To identify common elements of large-scale human exposures to rabid or presumed rabid animals in the United States from 1990 to 1996.Retrospective study.Health departments in 50 states and the District of Columbia were contacted regarding episodes of large-scale human exposures to rabid animals occurring between 1990 and 1996. A large-scale exposure was defined as administration of postexposure prophylaxis (PEP) to 25 or more people after an exposure to a rabid or presumed rabid animal or littermates. Incident-specific information was obtained through questionnaires sent to states reporting episodes. Data are reported as medians.Fifteen of 51 (29.4%) health departments reported 22 episodes; 72.7% involved companion animals or livestock. Twenty-six animals were involved in these 22 episodes, including 10 (38.5%) dogs, 4 (15.4%) livestock, 4 (15.4%) raccoons, 3 (11.5%) cats, 3 (11.5%) bats, and 2 (7.7%) ferrets. Schools (36.4%) and public places (22.7%) were the most common settings for exposures. Reportedly, 1,908 people received PEP. The cost for 10 episodes was $61,547/episode (range, $14,199 to $1,500,000). An episode-specific written algorithm for recommending PEP had been developed for use in only 4 (18.2%) episodes.Large-scale exposures most commonly involved a single companion animal. Exposures attributable to improper handling of wildlife and unrestricted access of animals in schools and public areas can be potentially remedied by targeted education. Use of an episode-specific algorithm to determine need for PEP may also reduce the number of unnecessary treatments.

In 1996, 49 states, the District of Columbia, and Puerto Rico reported 7,124 cases of rabies in non-human animals and 4 cases in human beings to the Centers for Disease Control and Prevention. Nearly 92% (6,550 cases) were wild animals, whereas 8% (574 cases) were domestic species. The total number of reported cases decreased 9.6% from that of 1995 (7,881 cases). Although much of the decline was the result of fewer reported cases of rabies in raccoons, fewer cases were also reported among most groups of animals. Numbers of cases associated with separate epizootics of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas attributable to canine variants have declined, with 56.2% fewer rabid foxes (60), 72.7% fewer rabid dogs (15), and 76.3% fewer rabid coyotes (19) during 1996, compared with cases of rabies reported among these same species during 1995. Nationally, the number of reported rabid bats (741) decreased 5.8%, with cases reported by 46 of the 48 contiguous states. Four Eastern Seaboard states, enzootic for the raccoon variant of the rabies virus, reported noteworthy increases in total numbers of reported cases: Maine (29.7%; 101 cases in 1995 to 131 in 1996), Maryland (44.2%; 441 to 636), North Carolina (59.0%; 466 to 741), and Virginia (33.3%; 459 to 612). Increases were also reported by Florida (6.4%; 251 to 267) and Georgia (3.1%; 294 to 303). Cats continued to be the domestic animal most frequently reported rabid, but reported cases of rabies in cats (266), cattle (131), and dogs (111) decreased by 7.6%, 3.7%, and 24.0%, respectively. Thirty-one states and the District of Columbia reported decreases in rabies in animals during 1996, compared with 18 states and Puerto Rico in 1995. Hawaii was the only state that did not report a case of rabies in 1996. Two indigenously acquired cases of rabies reported in human beings were the result of infection with rabies virus variants associated with bats, whereas the remaining 2 human rabies infections were acquired outside the United States, and the variants identified were consistent with those associated with rabid dogs.

To determine susceptibility, incubation and morbidity periods, clinical signs, serologic response, and excretion of virus in domestic ferrets inoculated with rabies virus.55 domestic ferrets.5 groups of 10 ferrets were inoculated with rabies virus, IM, at doses of 10(5.5) to 10(1.5) median mouse intracerebral lethal dose. Ferrets were observed and behavior was recorded. Rectal temperature, body weight, and samples from the oral cavity and samples of saliva and blood were obtained. Virus isolation was attempted, using intracranial mouse inoculation and cell culture. Virus neutralizing antibodies were determined by rapid fluorescent focus inhibition test. Ferrets were euthanatized immediately if clinical signs were severe. Rabies was confirmed by direct immunofluorescent antibody test.Mean incubation period was 33 days (range, 16 to 96 days). Clinical signs included ascending paralysis, ataxia, cachexia, bladder atony, fever, hyperactivity, tremors, and paresthesia. Mean morbidity period was 4 to 5 days (range, 2 to 10 days). Virus antigen was detected in brain tissue from all clinically rabid ferrets. Ferrets given the highest viral dose were euthanatized and had VNA; ferrets receiving the next dilution also were euthanatized, but only 4 had seroconverted. Of 17 ferrets that survived, 5 seroconverted. Survivors remained clinically normal except for 1 that recovered with severe paralytic sequelae. Rabies virus was isolated from the salivary gland of 1 ferret that was euthanatized.Rabies should be considered as a differential diagnosis in any ferret that has acute onset of paralysis or behavioral changes and a condition that rapidly deteriorates despite intense medical intervention.

In 1995, 49 states, the District of Columbia, and Puerto Rico reported 7,877 cases of rabies in nonhuman animals and 4 cases in human beings to the Centers for Disease Control and Prevention. Nearly 92% (7,247 cases) were wild animals, whereas 8% (630 cases) were domestic species. The total number of reported cases decreased 4.2% from that of 1994 (8,230 cases). Most of the decline was the result of 17.1% fewer reported cases of rabies in raccoons in areas of the Northeast, where rabies is now enzootic rather than epizootic. Exceptions to this decline were detected in states where the virus has only recently entered raccoon populations or where ongoing epizootics persist. States experiencing increasing epizootic activity associated with this variant include Maine (3 cases in 1993 to 101 cases in 1995), North Carolina (9 cases in 1990 to 466 cases in 1995), Rhode Island (1 case in 1993 to 324 cases in 1995), and Vermont (45 cases in 1993 to 179 cases in 1995). The raccoon variant of the rabies virus is now present in Alabama, Pennsylvania, Vermont, West Virginia, and all Atlantic Seaboard states from Florida to Maine. In Ohio, this variant, last detected in 1992 as a single case, was again detected in 1996. Epizootics of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas attributable to canine variants continue, with this state reporting 137 rabid foxes, 55 rabid dogs, and 80 of the 83 cases in coyotes during 1995. The number of rabid bats (787) increased by almost 25%, with cases reported by 47 of the 48 contiguous states. Nationally, reported cases of rabies in cattle (136) and cats (288) increased by 22.5 and 7.9%, respectively, whereas cases in dogs (146) decreased by 4.6%. Cats continued to be the domestic animal most frequently reported rabid. The cases of rabies reported in human beings were all caused by viral variants associated with bats. Eighteen states and Puerto Rico reported decreases in rabies in animals in 1995, compared with 28 states and the District of Columbia in 1994. Hawaii was the only state that did not report a case of rabies in 1995.

OVER THE LAST 100 years, rabies in the United States has changed dramatically. More than 90% of all animal rabies cases reported annually to the CDC now occur in wildlife, whereas before 1960 the majority were in domestic animals. The principal rabies hosts today are wild carnivores and bats infected with several viral variants. Annual human deaths have fallen from more than a hundred at the turn of the century to one to two per year despite major outbreaks of animal rabies in several geographic areas. Modern day prophylaxis has proven nearly 100% successful; most human fatalities now occur in people who fail to seek medical treatment, usually because they do not recognize a risk in the animal contact leading to the infection. Although these human rabies deaths are rare, the estimated public health costs associated with disease detection, prevention, and control have risen, exceeding millions of dollars each year. Cost considerations must be weighed along with other factors in addressing issues such as the appropriate handling of nontraditional and exotic pets, future guidelines for rabies prophylaxis, and novel methods of disease prevention.

A Sarcocystis neurona-like organism was associated with granulomatous encephalitis in an ataxic male juvenile striped skunk (Mephitis mephitis) from Cape Cod, Massachusetts. Various stages of schizonts and merozoites of S. neurona were seen within some of the granulomata.

In 1994, 48 states, the District of Columbia, and Puerto Rico reported 8,224 cases of rabies in nonhuman animals and 6 cases in human beings to the Centers for Disease Control and Prevention. Nearly 93% (7,632 cases) were wild animals, whereas 7% (592 cases) were domestic species. The total number of reported cases decreased 13.4% from that of 1993 (9,498 cases), with most of the decline resulting from 19.2% fewer cases of rabies in raccoons. Two previously described epizootics of rabies involving the raccoon variant of the rabies virus have converged in North Carolina, and the resulting region is now continuous from Alabama and Florida in the South to Maine in the North. Epizootics of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas continue to expand, with this state reporting 144 rabid foxes, 53 rabid dogs, and 77 of the 85 cases in coyotes during 1994. Maine and New Hampshire reported cases of rabies in foxes (6 and 9, respectively) for the first time in 10 years. Nationally, reported cases of rabies in dogs (153) increased by 17.7%, whereas cases in cattle (111) and cats (267) decreased by 14.6 and 8.3%, respectively. Cats continued to be the domestic animal most frequently reported rabid. Twenty-eight states and the District of Columbia reported decreases in rabies in animals in 1994, compared with 22 states, the District of Columbia, and Puerto Rico in 1993. Hawaii and Nebraska were the only states that did not report cases of rabies in 1994.

In 1993, 49 states, the District of Columbia, and Puerto Rico reported 9,495 cases of rabies in nonhuman animals and 3 cases in human beings to the Centers for Disease Control and Prevention. Greater than 93% (8,889 cases) were wild animals, whereas 6.4% (606 cases) were domestic species. The total number of reported cases increased 9.9% over that of 1992 (8,645 cases), with most of the increase resulting from continued spread of rabies in raccoons (37.1% increase in reported cases over 1992). The 2 epizootics of rabies in raccoons (Northeastern/mid-Atlantic and Southeastern regions) approach convergence in North Carolina (106 cases of rabies in 1993, compared with 49 in 1992). Maine, Rhode Island, and Vermont remained the only New England states without reported cases associated with the raccoon variant of the rabies virus. New York reported 2,747 cases of rabies, the largest number of cases ever reported during a single year by any state. Increases in reported cases of rabies in Texas and 8 other geographically dispersed states were attributed mainly to larger numbers of reported cases of rabies in bats. Texas reported 71 of the 74 cases in coyotes during 1993 (70 of 75 cases in 1992). Nationally, reported cases of rabies in dogs (130) and cattle (130) each decreased by 29% in 1993, whereas cats (291 cases in 1993, compared with 290 in 1992) continued to be the domestic animal most frequently reported rabid. Twenty-two states and Puerto Rico reported decreases in rabies in animals in 1993, compared with 20 states, the District of Columbia, and Puerto Rico in 1992. Hawaii was the only state that did not report a case of rabies in 1993.

With the advancement of recombinant DNA techniques, a number of potent biologicals are available for the oral vaccination of free-ranging animals. Once oral immunogenicity and vaccine safety have been demonstrated, efficacy then becomes of paramount importance. Classical assessment of efficacy is conducted under carefully controlled laboratory conditions, whereas efficacy of oral wildlife rabies vaccination programs, to date, have been assessed by the lack (or occurrence) of field cases of rabies in a vaccinated area. This communication describes an intermediate vaccine efficacy strategy in which self-vaccinated, free-ranging animals from a study site were captured seven months after vaccine-laden bait distribution for laboratory rabies challenge. This technique is specifically reviewed in the context of available recombinant products for the consideration of extension towards dog rabies control.

Six raccoons (Procyon lotor) without detectable Toxoplasma gondii antibodies were used. Four raccoons were inoculated orally (2 with oocysts and 2 with tissue cysts) with ME49 strain of T. gondii and 2 raccoons were not inoculated with T. gondii. All raccoons remained clinically normal. Raccoons were killed between 59 and 61 days after inoculation and portions of their heart, skeletal muscle, and brain were digested in pepsin solution, and homogenates were bioassayed in mice. Toxoplasma gondii was isolated from all 4 inoculated raccoons; from the heart of 3, skeletal muscles of 2 and the brain of none. All 4 inoculated raccoons developed antibody titersor = 1:1,600 in the modified direct agglutination test (MAT) using whole formalinized tachyzoites. Toxoplasma gondii antibody titers of the raccoons not inoculated with T. gondii remained1:25, and T. gondii was not isolated from their tissues. It was concluded that muscle tissue from multiple sites including the heart was the tissue of choice for conducting parasitologic surveys for T. gondii in raccoons. Evaluation of the sera of the experimentally infected raccoons in the Sabin-Feldman dye test, latex agglutination test, and the indirect hemagglutination tests indicated that the MAT detected antibodies faster and in higher titers than did the other serological tests.

During the field safety evaluation of a vaccinia-rabies glycoprotein recombinant virus vaccine for wildlife, two biomarkers were used to identify potential contact with vaccine-laden baits. Tetracycline, a commonly used and reliable calciphilic tissue marker, was included in a fish-meal polymer bait matrix and was evaluated from post-mortem bone samples. Additionally, an ante-mortem marker was needed to identify, for prospective study, raccoons which had contacted baits and thus, potentially, vaccine. Sulfadimethoxine (SDM) was included in an attractant slurry surrounding the bait, as a novel short-term seromarker. Preliminary laboratory studies in raccoons demonstrated SDM residues for up to one week following ingestion of a single 250 mg dose. During the first six days after bait distribution, 49 individual raccoons were live-trapped in the vaccination area. SDM was detectable in 38 of 49 (77.5%) serum samples. Similarly, 47 of 56 (83.9%) bone samples from raccoons collected in the vaccination area throughout the twelve-month study were tetracycline-positive. Conversely, none of the serum samples (n = 12) from the first six days of the trial nor any of the bone samples (n = 34) from raccoons in the surveillance area were biomarker-positive.

Rabies and Borna disease viruses have been regarded as classical neurotropic agents. Many pathogenetic similarities are shared by these two negative strand RNA viruses. In view of recently gained data on the virology and pathology of these two diseases, and up-to-date comparative pathogenetic study seems to be justified.This study is based on a survey of experimental and natural infections of laboratory animals and natural hosts. The morphologic damage to the nervous system has been evaluated by light and electron microscopy, with special emphasis on immunocytochemical methods.This comparative study disclosed that both viruses are transported inside axons, pass synapses and propagate along neuronal networks. At the sites of synaptic transfer, full virus particles can never be detected in the early phase of rabies virus infection; in Borna disease virus (BDV) infection, virus particles cannot be found in any phase of disease progression. Thus, a major difference exists between the two agents insofar as rabies virus is morphologically well characterized, whereas BDV has never been visualized in tissue sections. Furthermore, rabies virus infects only neurons, whereas BDV also infects glial cells. The host range and the scale of infection of extraneural tissues by both agents is extremely similar.These observations allow us to postulate that the synaptic transfer of both viruses likely ensures in the form of bare nucleocapsids (ribonucleoprotein-transcriptase complexes). While in the later phases of replication complete rabies virions are regularly assembled, BDV propagates within the central nervous system in an incomplete form, so that it remains morphologically imperceptible. Thus, BDV may appear in a complete, enveloped form only when exiting the host organism. The dissemination patterns of the two agents may be influenced by specific affinities to neurotransmitter receptor sites. It remains unresolved, why BDV readily infects non-neuronal central nervous system cells, while rabies virus remains restricted to neuronal elements.

Serum samples from 427 raccoons (93 from Pennsylvania, 45 from New Jersey, 72 from South Carolina, 68 from Virginia, 30 from Iowa, and 119 from Ohio) were evaluated for Toxoplasma gondii antibodies in dilutions of 1:25, 1:50, and 1:500. The distribution of T gondii antibody titers was less than 1:25 for 212 raccoons (49.6%), 1:25 for 34 raccoons (7.9%), 1:50 for 117 raccoons (27.4%), and greater than or equal to 1:500 for 64 raccoons (14.9%). Tissue cysts were seen in the liver, and tachyzoites were in the brain of a raccoon with abnormal neurologic signs and concurrent infection with canine distemper virus. Organisms in the liver were stained with anti-T gondii serum, and the raccoon had a T gondii titer of 1:160 in the agglutination test.

Efficacy of an SC-administered commercial inactivated vaccine for prevention of rabies was evaluated in domestic ferrets. Ferret immunity was challenged by the IM inoculation of street rabies virus. All ferrets developed titers of rabies virus-neutralizing antibodies within 30 days of vaccination (geometric mean titer [GMT] = 154, n = 41) that were maintained for at least one year (GMT = 106, n = 36), compared with no seroconversion in controls (GMT less than 5, n = 39). Following rabies virus challenge inoculation, 89% (32/36) of vaccinated ferrets survived vs less than 6% (2/38) survival in control ferrets. These results demonstrate the protective efficacy of a commercial, inactivated rabies vaccine of at least one year's duration for domestic ferrets.

Concurrent infection of a raccoon by rabies and canine distemper viruses is described. Fluorescent antibody (FA) test demonstrated rabies antigen in the brain of this animal, however, histologically only lesions characteristic of canine distemper infection were seen. We recommend testing tissues for rabies of animals that histologically are positive for canine distemper.

Five hundred healthy Nigerian dogs were randomly selected and bled for serological detection of antibodies to lyssa-viruses, including Mokola, Lagos bat and Duvenhage viruses. The canine sera were screened for virus neutralising antibodies by a modification of the rapid fluorescent focus inhibition technique. Three serum samples were seropositive to Mokola virus but all were negative to Lagos bat and Duvenhage viruses. The three seropositive Mokola samples were also negative for rabies virus neutralising antibodies. This finding may explain occasional rabies-like canine mortalities within one year of antirabies vaccination in Nigeria.

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.