Public awareness of rabies and compliance with pet vaccination laws in Connecticut, 1993

OBJECTIVE: To determine the degree of public awareness of rabies and compliance with cat and dog vaccination laws in Connecticut in 1993. DESIGN: Monthly telephone surveys. SAMPLE POPULATION: 1,810 households. PROCEDURE: A telephone interview was conducted, using rables-related questions contained in the Behavioral Risk Factor Surveillance System, with an adult member from households randomly selected statewide by telephone number. Results of the surveys for the year were aggregated, and weighted data were analyzed. RESULTS: Ninety percent of respondents had heard about rabies during the preceding year, and 84% considered it a problem in Connecticut. Forty-seven percent of households surveyed owned dogs or cats. Ninety-three percent of dogs and 80% of cats were reported to be vaccinated against rabies. Twenty-two percent of households with cats had at least 1 cat that was not current on rabies vaccination. CLINICAL RELEVANCE: In Connecticut, an epizootic of rabies in raccoons was accompanied by a high degree of awareness of rabies and rate of reported vaccination of dogs and cats. However, vaccination of cats was less common than that of dogs. Public education efforts should emphasize the necessity to vaccinate cats and to avoid contact with unknown cats in rabies epizootic or enzootic areas. A surveillance system can be used to help evaluate public health programs.     

Bats, cats, and rabies in an urban community

Bats are the primary vectors of rabies in humans in the United States. In the urban environment they generally are found within buildings where they may bite people or be attacked by cats or dogs. Given the high probability that any bat that bites a person may be rabid, antirabies prophylaxis should be administered as soon as possible after the incident. This should not be delayed pending laboratory results on the bat. Children should be taught to avoid contact with moribund bats. Cats are more likely to be involved with rabid bats than dogs, but they are less likely to be vaccinated against rabies. The occasional rabid cat in an urban community may have acquired its infection from a bat. Therefore, it is vital that communities enforce rabies vaccination for cats as well as dogs.     

Human diploid cell culture rabies vaccine (HDCV) and purified chick embryo cell culture rabies vaccine (PCECV) both confer protective immunity against infection with the silver-haired bat rabies virus strain (SHBRV)

The demonstration of extensive differences in the antigenic makeups of the silver-haired bat rabies virus (SHBRV) and canine rabies virus (COSRV) strains raised concerns as to whether current licensed rabies vaccines are sufficiently protective against SHBRV. NIH mouse protection test results show that both the human diploid cell culture rabies vaccine (HDCV) and the purified chicken embryo cell rabies vaccine (PCECV) protected against lethal infection with SHBRV as well as the canine rabies strain COSRV. However, in this investigation, the potencies of both vaccines in mice were found to be significantly higher for COSRV than for SHBRV. The in vivo protection data are confirmed by in vitro virus neutralizing antibody (VNA) test results which demonstrate that mice immunized with HDCV or PCECV develop significantly higher VNA titres against COSRV than against SHBRV. In contrast, VNA tests of sera from individuals immunized with HDCV or PCECV showed that humans, as opposed to mice, develop significantly higher VNA titres against SHBRV than against COSRV. These data suggest that HDCV and PCECV will protect humans against infection with the silver-haired but rabies virus strain in addition to canine rabies virus strains.     

Failure of protection induced by a Brazilian vaccine against Brazilian wild rabies viruses

This report shows that the SMB vaccine currently used in Brazil for human immunisation provides different degrees of protection in mice, depending on the rabies virus strain used as challenge. Using the NIH and Habel potency tests to evaluate the protective activity of rabies vaccine, we observed that vaccinated mice showed a higher resistance to a challenge with a fixed rabies virus (CVS-Challenge Virus Strain). The vaccine potency using the Habel or NIH tests was respectively > 6.4 (log 10) and 1.0 (Relative Potency-RP) when the fixed rabies virus was used for challenge, and from 2.9 to 4.3 (log 10) or 0.13 to 0.8 (RP) when different wild rabies viruses were used for challenge. The presence of virus neutralising antibodies (VNA) could not explain the differences of susceptibility after vaccination, since sera of vaccinated animals had similar VNA levels against both fixed and wild strains before virus challenge (respectively, 5.6 +/- 0.24 and 5.0 +/- 0.25 IU/ml of VNA against the fixed rabies virus and the 566-M strain of wild rabies virus in sera of mice vaccinated with 0.2 units of vaccine). Only cell-mediated immunity parameters correlated with the protection induced by vaccination. The IFN gamma titers found in sera and brain tissues of animals challenged with CVS strain were higher (from 36.7 +/- 5.7 to 293.3 +/- 46.2 IU/ml) than those found in mice challenged with 566-M virus strain (from 16.7 +/- 5.8 to 36.7 +/- 5.8). The proliferation index of spleen cells obtained with CVS stimulation reached a maximal value of 15.1 +/- 0.7 while spleen cells from vaccinated mice stimulated with 566-M virus failed to proliferate. The implications of these data in human protection by vaccination are discussed.     

Immunization against rabies with plant-derived antigen

We previously demonstrated that recombinant plant virus particles containing a chimeric peptide representing two rabies virus epitopes stimulate virus neutralizing antibody synthesis in immunized mice. We show here that mice immunized intraperitoneally or orally (by gastric intubation or by feeding on virus-infected spinach leaves) with engineered plant virus particles containing rabies antigen mount a local and systemic immune response. After the third dose of antigen, given intraperitoneally, 40% of the mice were protected against challenge infection with a lethal dose of rabies virus. Oral administration of the antigen stimulated serum IgG and IgA synthesis and ameliorated the clinical signs caused by intranasal infection with an attenuated rabies virus strain.     

Duration of protective immunity in experimental canine babesiosis after homologous and heterologous challenge

Three Beagle dogs were monitored clinically and serologically for 55 weeks following an experimental primo-infection and two challenge infections with a heterologous strain of Babesia canis. There was no cross-protection when dogs were challenged with the heterologous strain after 7 months, but there was complete protection when challenged a second time with this heterologous strain 5 months later. Although the serological profile using indirect immunofluorescence showed the same trend whether homologous or heterologus antigen was used, antibody titres generally reached higher values for homologous antigen. Seropositivity in itself was no guarantee for protective immunity against heterologous challenge.     

Chromosomal abnormalities and tumor development: from genes to therapeutic mechanisms

PURPOSE: To summarize the epidemiologic, diagnostic, and clinical features of the 32 laboratory-confirmed cases of human rabies diagnosed in the United States from 1980 to 1996. DATA SOURCES: Data were obtained from case reports of human rabies submitted to the Centers for Disease Control and Prevention by state or local health authorities. STUDY SELECTION: All cases of human rabies reported in the United States from 1980 to 1996 in which infection with rabies virus was confirmed by laboratory studies. DATA EXTRACTION: Patients were reviewed for demographic characteristics, exposure history, rabies prophylaxis, clinical presentation, treatment, clinical course, diagnostic laboratory tests, identification of rabies virus variants, and the number of medical personnel or family members who required postexposure prophylaxis after coming in contact with an exposed person. DATA SYNTHESIS: 32 cases of human rabies were reported from 20 states. Patients ranged in age from 4 to 82 years and were predominantly male (63%). Most patients (25 of 32) had no definite history of an animal bite or other event associated with rabies virus transmission. Of the 32 cases, 17 (53%) were associated with rabies virus variants found in insectivorous bats, 12 (38%) with variants found in domestic dogs outside the United States, 2 (6%) with variants found in indigenous domestic dogs, and 1 (3%) with a variant found in indigenous skunks. Among the 7 patients with a definite exposure history, 6 cases were attributable to dog bites received in foreign countries and 1 was attributable to a bat bite received in the United States. In 12 of the 32 patients (38%), rabies was not clinically suspected and was diagnosed after death. In the remaining 20 cases (63%), the diagnosis of rabies was considered before death and samples were obtained specifically for laboratory confirmation a median of 7 days (range, 3 to 17 days) after the onset of clinical signs. Of the clinical differences between patients in whom rabies was diagnosed before death and those in whom it was diagnosed after death, the presence of hydrophobia or aerophobia was significantly associated with antemortem diagnosis (odds ratio, 11.0 [95% CI, 1.05 to 273.34]). The median number of medical personnel or familial contacts of the patients who received postexposure prophylaxis was 54 per patient (range, 4 to 179). None of the 32 patients with rabies received postexposure prophylaxis before the onset of clinical disease. CONCLUSIONS: In the United States, human rabies is rare but probably underdiagnosed. Rabies should be included in the differential diagnosis of any case of acute, rapidly progressing encephalitis, even if the patient does not recall being bitten by an animal. In addition to situations involving an animal bite, a scratch from an animal, or contact of mucous membranes with infectious saliva, postexposure prophylaxis should be considered if the history indicates that a bat was physically present, even if the person is unable to reliably report contact that could have resulted in a bite. Such a situation may arise when a bat bite causes an insignificant wound or the circumstances do not allow recognition of contact, such as when a bat is found in the room of a sleeping person or near a previously unattended child.     

Protective activity of a murine monoclonal antibody against European bat lyssavirus 1 (EBL1) infection in mice

A mouse model was designed to test in vivo the efficacy of rabies immune globulins and specific neutralizing monoclonal antibodies to prevent European bat lyssavirus 1 infection. Human or equine rabies immune globulins previously found to contain variable amounts of neutralizing bat lyssavirus crossreactive antibodies were passively transferred to mice receiving intramuscularly a lethal dose of bat lyssavirus type 1. Immune globulins did not protect mice well against bat lyssavirus 1 whereas they reduced the mortality caused by rabies virus. In contrast, mice inoculated with bat lyssavirus 1 or rabies virus survived when passively immunized with bat lyssavirus 1 specific monoclonal antibody (mAb 8-2). This monoclonal antibody, an IgG2 alpha, recognized an epitope located in the antigenic site IIa of rabies glycoprotein. A mutation replacing the lysine 198 by glutamate in a rabies variant abrogated sensitivity to this neutralizing antibody. Because of its broad neutralizing spectrum against wild virus isolates, including European bat lyssaviruses, this monoclonal antibody should be a good candidate for rabies immune globulin replacement. It could improve efficacy of rabies vaccination, used either alone or in conjunction with human rabies immune globulins or monoclonal antibody cocktail to supplement their lack of crossreactivity to European bat lyssavirus 1.     

Rabies surveillance in the United States during 1997

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.     

Effect of passive immunization or maternally transferred immunity on the antibody response to a genetic vaccine to rabies virus

A plasmid vector, termed pSG5rab.gp, expressing the glycoprotein of rabies virus was tested in young adult or neonatal mice in the presence of maternally transferred immunity or passively administered antibodies to rabies virus for induction of an antibody response. Mice born to rabies virus-immune dams developed an impaired antibody response to genetic immunization at 6 weeks of age, as had been previously observed upon vaccination with an inactivated viral vaccine. Similarly, mice passively immunized with hyperimmune serum showed an inhibited B-cell response upon vaccination with the pSG5rab.gp vector, resulting in both cases in vaccine failures upon challenge with a virulent strain of rabies virus. In contrast, the immune responses of mice vaccinated as neonates in the presence of maternal immunity or upon passive immunization to rabies virus with the pSG5rab.gp construct were only marginally affected.     

Transmission of rabies virus: importance of the species barrier

The authors describe experimental inoculations of different animal species with either the wild-type rabies virus or the modified one through in vivo or in vitro passages. With these experiments, it was possible to determine the 50% lethal dose of these viruses for these species, and to thus quantify the importance of the species barrier that opposes, in particular, the transmission of vulpine rabies to cats and dogs (respectively 10(5) and 10(6) times more resistant than foxes). Studies were also undertaken on the influence of the inoculation route and that of serial passages of the virus in vivo or in vitro on the importance of resistance to rabies. The epidemiological consequences of the existence of a species barrier, its nature and variability, are discussed.     

No rabies detected in voles and field mice in a rabies-endemic area

Brain samples were collected from 514 voles and wild mice in Estonia, and examined for rabies. The samples were tested with antigen ELISA, and 8.6% of them additionally by virus isolation assay. The results were negative. Our data show that in areas of north-eastern Europe, where rabies is endemic in raccoon dogs and red foxes, populations of smaller mammals may remain free of rabies.     

A survey of tick-borne bacteria and protozoa in naturally exposed dogs from Israel

Antibody reactivity against seven bacterial or protozoal pathogens was measured in sera derived from 40 dogs suspected of a tick-borne disease. Sera from 73% (29/40) of the dogs reacted with three or more test antigens. Seroreactivity was most prevalent to Babesia canis antigen (90%) followed by Babesia gibsoni (75%), Ehrlichia canis (63%), Rickettsia conorii--Moroccan strain (58%), Rickettsia conorii--Israeli strain no. 2 (28%), Borrelia burgdorferi (10%) or Bartonella vinsonii (berkhoffii) (10%). Seroconversion documented in seven dogs, supported an acute phase diagnosis of ehrlichiosis in four dogs, R. conorii infection in three dogs and babesiosis in one dog. In the remaining dogs, correlation of clinical abnormalities with increased seroreactivity was not established through the design of this study. Although Lyme borreliosis has not been reported in people in Israel, Western blot analysis for antibodies reactive to B. burgdorferi identified genus-specific antiflagellin antibodies indicating that dogs in Israel are exposed to a Borrelia species. Identification of species-specific seroreactivity was not possible and infection with a Borrelia species other than B. burgdorferi is likely. Seroreactivity to B. vinsonii (berkhoffii) in dogs outside the USA is reported here for the first time.     

Efficacy of the first oral vaccination against fox rabies in Slovenia

Fox population reduction was the first measure undertaken to control rabies in foxes, but this proved unsuccessful. The promising results of oral immunisation of foxes against rabies in some European countries encouraged the authorization of the first rabies vaccination of foxes in the field in Slovenia, in October 1988. In the present study, intervention analysis is used to evaluate the results of this vaccination campaign. The analysis took into account the cyclic nature of fox rabies and the possible effects of variability in the fox carcass submission rate. The results confirmed the decrease in fox rabies after the launch of the vaccination campaign. The reduction was independent of both cyclic oscillations in fox rabies and variability in carcass submission rate, thus indicating a positive net effect of the vaccination.     

Effects of environmental enrichment on cortical depth and Morris-maze performance in B6D2F2 mice exposed prenatally to ethanol

The most recent advances in rabies epidemiology in various wildlife and domestic reservoirs are presented, especially in foxes, bats and dogs. Rabies epidemiology in the dog reservoir is directly associated to dog ecology which needs to be better understood in order to implement appropriate rabies control measures in the dog population. The progress of molecular biology, especially the development of the Polymerase Chain Reaction technique offers many interesting possibilities in epidemiological investigations.     

NMR studies of Borrelia burgdorferi OspA, a 28 kDa protein containing a single-layer beta-sheet

Viruses such as HIV, influenza, picornavirus and others are known stimulators of apoptosis. This individual cellular elimination is a preferential host defense in regenerative tissues. In contrast, if this death occurred in nonregenerating cells, such as neurons of the central nervous system, may result in disease. The target cell for rabies virus is the neuron. Here we studied the outcome of the interaction between rabies virus (CVS-11) and mouse brain cells. Replication of rabies virus in suckling mouse brain cells resulted in brain cell apoptosis, detected by DNA fragmentation and in situ apoptosis within 25 h after infection and before evidence of intracerebral immune activation. Cell death occurred simultaneously with rabies virus replication. There were clinical signs of illness in infected newborn mice within 24 h after the appearance of DNA fragmentation and before infiltration by lymphocytes. This suggested that onset of illness started independently of the immune function. This conclusion was supported by the occurrence of massive apoptosis followed by paralysis in rabies virus-infected immunosuppressed mice. Direct, viral-induced, neuronal apoptosis was the earliest death mechanism detected in these mice. We propose that pathogenesis of this fixed strain of rabies virus in mice begins with the induction of apoptosis by rabies virus replication. Cerebral damage may then be amplified by immunological mechanisms plus an additional unidentified factor. This is followed by increased permeability of the blood brain barrier.     

Characterisation of a novel lyssavirus isolated from Pteropid bats in Australia

A novel lyssavirus isolated from Pteropid bats in Australia (Australian Bat Lyssavirus, ABLV) has been characterised using gene sequence analyses, electron microscopy and a panel of monoclonal antibodies. Electron microscopic examination of Pteropid bat and mouse brain material as well as virus isolated from tissue culture medium, showed the presence of bullet-shaped rhabdovirus particles and structures characteristic of lyssavirus. Analysis using nucleocapsid (N) specific monoclonal antibodies, showed a strong relationship between this new lyssavirus and serotype 1 rabies. The nucleotide sequence of the prototype strain of ABLV was determined from the initiator methionine codon for the nucleocapsid protein (N protein) to the amino terminus of the polymerase gene (L protein), a distance of 5344 nucleotides. Comparisons of the deduced N, phosphoprotein (P), matrix protein (M), and glycoprotein (G) proteins showed that ABLV was more closely related to serotype 1 classic rabies viruses than to other members of the Lyssavirus genus. The percent relatedness of the ABLV proteins when compared to the cognate proteins of PV (Pasteur vaccine strain) rabies was 92, 75, 87 and 75% for the N, P, M and G proteins, respectively. Phylogenetic studies of N protein sequences showed clearly that ABLV is an unrecognised member of the Lyssavirus genus and represents a new genotype, genotype 7.     

Inflammatory diseases of the central nervous system in dogs

Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.