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Sample records for bat-associated rabies virus

  1. Intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers.

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    Mirjam A R Preuss

    2009-06-01

    Full Text Available The majority of rabies virus (RV infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown whether hematogenous spread has any relevance in RV pathogenesis. To determine whether certain RV variants might have the capacity to invade the CNS from the periphery via hematogenous spread, we infected mice either intramuscularly (i.m. or intravenously (i.v. with the dog-associated RV DOG4 or the silver-haired bat-associated RV SB. In addition to monitoring the progression of clinical signs of rabies we used immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR to follow the spread of the virus from the infection site to the brain. In contrast to i.m. infection where both variants caused a lethal encephalopathy, only i.v. infection with SB resulted in the development of a lethal infection. While qRT-PCR did not reveal major differences in virus loads in spinal cord or brain at different times after i.m. or i.v. infection of SB, immunohistochemical analysis showed that only i.v. administered SB directly infected the forebrain. The earliest affected regions were those hypothalamic nuclei, which are connected by neurosecretory fibers to the circumventricular organs neurohypophysis and median eminence. Our data suggest that hematogenous spread of SB can lead to a fatal encephalopathy through direct retrograde invasion of the CNS at the neurovascular interface of the hypothalamus-hypophysis system

  2. Rabies.

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    Burnett, Nark

    2013-01-01

    Rabies has been a scourge of mankind since antiquity. The name itself, ?rabies? is derived from the ancient Sanskrit rabhas meaning ?to do violence? and has been found described in medical writings several thousand years old. The rabies virus is an RNA virus of the family Rhabdoviridae (Greek for ?rod-shaped virus?), genus Lyssavirus (Lyssa being the Greek God of frenzy and rage). Rabies infections have a worldwide spread, with only a few, mostly island nations laying claim to being ?rabies free.?

  3. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Live Virus. 113.312... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from...

  4. Rabies direct fluorescent antibody test does not inactivate rabies or eastern equine encephalitis viruses.

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    Jarvis, Jodie A; Franke, Mary A; Davis, April D

    2016-08-01

    An examination using the routine rabies direct fluorescent antibody test was performed on rabies or Eastern equine encephalitis positive mammalian brain tissue to assess inactivation of the virus. Neither virus was inactivated with acetone fixation nor the routine test, thus laboratory employees should treat all samples as rabies and when appropriate Eastern equine encephalitis positive throughout the whole procedure.

  5. Therapeutic immune clearance of rabies virus from the CNS

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    Hooper, D Craig; Roy, Anirban; Kean, Rhonda B; Phares, Timothy W; Barkhouse, Darryll A

    2011-01-01

    The long-held concept that rabies infection is lethal in humans once the causative rabies virus has reached the CNS has been called into question by the recent survival of a number of patients with clinical rabies. Studies in animal models provide insight into why survival from a rabies virus infection that has spread to the CNS is possible and the immune mechanisms involved. In the CNS, both innate mechanisms capable of inhibiting virus replication and the activity of infiltrating rabies virus-specific T and B cells with the capacity to clear the virus are required. Deficiencies in the induction of either aspect of rabies immunity can lead to lethal consequences but may be overcome by novel approaches to active and passive immunization. PMID:21686076

  6. Phylogeographic analysis of rabies viruses in the Philippines.

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    Tohma, Kentaro; Saito, Mariko; Kamigaki, Taro; Tuason, Laarni T; Demetria, Catalino S; Orbina, Jun Ryan C; Manalo, Daria L; Miranda, Mary E; Noguchi, Akira; Inoue, Satoshi; Suzuki, Akira; Quiambao, Beatriz P; Oshitani, Hitoshi

    2014-04-01

    Rabies still remains a public health threat in the Philippines. A significant number of human rabies cases, about 200-300 cases annually, have been reported, and the country needs an effective strategy for rabies control. To develop an effective control strategy, it is important to understand the transmission patterns of the rabies viruses. We conducted phylogenetic analyses by considering the temporal and spatial evolution of rabies viruses to reveal the transmission dynamics in the Philippines. After evaluating the molecular clock and phylogeographic analysis, we estimated that the Philippine strains were introduced from China around the beginning of 20th century. Upon this introduction, the rabies viruses evolved within the Philippines to form three major clades, and there was no indication of introduction of other rabies viruses from any other country. However, within the Philippines, island-to-island migrations were observed. Since then, the rabies viruses have diffused and only evolved within each island group. The evolutionary pattern of these viruses was strongly shaped by geographical boundaries. The association index statistics demonstrated a strong spatial structure within the island group, indicating that the seas were a significant geographical barrier for viral dispersal. Strong spatial structure was also observed even at a regional level, and most of the viral migrations (79.7% of the total median number) in Luzon were observed between neighboring regions. Rabies viruses were genetically clustered at a regional level, and this strong spatial structure suggests a geographical clustering of transmission chains and the potential effectiveness of rabies control that targets geographical clustering. Dog vaccination campaigns have been conducted independently by local governments in the Philippines, but it could be more effective to implement a coordinated vaccination campaign among neighboring areas to eliminate geographically-clustered rabies

  7. Preparation and Identification of Anti-rabies Virus Monoclonal Antibodies

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    Wen-juan Wang; Xiong Li; Li-hua Wang; Hu Shan; Lei Cao; Peng-cheng Yu; Qing Tang; Guo-dong Liang

    2012-01-01

    To provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection,anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (PV strain) were used as immunogens to immunize 6-8 week old female BALB/c mice.Spleen cells and SP2/0 myeloma cells were fused according to conventional methods:the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; this was followed by preparation of monoclonal antibody ascitic fluid; and finally,systematic identification of subclass,specificity and sensitivity was carried out.Two high potency and specific monoclonal antibodies against rabies virus were obtained and named 3B12 and 4A12,with ascitic fluid titers of 1∶8000 and 1∶10000,respectively.Both belonged to the IgG2a subclass.These strains secrete potent,stable and specific anti-rabies virus monoclonal antibodies,which makes them well suited for the development of rabies diagnosis reagents.

  8. Detection and Genetic Characterization of Rabies Virus from Human Patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Saliva and blood were collected from two patients who had not received post exposure prophylaxis in the cities of Wenzhou and Xinning respectively. Both patients were confirmed as positive for rabies by detection of rabies virus specific nucleoprotein antibodies in the sera by Western Blot. However, rabies virus specific RNA was only identified in the saliva collected from the patient in Wenzhou. Furthermore, the isolate Zhejiang Wz0 (H) was obtained by inoculating one-day-old suckling mice. Both nucleoprotein (N) and glycoprotein (G) genes from the isolate were amplified by RT-PCR and sequenced. Phylogenetic analysis indicated that the isolate belonged to classic rabies virus, and shared a higher homology with the street viruses from dogs in the main endemic areas in China and the street virus from dogs in Indonesia than with other known strains. Further comparison of the deduced amino acid sequences between the isolate and the vaccine strains used in China showed that the virus had a higher level of homology with the vaccine strain CTN than with the other vaccine strains (3aG, PV, PM and ERA). In particular, amino acid residues substitutions located in antigenic site Ⅲ in the G protein, which could react with the neutralizing antibodies, were observed. These results suggested that the virus belonged to the classic rabies virus, and both N and G genes diverged from the current vaccine strains used in China at either the nucleotide or the amino acid level.

  9. The phylodynamics of the rabies virus in the Russian Federation

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    Lukashev, Alexander N.; Poleshchuk, Elena M.; Dedkov, Vladimir G.; Tkachev, Sergey E.; Sidorov, Gennadiy N.; Karganova, Galina G.; Galkina, Irina V.; Shchelkanov, Mikhail Yu.; Shipulin, German A.

    2017-01-01

    Near complete rabies virus N gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of Russia between 2008 and 2016. These sequences were analyzed together with 108 representative GenBank sequences from 1977–2016 using the Bayesian coalescent approach. The timing of the major evolutionary events was estimated. Most of the isolates represented the steppe rabies virus group C, which was found over a vast geographic region from Central Russia to Mongolia and split into three groups (C0-C2) with discrete geographic prevalence. A single strain of the steppe rabies virus lineage was isolated in the far eastern part of Russia (Primorsky Krai), likely as a result of a recent anthropogenic introduction. For the first time the polar rabies virus group A2, previously reported in Alaska, was described in the northern part of European Russia and at the Franz Josef Land. Phylogenetic analysis suggested that all currently circulating rabies virus groups in the Russian Federation were introduced within the few last centuries, with most of the groups spreading in the 20th century. The dating of evolutionary events was highly concordant with the historical epidemiological data. PMID:28225771

  10. Overwintering of Rabies Virus in Silver Haired Bats (Lasionycteris noctivagans.

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    April D Davis

    Full Text Available Silver-haired bats, (Lasionycteris noctivagans are semi-colonial, migratory tree bats that have infrequent contact with humans. Despite the species rarity, the L. noctivagans rabies variant is the most commonly reported rabies virus variant (RABV in domestically acquired human rabies cases in the US. Unlike big brown bats (Eptesicus fuscus and little brown bats (Myotis lucifugus, L. noctivagans are not considered true hibernators. It is unknown if RABV can overwinter in hibernating L. noctivagans or is only maintained in members of this taxa that migrate to warmer climates. To better understand RABV overwintering in this species, L. noctivagans were inoculated intramuscularly with either a homologous RABV (L. noctivagans Virus 1 or one of two heterologous RABV (Eptesicus fuscus Virus 2 and Myotis lucifugus Virus 1. Five days following inoculation, L. noctivagans were placed in a hibernation chamber for 6 weeks. Our results demonstrate that rabies virus can overwinter in L. noctivagans yet the incubation period was extended 6 weeks when compared to bats maintained at ambient temperatures. Additionally, we found that the longer the incubation period, the greater the viral dissemination to the salivary glands. Similar to our previous studies, L. noctivagans were most susceptible to a homologous variant. In summary, we found that RABV incubation is extended following a subcutaneous exposure or maintenance in hibernation and longer incubation times increase dissemination and potential for transmission.

  11. Innate immune responses in raccoons after raccoon rabies virus infection.

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    Srithayakumar, Vythegi; Sribalachandran, Hariharan; Rosatte, Rick; Nadin-Davis, Susan A; Kyle, Christopher J

    2014-01-01

    Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.

  12. Chimeric Rabies Virus-Like Particles Containing Membrane-Anchored GM-CSF Enhances the Immune Response against Rabies Virus

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    Hongtao Kang

    2015-03-01

    Full Text Available Rabies remains an important public health threat in most developing countries. To develop a more effective and safe vaccine against rabies, we have constructed a chimeric rabies virus-like particle (VLP, which containing glycoprotein (G and matrix protein (M of rabies virus (RABV Evelyn-Rokitnicki-Abelseth (ERA strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF, and it was named of EVLP-G. The immunogenicity and protective efficacy of EVLP-G against RABV were evaluated by intramuscular administration in a mouse model. The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively. The membrane-anchored GM-CSF possesses a strong adjuvant activity. More B cells and dendritic cells (DCs were recruited and/or activated in inguinal lymph nodes in mice immunized with EVLP-G. EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M. The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP. Moreover, the immune responses induced by EVLP-G protect all vaccinated mice from lethal challenge with RABV. These results suggest that EVLP-G has the potential to be developed as a novel vaccine candidate for the prevention and control of animal rabies.

  13. Improved Monosynaptic Neural Circuit Tracing Using Engineered Rabies Virus Glycoproteins

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    Euiseok J. Kim

    2016-04-01

    Full Text Available Monosynaptic rabies virus tracing is a unique and powerful tool used to identify neurons making direct presynaptic connections onto neurons of interest across the entire nervous system. Current methods utilize complementation of glycoprotein gene-deleted rabies of the SAD B19 strain with its glycoprotein, B19G, to mediate retrograde transsynaptic spread across a single synaptic step. In most conditions, this method labels only a fraction of input neurons and would thus benefit from improved efficiency of transsynaptic spread. Here, we report newly engineered glycoprotein variants to improve transsynaptic efficiency. Among them, oG (optimized glycoprotein is a codon-optimized version of a chimeric glycoprotein consisting of the transmembrane/cytoplasmic domain of B19G and the extracellular domain of rabies Pasteur virus strain glycoprotein. We demonstrate that oG increases the tracing efficiency for long-distance input neurons up to 20-fold compared to B19G. oG-mediated rabies tracing will therefore allow identification and study of more complete monosynaptic input neural networks.

  14. Complex genetic structure of the rabies virus in Bangkok and its surrounding provinces, Thailand: implications for canine rabies control.

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    Lumlertdacha, Boonlert; Wacharapluesadee, Supaporn; Denduangboripant, Jessada; Ruankaew, Nipada; Hoonsuwan, Wirongrong; Puanghat, Apirom; Sakarasaeranee, Plyyonk; Briggs, Deborrah; Hemachudha, Thiravat

    2006-03-01

    Dog vaccination and population management have been suggested as priorities in attempts at disease control in canine rabies-endemic countries. Budget limitations and the complexity of social, cultural and religious variables have complicated progress in the developing world. In Bangkok, Thailand, an intensive canine vaccination and sterilization programme has been in place since November 2002. Our objective was to determine if the rabies virus could be mapped according to its genetic variations and geographical location on the small localized scale of Bangkok and its surrounding provinces. Phylogenetic characterization of 69 samples from Bangkok and five neighbouring and two remote provinces, by limited sequence analysis of the rabies virus nucleoprotein gene, distinguished six different clades. Rabies viruses of four clades were intermixed in Bangkok and in the surrounding highly populated regions whereas the other two clades were confined to rural and less populated provinces. Such a complex pattern of gene flow, particularly in Bangkok, may affect the outcome of canine control programmes.

  15. Experimental oral and nasal transmission of rabies virus in mice.

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    Charlton, K M; Casey, G A

    1979-01-01

    Weanling female white Swiss mice were exposed to challenge virus standard rabies virus and street virus isolates from various domestic and wild animals. Virus was given free choice as suspension or as infected mouse brain by stomach tube, by single injection of suspension into the oral cavity of unanesthetized mice, by repeated injection into the oral cavity of anesthetized mice and by single application to the external nares of anesthetized mice. Challenge virus standard virus in mouse brain suspension and a suspension of skunk salivary glands infected with street virus (titers greater than or equal to 10(6)MICLD50/0.03 ml) consistently produced high rates of infection in mice exposed intranasally, low to high rates of infection in mice exposed by forced feeding and other artificial methods of oral exposure and very low rates of infection when given free choice. Street virus isolates passaged intracerebrally in mice had titers less than or equal to 10(4.5) MICLD50/0.03 ml and rarely caused rabies in mice exposed orally or nasally by any method. The results indicate that with the isolates used, virus of high titer (greater than or equal to 10(6)MICLD50/0.03 ml) is required to consistently produce infection in mice by the nasal route and that the mucosa of the nasal cavity probably is the chief route of infection even after oral administration.

  16. Molecular characterization of China rabies virus vaccine strain

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    Jiao Wenqiang

    2011-11-01

    Full Text Available Abstract Background Rabies virus (RV, the agent of rabies, can cause a severe encephalomyelitis in several species of mammals, including humans. As a human rabies vaccine strain employed in China, the genetic knowledge of the aG strain has not been fully studied. The main goal of the present study is to amplify the whole genome of aG strain, and genetic relationships between other vaccine strains and wild strains were analyzed. Results The entire genome of human rabies virus vaccine strain aG employed in China was sequenced; this is the second rabies virus vaccine strain from China to be fully characterized. The overall organization and the length of the genome were similar to that of other lyssaviruses. The length of aG strain was 11925nt, comprising a leader sequence of 58nt, nucleoprotein (N gene of 1353nt, phosphoprotein (P gene of 894 nt, matrix protein (M gene of 609nt, glycoprotein (G gene of 1575nt, RNA-dependent RNA polymerase (RdRp,L gene of 6384nt, and a trailer region of 70 nt. There was TGAAAAAAA (TGA7 consensus sequence in the end of each gene, except AGA7 at the end of G gene. There was AACAYYYCT consensus start signal at the beginning of each gene. Conclusions In this report, we analyzed the full genome of China human rabies vaccine strain aG. Our studies indicated that the genome of aG retained the basic characteristics of RV. At gene level, N was the most conserved among the five coding genes, indicating this gene is the most appropriate for quantitative genotype definition. The phylogenetic analysis of the N indicated the aG strain clustered most closely with Japanese and Russian rabies vaccine strains, suggesting that they may share the same ancestor; also, the aG strain did not share high homology with wild strains isolated from China, making it may not be the best vaccine strain, more research is needed to elucidate the genetic relationship among the RV circulating in China.

  17. Rabies

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    ... are expected from rabies biological suppliers in both India and Viet Nam. Once complete, the data will ... and affected communities. For more information contact: WHO Media centre E-mail: mediainquiries@who.int Related links ...

  18. Report of isolations of unusual lyssaviruses (rabies and Mokola virus identified retrospectively from Zimbabwe : short communication

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    J. Bingham

    2001-07-01

    Full Text Available Rabies isolates that had been stored between 1983 and 1997 were examined with a panel of anti-lyssavirus nucleocapsid monoclonal antibodies. Out of 56 isolates from cats and various wild carnivore species, 1 isolate of Mokola virus and 5 other non-typical rabies viruses were identified. The Mokola virus isolate was diagnosed as rabies in 1993 from a cat. Genetic analysis of this isolate suggests that it falls in a distinct subgroup of the Mokola virus genotype. The 5 non-typical rabies viruses were isolated from honey badgers (Mellivora capensis, African civets (Civettictis civetta and an unidentified mongoose (Herpestidae. These isolates are representatives of rarely-reported wildlife-associated strains of rabies, probably maintained by the slender mongoose (Galerella sanguinea. These findings indicate that both Mokola virus and the mongoose-associated variant may be more common in Zimbabwe than is apparent from routine surveillance.

  19. Epidemic and Maintenance of Rabies in Chinese Ferret Badgers (Melogale moschata) indicated by Epidemiology and the Molecular Signatures of Rabies Viruses

    Institute of Scientific and Technical Information of China (English)

    Shoufeng Zhang; Ye Liu; Yanli Hou; Jinghui Zhao; Fei Zhang; Ying Wang; Rongliang Hu

    2013-01-01

    An epidemic of Chinese ferret badger-associated human rabies was investigated in Wuyuan county,Jiangxi province and rabies viruses isolates from ferret badgers in different districts in Jiangxi and Zhejiang provinces were sequenced with their nucleotides and amino acids and aligned for epidemiological analysis.The results showed that the human rabies in Wuyuan are only associated with ferret badger bites; the rabies virus can be isolated in a high percentage of ferret badgers in the epidemic areas in Jiangxi and Zhejiang provinces; the isolates share the same molecular features in nucleotides and have characteristic amino acid signatures,i.e.,2 sites in the nucleoprotein and 3 sites in the glycoprotein,that are distinct from virus isolates from dogs in the same region.We conclude that rabies in Chinese ferret badgers has formed an independent transmission cycle and ferret badgers may serve as another important rabies reservoir independent of dog rabies in China.

  20. Studies on antigenic and genomic properties of Brazilian rabies virus isolates

    NARCIS (Netherlands)

    Schaefer, R.; Batista, H.B.; Franco, A.C.; Rijsewijk, F.A.M.; Roehe, P.M.

    2005-01-01

    Despite the recognized stability of rabies virus, differences among isolates from different species have been found. This work was carried out with the aim to identify antigenic and genomic differences in Brazilian rabies virus isolates and to verify whether such alterations would bear any relations

  1. Antigenic and genetic characterization of rabies virus isolates from Uruguay.

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    Guarino, Helena; Castilho, Juliana Galera; Souto, Juanita; Oliveira, Rafael de Novaes; Carrieri, Maria Luiza; Kotait, Ivanete

    2013-05-01

    After 25 years without any reported cases of rabies in Uruguay, the northern region of the country experienced an epizootic of bovine paralytic rabies in October 2007. The outbreak affected bovines and equines, and the main source of infection was the bat Desmodus rotundus, the only hematophagous species in the country. From October 2007 to July 2008, 42 bovine, 3 equine and 120 chiropteran samples were submitted to the National Veterinary Diagnostic Laboratory for rabies testing. A total of 12 samples (7 bovine, 2 equine and 3 from D. rotundus) were positive by the fluorescent antibody test, and viruses were isolated by the mouse inoculation test. The objective of this study was to compare the antigenic and genetic characteristics of these isolates and three isolates from insectivorous bats from other regions. Antigenic typing using a panel of eight monoclonal antibodies identified all 12 viruses as variant 3 (AgV3), a variant associated with D. rotundus. Two isolates from insectivorous bats (Tadarida brasiliensis and Molossus sp.) were characterized as antigenic variant 4 (AgV4) while the third, from Myotis sp., could not be characterized using this panel as its reactivity pattern did not match that of any of the known antigenic variants. Partial N-gene sequences (nt 149-1420) of these isolates were aligned with homologous sequences derived from GenBank by the CLUSTAL/W method and used to build a neighbor-joining distance tree with the Kimura 2-parameter model. All 12 isolates were genetically grouped into the D. rotundus cluster as they shared 100% identity. In the phylogenetic analysis, the three isolates from insectivorous bats segregated into three clusters: one related to T. brasiliensis, one to Myotis sp. and the other to Lasiurus sp., although the isolate associated with the latter came from a Molossus sp. specimen. These results indicate that AgV3 was associated with the outbreak of bovine paralytic rabies in Uruguay. This is the first report of rabies

  2. Subversion of the Immune Response by Rabies Virus

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    Terence P. Scott

    2016-08-01

    Full Text Available Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses—including age, sex, cerebral lateralization and temperature—are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host’s response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment.

  3. Intracellular Spread of Rabies Virus Is Reduced in the Paralytic Form of Canine Rabies Compared to the Furious Form.

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    Shanop Shuangshoti

    2016-06-01

    Full Text Available Studies of the furious and paralytic forms of canine rabies at the early stage of disease have shown a more rapid viral colonization of the cerebral hemispheres in the furious form, as measured by viral antigen within neuronal cell bodies and viral RNA levels. Measurement of cellular processes separate from neuronal cell body provides a visual record of the spread of rabies virus which occurs across synapses. In this study, the amount of rabies viral antigen within cell processes was quantitatively assessed by image analysis in a cohort of naturally rabies infected non-vaccinated dogs (5 furious and 5 paralytic that were sacrificed shortly after developing illness. Measurements were taken at different levels of the spinal cord, brain stem, and cerebrum. Results were compared to the amount of rabies viral antigen in neuronal cell bodies. Generally, the amount of rabies viral antigen in cell processes decreased in a rostral direction, following the pattern for the amount of rabies viral antigen in neuronal cell bodies and the percentage of involved cell bodies. However, there was a delay in cell process involvement following cell body involvement, consistent with replication occurring in the cell body region and subsequent transport out to cell processes. Greater amounts of antigen were seen in cell processes in dogs with the furious compared to paralytic form, at all anatomic levels examined. This difference was even evident when comparing (1 neurons with similar amounts of antigen, (2 similar percentages of involved neurons, and (3 anatomic levels that showed 100% positive neurons. These findings suggest that intracellular transport of the virus may be slower in the paralytic form, resulting in slower viral propagation. Possible mechanisms might involve host-specific differences in intracellular virus transport. The latter could be cytokine-mediated, since previous studies have documented greater inflammation in the paralytic form.

  4. Antigen detection of rabies virus in brain smear using direct Rapid Immunohistochemistry Test

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    Damayanti R

    2014-03-01

    Full Text Available Rabies is zoonotic disease caused by a fatal, neurotropic virus. Rabies virus is classified into the Genus of Lyssavirus under the yang family of Rhabdoviridae. Rabies affecting hot- blooded animals, as well as human. Dogs, cats, monkeys are the vectors or reservoirs for rabies and the virus was transmitted through the saliva after infected animal’s bites. The aim of this study was to conduct rapid diagnosis to detect rabies viral antigen in brain smear using immunohistochemical (IHC method namely direct Rapid Immunohistochemical Test (dRIT. A total number of 119 brain samples were achieved from Bukittinggi Veterinary Laboratory, West Sumatra. Standardisation and validation of the method were compared to Fluorescent Antibody Test (FAT as a golden standard for rabies diagnosis. Results show that dRIT was a very good method, it can be performed within two hours without the need of fluorescent microscope. The samples were tested using FAT and from 119 samples tested, 80 (67.23% samples were positive for rabies and 39 (32.77% samples were negative for rabies whereas using dRIT showed that 78 (65.54% samples were positive for rabies and 41 (34.45% samples were negative for rabies. The dRIT results were validated by comparing them with FAT results as a golden standard for rabies. The relative sensitivity of dRIT to FAT was 97.5% and the relative specificity to FAT was 100% (with Kappa value of 0.976, stated as excellent. The achievement showed that dRIT is very potential diagnostic tool and is highly recommended to be used widely as a rapid diagnosis tool for rabies.

  5. Phylogeography of the current rabies viruses in Indonesia.

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    Dibia, I Nyoman; Sumiarto, Bambang; Susetya, Heru; Putra, Anak Agung Gde; Scott-Orr, Helen; Mahardika, Gusti Ngurah

    2015-01-01

    Rabies is a major fatal zoonotic disease in Indonesia. This study was conducted to determine the recent dynamics of rabies virus (RABV) in various areas and animal species throughout Indonesia. A total of 27 brain samples collected from rabid animals of various species in Bali, Sumatra, Kalimantan, Sulawesi, Java, and Flores in 2008 to 2010 were investigated. The cDNA of the nucleoprotein gene from each sample was generated and amplified by one-step reverse transcription-PCR, after which the products were sequenced and analyzed. The symmetric substitution model of a Bayesian stochastic search variable selection extension of the discrete phylogeographic model of the social network was applied in BEAST ver. 1.7.5 software. The spatial dispersal was visualized in Cartographica using Spatial Phylogenetic Reconstruction of Evolutionary Dynamics. We demonstrated inter-island introduction and reintroduction, and dog was found to be the only source of infection of other animals. Ancestors of Indonesian RABVs originated in Java and its descendants were transmitted to Kalimantan, then further to Sumatra, Flores, and Bali. The Flores descendent was subsequently transmitted to Sulawesi and back to Kalimantan. The viruses found in various animal species were transmitted by the dog.

  6. Phylogeography of the current rabies viruses in Indonesia

    Science.gov (United States)

    Dibia, I Nyoman; Sumiarto, Bambang; Susetya, Heru; Putra, Anak Agung Gde; Scott-Orr, Helen

    2015-01-01

    Rabies is a major fatal zoonotic disease in Indonesia. This study was conducted to determine the recent dynamics of rabies virus (RABV) in various areas and animal species throughout Indonesia. A total of 27 brain samples collected from rabid animals of various species in Bali, Sumatra, Kalimantan, Sulawesi, Java, and Flores in 2008 to 2010 were investigated. The cDNA of the nucleoprotein gene from each sample was generated and amplified by one-step reverse transcription-PCR, after which the products were sequenced and analyzed. The symmetric substitution model of a Bayesian stochastic search variable selection extension of the discrete phylogeographic model of the social network was applied in BEAST ver. 1.7.5 software. The spatial dispersal was visualized in Cartographica using Spatial Phylogenetic Reconstruction of Evolutionary Dynamics. We demonstrated inter-island introduction and reintroduction, and dog was found to be the only source of infection of other animals. Ancestors of Indonesian RABVs originated in Java and its descendants were transmitted to Kalimantan, then further to Sumatra, Flores, and Bali. The Flores descendent was subsequently transmitted to Sulawesi and back to Kalimantan. The viruses found in various animal species were transmitted by the dog. PMID:25643792

  7. Bat Rabies Surveillance in Europe

    DEFF Research Database (Denmark)

    Schatz, J.; Fooks, A. R.; McElhinney, L.

    2013-01-01

    Rabies is the oldest known zoonotic disease and was also the first recognized bat associated infection in humans. To date, four different lyssavirus species are the causative agents of rabies in European bats: the European Bat Lyssaviruses type 1 and 2 (EBLV-1, EBLV-2), the recently discovered pu...

  8. Diagnostic evaluation of RT-PCR-ELISA for the detection of rabies virus.

    Science.gov (United States)

    Aravindhbabu, R P; Manoharan, S; Ramadass, P

    2014-01-01

    Rabies is primarily a disease of terrestrial and airborne mammals. In most cases, rabies is diagnosed primarily on the basis of clinical symptoms and signs, and a corroborative history of or evidence of an animal bite, death of an animal and incomplete or no vaccination following exposure. The facility for laboratory diagnosis and confirmation of rabies is available in only a few institutions in India. Diagnostic tests using conventional assays like fluorescent antibody test (FAT) are unreliable at times, despite the clinical diagnosis. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. We have developed and evaluated an RT-PCR-ELISA using a panel of brain tissue samples from rabies suspected animals of various species. This assay was able to detect rabies virus genome in all the 43 samples that were previously tested positive for rabies. Moreover this assay was shown to be 100 % sensitive and specific in detecting the rabies virus genome in post-mortem brain tissue samples from different species of animals. Our pilot study shows the potential of this assay as an alternative diagnostic test when the samples are unsuitable for use in FAT and also a supplementary test to FAT. In addition, the region of nucleoprotein gene amplified using this assay can be used for the molecular investigation of geographical origin of the field strains.

  9. Oral vaccination of raccoons (Procyon lotor) with genetically modified rabies virus vaccines

    Science.gov (United States)

    Blanton, Jesse D.; Self, Joshua; Niezgoda, Michael; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles

    2007-01-01

    Oral vaccination is an important tool currently in use to control the spread of rabies in wildlife populations in various programs around the world. Oral rabies vaccination (ORV) of raccoons represents the largest targeted program to control wildlife rabies in the United States. Currently, the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG) is the only licensed oral rabies vaccine in the US. In the current study, captive raccoons were used to evaluate two previously described constructs of a rabies virus vaccine developed by reverse genetics (SPBNGAS and SPBNGAS-GAS) for immunogenicity and efficacy compared to the V-RG vaccine. Four of five control animals succumbed to rabies virus after severe challenge, while three of five animals vaccinated orally with SPBNGAS succumbed. No mortality was observed for animals administered SPBNGAS-GAS or the V-RG vaccine. The results of this preliminary study suggest that SPBNGAS-GAS provides comparable efficacy to V-RG. Additional studies will be needed to determine the duration of immunity and optimal dosage of SPBNGAS-GAS and to examine its efficacy in other reservoir species. PMID:17826874

  10. Complete Genome Sequence of a Street Rabies Virus Isolated from a Dog in Nigeria

    Science.gov (United States)

    Zhou, Ming; Zhou, Zutao; Kia, Grace S. N.; Gnanadurai, Clement W.; Leyson, Christina M.; Umoh, Jarlath U.; Kwaga, Jacob P.; Kazeem, Haruna M.

    2013-01-01

    A canine rabies virus (RABV) was isolated from a trade dog in Nigeria. Its entire genome was sequenced and found to be closely related to canine RABVs circulating in Africa. Sequence comparison indicates that the virus is closely related to the Africa 2 RABV lineage. The virus is now termed DRV-NG11. PMID:23469344

  11. A sensitive in vitro assay for the detection of residual viable rabies virus in inactivated rabies vaccines.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Nakamichi, Kazuo; Kinoshita, Hitomi; Kakiuchi, Satsuki; Kurane, Ichiro; Saijo, Masayuki; Lim, Chang-Kweng

    2014-01-01

    Rabies is a viral disease transmitted through bites from rabid animals and can be prevented by vaccines. Clinically used rabies vaccines are prepared from inactivated rabies viruses grown in cell cultures or embryonated eggs. In Japan and across the world, tests that confirm complete inactivation, such as the in vivo suckling mouse assay, in which suckling mice are intracerebrally inoculated with vaccine products, are required for quality control. In this study, we developed a novel cell-based immunofluorescence assay that does not require mice for testing rabies vaccine inactivation for human use. The sensitivity of this cell-based in vitro assay was 5.7 times that of the in vivo suckling mouse assay, with a detection limit of one focus forming units per ml of test sample. This newly developed in vitro assay may replace the established in vivo suckling mouse assay for confirming viral vaccine inactivation. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  12. Predicted 3D Model of the Rabies Virus Glycoprotein Trimer

    Directory of Open Access Journals (Sweden)

    Bastida-González Fernando

    2016-01-01

    Full Text Available The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM, and the p75 neurotrophin receptor (p75NTR. This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained.

  13. Predicted 3D Model of the Rabies Virus Glycoprotein Trimer

    Science.gov (United States)

    Fernando, Bastida-González; Yersin, Celaya-Trejo; José, Correa-Basurto; Paola, Zárate-Segura

    2016-01-01

    The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained. PMID:27294109

  14. Molecular characterization of the complete genome of a street rabies virus WH11 isolated from donkey in China.

    Science.gov (United States)

    Xie, Tingbo; Yu, Hua; Wu, Jie; Ming, Pinggang; Huang, Sijia; Shen, Zhijun; Xu, Gelin; Yan, Jiaxin; Yu, Bin; Zhou, Dunjin

    2012-12-01

    The complete genomic sequence of a rabies virus isolate WH11, isolated from brain tissue of a rabid donkey in China, was determined and compared with other rabies viruses. This is the first Chinese street strain which was isolated from donkey and the entire length and organization of the virus was similar to that of other rabies viruses. Multiple alignments of amino acid sequences of the nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and large protein of WH11 with those of other rabies viruses were undertaken to examine the conservative degree of functional regions. Phylogenetic analysis using the complete genomic sequence of WH11 determined that this isolate is most closely related with rabies viruses previously isolated in China and the attenuated Chinese vaccine strain CTN181.

  15. Everything You Always Wanted to Know About Rabies Virus (But Were Afraid to Ask).

    Science.gov (United States)

    Davis, Benjamin M; Rall, Glenn F; Schnell, Matthias J

    2015-11-01

    The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the subject of large-scale public health interventions, chiefly through vaccination efforts, the disease continues to take the lives of about 40,000-70,000 people per year, roughly 40% of whom are children. Most of these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure prophylaxis and the ubiquity of domestic and wild animal hosts makes eradication unlikely. Moreover, although the disease is rarer than other human infections such as influenza, the prognosis following a bite from a rabid animal is poor: There is currently no effective treatment that will save the life of a symptomatic rabies patient. This review focuses on the major unanswered research questions related to rabies virus pathogenesis, especially those connecting the disease progression of rabies with the complex dysfunction caused by the virus in infected cells. The recent applications of cutting-edge research strategies to this question are described in detail.

  16. Establishment and Preliminary Application of a Rapid Fluorescent Focus Inhibition Test (RFFIT) for Rabies Virus

    Institute of Scientific and Technical Information of China (English)

    Pengcheng Yu; Xinjun Lv; Xinxin Shen; Qing Tang; Guodong Liang

    2013-01-01

    The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT),which is used to evaluate the immunity effect after vaccination against rabies.For RFFIT,CVS-11 was used as the challenge virus,BSR cells as the adapted cells,and WHO rabies immunoglobulin (WHO STD) as the reference serum in this study.With reference to WHO and Pasteur RFFIT procedures,a micro-RFFIT procedure adapted to our laboratory was produced,and its specificity and reproducibility were tested.We tested levels of RVNA in human serum samples after immunization with different human rabies vaccines (domestic purified Vero cell rabies vaccine (PVRV) and imported purified chick embryo cell vaccine (PCECV)) using different regimens (Zagreb regimen and Essen regimen).We analyzed the levels of RVNA,and compared the immune efficacy of domestic PVRV and imported PCECV using different immunization regimens.The results showed that the immune efficacy of domestic PVRV using the Zagreb regimen was as good as that of the imported PCECV,but virus antibodies were generated more rapidly with the Zagreb regimen than with the Essen regimen.The RFFIT procedure established in our laboratory will enhance the comprehensive detection ability of institutions involved in rabies surveillance in China.

  17. The production of antibody by invading B cells is required for the clearance of rabies virus from the central nervous system.

    Directory of Open Access Journals (Sweden)

    D Craig Hooper

    2009-10-01

    Full Text Available The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies virus-neutralizing antibody reach infected cells in the cerebellum of B cell-deficient mice but are not sufficient to mediate virus clearance. Production of rabies virus-specific antibody by B cells invading CNS tissues is required for this process, and a substantial proportion of the B cells that accumulate in the CNS of mice infected with attenuated rabies virus produce virus-specific antibodies.The mechanisms required for immune effectors to enter rabies virus-infected tissues are induced by infection with attenuated rabies virus but not by infection with pathogenic rabies viruses or immunization with killed virus. T cell activities can inhibit rabies virus replication, but the production of rabies virus-specific antibodies by infiltrating B cells, as opposed to the leakage of circulating antibody across the BBB, is critical to elimination of the virus. These findings suggest that a pathogenic rabies virus infection may be treatable after the virus has reached the CNS tissues, providing that the appropriate immune effectors can be targeted to the infected tissues.

  18. Antigens produced in plants by infection with chimeric plant viruses immunize against rabies virus and HIV-1

    OpenAIRE

    Yusibov, Vidadi; Modelska, Anna; Steplewski, Klaudia; Agadjanyan, Michail; Weiner, David; Hooper, D. Craig; Koprowski, Hilary

    1997-01-01

    The coat protein (CP) of alfalfa mosaic virus was used as a carrier molecule to express antigenic peptides from rabies virus and HIV. The antigens were separately cloned into the reading frame of alfalfa mosaic virus CP and placed under the control of the subgenomic promoter of tobacco mosaic virus CP in the 30BRz vector. The in vitro transcripts of recombinant virus with sequences encoding the antigenic peptides were synthesized from DNA constructs and used to inoculate tobacco plants. The p...

  19. Rabies virus cross-reactive murine T cell clones: analysis of helper and delayed-type hypersensitivity function.

    NARCIS (Netherlands)

    H. Bunschoten; B. Dietzschold; I.J.Th.M. Claassen (Ivo); R. Klapmuts; F. UytdeHaag; A.D.M.E. Osterhaus (Albert)

    1990-01-01

    textabstractThree T cell clones derived from rabies virus-immunized BALB/c mice were analysed for specificity and function. The clones proved to be broadly cross-reactive by responding to different rabies virus isolates (PM, ERA, CVS, HEP) and other representatives of the genus Lyssavirus, like the

  20. Genetic diversity and geographic distribution of genetically distinct rabies viruses in the Philippines.

    Science.gov (United States)

    Saito, Mariko; Oshitani, Hitoshi; Orbina, Jun Ryan C; Tohma, Kentaro; de Guzman, Alice S; Kamigaki, Taro; Demetria, Catalino S; Manalo, Daria L; Miranda, Mary Elizabeth G; Noguchi, Akira; Inoue, Satoshi; Quiambao, Beatriz P

    2013-01-01

    Rabies continues to be a major public health problem in the Philippines, where 200-300 human cases were reported annually between 2001 and 2011. Understanding the phylogeography of rabies viruses is important for establishing a more effective and feasible control strategy. We performed a molecular analysis of rabies viruses in the Philippines using rabied animal brain samples. The samples were collected from 11 of 17 regions, which covered three island groups (Luzon, Visayas, and Mindanao). Partial nucleoprotein (N) gene sequencing was performed on 57 samples and complete glycoprotein (G) gene sequencing was performed on 235 samples collected between 2004 and 2010. The Philippine strains of rabies viruses were included in a distinct phylogenetic cluster, previously named Asian 2b, which appeared to have diverged from the Chinese strain named Asian 2a. The Philippine strains were further divided into three major clades, which were found exclusively in different island groups: clades L, V, and M in Luzon, Visayas, and Mindanao, respectively. Clade L was subdivided into nine subclades (L1-L9) and clade V was subdivided into two subclades (V1 and V2). With a few exceptions, most strains in each subclade were distributed in specific geographic areas. There were also four strains that were divided into two genogroups but were not classified into any of the three major clades, and all four strains were found in the island group of Luzon. We detected three major clades and two distinct genogroups of rabies viruses in the Philippines. Our data suggest that viruses of each clade and subclade evolved independently in each area without frequent introduction into other areas. An important implication of these data is that geographically targeted dog vaccination using the island group approach may effectively control rabies in the Philippines.

  1. Genetic diversity and geographic distribution of genetically distinct rabies viruses in the Philippines.

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    Full Text Available BACKGROUND: Rabies continues to be a major public health problem in the Philippines, where 200-300 human cases were reported annually between 2001 and 2011. Understanding the phylogeography of rabies viruses is important for establishing a more effective and feasible control strategy. METHODS: We performed a molecular analysis of rabies viruses in the Philippines using rabied animal brain samples. The samples were collected from 11 of 17 regions, which covered three island groups (Luzon, Visayas, and Mindanao. Partial nucleoprotein (N gene sequencing was performed on 57 samples and complete glycoprotein (G gene sequencing was performed on 235 samples collected between 2004 and 2010. RESULTS: The Philippine strains of rabies viruses were included in a distinct phylogenetic cluster, previously named Asian 2b, which appeared to have diverged from the Chinese strain named Asian 2a. The Philippine strains were further divided into three major clades, which were found exclusively in different island groups: clades L, V, and M in Luzon, Visayas, and Mindanao, respectively. Clade L was subdivided into nine subclades (L1-L9 and clade V was subdivided into two subclades (V1 and V2. With a few exceptions, most strains in each subclade were distributed in specific geographic areas. There were also four strains that were divided into two genogroups but were not classified into any of the three major clades, and all four strains were found in the island group of Luzon. CONCLUSION: We detected three major clades and two distinct genogroups of rabies viruses in the Philippines. Our data suggest that viruses of each clade and subclade evolved independently in each area without frequent introduction into other areas. An important implication of these data is that geographically targeted dog vaccination using the island group approach may effectively control rabies in the Philippines.

  2. Inactivated Recombinant Rabies Viruses Displaying the Canine Distemper Virus Glycoproteins Induce Protective Immunity Against Both Pathogens.

    Science.gov (United States)

    Budaszewski, Renata da Fontoura; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Xiangping, Yin; Schnell, Matthias J; von Messling, Veronika

    2017-02-01

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Canine distemper (CDV) and rabies (RABV) viruses both cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wild life species. In the current study, we have developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near wild type titers and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were only immunized with a RABV expressing the attachment protein of the CDV vaccine strain Onderstepoort succumbed to the infection with a more recent wild type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains.

  3. Effect of cellular cholesterol depletion on rabies virus infection.

    Science.gov (United States)

    Hotta, Kozue; Bazartseren, Boldbarrtar; Kaku, Yoshihiro; Noguchi, Akira; Okutani, Akiko; Inoue, Satoshi; Yamada, Akio

    2009-01-01

    Although there are several reports on candidates for rabies virus (RABV) receptor, possible roles played by these receptor candidates in determination of highly neurotropic nature of RABV have not been well understood. Since these candidate receptors for RABV were reported to be frequently associated with cholesterol-rich microdomains characterized by lipid rafts and caveolae structures, we attempted to determine whether the disturbance of microdomains caused by the cholesterol depletion showed any effects on RABV infection. When the cellular cholesterol was depleted by methyl-beta-cyclodextrin (MBCD) treatment, increase in RABV adsorption and infection, but not multiplication rather than suppression was observed in both BHK-21 and HEp-2 cells. These effects exerted by MBCD treatment on RABV infection could be reversed by cholesterol reconstitution. These results suggest that RABV enters BHK-21 or HEp-2 cells through ports of entry other than those located on cholesterol-rich microdomains and raise the possibility that RABV uses different mechanisms to enter the non-neuronal cells.

  4. Generation and characterization of the human neutralizing antibody fragment Fab091 against rabies virus

    Institute of Scientific and Technical Information of China (English)

    Chen LI; Feng ZHANG; Hong LIN; Zhong-can WANG; Xin-jian LIU; Zhen-qing FENG; Jin ZHU; Xiao-hong GUAN

    2011-01-01

    Aim: To transform the human anti-rabies virus glycoprotein (anti-RABVG) single-chain variable fragment (scFv) into a Fab fragment and to analyze its immunological activity.Methods: The Fab gene was amplified using overlap PCR and inserted into the vector pComb3XSS. The recombinant vector was then transformed into E coli Top10F' for expression and purification. The purified Fab was characterized using SDS-PAGE, Western blotting,indirect ELISA, competitive ELISA, and the fluorescent antibody virus neutralization test (FAVN), respectively, and examined in a Kunming mouse challenge model in vivo.Results: A recombinant vector was constructed. The Fab was expressed in soluble form In E coll Top10F'. Specific binding of the Fab to rabies virus was confirmed by indirect ELISA and immunoprecipitation (IP). The neutralizing antibody titer of Fab was 10.26 IU/mL.The mouse group treated with both vaccine and human rabies immunoglobulin (HRIG)/Fab091 (32 IU/kg) showed protection against rabies, compared with the control group (P<0.05, Logrank test).Conclusion: The antibody fragment Fab was shown to be a neutralizing antibody against RABVG. It can be used together with other monoclonal antibodies for post-exposure prophylaxis of rabies virus in future studies.

  5. Signs Observed Among Animal Species Infected with Raccoon Rabies Variant Virus, Massachusetts, USA, 1992–2010

    Directory of Open Access Journals (Sweden)

    Linda L. Han

    2011-11-01

    Full Text Available We analyzed signs occurring among domestic and wild terrestrial animal species infected with raccoon rabies variant virus (RRV in Massachusetts, 1992–2010. The clinical sign of aggression was significantly associated with rabid stray cats (odds ratio, OR = 2.3 and RRV affected major wild terrestrial animal species individually, which included raccoons (OR = 2.8, skunks (OR = 8.0, gray foxes (OR = 21.3, red foxes (OR = 10.4, woodchucks (OR = 4.7 and coyotes (OR = 27.6. While aggression is a useful predictor of rabies among wild animals, combinations of other signs such as ataxia, disorientation, and salivation are useful predictors of rabies among domestic animals. Pets reported with multiple clinical signs had significantly higher rabies positive testing result than those reported with single clinical sign (p < 0.001. The result suggested the importance of avoiding aggressive terrestrial wild animals and giving additional attention to pets with multiple clinical signs.

  6. Characterization of rabies virus isolated from a colony of Eptesicus furinalis bats in Brazil

    Directory of Open Access Journals (Sweden)

    Marilene Fernandes de Almeida

    2011-02-01

    Full Text Available Some bat species have adapted to the expanding human population by acquiring the ability to roost in urban buildings, increasing the exposure risk for people and domestic animals, and consequently, the likelihood of transmitting rabies. Three dead bats were found in the yard of a house in an urban area of Jundiaí city in the state of São Paulo in southeast Brazil. Two of the three bats tested positive for rabies, using Fluorescent Antibody and Mouse Inoculation techniques. A large colony of Eptesicus furinalis was found in the house's attic, and of the 119 bats captured, four more tested positive for rabies. The objectives of this study were to report the rabies diagnosis, characterize the isolated virus antigenically and genetically, and study the epidemiology of the colony.

  7. [Sequencing and analysis of the complete genome of a rabies virus isolate from Sika deer].

    Science.gov (United States)

    Zhao, Yun-Jiao; Guo, Li; Huang, Ying; Zhang, Li-Shi; Qian, Ai-Dong

    2008-05-01

    One DRV strain was isolated from Sika Deer brain and sequenced. Nine overlapped gene fragments were amplified by RT-PCR through 3'-RACE and 5'-RACE method, and the complete DRV genome sequence was assembled. The length of the complete genome is 11863bp. The DRV genome organization was similar to other rabies viruses which were composed of five genes and the initiation sites and termination sites were highly conservative. There were mutated amino acids in important antigen sites of nucleoprotein and glycoprotein. The nucleotide and amino acid homologies of gene N, P, M, G, L in strains with completed genomie sequencing were compared. Compared with N gene sequence of other typical rabies viruses, a phylogenetic tree was established . These results indicated that DRV belonged to gene type 1. The highest homology compared with Chinese vaccine strain 3aG was 94%, and the lowest was 71% compared with WCBV. These findings provided theoretical reference for further research in rabies virus.

  8. Recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.

    Science.gov (United States)

    Wang, Xijun; Feng, Na; Ge, Jinying; Shuai, Lei; Peng, Liyan; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu; Bu, Zhigao

    2012-07-20

    Effective, safe, and affordable rabies vaccines are still being sought. Attenuated live vaccine has been widely used to protect carnivores from canine distemper. In this study, we generated a recombinant canine distemper virus (CDV) vaccine strain, rCDV-RVG, expressing the rabies virus glycoprotein (RVG) by using reverse genetics. The recombinant virus rCDV-RVG retained growth properties similar to those of vector CDV in Vero cell culture. Animal studies demonstrated that rCDV-RVG was safe in mice and dogs. Mice inoculated intracerebrally or intramuscularly with rCDV-RVG showed no apparent signs of disease and developed a strong rabies virus (RABV) neutralizing antibody response, which completely protected mice from challenge with a lethal dose of street virus. Canine studies showed that vaccination with rCDV-RVG induced strong and long-lasting virus neutralizing antibody responses to RABV and CDV. This is the first study demonstrating that recombinant CDV has the potential to serve as bivalent live vaccine against rabies and canine distemper in animals.

  9. Biotechnology advances: a perspective on the diagnosis and research of Rabies Virus.

    Science.gov (United States)

    Silva, S R; Katz, I S S; Mori, E; Carnieli, P; Vieira, L F P; Batista, H B C R; Chaves, L B; Scheffer, K C

    2013-07-01

    Rabies is a widespread zoonotic disease responsible for approximately 55,000 human deaths/year. The direct fluorescent antibody test (DFAT) and the mouse inoculation test (MIT) used for rabies diagnosis, have high sensitivity and specificity, but are expensive and time-consuming. These disadvantages and the identification of new strains of the virus encourage the use of new techniques that are rapid, sensitive, specific and economical for the detection and research of the Rabies Virus (RABV). Real-time RT-PCR, phylogeographic analysis, proteomic assays and DNA recombinant technology have been used in research laboratories. Together, these techniques are effective on samples with low virus titers in the study of molecular epidemiology or in the identification of new disease markers, thus improving the performance of biological assays. In this context, modern advances in molecular technology are now beginning to complement more traditional approaches and promise to revolutionize the diagnosis of rabies. This brief review presents some of the recent molecular tools used for RABV analysis, with emphasis on rabies diagnosis and research.

  10. Potential effect of prior raccoonpox virus infection in raccoons on vaccinia-based rabies immunization

    Science.gov (United States)

    Root, J Jeffrey; McLean, Robert G; Slate, Dennis; MacCarthy, Kathleen A; Osorio, Jorge E

    2008-01-01

    Background The USDA, Wildlife Services cooperative oral rabies vaccination (ORV) program uses a live vaccinia virus-vectored (genus Orthopoxvirus) vaccine, Raboral V-RG® (V-RG), to vaccinate specific wildlife species against rabies virus in several regions of the U.S. Several naturally occurring orthopoxviruses have been found in North America, including one isolated from asymptomatic raccoons (Procyon lotor). The effect of naturally occurring antibodies to orthopoxviruses on successful V-RG vaccination in raccoons is the focus of this study. Results Overall, raccoons pre-immunized (n = 10) with a recombinant raccoonpox virus vaccine (RCN-F1) responded to vaccination with V-RG with lower rabies virus neutralizing antibody (VNA) titers than those which were not pre-immunized (n = 10) and some failed to seroconvert for rabies VNA to detectable levels. Conclusion These results suggest that the success of some ORV campaigns may be hindered where raccoonpox virus or possibly other orthopoxvirus antibodies are common in wildlife species targeted for ORV. If these areas are identified, different vaccination strategies may be warranted. PMID:18834520

  11. Potential effect of prior raccoonpox virus infection in raccoons on vaccinia-based rabies immunization

    Directory of Open Access Journals (Sweden)

    MacCarthy Kathleen A

    2008-10-01

    Full Text Available Abstract Background The USDA, Wildlife Services cooperative oral rabies vaccination (ORV program uses a live vaccinia virus-vectored (genus Orthopoxvirus vaccine, Raboral V-RG® (V-RG, to vaccinate specific wildlife species against rabies virus in several regions of the U.S. Several naturally occurring orthopoxviruses have been found in North America, including one isolated from asymptomatic raccoons (Procyon lotor. The effect of naturally occurring antibodies to orthopoxviruses on successful V-RG vaccination in raccoons is the focus of this study. Results Overall, raccoons pre-immunized (n = 10 with a recombinant raccoonpox virus vaccine (RCN-F1 responded to vaccination with V-RG with lower rabies virus neutralizing antibody (VNA titers than those which were not pre-immunized (n = 10 and some failed to seroconvert for rabies VNA to detectable levels. Conclusion These results suggest that the success of some ORV campaigns may be hindered where raccoonpox virus or possibly other orthopoxvirus antibodies are common in wildlife species targeted for ORV. If these areas are identified, different vaccination strategies may be warranted.

  12. Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.

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    Clement W Gnanadurai

    Full Text Available Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico correlates with the presence of high level of virus neutralizing antibodies (VNA in the cerebral spinal fluid (CSF and mild immune cell accumulation in the central nervous system (CNS. By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

  13. Generation of Recombinant Rabies Virus CVS-11 Expressing eGFP Applied to the Rapid Virus Neutralization Test

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    Xianghong Xue

    2014-04-01

    Full Text Available The determination of levels of rabies virus-neutralizing antibody (VNA provides the foundation for the quantitative evaluation of immunity effects. The traditional fluorescent antibody virus neutralization test (FAVN using a challenge virus standard (CVS-11 strain as a detection antigen and staining infected cells with a fluorescein isothiocyanate (FITC-labeled monoclonal antibody, is expensive and high-quality reagents are often difficult to obtain in developing countries. Indeed, it is essential to establish a rapid, economical, and specific rabies virus neutralization test (VNT. Here, we describe a recombinant virus rCVS-11-eGFP strain that stably expresses enhanced green fluorescent protein (eGFP based on a reverse genetic system of the CVS-11 strain. Compared to the rCVS-11 strain, the rCVS-11-eGFP strain showed a similar growth property with passaging stability in vitro and pathogenicity in vivo. The rCVS-11-eGFP strain was utilized as a detection antigen to determine the levels of rabies VNAs in 23 human and 29 canine sera; this technique was termed the FAVN-eGFP method. The good reproducibility of FAVN-eGFP was tested with partial serum samples. Neutralization titers obtained from FAVN and FAVN-eGFP were not significantly different. The FAVN-eGFP method allows rapid economical, specific, and high-throughput assessment for the titration of rabies VNAs.

  14. Co-culture: A quick approach for isolation of street rabies virus in murine neuroblastoma cells

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    A. Sasikalaveni

    2015-05-01

    Full Text Available Background: Laboratory detection of rabies in most cases is based on detection of the antigen by fluorescent antibody test, however, in weak positive cases confirmative laboratory diagnosis depends on widely accepted mouse inoculation test. Cell lines like neuroblastoma have been used to isolate the virus with greater success not only to target for diagnosis, but also for molecular studies that determine the epidemiology of the circulating street rabies strains and in studies that look at the efficiency of the developed monoclonal antibodies to neutralize the different rabies strains. Due to the recent issues in obtaining ethical permission for mouse experimentation, and also the passages required in the cell lines to isolate the virus, we report herewith a co-culture protocol using the murine neuroblastoma (MNA cells, which enable quicker isolation of street rabies virus with minimum passages. Objective: This study is not to have an alternative diagnostic assay, but an approach to produce sufficient amount of rabies virus in minimum passages by a co-culture approach in MNA cells. Materials and Methods: The MNA cells are co-cultured by topping the normal cells with infected cells every 48 h and the infectivity was followed up by performing direct fluorescent-antibody test. Results: The co-culture approach results in 100% infectivity and hence the use of live mouse for experimentation could be avoided. Conclusion: Co-culture method provides an alternative for the situations with limited sample volume and for the quicker isolation of virus which warrants the wild type strains without much modification.

  15. Transmission dynamics of rabies virus in Thailand: Implications for disease control

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    Puanghat Apirom

    2005-06-01

    Full Text Available Abstract Background In Thailand, rabies remains a neglected disease with authorities continuing to rely on human death statistics while ignoring the financial burden resulting from an enormous increase in post-exposure prophylaxis. Past attempts to conduct a mass dog vaccination and sterilization program have been limited to Bangkok city and have not been successful. We have used molecular epidemiology to define geographic localization of rabies virus phylogroups and their pattern of spread in Thailand. Methods We analyzed 239 nucleoprotein gene sequences from animal and human brain samples collected from all over Thailand between 1998 and 2002. We then reconstructed a phylogenetic tree correlating these data with geographical information. Results All sequences formed a monophyletic tree of 2 distinct phylogroups, TH1 and TH2. Three subgroups were identified in the TH1 subgroup and were distributed in the middle region of the country. Eight subgroups of TH2 viruses were identified widely distributed throughout the country overlapping the TH1 territory. There was a correlation between human-dependent transportation routes and the distribution of virus. Conclusion Inter-regional migration paths of the viruses might be correlated with translocation of dogs associated with humans. Interconnecting factors between human socioeconomic and population density might determine the transmission dynamics of virus in a rural-to-urban polarity. The presence of 2 or more rabies virus groups in a location might be indicative of a gene flow, reflecting a translocation of dogs within such region and adjacent areas. Different approaches may be required for rabies control based on the homo- or heterogeneity of the virus. Areas containing homogeneous virus populations should be targeted first. Control of dog movement associated with humans is essential.

  16. Antigenic typing of brazilian rabies virus samples isolated from animals and humans, 1989-2000

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    FAVORETTO Silvana Regina

    2002-01-01

    Full Text Available Animal and human rabies samples isolated between 1989 and 2000 were typified by means of a monoclonal antibody panel against the viral nucleoprotein. The panel had been previously established to study the molecular epidemiology of rabies virus in the Americas. Samples were isolated in the Diagnostic Laboratory of the Pasteur Institute and in other rabies diagnostic centers in Brazil. In addition to the fixed virus samples CVS-31/96-IP, preserved in mouse brain, and PV-BHK/97, preserved in cell culture, a total of 330 rabies virus samples were isolated from dogs, cats, cattle, horses, bats, sheep, goat, swine, foxes, marmosets, coati and humans. Six antigenic variants that were compatible with the pre-established monoclonal antibodies panel were defined: numbers 2 (dog, 3 (Desmodus rotundus, 4 (Tadarida brasiliensis, 5 (vampire bat from Venezuela, 6 (Lasiurus cinereus and Lab (reacted to all used antibodies. Six unknown profiles, not compatible with the panel, were also found. Samples isolated from insectivore bats showed the greatest variability and the most commonly isolated variant was variant-3 (Desmodus rotundus. These findings may be related to the existence of multiple independent transmission cycles, involving different bat species.

  17. Comparison of a modified shell vial culture procedure with conventional mouse inoculation for rabies virus isolation

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    María de los Angeles Ribas Antúnez

    2013-04-01

    Full Text Available Rabies is a neurotropic disease that is often lethal. The early diagnosis of rabies infection is important and requires methods that allow for the isolation of the virus from animals and humans. The present study compared a modified shell vial (MSV procedure using 24-well tissue culture plates with the mouse inoculation test (MIT, which is considered the gold standard for rabies virus isolation. Thirty brain samples (25 positive and 5 negative by the fluorescent antibody test obtained from different animal species at the National Institute of Hygiene Rafael Rangel in Caracas, Venezuela, were studied by the MIT and MSV assays. Nine samples (36% were positive at 24 h, 10 (40% were positive at 48 h and six (24% were positive at 72 h by the MSV assay. With the MIT assay, 76% were positive at six days post inoculation and 12% were positive at 12 and 18 days post inoculation. One sample that was negative according to the MSV assay was positive with MIT on the 12th day. The MSV procedure exhibited a sensitivity of 96.2%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value 80%. This procedure allowed for rapid rabies virus detection. MIT can be employed as an alternative method in laboratories without tissue culture facilities.

  18. Molecular characterization of rabies virus isolated from non-haematophagous bats in Brazil

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    Avelino Albas

    2011-12-01

    Full Text Available INTRODUCTION: Rabies is an important zoonosis that causes thousands of deaths worldwide each year. Although the terrestrial cycle, mainly transmitted by dogs, is controlled in Brazil, the aerial cycle remains a serious public health issue, besides the economic problem. In the aerial cycle, the haematophagous bat Desmodus rotundus is the main source of infection, where several different species of non-haematophagous bats can be infected and can transmit the virus. METHODS: The aim of this work was to study the epidemiological pattern of rabies using antigenic characterization with monoclonal antibodies and genetic characterization by reverse-transcriptase polymerase chain reaction followed by sequencing and phylogenetic analysis of non-haematophagous bats' and herbivorous animals' central nervous system samples from the western region of the State of São Paulo, Brazil. RESULTS: From 27 samples, 3 antigenic variants were identified: AgV-3, AgV-4, and AgV-6; and from 29 samples, 5 different clusters were identified, all belonging to the rabies virus species. CONCLUSIONS: Although only non-haematophagous bats were evaluated in the studied region, the majority of samples were from antigenic and genetic variants related to haematophagous bats Desmodus rotundus. Samples from the same antigenic variant were segregated in more than one genetic cluster. This study demonstrated the diversity of rabies virus genetic lineages presented and circulating in non-haematophagous bats in the studied region.

  19. Utility of forensic detection of rabies virus in decomposed exhumed dog carcasses

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    Wanda Markotter

    2015-03-01

    Full Text Available This report describes four suspected rabies cases in domestic dogs that were involved inhuman exposures. In all these cases, the animals were buried for substantial times beforerabies testing was performed. Animal rabies is endemic in South Africa and domestic dogsare the main vector for transmission to humans. Diagnosis of rabies in humans is complicated,and diagnosis in the animal vector can provide circumstantial evidence to support clinicaldiagnosis of rabies in humans. The gold standard diagnostic method, fluorescent antibodytest (FAT, only delivers reliable results when performed on fresh brain material and thereforedecomposed samples are rarely submitted for diagnostic testing. Severely decomposed brainmaterial was tested for the presence of rabies virus genomic material using a quantitativereal-time reverse transcription polymerase chain reaction (q-real-time RT-PCR assaywhen conventional molecular methods were unsuccessful. This may be a useful tool in theinvestigation of cases where the opportunity to sample the suspected animals post mortem wasforfeited and which would not be possible with conventional testing methodologies becauseof the decomposition of the material.

  20. Utility of forensic detection of rabies virus in decomposed exhumed dog carcasses.

    Science.gov (United States)

    Markotter, Wanda; Coertse, Jessica; le Roux, Kevin; Peens, Joey; Weyer, Jacqueline; Blumberg, Lucille; Nel, Louis H

    2015-05-18

    This report describes four suspected rabies cases in domestic dogs that were involved inhuman exposures. In all these cases, the animals were buried for substantial times beforerabies testing was performed. Animal rabies is endemic in South Africa and domestic dogsare the main vector for transmission to humans. Diagnosis of rabies in humans is complicated,and diagnosis in the animal vector can provide circumstantial evidence to support clinicaldiagnosis of rabies in humans. The gold standard diagnostic method, fluorescent antibodytest (FAT), only delivers reliable results when performed on fresh brain material and thereforedecomposed samples are rarely submitted for diagnostic testing. Severely decomposed brainmaterial was tested for the presence of rabies virus genomic material using a quantitativereal-time reverse transcription polymerase chain reaction (q-real-time RT-PCR) assaywhen conventional molecular methods were unsuccessful. This may be a useful tool in theinvestigation of cases where the opportunity to sample the suspected animals post mortem wasforfeited and which would not be possible with conventional testing methodologies becauseof the decomposition of the material.

  1. Ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission.

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    Monica K Borucki

    2013-11-01

    Full Text Available One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350 in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009 and geographic location (northern vs. southern. A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.

  2. The effect of neurotoxin on rabies virus binding to mouse neuroblastoma cells.

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    Briggs, D J; Phillips, R M

    1991-08-01

    Mouse neuroblastoma cells were exposed to alpha bungarotoxin, a neurotoxin known to inhibit rabies virus binding to the nicotinic acetylcholine receptor located at the neuromuscular junction in muscle tissue. The total amount of 3H-CVS virus that bound to neurotoxin treated cells was separated into specific and non-specific binding using a cold competition assay. Comparison of untreated and neurotoxin treated cells demonstrated that the majority of cell-associated virus in untreated cells was of a specific nature whereas the majority of the cell-associated virus in neurotoxin treated cells was due to non-specific binding.

  3. Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century.

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    Anthony R Fooks

    2009-09-01

    Full Text Available The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem

  4. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

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    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  5. Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo

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    Kevin T Beier

    2013-02-01

    Full Text Available Defining the connections among neurons is critical to our understanding of the structure and function of the nervous system. Recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo. We recently demonstrated that recombinant vesicular stomatitis virus (VSV can be endowed with anterograde or retrograde synaptic tracing ability by providing the virus with different glycoproteins. Here we extend the characterization of the transmission and gene expression of VSV with the rabies virus glycoprotein (RABV-G, and provide examples of its activity relative to the anterograde tracer form of rVSV. rVSV with RABV-G was found to drive strong expression of transgenes and to spread rapidly from neuron to neuron in only a retrograde manner. Depending upon how the RABV-G was delivered, VSV served as a polysynaptic or monosynaptic tracer, or was able to define projections through axonal uptake and retrograde transport. In animals co-infected with rVSV in its anterograde form, rVSV with RABV-G could be used to begin to characterize the similarities and differences in connections to a given area. rVSV with RABV-G provides a flexible, rapid, and versatile tracing tool that complements the previously described VSV-based anterograde transsynaptic tracer.

  6. An outbreak of post-vaccinal rabies (rage de laboratoire) in Fortaleza, Brazil, in 1960. Residual fixed virus as the etiological agent.

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    Pará, M

    1965-01-01

    The repeated isolation of fixed rabies virus from the CNS tissues of victims of an acute and lethal outbreak of encephalomyelitis in Fortaleza, Brazil, in November 1960, following vaccination with a locally produced killed-virus anti-rabies vaccine of the Fermi type is considered as definitive evidence of the rabic etiology (vaccinal fixed-virus rabies, rage de laboratoire) of this outbreak. Eighteen persons were affected, all of whom died.The clinical picture of paralytic rabies was recognizable in all of these 18 patients. The well-marked characteristics of an acute infection permit the easy differentiation of the paralysis caused by fixed rabies virus from post-vaccinal accidents that occur as allergic reactions.The incriminated anti-rabies vaccine was found to contain fixed live rabies virus at a titre of 10(-3.0). After one year of storage under refrigeration, the vaccine still contained fixed rabies virus, at a titre of 0,2x10(-1.0).Subsequent laboratory studies tend to indicate that the curve of inactivation of fixed virus by phenol does not follow a linear function but rather resembles the curve of inactivation of poliomyelitis virus by heat and formol according to the Salk technique. It is suggested that the antigenicity of the so-called "killed-virus" anti-rabies vaccines is actually due to the presence in them of residual amounts of live virus.

  7. Development and evaluation of an In vitro isolation of street rabies virus in mouse neuroblastoma cells as compared to conventional tests used for diagnosis of rabies

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    Chhabra M

    2007-01-01

    Full Text Available In vitro isolation of rabies virus using mouse neuroblastoma cells (MNA was evaluated. The sensitivity and reliability of in vitro procedure was performed in comparison with mouse inoculation test (MIT, the in vivo method of virus isolation, direct fluorescent antibody test (FAT and Sellers staining. Of the 33 animal brain samples tested, 24 (72.72% were positive by MIT. Sensitivity of Sellers stain, FAT and rapid tissue culture infection test (RTCIT was found to be 54.16, 100 and 91.6% respectively. Concordance of Sellers stain, FAT, RTCIT with MIT was found to be 66.6, 100 and 93.93% respectively. Two samples which were positive by FAT and MIT showed gross contamination in cell lines, which is one of the drawbacks of RTCIT. However, rabies virus could be isolated in MNA cells from two of the eight human cerebrospinal fluid (CSF samples from clinico-epidemiologically suspected cases of rabies. Both MIT and FAT showed negative results in the two CSF samples. RTCIT appears to be a fast and reliable alternative to MIT and holds promise in antemortem diagnosis of rabies, which is otherwise, a challenging task for a reference laboratory.

  8. Evolutionary history and dynamics of dog rabies virus in western and central Africa.

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    Talbi, Chiraz; Holmes, Edward C; de Benedictis, Paola; Faye, Ousmane; Nakouné, Emmanuel; Gamatié, Djibo; Diarra, Abass; Elmamy, Bezeid Ould; Sow, Adama; Adjogoua, Edgard Valery; Sangare, Oumou; Dundon, William G; Capua, Ilaria; Sall, Amadou A; Bourhy, Hervé

    2009-04-01

    The burden of rabies in Africa is estimated at 24,000 human deaths year(-1), almost all of which result from infection with dog rabies viruses (RABV). To investigate the evolutionary dynamics of RABV in western and central Africa, 92 isolates sampled from 27 African countries over 29 years were collected and sequenced. This revealed that RABV currently circulating in dogs in this region fell into a single lineage designated 'Africa 2'. A detailed analysis of the phylogeographical structure of this Africa 2 lineage revealed strong population subdivision at the country level, with only limited movement of virus among localities, including a possible east-to-west spread across Africa. In addition, Bayesian coalescent analysis suggested that the Africa 2 lineage was introduced into this region of Africa only recently (probably colonial influence and urbanization, and then spread relatively slowly, perhaps occupying the entire region in a 100 year period.

  9. High Diversity of Rabies Viruses Associated with Insectivorous Bats in Argentina: Presence of Several Independent Enzootics

    Science.gov (United States)

    Piñero, Carolina; Gury Dohmen, Federico; Beltran, Fernando; Martinez, Leila; Novaro, Laura; Russo, Susana; Palacios, Gustavo; Cisterna, Daniel M.

    2012-01-01

    Background Rabies is a fatal infection of the central nervous system primarily transmitted by rabid animal bites. Rabies virus (RABV) circulates through two different epidemiological cycles: terrestrial and aerial, where dogs, foxes or skunks and bats, respectively, act as the most relevant reservoirs and/or vectors. It is widely accepted that insectivorous bats are not important vectors of RABV in Argentina despite the great diversity of bat species and the extensive Argentinean territory. Methods We studied the positivity rate of RABV detection in different areas of the country, and the antigenic and genetic diversity of 99 rabies virus (RABV) strains obtained from 14 species of insectivorous bats collected in Argentina between 1991 and 2008. Results Based on the analysis of bats received for RABV analysis by the National Rabies system of surveillance, the positivity rate of RABV in insectivorous bats ranged from 3.1 to 5.4%, depending on the geographic location. The findings were distributed among an extensive area of the Argentinean territory. The 99 strains of insectivorous bat-related sequences were divided into six distinct lineages associated with Tadarida brasiliensis, Myotis spp, Eptesicus spp, Histiotus montanus, Lasiurus blosseviilli and Lasiurus cinereus. Comparison with RABV sequences obtained from insectivorous bats of the Americas revealed co-circulation of similar genetic variants in several countries. Finally, inter-species transmission, mostly related with Lasiurus species, was demonstrated in 11.8% of the samples. Conclusions This study demonstrates the presence of several independent enzootics of rabies in insectivorous bats of Argentina. This information is relevant to identify potential areas at risk for human and animal infection. PMID:22590657

  10. Ambivalent Role of the Innate Immune Response in Rabies Virus Pathogenesis▿†

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    Chopy, Damien; Pothlichet, Julien; Lafage, Mireille; Mégret, Françoise; Fiette, Laurence; Si-Tahar, Mustapha; Lafon, Monique

    2011-01-01

    The neurotropic rabies virus (RABV) has developed several evasive strategies, including immunoevasion, to successfully infect the nervous system (NS) and trigger a fatal encephalomyelitis. Here we show that expression of LGP2, a protein known as either a positive or negative regulator of the RIG-I-mediated innate immune response, is restricted in the NS. We used a new transgenic mouse model (LGP2 TG) overexpressing LGP2 to impair the innate immune response to RABV and thus revealed the role o...

  11. Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model.

    Science.gov (United States)

    Brunker, K; Hampson, K; Horton, D L; Biek, R

    2012-12-01

    Landscape epidemiology and landscape genetics combine advances in molecular techniques, spatial analyses and epidemiological models to generate a more real-world understanding of infectious disease dynamics and provide powerful new tools for the study of RNA viruses. Using dog rabies as a model we have identified how key questions regarding viral spread and persistence can be addressed using a combination of these techniques. In contrast to wildlife rabies, investigations into the landscape epidemiology of domestic dog rabies requires more detailed assessment of the role of humans in disease spread, including the incorporation of anthropogenic landscape features, human movements and socio-cultural factors into spatial models. In particular, identifying and quantifying the influence of anthropogenic features on pathogen spread and measuring the permeability of dispersal barriers are important considerations for planning control strategies, and may differ according to cultural, social and geographical variation across countries or continents. Challenges for dog rabies research include the development of metapopulation models and transmission networks using genetic information to uncover potential source/sink dynamics and identify the main routes of viral dissemination. Information generated from a landscape genetics approach will facilitate spatially strategic control programmes that accommodate for heterogeneities in the landscape and therefore utilise resources in the most cost-effective way. This can include the efficient placement of vaccine barriers, surveillance points and adaptive management for large-scale control programmes.

  12. Interferon-inducible GTPase: a novel viral response protein involved in rabies virus infection.

    Science.gov (United States)

    Li, Ling; Wang, Hualei; Jin, Hongli; Cao, Zengguo; Feng, Na; Zhao, Yongkun; Zheng, Xuexing; Wang, Jianzhong; Li, Qian; Zhao, Guoxing; Yan, Feihu; Wang, Lina; Wang, Tiecheng; Gao, Yuwei; Tu, Changchun; Yang, Songtao; Xia, Xianzhu

    2016-05-01

    Rabies virus infection is a major public health concern because of its wide host-interference spectrum and nearly 100 % lethality. However, the interactions between host and virus remain unclear. To decipher the authentic response in the central nervous system after rabies virus infection, a dynamic analysis of brain proteome alteration was performed. In this study, 104 significantly differentially expressed proteins were identified, and intermediate filament, interferon-inducible GTPases, and leucine-rich repeat-containing protein 16C were the three outstanding groups among these proteins. Interferon-inducible GTPases were prominent because of their strong upregulation. Moreover, quantitative real-time PCR showed distinct upregulation of interferon-inducible GTPases at the level of transcription. Several studies have shown that interferon-inducible GTPases are involved in many biological processes, such as viral infection, endoplasmic reticulum stress response, and autophagy. These findings indicate that interferon-inducible GTPases are likely to be a potential target involved in rabies pathogenesis or the antiviral process.

  13. Rabies virus infection in Eptesicus fuscus bats born in captivity (naive bats.

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    April D Davis

    Full Text Available The study of rabies virus infection in bats can be challenging due to quarantine requirements, husbandry concerns, genetic differences among animals, and lack of medical history. To date, all rabies virus (RABV studies in bats have been performed in wild caught animals. Determining the RABV exposure history of a wild caught bat based on the presence or absence of viral neutralizing antibodies (VNA may be misleading. Previous studies have demonstrated that the presence of VNA following natural or experimental inoculation is often ephemeral. With this knowledge, it is difficult to determine if a seronegative, wild caught bat has been previously exposed to RABV. The influence of prior rabies exposure in healthy, wild caught bats is unknown. To investigate the pathogenesis of RABV infection in bats born in captivity (naïve bats, naïve bats were inoculated intramuscularly with one of two Eptesicus fuscus rabies virus variants, EfV1 or EfV2. To determine the host response to a heterologous RABV, a separate group of naïve bats were inoculated with a Lasionycteris noctivagans RABV (LnV1. Six months following the first inoculation, all bats were challenged with EfV2. Our results indicate that naïve bats may have some level of innate resistance to intramuscular RABV inoculation. Additionally, naïve bats inoculated with the LnV demonstrated the lowest clinical infection rate of all groups. However, primary inoculation with EfV1 or LnV did not appear to be protective against a challenge with the more pathogenic EfV2.

  14. Rabies virus in Molossus molossus (Chiroptera: Molossidae in the State of Pernambuco, Northeastern Brazil

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    Luiz Augustinho Menezes da Silva

    2011-08-01

    Full Text Available Rabies virus was detected in bats (Molossus molossus from an urban area in the City of Recife, State of Pernambuco, Brazil. Four individuals were found during the day in visible, non-habitual places, lying on the ground, but still alive. No contact occurred with people or animals. Of these, only two were identified; it was not possible to identify two specimens, since they were incinerated prior to identification. Diagnosis was positive by direct immunofluorescence and intracerebral inoculation in mice. This study presents the first instance in which the virus was detected in insectivorous bats in the State of Pernambuco.

  15. In situ apoptosis of adaptive immune cells and the cellular escape of rabies virus in CNS from patients with human rabies transmitted by Desmodus rotundus.

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    Fernandes, Elaine Raniero; de Andrade, Heitor Franco; Lancellotti, Carmen Lúcia Penteado; Quaresma, Juarez Antônio Simões; Demachki, Samia; da Costa Vasconcelos, Pedro Fernando; Duarte, Maria Irma Seixas

    2011-03-01

    The aim of the current study was to investigate the apoptosis of neurons, astrocytes and immune cells from human patients that were infected with rabies virus by vampire bats bite. Apoptotic neurons were identified by their morphology and immune cells were identified using double immunostaining. There were very few apoptotic neurons present in infected tissue samples, but there was an increase of apoptotic infiltrating CD4+ and TCD8+ adaptive immune cells in the rabies infected tissue. No apoptosis was present in NK, macrophage and astrocytes. The dissemination of the human rabies virus within an infected host may be mediated by viral escape of the virus from an infected cell and may involve an anti-apoptotic mechanism, which does not kill the neuron or pro-apoptosis of TCD4+ and TCD8+ lymphocytes and which allows for increased proliferation of the virus within the CNS by attenuation of the adaptive immune response. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Improved Safety for Molecular Diagnosis of Classical Rabies Viruses by Use of a TaqMan Real-Time Reverse Transcription-PCR "Double Check" Strategy

    DEFF Research Database (Denmark)

    Hoffmann, B.; Freuling, C. M.; Wakeley, P. R.

    2010-01-01

    by a combined assay that detected all samples as positive. In addition, the introduction of labeled positive controls (LPC) increased the diagnostic safety of the single as well as the combined assay. Based on the newly developed, alternative assay for the detection of rabies virus and the application of LPCs......To improve the diagnosis of classical rabies virus with molecular methods, a validated, ready-to-use, real-time reverse transcription-PCR (RT-PCR) assay was developed. In a first step, primers and 6-carboxyfluorescien-labeled TaqMan probes specific for rabies virus were selected from the consensus...... sequence of the nucleoprotein gene of 203 different rabies virus sequences derived from GenBank. The selected primer-probe combination was highly specific and sensitive. During validation using a sample set of rabies virus strains from the virus archives of the Friedrich-Loeffler-Institut (FLI; Germany...

  17. Immunogenicity Studies in Carnivores Using a Rabies Virus Construct with a Site-Directed Deletion in the Phosphoprotein

    Directory of Open Access Journals (Sweden)

    Ad Vos

    2011-01-01

    Full Text Available Different approaches have been applied to develop highly attenuated rabies virus vaccines for oral vaccination of mesocarnivores. One prototype vaccine construct is SAD dIND1, which contains a deletion in the P-gene severely limiting the inhibition of type-1 interferon induction. Immunogenicity studies in foxes and skunks were undertaken to investigate whether this highly attenuated vaccine would be more immunogenic than the parental SAD B19 vaccine strain. In foxes, it was demonstrated that SAD dIND1 protected the animals against a rabies infection after a single oral dose, although virus neutralizing antibody titres were lower than in foxes orally vaccinated with the SAD B19 virus as observed in previous experiments. In contrast, skunks receiving 107.5 FFU SAD dIND1 did not develop virus neutralizing antibodies and were not protected against a subsequent rabies infection.

  18. Molecular docking studies with rabies virus glycoprotein to design viral therapeutics

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    Tomar N

    2010-01-01

    Full Text Available The genome of rabies virus encodes five proteins; the nucleoprotein, the phosphoprotein, the matrix protein, the glycoprotein, and the RNA-dependent RNA polymerase. Among these, the glycoprotein is the most important as it is the major contributor to pathogenicity and virus neutralizing antibody response. Keeping in mind that glycoprotein is the only protein exposed on the surface of virus and is thought to be responsible for the interaction with the cell membrane, it was attempted to target glycoprotein by a ligand polyethylene glycol 4000, which blocks its active site, as seen by molecular operating environment software, so that it may be possible to prevent the spread of virus into the host. The ligand polyethylene glycol 4000 was retrieved from Research Collaboratory for Structural Bioinformatics protein data bank by providing the glycoprotein sequence to the databank. In this study it was observed that the ligand was successfully docked on a major portion of antigenic site II of glycoprotein by mimicking the virus neutralizing antibodies. This knowledge may be important for the development of novel therapies for the treatment of rabies and other viral diseases in the future.

  19. Hematologic profile of hematophagous Desmodus rotundus bats before and after experimental infection with rabies virus

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    Marilene Fernandes de Almeida

    2014-06-01

    Full Text Available Introduction Hematophagous Desmodus rotundus bats play an important role in the rabies lifecycle. This study describes the hematological profile of these bats before and after experimental infection with rabies virus. Methods Cells counts were performed in a Neubauer chamber. Results The average values of erythrocytes and leucocytes counts in blood before experimental infections were 9.97 × 106mm3 and 4.80 × 103mm3, respectively. Neutrophils represented 69.9% of white blood cells and the lymphocytes represented 26.9%. Following the experimental infections, the average numbers of erythrocytes and leucocytes was 9.43 × 106mm3 and 3.98 × 103mm3, respectively. Neutrophils represented 40% of white blood cells and the lymphocytes represented 59%. Conclusions The hematological profile given in this study can serve as reference values for D. rotundus bats.

  20. Development of Rabies Virus-Like Particles for Vaccine Applications: Production, Characterization, and Protection Studies.

    Science.gov (United States)

    Fontana, Diego; Etcheverrigaray, Marina; Kratje, Ricardo; Prieto, Claudio

    2016-01-01

    Rabies is a viral infection of the central nervous system for which vaccination is the only treatment possible. Besides preexposure, vaccination is highly recommended for people living in endemic areas, veterinarians, and laboratory workers. Our group has developed rabies virus-like particles (RV-VLPs) with immunogenic features expressed in mammalian cells for vaccine applications. In this chapter the methods to obtain and characterize a stable HEK293 cell line expressing RV-VLPs are detailed. Further, analytical ultracentrifugation steps to purify the obtained VLPs are developed, as well as western blot, dynamic light scattering, and immunogold electron microscopy to analyze the size, distribution, shape, and antigenic conformation of the purified particles. Finally, immunization protocols are described to study the immunogenicity of RV-VLPs.

  1. Structural and functional studies on a unique linear neutralizing antigenic site (G5) of the rabies virus glycoprotein.

    NARCIS (Netherlands)

    R.W.J. van der Heijden (Roger); J.P.M. Langedijk; J. Groen (Jan); F.G.C.M. Uytdehaag (Fons); R.H. Meloen; A.D.M.E. Osterhaus (Albert)

    1993-01-01

    textabstractThe core of a unique linear neutralization epitope (G5) on the glycoprotein of rabies virus, recognized by a virus-neutralizing mouse monoclonal antibody (MAb 6-15C4), was determined by Pepscan analysis. The G5 epitope was defined as an octapeptide (LHDFRSDE). The contribution of the

  2. Evaluation of In vitro antiviral activity of Datura metel Linn. against rabies virus

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    Soumen Roy

    2016-01-01

    Full Text Available Objective: The soxhlet and cold extracts of Datura metel Linn. were evaluated for in vitro antirabies activity. Materials and Methods: Soxhlet and cold extraction method were used to extract Datura (fruit and seed extracts. In vitro cytotoxicity assay was performed by 3-(4,5-dimethylthiazolyl-2-2,5-diphenyltetrazolium bromide assay. Based on the CC50 range, the in vitro antirabies activity of the extracts was screened by rapid fluorescent focus inhibition test and molecular method. Results: The Datura (fruit and seed extracts were not cytotoxic below 5 mg/ml (CC50. Titer of 10−4 rabies virus challenge virus standard (RV CVS (1 50% tissue culture infective dose [1 TCID50] was obtained by RFFT method and the challenge dose of 10 TCID50 was used for antirabies assay. Datura fruit and seed (soxhlet and cold extracts showed 50% inhibition of RV CVS at 2.5 mg/ml and 1.25 mg/ml (inhibitory concentration 50% [IC50], respectively. The tested extracts showed selectivity index (CC50/IC50 ranging from 2 to 4. The viral RNA was extracted and real-time reverse transcription-polymerase chain reaction was performed which also revealed a 2-fold reduction of viral load at 1.25 mg/ml of the Datura seed (soxhlet methanolic and cold aqueous extracts. Conclusion: To the best of our knowledge, this is the first study of in vitro antiviral activity of D. metel Linn. against rabies virus. Datura seed extracts have a potential in vitro antirabies activity and, in future, can be further screened for in vivo activity against rabies virus in murine model.

  3. The feasibility of rabies virus-vectored immunocontraception in a mouse model

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    Xianfu Wu

    2014-01-01

    Full Text Available Immunocontraceptive vaccines may be an alternative to surgical sterilization. Dual rabies vaccination and dog population management is a helpful tool for rabies prevention. A synthetic gonadotropin-releasing hormone (GnRH peptide coupled to a carrier protein or T cell epitope is efficacious in inducing immunocontraception in a variety of mammals. However, virus-vectored GnRH recombinant vaccines have advantages over the conjugation method. In a previous in vitro study, we were able to insert a GnRH-coding sequence into the rabies virus (RABV glycoprotein (G gene, and the recombinant viruses grew to high titers in cells. Here, we further focused on the RABV G in accepting various copy numbers of GnRH. We demonstrated although RABV G protein with up to 4 copies of GnRH was well expressed, the recombinant virus was recovered only when 2 copies of GnRH (20 amino acids were incorporated into the G, indicating a possible insertion limit in making a full infectious clone. The investigation provides insight into the utility of RABV G as a carrier for small peptides and its suitability for vaccine studies. Following our previous study, we selected ERAg3p/2GnRH and tested the construct in mice. The vaccine induced ⩾80% infertility after three doses without any adjuvant, in live (8 of 10 mice infertility or inactivated (13 of 14 mice infertility formulations; while the pregnancy rate was 100% (10 of 10 mice in the controls. This initial success of immunocontraception in mice is promising, and we are now optimizing the vaccine formulation by using adjuvants and exploring novel delivery methods to minimize the dosage.

  4. Studies on an inactivated vaccine against rabies virus in domestic animals.

    Science.gov (United States)

    Monaco, F; Franchi, P M; Lelli, R

    2006-01-01

    An inactivated vaccine against rabies virus was prepared from the attenuated ATCC PV-12 viral rabbit Pasteur strain. The virus was grown on Baby Hamster Kidney (BHK21) cells, and the supernatant was purified by filtration and inactivated with beta-propriolactone. The inactivated product was checked according to the NHI and European Pharmacopoeia methods. Part of the product was then lyophilised and the other part was adjuvanted with Al(OH)3. Both parts were used to vaccinate and boost groups of horses, cattle and sheep at different intervals. Their immunogenicity was compared with a similar commercial product. Blood samples were collected on a regular basis and the antibody titre was determined by the Fluorescence Antibody Virus Neutralisation (FAVN) test. No significant differences were found between species after both inoculations even though the immune response increased in intensity and duration after the booster dose in all the animals tested and was stronger and lasted longer with the adjuvanted aliquot.

  5. Right place, wrong species: a 20-year review of rabies virus cross species transmission among terrestrial mammals in the United States.

    Directory of Open Access Journals (Sweden)

    Ryan M Wallace

    Full Text Available INTRODUCTION: In the continental US, four terrestrial mammalian species are reservoirs for seven antigenic rabies virus variants. Cross species transmission (CST occurs when a rabies virus variant causes disease in non-reservoir species. METHODS: This study analyzed national surveillance data for rabies in terrestrial mammals. The CST rate was defined as: number of rabid non-reservoir animals/number of rabid reservoir animals. CST rates were analyzed for trend. Clusters of high CST rate counties were evaluated using space-time scanning statistics. RESULTS: The number of counties reporting a raccoon variant CST rate >1.0 increased from 75 in 1992 to 187 in 2011; counties with skunk variant CST rates >1.0 remained unchanged during the same period. As of 2011, for every rabid raccoon reported within the raccoon variant region, there were 0.73 cases of this variant reported in non-reservoir animals. Skunks were the most common non-reservoir animal reported with the raccoon rabies variant. Domestic animals were the most common non-reservoir animal diagnosed with a skunk rabies virus variant (n = 1,601. Cross species transmission rates increased fastest among domestic animals. CONCLUSIONS: Cross species transmission of rabies virus variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control. Cross species transmission in raccoon rabies enzootic regions increased dramatically during the study period. Pet owners should vaccinate their dogs and cats to ensure against CST, particularly in regions with active foci of rabies circulation. Clusters of high CST activity represent areas for further study to better understand interspecies disease transmission dynamics. Each CST event has the potential to result in a rabies virus adapted for sustained transmission in a new species; therefore further understanding of the dynamics of CST may help in early detection or prevention of the emergence

  6. The Glycoprotein and the Matrix Protein of Rabies Virus Affect Pathogenicity by Regulating Viral Replication and Facilitating Cell-to-Cell Spread▿

    OpenAIRE

    Pulmanausahakul, Rojjanaporn; Li, Jianwei; Schnell, Matthias J.; Dietzschold, Bernhard

    2007-01-01

    While the glycoprotein (G) of rabies virus (RV) is known to play a predominant role in the pathogenesis of rabies, the function of the RV matrix protein (M) in RV pathogenicity is not completely clear. To further investigate the roles of these proteins in viral pathogenicity, we constructed chimeric recombinant viruses by exchanging the G and M genes of the attenuated SN strain with those of the highly pathogenic SB strain. Infection of mice with these chimeric viruses revealed a significant ...

  7. Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan

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    Yung-Cheng Lin

    2016-03-01

    Full Text Available Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G, matrix protein (M, and nucleoprotein (N genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10−4–4.75 × 10−4 substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers.

  8. Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan.

    Science.gov (United States)

    Lin, Yung-Cheng; Chu, Pei-Yu; Chang, Mei-Yin; Hsiao, Kuang-Liang; Lin, Jih-Hui; Liu, Hsin-Fu

    2016-03-17

    Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10(-4)-4.75 × 10(-4) substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers.

  9. Ultrastructure of peripheral nerves of mice inoculated with rabies virus

    Directory of Open Access Journals (Sweden)

    Guilberto Minguetti

    1979-06-01

    Full Text Available Alterações ultraestruturais bastante significativas foram encontrados em nervos periféricos de ratos inoculados com virus da raiva. Tais achados se caracterizam por degeneração axonal com desmielinização secundária. Os achados são precedidos em cerca de 24 horas por sinais clínicos correspondentes. Contudo, os nervos examinados não apresentaram partículas com as características das do virus da raiva. É possível que após a inoculação os virus percam suas cápsulas e as molésculas de ARN que os constituem se confundam com o conteúdo axoplasmático, tornando-se indistinguíveis pela microscopia eletrônica. Só dessa forma poder-se-ia explicar a ação deletéria das partículas virais nos axônios e conseqüente tramitação centrípeta em direção à medula e partes mais altas do sistema nervoso central, sem serem detectados pela microscopia eletrônica. A degeneração axonal encontrada, com conseqüente quadro de polineurite, mostra que os sinais periféricos não são exclusivamente de uma mielite ascendente. Ambos os processos podem estar envolvidos.

  10. Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus.

    Science.gov (United States)

    Leroy, M; Pire, G; Baise, E; Desmecht, D

    2006-03-01

    Rabies is a fatal anthropozoonotic viral infection of the central nervous system that remains a serious public health problem in many countries. As several animal cases of spontaneous survival to infection were reported and because type 1 interferons were shown to protect against the virus, it was suggested that innate resistance mechanisms exist. Among the antiviral proteins that are synthesized in response to interferon-alpha/beta stimulation, Mx proteins from several species are long known to block the replication of vesicular stomatitis virus (VSV). As both VSV and rabies virus belongs to the Rhabdoviridae family, this study was started with the aim to establish whether the anti-VSV activity of a mammalian Mx protein could be extended to rabies virus. This question was addressed by inoculating the virus onto a bovine Mx1 or human MxA-expressing Vero cell clone. Plaque formation was unambiguously blocked, and viral yields were reduced 100- to 1000-fold by bovine Mx1 expression for both SAG2 and SADB19 viral strains. In opposition, only SAG2 strain could be inhibited by the expression of human MxA protein. The effect of both proteins expression was then evaluated at the viral protein expression level. Again, boMx1 was able to repress protein expression in both strain, whereas only SAG2 proteins were inhibited in human MxA-expressing cells. These results suggest that protection conferred by interferon-alpha/beta against rabies could be, at least partially, attributable to the Mx pathway. Alternatively, bovine Mx1 could be unique in its ability to repress rabies virus which, if confirmed in vivo, would open an avenue for the development of new antirabies therapeutic strategies.

  11. Molecular epidemiological study of Arctic rabies virus isolates from Greenland and comparison with isolates from throughout the Arctic and Baltic regions

    DEFF Research Database (Denmark)

    Mansfield, K.L.; Racloz, V.; McElhinney, L.M.

    2006-01-01

    We report a Molecular epidemiological study of rabies in Arctic Countries by comparing a panel of novel Greenland isolates to a larger cohort of viral sequences from both Arctic and Baltic regions. Rabies Virus isolates originating from wildlife (Arctic/red foxes, raccoon-dogs and reindeer), from...

  12. Application of a Real-time Reverse Transcription Loop Mediated Amplification Method to the Detection of Rabies Virus in Arctic Foxes in Greenland

    DEFF Research Database (Denmark)

    Wakeley, Philip; Johnson, Nicholas; Rasmussen, Thomas Bruun

    Reverse transcription loop mediated amplification (RT-LAMP) offers a rapid, isothermal method for amplification of virus RNA. In this study a panel of positive rabies virus samples originally prepared from arctic fox brain tissue was assessed for the presence of rabies viral RNA using a real time...... RT-LAMP. The method had previously been shown to work with samples from Ghana which clustered with cosmopolitan lineage rabies viruses but the assay had not been assessed using samples from animals infected with rabies from the arctic region. The assay is designed to amplify both cosmopolitan strains...... virus of arctic origin virus can be detected using RT-LAMP and the method reported is more rapid than the real-time RT-PCR. Further arctic fox samples are under analysis in order to confirm these findings....

  13. Virus isolation in cell culture for confirmatory diagnostic of rabies in bovine specimens

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    Fabio Adriano Kanitz

    2015-12-01

    Full Text Available ABSTRACT: This study investigated the suitability of virus isolation (VI in mouse neuroblastoma cells (N2A and baby hamster kidney cells (BHK-21 as a confirmatory test for diagnosis of bovine rabies. Fourty-eight brain samples from cattle suspected of rabies were initially submitted to fluorescent antibody test (FAT and mouse inoculation test (MIT for routine diagnostic. Subsequently, these specimens were submitted to three protocols of VI in each cell line: a single 24h or 72h passage (T1, T2, or three 48h passages (T3. The FAT and MIT combined detected 32/48 positive samples, from which MIT detected 32 and FAT 31. The average time required for final MIT results was 12.3 days (8 - 21. VI in BHK-21 cells provided definitive, positive results in 100% of the samples in 72h (T2 and in 96.9% after three 48h passages (T3. VI in N2A cells yielded positive results in 100% in 72h (T2 and in 93.7% of samples after three 48h passages (T3. Sensitivity, specificity, positive and negative predictive values were 100% in T2 in N2A and BHK-21 cells, and the Kappa value was excellent in both cells (k=1. A single 24h passage (T1 in both cell lines performed poorly, detecting less than 40% of the positive samples. Taking together, these results indicate that VI in both cell lines, especially in BHK-21 cells that grow faster and are much easier to maintain, does represent an adequate alternative for MIT as a confirmatory test for rabies diagnostic in bovine specimens, yielding reliable results in reduced time.

  14. Recombinant rabies virus expressing the H protein of canine distemper virus protects dogs from the lethal distemper challenge.

    Science.gov (United States)

    Wang, Feng-Xue; Zhang, Shu-Qin; Zhu, Hong-Wei; Yang, Yong; Sun, Na; Tan, Bin; Li, Zhen-Guang; Cheng, Shi-Peng; Fu, Zhen F; Wen, Yong-Jun

    2014-12-05

    The rabies virus (RV) vector LBNSE expressing foreign antigens have shown considerable promise as vaccines against viral and bacteria diseases, which is effective and safe. We produced a new RV-based vaccine vehicle expressing 1.824 kb hemagglutinin (H) gene of the canine distemper virus (CDV) by reverse genetics technology. The recombinant virus LBNSE-CDV-H retained growth properties similar to those of vector LBNSE both in BSR and mNA cell culture. The H gene of CDV was expressed and detected by immunostaining. To compare the immunogenicity of LBNSE-CDV-H, dogs were immunized with each of these recombinant viruses by intramuscular (i.m.). The dogs were bled at third weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with virulent virus (ZJ 7) at fourth weeks. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. Dogs inoculated with LBNSE-CDV-H showed no any signs of disease and exhibited seroconversion against both RV and CDV H protein. The LBNSE-CDV-H did not cause disease in dogs and conferred protection from challenge with a lethal wild type CDV strain, demonstrating its potential value for wildlife conservation efforts. Together, these studies suggest that recombinant RV expressing H protein from CDV stimulated high levels of adaptive immune responses (VNA), and protected all dogs challenge infection.

  15. Update on rabies

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    Alan C Jackson

    2011-02-01

    Full Text Available Alan C JacksonDepartments of Internal Medicine (Neurology and Medical Microbiology, University of Manitoba, Winnipeg, MB, CanadaAbstract: 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

  16. [Sequencing and analysis of complete genome of rabies viruses isolated from Chinese Ferret-Badger and dog in Zhejiang province].

    Science.gov (United States)

    Lei, Yong-Liang; Wang, Xiao-Guang; Tao, Xiao-Yan; Li, Hao; Meng, Sheng-Li; Chen, Xiu-Ying; Liu, Fu-Ming; Ye, Bi-Feng; Tang, Qing

    2010-01-01

    Based on sequencing the full-length genomes of four Chinese Ferret-Badger and dog, we analyze the properties of rabies viruses genetic variation in molecular level, get the information about rabies viruses prevalence and variation in Zhejiang, and enrich the genome database of rabies viruses street strains isolated from China. Rabies viruses in suckling mice were isolated, overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses from Chinese Ferret-Badger, dog, sika deer, vole, used vaccine strain were determined. The four full-length genomes were sequenced completely and had the same genetic structure with the length of 11, 923 nts or 11, 925 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions(IGRs), 423 nts-Pseudogene-like sequence (psi), 70 nts-Trailer. The four full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by BLAST and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the four full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so the nucleotide mutations happened in these four genomes were most synonymous mutations. Compared with the reference rabies viruses, the lengths of the five protein coding regions had no change, no recombination, only with a few point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the four genomes were similar to the reference vaccine or street strains. And the four strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessed the distinct district characteristics of China. Therefore, these four rabies viruses are likely to be street viruses

  17. Biological and immunological studies of five Brazilian rabies virus isolates

    Directory of Open Access Journals (Sweden)

    Fernanda Bernardi

    2005-08-01

    Full Text Available Estudou-se em camundongos aspectos do comportamento biológico de amostras brasileiras de virus rábico isoladas de cão, bovino, eqüino, morcegos hematófago e insetívoro. Observou-se transmissão oral em camundongos alimentados com cérebros infectados de morcego insetívoro (8,82%, cão (8,57% e eqüino (3,03%. O período de incubação médio para todas as amostras foi de 6 dias após a inoculação intracerebral, com sintomas variando, desde hiperexitabilidade (amostra canina, paralisia progressiva principalmente de membros posteriores e maior duração do curso clínico até a morte (eqüino e morte repentina, sem sintomas aparentes (morcego insetívoro. Pela imunoistoquímica detectou-se produção de IFN nos cérebros dos camundongos inoculados com amostra de bovino e morcego insetívoro, TNF e iNOS nos animais infectados com amostra de cão, bovino e morcego insetívoro e reação astrocitária com aumento da expressão de GFAP em todas as cinco amostras. A eficácia de 2 vacinas comerciais inativadas, uma nacional e outra importada, para a proteção contra a infecção experimental em camundongos foi avaliada através dos testes NIH e CDC, usando as amostras de campo para o desafio. Não houve diferença significativa entre o desempenho das vacinas, quando comparadas para um mesmo teste de potência e amostra de desafio sugerindo que não há necessidade de se produzir vacinas com amostras isoladas de campo.

  18. Genetic demography at the leading edge of the distribution of a rabies virus vector.

    Science.gov (United States)

    Piaggio, Antoinette J; Russell, Amy L; Osorio, Ignacio A; Jiménez Ramírez, Alejandro; Fischer, Justin W; Neuwald, Jennifer L; Tibbels, Annie E; Lecuona, Luis; McCracken, Gary F

    2017-07-01

    The common vampire bat, Desmodus rotundus, ranges from South America into northern Mexico in North America. This sanguivorous species of bat feeds primarily on medium to large-sized mammals and is known to rely on livestock as primary prey. Each year, there are hotspot areas of D. rotundus-specific rabies virus outbreaks that lead to the deaths of livestock and economic losses. Based on incidental captures in our study area, which is an area of high cattle mortality from D. rotundus transmitted rabies, it appears that D. rotundus are being caught regularly in areas and elevations where they previously were thought to be uncommon. Our goal was to investigate demographic processes and genetic diversity at the north eastern edge of the range of D. rotundus in Mexico. We generated control region sequences (441 bp) and 12-locus microsatellite genotypes for 602 individuals of D. rotundus. These data were analyzed using network analyses, Bayesian clustering approaches, and standard population genetic statistical analyses. Our results demonstrate panmixia across our sampling area with low genetic diversity, low population differentiation, loss of intermediate frequency alleles at microsatellite loci, and very low mtDNA haplotype diversity with all haplotypes being very closely related. Our study also revealed strong signals of population expansion. These results follow predictions from the leading-edge model of expanding populations and supports conclusions from another study that climate change may allow this species to find suitable habitat within the U.S. border.

  19. Rabies Vaccine

    Science.gov (United States)

    ... high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers should be offered rabies vaccine. The vaccine should also be considered for: (1) ...

  20. Evolutionary history and phylogeography of rabies viruses associated with outbreaks in Trinidad.

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    Janine F R Seetahal

    Full Text Available Bat rabies is an emerging disease of public health significance in the Americas. The Caribbean island of Trinidad experiences periodic outbreaks within the livestock population. We performed molecular characterisation of Trinidad rabies virus (RABV and used a Bayesian phylogeographic approach to investigate the extent to which outbreaks are a result of in situ evolution versus importation of virus from the nearby South American mainland. Trinidadian RABV sequences were confirmed as bat variant and clustered with Desmodus rotundus (vampire bat related sequences. They fell into two largely temporally defined lineages designated Trinidad I and II. The Trinidad I lineage which included sequences from 1997-2000 (all but two of which were from the northeast of the island was most closely related to RABV from Ecuador (2005, 2007, French Guiana (1990 and Venezuela (1993, 1994. Trinidad II comprised sequences from the southwest of the island, which clustered into two groups: Trinidad IIa, which included one sequence each from 2000 and 2007, and Trinidad IIb including all 2010 sequences. The Trinidad II sequences were most closely related to sequences from Brazil (1999, 2004 and Uruguay (2007, 2008. Phylogeographic analyses support three separate RABV introductions from the mainland from which each of the three Trinidadian lineages arose. The estimated dates for the introductions and subsequent lineage expansions suggest periods of in situ evolution within Trinidad following each introduction. These data also indicate co-circulation of Trinidad lineage I and IIa during 2000. In light of these findings and the likely vampire bat origin of Trinidadian RABV, further studies should be conducted to investigate the relationship between RABV spatiotemporal dynamics and vampire bat population ecology, in particular any movement between the mainland and Trinidad.

  1. Detection and molecular characterization of rabies virus in Mongolia during 2008-2010

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    Bumduuren Tuvshintulga

    2015-09-01

    Full Text Available Aim: We aimed to investigate the prevalence and molecular characterization of rabies virus (RABV from wild and domestic animals in Mongolia during 2008-2010. Materials and Methods: Brain tissue samples were collected from 24 rabid animals in Zavkhan, Omnogovi, Tov, Dundgovi, Govi-Altai, Selenge, Ovorkhangai, and Khentii provinces in Mongolia. Herein, samples were included from 13 domestic animals (dogs, cattle, camels, sheep, and goat and 11 wild animals (wolves and foxes in this study. Direct fluorescent antibody (DFA test and reverse transcriptase polymerase chain reaction (RT-PCR were performed for detection of RABV, and positive samples were further processed for molecular characterization of the virus using nucleoprotein gene. Subsequently, the molecular characterization was determined based on the nucleoprotein gene. Results: Out of 24 samples, 22 samples were detected positive for RABV by DFA test, and its nucleoprotein gene was amplified in all of the 24 samples by RT-PCR. These Mongolian RABVs were classified within steppe-type virus clade by phylogenetic analysis of nucleoprotein gene sequences. This steppe-type virus clade was clearly divided by two Sub-clades (A and B. The most of Mongolian RABVs belongs to the Sub-clade A in the phylogenetic tree. Conclusion: These findings have clearly confirmed RABV in domestic and wild animals of Mongolia. Further molecular characterization indicated that this Mongolian strain is steppe-type virus clade consisting of two sub-clades; the Subclade A might be prevalent in Altai, Khangai, Khentii Mountains as a major genotype, whereas the Subclade B seems to be cosmopolitan in the steppe-type virus clade, is spread in northern central Eurasia.

  2. [Effect of rabies virus infection on the expression of parvalbumin, calbindin and calretinin in mouse cerebral cortex].

    Science.gov (United States)

    Torres-Fernández, Orlando; Yepes, Gloria E; Gómez, Javier E; Pimienta, Hernán J

    2004-03-01

    Some clinical features of rabies and experimental evidence from cell culture and laboratory animals suggest impairment of gabaergic neurotransmission. Several types of gabaergic neurons occur in the cerebral cortex. They can be identified by three neuronal markers: the calcium binding proteins (CaBPs) parvalbumin (PV), calbindin (CB) and calretinin (CR). Rabies virus spreads throughout the cerebral cortex; however, rabies cytopathic effects on gabaergic neurons are unknown. The expression of calcium-binding proteins (CaBPs) parvalbumin (PV), calbindin (CB) and calretinin (CR) was studied in the frontal cortex of mice. The effect of gabaergic neurons was evaluated immunohistochemically. The distribution patterns of CaBPs in normal mice and in mice infected with 'fixed' or 'street' rabies virus were compared. PV was found in multipolar neurons located in all cortical layers except layer I, and in pericellular clusters of terminal knobs surrounding the soma of pyramidal neurons. CB-immunoreactivity was distributed in two cortical bands. One was composed of round neurons enclosed by a heavily labeled neuropil; this band corresponds to supragranular layers II and III. The other was a weakly stained band of neuropil which contained scattered multipolar CB-ir neurons; this corresponds to infragranular layers V and VI. The CR-ir neurons were bipolar fusiform cells located in all layers of cortex, but concentrated in layers II and III. A feature common to samples infected with both types of viruses was a more intense immunoreactivity to PV in contrast to normal samples. The infection with 'street' virus did not cause additional changes in the expression of CaBPs. However, the infection with 'fixed' virus produced a remarkable reduction of CB-immunoreactivity demonstrated by the loss of CB-ir neurons and low neuropil stain in the frontal cortex. In addition, the size of CR-ir neurons in the cingulate cortex was decreased.

  3. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

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    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  4. The Full-length Genome Analysis of a Street Rabies Virus Strain Isolated in Yunnan Province of China

    Institute of Scientific and Technical Information of China (English)

    Jian Zhang; Hai-lin Zhang; Xiao-yan Tao; Hao Li; Qing Tang; Xiu-yun Jiang; Guo-dong Liang

    2012-01-01

    The epidemic of rabies has rapidly increased and expanded in Yunnan province in recent years.In order to further analyze and understand the etiological reasons for the rapid expansion of rabies in Yunnan,a strain of rabies virus CYN1009D in Yunnan was isolated,and the complete genomic sequencing was carried out,and the bioimfomative analysis on genes/encoded proteins and phylogeny with reference to sequences in GenBank was performed.The complete genome of CYN1009D was 11923 nt in length and belonged to genotype I.The genes encoding different structural proteins were all conserved in their lengths,in comparison to other strains in China.The amino acid sequence was conserved at different antigen sites of NP,but the variation was detected at the secondary phosphorylation site of position 375; variations were also detected in the phosphorylation sites at positions 63-63 and 162 of PP; the sites playing important roles in virus synthesis,budding and viral morphology in MP were conserved; two glycosylation sites were detected at Asn37 and Asn319in GP,the neutralizing antigen sites in GP were conserved; the initial amino acid of LP (ML) was different from that of most of the strains in China (MM); the variations in G-L region in the intergenic region were significant.The phylogenic tree showed that CYN1009D has a closer genetic relationship to the strains in Southeast Asia,indicating that prevention and control on rabies in borderland areas should be reinforced meanwhile efforts are made to control rabies in China.

  5. MHC class II DRB diversity in raccoons (Procyon lotor) reveals associations with raccoon rabies virus (Lyssavirus).

    Science.gov (United States)

    Srithayakumar, Vythegi; Castillo, Sarrah; Rosatte, Rick C; Kyle, Christopher J

    2011-02-01

    In North America, the raccoon rabies virus (RRV) is an endemic wildlife disease which causes acute encephalopathies and is a strong selective force on raccoons (Procyon lotor), with estimates of ∼85% of the population succumbing to the disease when epizootic. RRV is regarded as a lethal disease if untreated; therefore, no evolutionary response would be expected of raccoon populations. However, variable immune responses to RRV have been observed in raccoons indicating a potential for evolutionary adaptation. Studies of variation within the immunologically important major histocompatibility complex (MHC) have revealed relationships between MHC alleles and diseases in humans and other wildlife species. This enhances our understanding of how hosts and pathogens adapt and co-evolve. In this study, we used RRV as a model system to study host-pathogen interaction in raccoons from a challenge study and from four wild populations that differ in exposure times and viral lineages. We investigated the potential role of Prlo-DRB polymorphism in relation to susceptibility/resistance to RRV in 113 RRV positive and 143 RRV negative raccoons. Six alleles were found to be associated with RRV negative status and five alleles with RRV positive animals. We found variable patterns of MHC associations given the relative number of selective RRV sweeps in the studied regions and correlations between MHC diversity and RRV lineages. The allelic associations established provide insight into how the genetic variation of raccoons may affect the disease outcome and this can be used to examine similar associations between other rabies variants and their hosts.

  6. Impact of caspase-1/11, -3, -7, or IL-1β/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease

    Science.gov (United States)

    Kip, E; Nazé, F; Suin, V; Vanden Berghe, T; Francart, A; Lamoral, S; Vandenabeele, P; Beyaert, R; Van Gucht, S; Kalai, M

    2017-01-01

    Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn–Rotnycki–Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals. Infection of Mf4/4 macrophages with both strains led to caspase-1 activation and IL-1β and IL-18 production, as well as activation of caspases-3, -7, -8, and -9. Moreover, absence of caspase-3, but not of caspase-1 and -11 or -7, partially inhibited virus-induced cell death of bone marrow-derived macrophages. Intranasal inoculation with CVS-11 of mice deficient for either caspase-1 and -11 or -7 or both IL-1β and IL-18 led to general brain infection and lethal disease similar to wild-type mice. Deficiency of caspase-3, on the other hand, significantly delayed the onset of disease, but did not prevent final lethal outcome. Interestingly, deficiency of caspase-1/11, the key executioner of pyroptosis, aggravated disease severity caused by ERA virus, whereas wild-type mice or mice deficient for either caspase-3, -7, or both IL-1β and IL-18 presented the typical mild symptoms associated with ERA virus. In conclusion, rabies virus infection of macrophages induces caspase-1- and caspase-3-dependent cell death. In vivo caspase-1/11 and caspase-3 differently affect disease development in response to infection with the attenuated ERA strain or the virulent CVS-11 strain, respectively. Inflammatory caspases seem to control attenuated rabies virus infection, while caspase-3 aggravates virulent rabies virus infection. PMID:28280602

  7. Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.

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    Gluska, Shani; Zahavi, Eitan Erez; Chein, Michael; Gradus, Tal; Bauer, Anja; Finke, Stefan; Perlson, Eran

    2014-08-01

    Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS). The strategy RABV uses to hijack the cellular transport machinery is still not clear. It is thought that RABV interacts with membrane receptors in order to internalize and exploit the endosomal trafficking pathway, yet this has never been demonstrated directly. The p75 Nerve Growth Factor (NGF) receptor (p75NTR) binds RABV Glycoprotein (RABV-G) with high affinity. However, as p75NTR is not essential for RABV infection, the specific role of this interaction remains in question. Here we used live cell imaging to track RABV entry at nerve terminals and studied its retrograde transport along the axon with and without the p75NTR receptor. First, we found that NGF, an endogenous p75NTR ligand, and RABV, are localized in corresponding domains along nerve tips. RABV and NGF were internalized at similar time frames, suggesting comparable entry machineries. Next, we demonstrated that RABV could internalize together with p75NTR. Characterizing RABV retrograde movement along the axon, we showed the virus is transported in acidic compartments, mostly with p75NTR. Interestingly, RABV is transported faster than NGF, suggesting that RABV not only hijacks the transport machinery but can also manipulate it. Co-transport of RABV and NGF identified two modes of transport, slow and fast, that may represent a differential control of the trafficking machinery by RABV. Finally, we determined that p75NTR-dependent transport of RABV is faster and more directed than p75NTR-independent RABV transport. This fast route to the neuronal cell body is characterized by both an increase in instantaneous velocities and fewer, shorter stops en route. Hence, RABV may employ p75NTR-dependent transport as a fast mechanism to facilitate movement to the CNS.

  8. Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.

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    Shani Gluska

    2014-08-01

    Full Text Available Rabies virus (RABV is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS. The strategy RABV uses to hijack the cellular transport machinery is still not clear. It is thought that RABV interacts with membrane receptors in order to internalize and exploit the endosomal trafficking pathway, yet this has never been demonstrated directly. The p75 Nerve Growth Factor (NGF receptor (p75NTR binds RABV Glycoprotein (RABV-G with high affinity. However, as p75NTR is not essential for RABV infection, the specific role of this interaction remains in question. Here we used live cell imaging to track RABV entry at nerve terminals and studied its retrograde transport along the axon with and without the p75NTR receptor. First, we found that NGF, an endogenous p75NTR ligand, and RABV, are localized in corresponding domains along nerve tips. RABV and NGF were internalized at similar time frames, suggesting comparable entry machineries. Next, we demonstrated that RABV could internalize together with p75NTR. Characterizing RABV retrograde movement along the axon, we showed the virus is transported in acidic compartments, mostly with p75NTR. Interestingly, RABV is transported faster than NGF, suggesting that RABV not only hijacks the transport machinery but can also manipulate it. Co-transport of RABV and NGF identified two modes of transport, slow and fast, that may represent a differential control of the trafficking machinery by RABV. Finally, we determined that p75NTR-dependent transport of RABV is faster and more directed than p75NTR-independent RABV transport. This fast route to the neuronal cell body is characterized by both an increase in instantaneous velocities and fewer, shorter stops en route. Hence, RABV may employ p75NTR-dependent transport as a fast mechanism to facilitate movement to the CNS.

  9. BLACK-BACKED JACKAL EXPOSURE TO RABIES VIRUS, CANINE DISTEMPER VIRUS, AND BACILLUS ANTHRACIS IN ETOSHA NATIONAL PARK, NAMIBIA

    Science.gov (United States)

    Bellan, Steve E.; Cizauskas, Carrie A.; Miyen, Jacobeth; Ebersohn, Karen; Küsters, Martina; Prager, Katie; Van Vuuren, Moritz; Sabeta, Claude; Getz, Wayne M.

    2017-01-01

    Canine distemper virus (CDV) and rabies virus (RABV) occur worldwide in wild carnivore and domestic dog populations and pose threats to wildlife conservation and public health. In Etosha National Park (ENP), Namibia, anthrax is endemic and generates carcasses frequently fed on by an unusually dense population of black-backed jackals (Canis mesomelas). Using serology and phylogenetic analyses (on samples obtained from February, 2009 to July, 2010), and historical mortality records (1975–2011), we assessed jackal exposure to Bacillus anthracis (BA; the causal bacterial agent of anthrax), CDV, and RABV. Seroprevalence to all three pathogens was relatively high with 95% (n = 86), 73% (n = 86), and 9% (n = 81) of jackals exhibiting antibodies to BA, CDV, and RABV, respectively. Exposure to BA, as assessed with an anti-Protective Antigen ELISA test, increased significantly with age and all animals >1 yr old tested positive. Seroprevalence of exposure to CDV also increased significantly with age, with similar age-specific trends during both years of the study. No significant effect of age was found on RABV seroprevalence. Three of the seven animals exhibiting immunity to RABV were monitored for more than one year after sampling and did not succumb to the disease. Mortality records revealed that rabid animals are destroyed nearly every year inside the ENP tourist camps. Phylogenetic analyses demonstrated that jackal RABV in ENP is part of the same transmission cycle as other dog-jackal RABV cycles in Namibia. PMID:22493112

  10. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

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    Joseph E Blaney

    Full Text Available We have previously described the generation of a novel Ebola virus (EBOV vaccine platform based on (a replication-competent rabies virus (RABV, (b replication-deficient RABV, or (c chemically inactivated RABV expressing EBOV glycoprotein (GP. Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

  11. Genome-wide transcriptional profiling reveals two distinct outcomes in central Nervous system infections of rabies virus

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    Daiting eZhang

    2016-05-01

    Full Text Available Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq to compare the brain transcriptomes of normal mice versus HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV infection can effectively prevent the CVS-11 to invade central nervous system (CNS, but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4+ T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the postexposure treatment window

  12. Evaluation of short-interfering RNAs treatment in experimental rabies due to wild-type virus

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    Camila Michele Appolinario

    2015-10-01

    Full Text Available ABSTRACTWe have evaluated the efficacy of short-interfering RNAs targeting the nucleoprotein gene and also the brain immune response in treated and non-treated infected mice. Mice were inoculated with wild-type virus, classified as dog (hv2 or vampire bat (hv3 variants and both groups were treated or leaved as controls. No difference was observed in the lethality rate between treated and non-treated groups, although clinical evaluation of hv2 infected mice showed differences in the severity of clinical disease (p = 0.0006. Evaluation of brain immune response 5 days post-inoculation in treated hv2 group showed no difference among the analyzed genes, whereas after 10 days post-inoculation there was increased expression of 2',5'-oligoadenylate synthetase 1, tumor necrosis factor alpha, interleukin 12, interferon gamma, and C-X-C motif chemokine 10 associated with higher expression of Ngene in the same period (p < 0.0001. In hv2 non-treated group only higher interferon beta expression was found at day 5. The observed differences in results of the immune response genes between treated and non-treated groups is not promising as they had neither impact on mortality nor even a reduction in the expression of N gene in siRNA treated animals. This finding suggests that the use of pre-designed siRNA alone may not be useful in rabies treatment.

  13. The Rabies Virus L Protein Catalyzes mRNA Capping with GDP Polyribonucleotidyltransferase Activity.

    Science.gov (United States)

    Ogino, Minako; Ito, Naoto; Sugiyama, Makoto; Ogino, Tomoaki

    2016-05-21

    The large (L) protein of rabies virus (RABV) plays multiple enzymatic roles in viral RNA synthesis and processing. However, none of its putative enzymatic activities have been directly demonstrated in vitro. In this study, we expressed and purified a recombinant form of the RABV L protein and verified its guanosine 5'-triphosphatase and GDP polyribonucleotidyltransferase (PRNTase) activities, which are essential for viral mRNA cap formation by the unconventional mechanism. The RABV L protein capped 5'-triphosphorylated but not 5'-diphosphorylated RABV mRNA-start sequences, 5'-AACA(C/U), with GDP to generate the 5'-terminal cap structure G(5')ppp(5')A. The 5'-AAC sequence in the substrate RNAs was found to be strictly essential for RNA capping with the RABV L protein. Furthermore, site-directed mutagenesis showed that some conserved amino acid residues (G1112, T1170, W1201, H1241, R1242, F1285, and Q1286) in the PRNTase motifs A to E of the RABV L protein are required for cap formation. These findings suggest that the putative PRNTase domain in the RABV L protein catalyzes the rhabdovirus-specific capping reaction involving covalent catalysis of the pRNA transfer to GDP, thus offering this domain as a target for developing anti-viral agents.

  14. Limited brain metabolism changes differentiate between the progression and clearance of rabies virus.

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    Keith Schutsky

    Full Text Available Central nervous system (CNS metabolic profiles were examined from rabies virus (RABV-infected mice that were either mock-treated or received post-exposure treatment (PET with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral RNA. Although the large majority of these metabolic changes were completely absent in the brains of TriGAS-treated mice most likely due to the strong reduction in virus spread, TriGAS treatment resulted in the up-regulation of the expression of carnitine and several acylcarnitines, suggesting that these compounds are neuroprotective. The most striking change seen in mock-treated RABV-infected mice was a dramatic increase in brain and serum corticosterone levels, with the later becoming elevated before clinical signs or loss of body weight occurred. We speculate that the rise in corticosterone is part of a strategy of RABV to block the induction of immune responses that would otherwise interfere with its spread. In support of this concept, we show that pharmacological intervention to inhibit corticosterone biosynthesis, in the absence of vaccine treatment, significantly reduces the pathogenicity of RABV. Our results suggest that widespread metabolic changes, including hypothalamic-pituitary-adrenal axis activation, contribute to the pathogenesis of RABV and that preventing these alterations early in infection with PET or pharmacological blockade helps protect brain homeostasis, thereby reducing disease mortality.

  15. [Rabies in bats].

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    Beranová, Kateřina; Zendulková, Dagmar

    2016-06-01

    Rabies is a zoonosis ending fatally in all mammals, including humans. Unlike the other mammals, this disease is usually not fatal in bats. Rabies is caused by lyssaviruses which are divided into several distinct phylogroups comprising 15 known viruses. It is believed that the original hosts of all lyssaviruses are bats. Classical rabies virus (RABV) occurs in bats across Americas and represents the major cause of rabies in humans and domestic animals there. European bat lyssavirus type 1 (EBLV-1) and European bat lyssavirus type 2 (EBLV-2) are the most frequently diagnosed lyssaviruses in Eurasia. The transmission of EBLV-1 and EBLV-2 from bats to other mammals is very rare. As of now, more detailed information is missing about the other Eurasian lyssaviruses - West Caucasian bat virus (WCBV), Bokeloh bat lyssavirus (BBLV), Aravan virus (ARAV), Irkut virus (IRKV), Khujand virus (KHUV) and Lleida virus. The lyssavirus most frequently found in Africa is Lagos bat virus (LBV). In Australia, only Australian bat lyssavirus (ABLV) has been demonstrated as yet. In the Czech Republic, a total of five cases of rabies in bats were confirmed between 1994 and 2015. Rabies can be transmitted from bats mainly by biting or scratching. Clinically ill bats suffer from nervous disorders or produce abnormal sounds. If rabies is suspected, laboratory tests are essential. Protection of human health is based on pre-exposure and/or post-exposure vaccination. However, the available vaccines do not protect against some newly identified lyssaviruses such as WCBV. Nevertheless, most bat species pose a minimal risk to humans.

  16. Molecular epidemiology and a loop-mediated isothermal amplification method for diagnosis of infection with rabies virus in Zambia.

    Science.gov (United States)

    Muleya, Walter; Namangala, Boniface; Mweene, Aaron; Zulu, Luke; Fandamu, Paul; Banda, Douglas; Kimura, Takashi; Sawa, Hirofumi; Ishii, Akihiro

    2012-01-01

    The National Livestock Epidemiology and Information Center (NALEIC) in Zambia reported over 132 cases of canine rabies diagnosed by the direct fluorescent antibody test (DFAT) from 2004 to 2009. In this study, the lineage of rabies virus (RABV) in Zambia was determined by phylogenetic analysis of the nucleoprotein (N) and glycoprotein (G) gene sequences. Total RNA was extracted from 87-DFAT brain specimens out of which only 35 (40%) were positive on nested reverse transcription polymerase chain reaction (RT-PCR) for each gene, and 26 being positive for both genes. Positive specimens for the N (n=33) and G (n=35) genes were used for phylogenetic analysis. Phylogenetic analysis of the N gene showed two phylogenetic clusters in Zambia belonging to the Africa 1b lineage present in eastern and southern Africa. While one cluster exclusively comprised Zambian strains, the other was more heterogeneous regarding the RABV origins and included strains from Tanzania, Mozambique and Zambia. Phylogenetic analysis of the G gene revealed similar RABV strains in different hosts and regions of Zambia. We designed primers for reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay from the consensus sequence of the N gene in an attempt to improve the molecular diagnosis of RABV in Zambia. The specificity and reproducibility of the RT-LAMP assay was confirmed with actual clinical specimens. Therefore, the RT-LAMP assay presented in this study may prove to be useful for routine diagnosis of rabies in Zambia.

  17. A survey of rabies virus antibodies in confined, hunting and roaming dogs in Ogun and Oyo States, Southwestern Nigeria

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    Daniel Oladimeji Oluwayelu

    2015-01-01

    Full Text Available Objective: To screen for rabies virus (RABV antibodies in apparently healthy confined, hunting and roaming dogs by a community-based approach. Methods: Sera from 230 (80 confined, 92 hunting and 58 roaming dogs in some urban and periurban communities in Ogun and Oyo states, Southwestern Nigeria were screened for RABV antibodies using the indirect ELISA method. Results: Analysis of administered questionnaires showed that of 80 confined dog owners, 37 were aware of anti-rabies vaccination (i.e. they were informed while 17 were negligent and 26 uninformed. Of the 230 sera tested, only 13 (5.7% from vaccinated confined dogs in Oyo state were positive (i.e. had optimal RABV antibody titres (mean 0.54, 95% CI: 0.42–0.67 while all confined dog sera in Ogun state were negative. Eleven (12.0% and 14 (24.1% of the hunting and roaming dogs respectively had sub-optimal RABV antibody titres while the rest were negative. Conclusions: Evidently, these groups of dogs are a totally unprotected and susceptible dog population that can serve as potential reservoirs of RABV in the study area. Responsible pet ownership, vaccination of hunting and roaming dogs, and community-based active rabies surveillance are therefore advocated in Nigeria.

  18. Diagnostics procedures in rabies

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    Malovrh Tadej

    2005-01-01

    Full Text Available Rabies is a major zoonosis for which diagnostic techniques can only be performed in the laboratory. Laboratory techniques are preferably oriented on tissue removed from the cranium: hippocampus (Ammon's horn, cerebellum and the medulla oblongata or tissue liquids. Clinical observation may only lead to a suspicion of rabies. The only way to perform a reliable diagnosis of the disease is to identify the virus or some of its specific components using laboratory tests such as histological identification of characteristic cell lesions, immunochemical identification of rabies virus antigen and virus isolation. Serological tests are rarely used in epidemiological surveys but much more frequently in control of the vaccination programs (e.g. oral vaccination. Most commonly used serological tests are the virus neutralization test on cell culture (FAVN, virus neutralization in mice and ELISA.

  19. Rabies and canine distemper virus epidemics in the red fox population of northern Italy (2006-2010.

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    Pierre Nouvellet

    Full Text Available Since 2006 the red fox (Vulpes vulpes population in north-eastern Italy has experienced an epidemic of canine distemper virus (CDV. Additionally, in 2008, after a thirteen-year absence from Italy, fox rabies was re-introduced in the Udine province at the national border with Slovenia. Disease intervention strategies are being developed and implemented to control rabies in this area and minimise risk to human health. Here we present empirical data and the epidemiological picture relating to these epidemics in the period 2006-2010. Of important significance for epidemiological studies of wild animals, basic mathematical models are developed to exploit information collected from the surveillance program on dead and/or living animals in order to assess the incidence of infection. These models are also used to estimate the rate of transmission of both diseases and the rate of vaccination, while correcting for a bias in early collection of CDV samples. We found that the rate of rabies transmission was roughly twice that of CDV, with an estimated effective contact between infected and susceptible fox leading to a new infection occurring once every 3 days for rabies, and once a week for CDV. We also inferred that during the early stage of the CDV epidemic, a bias in the monitoring protocol resulted in a positive sample being almost 10 times more likely to be collected than a negative sample. We estimated the rate of intake of oral vaccine at 0.006 per day, allowing us to estimate that roughly 68% of the foxes would be immunised. This was confirmed by field observations. Finally we discuss the implications for the eco-epidemiological dynamics of both epidemics in relation to control measures.

  20. Molecular Epidemiology and Sequencing of the G-L Intergenic Region of Rabies Viruses Isolated in China

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li MENG; QI-You XIAO; Guan-Mu DONG; Ge-Lin XU; Jia-Xin YAN; Ping-Gang MING; Jie WU; Xiao-Ming YANG; He-Tian MING; Feng-Cai ZHU; Dun-Jin ZHOU

    2007-01-01

    A group of 25 rabies viruses (RABVs),recovered from 24 dogs and one human case,were collected from various areas in China between 2004 and 2006.Genetic and phylogenetic analyses of the G-L intergenic region were carried out in 25 street RABV isolates and CTN vaccine strains of 7 generations.The study was based on the comparison of a 519 bp nucleotide sequence,encompassing the G-L intergenic region.The nucleotide sequence homologies of Chinese street strains were from 95.5% to 100%.The phylogenetic analysis showed that all Chinese isolates clearly supported the placement of all Chinese viruses in Lyssavirus genotype 1 and they were distributed according to their geographical origins.All of the Chinese strains were closely related but they could still be divided into two groups:group of street strains and group of CTN strains.This study presents details about the molecular epidemiology of rabies viruses based on the sequences of the G-L Intergenic region.

  1. Ambivalent role of the innate immune response in rabies virus pathogenesis.

    Science.gov (United States)

    Chopy, Damien; Pothlichet, Julien; Lafage, Mireille; Mégret, Françoise; Fiette, Laurence; Si-Tahar, Mustapha; Lafon, Monique

    2011-07-01

    The neurotropic rabies virus (RABV) has developed several evasive strategies, including immunoevasion, to successfully infect the nervous system (NS) and trigger a fatal encephalomyelitis. Here we show that expression of LGP2, a protein known as either a positive or negative regulator of the RIG-I-mediated innate immune response, is restricted in the NS. We used a new transgenic mouse model (LGP2 TG) overexpressing LGP2 to impair the innate immune response to RABV and thus revealed the role of the RIG-I-mediated innate immune response in RABV pathogenesis. After infection, LGP2 TG mice exhibited reduced expression of inflammatory/chemoattractive molecules, beta interferon (IFN-β), and IFN-stimulated genes in their NS compared to wild-type (WT) mice, demonstrating the inhibitory function of LGP2 in the innate immune response to RABV. Surprisingly, LGP2 TG mice showed more viral clearance in the brain and lower morbidity than WT mice, indicating that the host innate immune response, paradoxically, favors RABV neuroinvasiveness and morbidity. LGP2 TG mice exhibited similar neutralizing antibodies and microglia activation to those of WT mice but showed a reduction of infiltrating CD4(+) T cells and less disappearance of infiltrating CD8(+) T cells. This occurred concomitantly with reduced neural expression of the IFN-inducible protein B7-H1, an immunoevasive protein involved in the elimination of infiltrated CD8(+) T cells. Our study shows that the host innate immune response favors the infiltration of T cells and, at the same time, promotes CD8(+) T cell elimination. Thus, to a certain extent, RABV exploits the innate immune response to develop its immunoevasive strategy.

  2. Establishing conditions for the storage and elution of rabies virus RNA using FTA(®) cards.

    Science.gov (United States)

    Sakai, Takeo; Ishii, Ayako; Segawa, Takao; Takagi, Yukihiko; Kobayashi, Yuki; Itou, Takuya

    2015-04-01

    The Flinders Technology Associates filter paper cards (FTA(®) cards) can be used to store nucleic acid from various samples and are easily portable. However, RNA is physicochemically unstable compared with DNA, and appropriate methods have not been established for storage and extraction of RNA from FTA(®) cards. The present study investigated the optimum conditions for storage and elution of viral RNA (vRNA) using rabies virus (RABV) applied to FTA(®) cards. When TE buffer was used, the elution rates of vRNA increased with the length of the elution time. When the cards were stored at -80 °C or -20 °C, vRNA was stable over 3 months. Degradation of vRNAs occurred following storage at 4 °C and room temperature, suggesting that RNA should be extracted from cards as soon as possible if no freezer is available. When we tried to amplify vRNA from RABV-infected animal brains applied to FTA(®) cards and stored at -80 °C for 6 months, we did not detect any amplified products with the primer set for 964 bp of RABV N gene. However, we were able to detect amplified products by increasing the elution time of vRNA from FTA(®) cards from 30 min to 24 hr or by changing the primer sets to amplify 290 bp of N gene. Thus, we recommend extending the elution time for damaged or low concentration samples in FTA(®) cards.

  3. Localization of the rabies virus antigen in Merkel cells in the follicle-sinus complexes of muzzle skins of rabid dogs.

    Science.gov (United States)

    Shimatsu, Taichi; Shinozaki, Harumi; Kimitsuki, Kazunori; Shiwa, Nozomi; Manalo, Daria L; Perez, Rodolfo C; Dilig, Joselito E; Yamada, Kentaro; Boonsriroj, Hassadin; Inoue, Satoshi; Park, Chun-Ho

    2016-11-01

    The direct fluorescent antibody test (dFAT) on fresh brain tissues is the gold standard for rabies virus antigen detection in dogs. However, this method is laborious and holds a high risk of virus exposure for the experimenter. Skin biopsies are useful for the diagnosis of humans and animals. In mammals, the tactile hair, known as the follicle-sinus complex (FSC), is a specialized touch organ that is abundant in the muzzle skin. Each tactile hair is equipped with more than 2,000 sensory nerve endings. Therefore, this organ is expected to serve as an alternative postmortem diagnostic material. However, the target cells and localization of rabies virus antigen in the FSCs remain to be defined. In the present study, muzzle skins were obtained from 60 rabid dogs diagnosed with rabies by dFAT at the Research Institute of Tropical Medicine in the Philippines. In all dogs, virus antigen was clearly detected in a part of the outer root sheath at the level of the ring sinus of the FSCs, and the majority of cells were positive for the Merkel cell (MC) markers cytokeratin 20 and CAM5.2. Our results suggest that MCs in the FSCs of the muzzle skin are a target for virus replication and could serve as a useful alternative specimen source for diagnosis of rabies.

  4. Spatio-temporal Analysis of the Genetic Diversity of Arctic Rabies Viruses and Their Reservoir Hosts in Greenland.

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    Dennis Hanke

    2016-07-01

    Full Text Available There has been limited knowledge on spatio-temporal epidemiology of zoonotic arctic fox rabies among countries bordering the Arctic, in particular Greenland. Previous molecular epidemiological studies have suggested the occurrence of one particular arctic rabies virus (RABV lineage (arctic-3, but have been limited by a low number of available samples preventing in-depth high resolution phylogenetic analysis of RABVs at that time. However, an improved knowledge of the evolution, at a molecular level, of the circulating RABVs and a better understanding of the historical perspective of the disease in Greenland is necessary for better direct control measures on the island. These issues have been addressed by investigating the spatio-temporal genetic diversity of arctic RABVs and their reservoir host, the arctic fox, in Greenland using both full and partial genome sequences. Using a unique set of 79 arctic RABV full genome sequences from Greenland, Canada, USA (Alaska and Russia obtained between 1977 and 2014, a description of the historic context in relation to the genetic diversity of currently circulating RABV in Greenland and neighboring Canadian Northern territories has been provided. The phylogenetic analysis confirmed delineation into four major arctic RABV lineages (arctic 1-4 with viruses from Greenland exclusively grouping into the circumpolar arctic-3 lineage. High resolution analysis enabled distinction of seven geographically distinct subclades (3.I - 3.VII with two subclades containing viruses from both Greenland and Canada. By combining analysis of full length RABV genome sequences and host derived sequences encoding mitochondrial proteins obtained simultaneously from brain tissues of 49 arctic foxes, the interaction of viruses and their hosts was explored in detail. Such an approach can serve as a blueprint for analysis of infectious disease dynamics and virus-host interdependencies. The results showed a fine-scale spatial population

  5. Spatio-temporal Analysis of the Genetic Diversity of Arctic Rabies Viruses and Their Reservoir Hosts in Greenland

    Science.gov (United States)

    Hanke, Dennis; Freuling, Conrad M.; Fischer, Susanne; Hueffer, Karsten; Hundertmark, Kris; Nadin-Davis, Susan; Marston, Denise; Fooks, Anthony R.; Bøtner, Anette; Mettenleiter, Thomas C.; Beer, Martin; Rasmussen, Thomas B.; Müller, Thomas F.; Höper, Dirk

    2016-01-01

    There has been limited knowledge on spatio-temporal epidemiology of zoonotic arctic fox rabies among countries bordering the Arctic, in particular Greenland. Previous molecular epidemiological studies have suggested the occurrence of one particular arctic rabies virus (RABV) lineage (arctic-3), but have been limited by a low number of available samples preventing in-depth high resolution phylogenetic analysis of RABVs at that time. However, an improved knowledge of the evolution, at a molecular level, of the circulating RABVs and a better understanding of the historical perspective of the disease in Greenland is necessary for better direct control measures on the island. These issues have been addressed by investigating the spatio-temporal genetic diversity of arctic RABVs and their reservoir host, the arctic fox, in Greenland using both full and partial genome sequences. Using a unique set of 79 arctic RABV full genome sequences from Greenland, Canada, USA (Alaska) and Russia obtained between 1977 and 2014, a description of the historic context in relation to the genetic diversity of currently circulating RABV in Greenland and neighboring Canadian Northern territories has been provided. The phylogenetic analysis confirmed delineation into four major arctic RABV lineages (arctic 1–4) with viruses from Greenland exclusively grouping into the circumpolar arctic-3 lineage. High resolution analysis enabled distinction of seven geographically distinct subclades (3.I – 3.VII) with two subclades containing viruses from both Greenland and Canada. By combining analysis of full length RABV genome sequences and host derived sequences encoding mitochondrial proteins obtained simultaneously from brain tissues of 49 arctic foxes, the interaction of viruses and their hosts was explored in detail. Such an approach can serve as a blueprint for analysis of infectious disease dynamics and virus-host interdependencies. The results showed a fine-scale spatial population structure

  6. Spatio-temporal Analysis of the Genetic Diversity of Arctic Rabies Viruses and Their Reservoir Hosts in Greenland.

    Science.gov (United States)

    Hanke, Dennis; Freuling, Conrad M; Fischer, Susanne; Hueffer, Karsten; Hundertmark, Kris; Nadin-Davis, Susan; Marston, Denise; Fooks, Anthony R; Bøtner, Anette; Mettenleiter, Thomas C; Beer, Martin; Rasmussen, Thomas B; Müller, Thomas F; Höper, Dirk

    2016-07-01

    There has been limited knowledge on spatio-temporal epidemiology of zoonotic arctic fox rabies among countries bordering the Arctic, in particular Greenland. Previous molecular epidemiological studies have suggested the occurrence of one particular arctic rabies virus (RABV) lineage (arctic-3), but have been limited by a low number of available samples preventing in-depth high resolution phylogenetic analysis of RABVs at that time. However, an improved knowledge of the evolution, at a molecular level, of the circulating RABVs and a better understanding of the historical perspective of the disease in Greenland is necessary for better direct control measures on the island. These issues have been addressed by investigating the spatio-temporal genetic diversity of arctic RABVs and their reservoir host, the arctic fox, in Greenland using both full and partial genome sequences. Using a unique set of 79 arctic RABV full genome sequences from Greenland, Canada, USA (Alaska) and Russia obtained between 1977 and 2014, a description of the historic context in relation to the genetic diversity of currently circulating RABV in Greenland and neighboring Canadian Northern territories has been provided. The phylogenetic analysis confirmed delineation into four major arctic RABV lineages (arctic 1-4) with viruses from Greenland exclusively grouping into the circumpolar arctic-3 lineage. High resolution analysis enabled distinction of seven geographically distinct subclades (3.I - 3.VII) with two subclades containing viruses from both Greenland and Canada. By combining analysis of full length RABV genome sequences and host derived sequences encoding mitochondrial proteins obtained simultaneously from brain tissues of 49 arctic foxes, the interaction of viruses and their hosts was explored in detail. Such an approach can serve as a blueprint for analysis of infectious disease dynamics and virus-host interdependencies. The results showed a fine-scale spatial population structure in

  7. Complete Genome Sequence of a Rabies Virus Strain Isolated from a Brown Bear (Ursus arctos) in Primorsky Krai, Russia (November 2014).

    Science.gov (United States)

    Shchelkanov, Michael Y; Deviatkin, Andrei A; Ananiev, Vasily Y; Dedkov, Vladimir G; Shipulin, German A; Sokol, Nataliya N; Dombrovskaya, Irina E; Galkina, Irina V; Shmelev, Mikhail E; Gorelikov, Vladimir N; Kozhan, Valentina N; Prosyannikova, Marina N; Aramilev, Sergei V; Fomenko, Pavel V

    2016-07-07

    We report here the complete genome sequence (GenBank KP997032) of rabies virus strain RABV/Ursus arctos/Russia/Primorye/PO-01/2014, isolated in November 2014 from a brown bear (Ursus arctos) that attacked a person in Primorsky Krai (Russian Federation). This strain was clustered into the Eurasian genetic subgroup of genotype 1 (street rage).

  8. Effect of functionalization of polymeric nanoparticles incorporated with whole attenuated rabies virus antigen on sustained release and efficacy

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    Kiran Nivedh

    2016-12-01

    Full Text Available Nanovaccines introduced a new dimension to prevent or cure diseases in an efficient and sustained manner. Various polymers have been used for the drug delivery to increase the therapeutic value with minimal side effects. Thus the present study incorporates both nanotechnology and polymers for the drug delivery. Poly(d,l-lactic-co-glycolic acid-b-poly(ethylene glycol was incorporated with the rabies whole attenuated viral antigen using double emulsion (W/O/W method and characterized by Scanning Electron Microscopy (SEM and Atomic Force Microscopy (AFM. Chitosan-PEG nanoparticles incorporated with the rabies whole attenuated virus antigen (CS-PEG NP-RV Ag. were prepared using Ionic Gelation method. The CS-PEG NP-RV Ag. was surface modified with biocompatible polymers such as Acacia, Bovine Serum Albumin (BSA, Casein, Ovalbumin and Starch by Ionic Gelation method. The morphology was confirmed by SEM and Transmission Electron Microscopy (TEM. The surface modification was confirmed by Fourier Transform Infrared Spectroscopy (FTIR, Zeta potential. The size distribution of CS-PEG-RV Ag. and surface modified CS-PEG-RV Ag. by respective biocompatible polymers was assessed by Zetasizer. Release profile of both stabilized nanoparticles was carried out by modified centrifugal ultrafiltration method which showed the sustained release pattern of the Rabies Ag. Immune stimulation under in-vitro condition was studied using rosette assay and phagocytosis assay. In-vitro toxicity using human blood and genotoxicity using human blood DNA was also studied to assess the toxicity of the nanoformulations. The results of these studies infer that PLGA-b-PEG nanoparticles, CS-PEG and surface modified CS-PEG nanoparticles may be an efficient nanocarrier for the RV Ag. to elicit immune response sustainably with negligible toxic effect to the human system.

  9. Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons

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    Shane Grealish

    2015-06-01

    Full Text Available Human embryonic stem cell (hESC-derived dopamine neurons are currently moving toward clinical use for Parkinson’s disease (PD. However, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown. In this study, we use modified rabies virus to trace afferent and efferent connectivity of transplanted hESC-derived neurons in a rat model of PD and report that grafted human neurons integrate into the host neural circuitry in an unexpectedly rapid and extensive manner. The pattern of connectivity resembled that of local endogenous neurons, while ectopic connections were not detected. Revealing circuit integration of human dopamine neurons substantiates their potential use in clinical trials. Additionally, our data present rabies-based tracing as a valuable and widely applicable tool for analyzing graft connectivity that can easily be adapted to analyze connectivity of a variety of different neuronal sources and subtypes in different disease models.

  10. Engineering of a recombinant trivalent single-chain variable fragment antibody directed against rabies virus glycoprotein G with improved neutralizing potency.

    Science.gov (United States)

    Turki, Imène; Hammami, Akil; Kharmachi, Habib; Mousli, Mohamed

    2014-02-01

    Human and equine rabies immunoglobulins are currently available for passive immunization against rabies. However, these are hampered by the limited supply and some drawbacks. Advances in antibody engineering have led to overcome issues of clinical applications and to improve the protective efficacy. In the present study, we report the generation of a trivalent single-chain Fv (scFv50AD1-Fd), that recognizes the rabies virus glycoprotein, genetically fused to the trimerization domain of the bacteriophage T4 fibritin, termed 'foldon' (Fd). scFv50AD1-Fd was expressed as soluble recombinant protein in bacterial periplasmic space and purified through affinity chromatography. The molecular integrity and stability were analyzed by polyacrylamide gradient-gel electrophoresis, size-exclusion chromatography and incubation in human sera. The antigen-binding properties of the trimeric scFv were analyzed by direct and competitive-ELISA. Its apparent affinity constant was estimated at 1.4 ± 0.25 × 10(9)M(-1) and was 75-fold higher than its monovalent scFv (1.9 ± 0.68 × 10(7)M(-1)). The scFv50AD1-Fd neutralized rabies virus in a standard in vitro and in vivo neutralization assay. We showed a high neutralization activity up to 75-fold compared with monovalent format and the WHO standard serum. The gain in avidity resulting from multivalency along with an improved biological activity makes the trivalent scFv50AD1-Fd construct an important reagent for rabies protection. The antibody engineering approach presented here may serve as a strategy for designing a new generation of anti-rabies for passive immunotherapy.

  11. Circulation of the rabies virus in non-hematophagous bats in the city of Rio de Janeiro, Brazil, during 2001-2010

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    Claudius Couto Cabral

    2012-04-01

    Full Text Available INTRODUCTION: Rabies is one of the most known lethal zoonosis, responsible for 55,000 human deaths per year. It is transmitted to humans mainly by the bite of domestic or wild animals infected with the virus. This paper shows the circulation of this virus in non-hematophagous bats in the City of Rio de Janeiro, Brazil. METHODS: A survey was performed on the number of bats that had been sent for diagnosis by the Seção de Virologia of the Instituto Municipal de Medicina Veterinária Jorge Vaitsman and were positive for rabies. The positive animals were identified, and the isolated viruses were sent for antigenic typification with indirect immunofluorescence. The results were compared with the antigenic panel of the Centers for Disease Control and Prevention. RESULTS: During 2001-2010, the laboratory received 555 non-hematophagous bats for rabies diagnosis, with 198 (35.7% from Rio de Janeiro City. A total of 11 (5.5% animals were positive for this disease. Antigenic typification revealed the predominance of variant 3 in 9 (81.8% of the isolated viruses; 1 virus was classified as variant 4 and 1 variant was identified that segregated with the viruses in insectivorous bats. CONCLUSIONS: The data obtained in this study showed the presence of the rabies virus in synanthropic populations of non-hematophagous bats in the City of Rio de Janeiro. The circulation of this agent in these animals represents a serious risk to human and animal health and requires attention and control measures by the authorities.

  12. Circulation of the rabies virus in non-hematophagous bats in the city of Rio de Janeiro, Brazil, during 2001-2010.

    Science.gov (United States)

    Cabral, Claudius Couto; Morais, Ana Carolina Nunes de; Dias, Alba Valéria de Almeida Barcelos; Araújo, Marcela Garcia; Moreira, Wildeberg Cal; Mattos, Gláucio Luis Mata

    2012-01-01

    Rabies is one of the most known lethal zoonosis, responsible for 55,000 human deaths per year. It is transmitted to humans mainly by the bite of domestic or wild animals infected with the virus. This paper shows the circulation of this virus in non-hematophagous bats in the City of Rio de Janeiro, Brazil. A survey was performed on the number of bats that had been sent for diagnosis by the Seção de Virologia of the Instituto Municipal de Medicina Veterinária Jorge Vaitsman and were positive for rabies. The positive animals were identified, and the isolated viruses were sent for antigenic typification with indirect immunofluorescence. The results were compared with the antigenic panel of the Centers for Disease Control and Prevention. During 2001-2010, the laboratory received 555 non-hematophagous bats for rabies diagnosis, with 198 (35.7%) from Rio de Janeiro City. A total of 11 (5.5%) animals were positive for this disease. Antigenic typification revealed the predominance of variant 3 in 9 (81.8%) of the isolated viruses; 1 virus was classified as variant 4 and 1 variant was identified that segregated with the viruses in insectivorous bats. The data obtained in this study showed the presence of the rabies virus in synanthropic populations of non-hematophagous bats in the City of Rio de Janeiro. The circulation of this agent in these animals represents a serious risk to human and animal health and requires attention and control measures by the authorities.

  13. The Epidemiological Importance of Bats in the Transmission of Rabies to Dogs and Cats in the State of São Paulo, Brazil, Between 2005 and 2014.

    Science.gov (United States)

    Castilho, J G; de Souza, D N; Oliveira, R N; Carnieli, P; Batista, H B C R; Pereira, P M C; Achkar, S M; Macedo, C I

    2017-09-01

    In Brazil, rabies control in dogs and cats was pioneered by the state of São Paulo with the adoption of the Pan American Health Organization recommendations for prophylaxis and control, which led to a reduction in rabies cases from 1994 onwards. As a result of these measures, the rabies virus (RABV) genetic lineage associated with dogs has not been found in the state since 1998, and all the cases in domestic animals reported since then have been caused by bat-associated lineages of RABV. In the light of this, this study sought to investigate rabies cases in dogs and cats in the state of São Paulo between 2005 and 2014 and identify the associated transmission cycles by characterizing the RABV lineages responsible for these cases. Nine samples from dogs (n = 5) and from cats (n = 4) were collected between 2005 and 2014. The tenth animal, a rabid cat, was analysed by a different laboratory. The N gene nucleotide sequences obtained were analysed with the neighbor-joining algorithm and Kimura 2-parameter model using the MEGA 6 program. Phylogenetic analysis revealed that the genetic lineages identified in all the samples were those circulating in Brazilian bats. The findings of this study demonstrate that bats play an important role in the transmission of rabies to domestic animals in São Paulo state and that emphasis should be placed on the implementation of public policies to support surveillance of chiropterans for rabies. © 2016 Blackwell Verlag GmbH.

  14. Incorporation of membrane-anchored flagellin or Escherichia coli heat-labile enterotoxin B subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs

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    Yinglin eQi

    2015-03-01

    Full Text Available Rabies remains an important worldwide public health threat, so safe, effective and affordable vaccines are still being sought. Virus-like particle (VLP-based vaccines targeting various viral pathogens have been successfully produced, licensed and commercialized. Here, we designed and constructed two chimeric rabies virus-like particles (cRVLPs containing rabies virus (RABV glycoprotein (G, matrix (M protein, and membrane-anchored flagellin (EVLP-F or Escherichia coli heat-labile enterotoxin B subunit (EVLP-L as molecular adjuvants to enhance the immune response against rabies. The immunogenicity and potential of cRVLPs as novel rabies vaccine were evaluated by intramuscular vaccination in mouse and dog models. Mouse studies demonstrated that both EVLP-F and EVLP-L induced faster and larger virus-neutralizing antibodies (VNA responses and elicited greater numbers of CD4+ and CD8+ T cells secreting IFN-γ or IL-4 compared with a standard rabies VLP (sRVLP containing only G and M. Moreover, cRVLPs recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. EVLP-F induced a strong, specific IgG2a response but not an IgG1 response, suggesting the activation of Th1 class immunity; in contrast, Th2 class immunity was observed with EVLP-L. The significantly enhanced humoral and cellular immune responses induced by cRVLPs provided complete protection against lethal challenge with RABV. Most importantly, dogs vaccinated with EVLP-F or EVLP-L exhibited increased VNA titers in sera and enhanced IFN-γ and IL-4 secretion from peripheral blood mononuclear cells. Taken together, these results illustrate that when incorporated into sRVLP, membrane-anchored flagellin and LTB possess strong adjuvant activity. EVLP-F and EVLP-L induce significantly enhanced RABV-specific humoral and cellular immune responses in both mouse and dog. Therefore, these cRVLPs may be developed as safe and more efficacious rabies vaccine candidate for animals.

  15. iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the rabies viruses rHep-Flury and Hep-dG

    Science.gov (United States)

    Yang, Youtian; Liu, Wenjun; Yan, Guangrong; Luo, Yongwen; Zhao, Jing; Yang, Xianfeng; Mei, Mingzhu; Wu, Xiaowei; Guo, Xiaofeng

    2015-01-01

    The rabies virus (RABV) glycoprotein (G) is the principal contributor to the pathogenicity and protective immunity of RABV. In a previous work, we reported that recombinant rabies virus Hep-dG, which was generated by reverse genetics to carry two copies of the G-gene, showed lower virulence than the parental virus rHep-Flury in suckling mice with a better immune protection effect. To better understand the mechanisms underlying rabies virus attenuation and the role of glycoprotein G, isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify and quantify distinct proteins. 10 and 111 differentially expressed proteins were obtained in rHep-Flury and Hep-dG infection groups, respectively. Selected data were validated by western blot and qRT-PCR. Bioinformatics analysis of the distinct protein suggested that glycoprotein over-expression in the attenuated RABV strain can induce activation of the interferon signaling. Furthermore, it may promote the antiviral response, MHC-I mediated antigen-specific T cell immune response, apoptosis and autophagy in an IFN-dependent manner. These findings might not only improve the understanding of the dynamics of RABV and host interaction, but also help understand the mechanisms underlying innate and adaptive immunity during RABV infection. PMID:26217322

  16. Further characterization of the immune response in mice to inactivated and live rabies vaccines expressing Ebola virus glycoprotein

    Science.gov (United States)

    Papaneri, Amy B.; Wirblich, Christoph; Cooper, Kurt; Jahrling, Peter B.; Schnell, Matthias J.; Blaney, Joseph E.

    2012-01-01

    We have previously developed (a) replication-competent, (b) replication-deficient, and (c) chemically inactivated rabies virus (RABV) vaccines expressing ebolavirus (EBOV) glycoprotein (GP) that induce humoral immunity against each virus and confer protection from both lethal RABV and mouse-adapted EBOV challenge in mice. Here, we expand our investigation of the immunogenic properties of these bivalent vaccines in mice. Both live and killed vaccines induced primary EBOV GP-specific T-cells and a robust recall response as measured by interferon-γ ELISPOT assay. In addition to cellular immunity, an effective filovirus vaccine will likely require a multivalent humoral immune response against multiple virus species. As a proof-of-principle experiment, we demonstrated that inactivated RV-GP could be formulated with another inactivated RABV vaccine expressing the nontoxic fragment of botulinum neurotoxin A heavy chain (HC50) without a reduction in immunity to each component. Finally, we demonstrated that humoral immunity to GP could be induced by immunization of mice with inactivated RV-GP in the presence of pre-existing immunity to RABV. The ability of these novel vaccines to induce strong humoral and cellular immunity indicates that they should be further evaluated in additional animal models of infection. PMID:22884661

  17. A Pan-Lyssavirus Taqman Real-Time RT-PCR Assay for the Detection of Highly Variable Rabies virus and Other Lyssaviruses.

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    Ashutosh Wadhwa

    2017-01-01

    Full Text Available Rabies, resulting from infection by Rabies virus (RABV and related lyssaviruses, is one of the most deadly zoonotic diseases and is responsible for up to 70,000 estimated human deaths worldwide each year. Rapid and accurate laboratory diagnosis of rabies is essential for timely administration of post-exposure prophylaxis in humans and control of the disease in animals. Currently, only the direct fluorescent antibody (DFA test is recommended for routine rabies diagnosis. Reverse-transcription polymerase chain reaction (RT-PCR based diagnostic methods have been widely adapted for the diagnosis of other viral pathogens, but there is currently no widely accepted rapid real-time RT-PCR assay for the detection of all lyssaviruses. In this study, we demonstrate the validation of a newly developed multiplex real-time RT-PCR assay named LN34, which uses a combination of degenerate primers and probes along with probe modifications to achieve superior coverage of the Lyssavirus genus while maintaining sensitivity and specificity. The primers and probes of the LN34 assay target the highly conserved non-coding leader region and part of the nucleoprotein (N coding sequence of the Lyssavirus genome to maintain assay robustness. The probes were further modified by locked nucleotides to increase their melting temperature to meet the requirements for an optimal real-time RT-PCR assay. The LN34 assay was able to detect all RABV variants and other lyssaviruses in a validation panel that included representative RABV isolates from most regions of the world as well as representatives of 13 additional Lyssavirus species. The LN34 assay was successfully used for both ante-mortem and post-mortem diagnosis of over 200 clinical samples as well as field derived surveillance samples. This assay represents a major improvement over previously published rabies specific RT-PCR and real-time RT-PCR assays because of its ability to universally detect RABV and other lyssaviruses

  18. Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs.

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    Clement W Gnanadurai

    Full Text Available The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N and not the glycoprotein (G. We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and B cells and further reduces CD4 T cell production. Further, we show that intrathecal (IT immunization of TriGAS not only induced high levels of VNA in the serum but also in the CSF while intramuscular (IM immunization of TriGAS induced VNA only in the serum. In addition, high levels of total protein and WBC were detected in the CSF of IT immunized dogs, indicating the transient enhancement of blood-brain barrier (BBB permeability, which is relevant to the passage of immune effectors from periphery into the CNS.IM infection of dogs with TriGAS induced the production of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of VNA in the periphery as well as in the CSF and transiently enhances BBB permeability. In contrast, infection with wt DRV-NG11 resulted in the production of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As a consequence, all of the dogs infected with wt DRV-NG11 succumbed to rabies. Thus the failure to activate protective immunity is one of the important features of RABV pathogenesis in dogs.

  19. Eliminating rabies in Estonia.

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    Florence Cliquet

    Full Text Available The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania.

  20. Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis.

    Science.gov (United States)

    Brice, Aaron; Whelan, Donna R; Ito, Naoto; Shimizu, Kenta; Wiltzer-Bach, Linda; Lo, Camden Y; Blondel, Danielle; Jans, David A; Bell, Toby D M; Moseley, Gregory W

    2016-09-21

    Although microtubules (MTs) are known to have important roles in intracellular transport of many viruses, a number of reports suggest that specific viral MT-associated proteins (MAPs) target MTs to subvert distinct MT-dependent cellular processes. The precise functional importance of these interactions and their roles in pathogenesis, however, remain largely unresolved. To assess the association with disease of the rabies virus (RABV) MAP, P3, we quantitatively compared the phenotypes of P3 from a pathogenic RABV strain, Nishigahara (Ni) and a non-pathogenic Ni-derivative strain, Ni-CE. Using confocal/live-cell imaging and dSTORM super-resolution microscopy to quantify protein interactions with the MT network and with individual MT filaments, we found that the interaction by Ni-CE-P3 is significantly impaired compared with Ni-P3. This correlated with an impaired capacity to effect association of the transcription factor STAT1 with MTs and to antagonize interferon (IFN)/STAT1-dependent antiviral signaling. Importantly, we identified a single mutation in Ni-CE-P3 that is sufficient to inhibit MT-association and IFN-antagonist function of Ni-P3, and showed that this mutation alone attenuates the pathogenicity of RABV. These data provide evidence that the viral protein-MT interface has important roles in pathogenesis, suggesting that this interface could provide targets for vaccine/antiviral drug development.

  1. Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts.

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    Cécile Troupin

    2016-12-01

    Full Text Available The natural evolution of rabies virus (RABV provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. Using 321 genome sequences spanning an unprecedented diversity of RABV, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. Two major phylogenetic groups, bat-related RABV and dog-related RABV, experiencing markedly different evolutionary dynamics were identified. While no correlation between time and genetic divergence was found in bat-related RABV, the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. Subsequent molecular clock dating indicated that dog-related RABV likely underwent a rapid global spread following the intensification of intercontinental trade starting in the 15th century. Strikingly, although dog RABV has jumped to various wildlife species from the order Carnivora, we found no clear evidence that these host-jumping events involved adaptive evolution, with RABV instead characterized by strong purifying selection, suggesting that ecological processes also play an important role in shaping patterns of emergence. However, specific amino acid changes were associated with the parallel emergence of RABV in ferret-badgers in Asia, and some host shifts were associated with increases in evolutionary rate, particularly in the ferret-badger and mongoose, implying that changes in host species can have important impacts on evolutionary dynamics.

  2. The Glycoprotein and the Matrix Protein of Rabies Virus Affect Pathogenicity by Regulating Viral Replication and Facilitating Cell-to-Cell Spread▿

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    Pulmanausahakul, Rojjanaporn; Li, Jianwei; Schnell, Matthias J.; Dietzschold, Bernhard

    2008-01-01

    While the glycoprotein (G) of rabies virus (RV) is known to play a predominant role in the pathogenesis of rabies, the function of the RV matrix protein (M) in RV pathogenicity is not completely clear. To further investigate the roles of these proteins in viral pathogenicity, we constructed chimeric recombinant viruses by exchanging the G and M genes of the attenuated SN strain with those of the highly pathogenic SB strain. Infection of mice with these chimeric viruses revealed a significant increase in the pathogenicity of the SN strain bearing the RV G from the pathogenic SB strain. Moreover, the pathogenicity was further increased when both G and M from SB were introduced into SN. Interestingly, the replacement of the G or M gene or both in SN by the corresponding genes of SB was associated with a significant decrease in the rate of viral replication and viral RNA synthesis. In addition, a chimeric SN virus bearing both the M and G genes from SB exhibited more efficient cell-to-cell spread than a chimeric SN virus in which only the G gene was replaced. Together, these data indicate that both G and M play an important role in RV pathogenesis by regulating virus replication and facilitating cell-to-cell spread. PMID:18094173

  3. The glycoprotein and the matrix protein of rabies virus affect pathogenicity by regulating viral replication and facilitating cell-to-cell spread.

    Science.gov (United States)

    Pulmanausahakul, Rojjanaporn; Li, Jianwei; Schnell, Matthias J; Dietzschold, Bernhard

    2008-03-01

    While the glycoprotein (G) of rabies virus (RV) is known to play a predominant role in the pathogenesis of rabies, the function of the RV matrix protein (M) in RV pathogenicity is not completely clear. To further investigate the roles of these proteins in viral pathogenicity, we constructed chimeric recombinant viruses by exchanging the G and M genes of the attenuated SN strain with those of the highly pathogenic SB strain. Infection of mice with these chimeric viruses revealed a significant increase in the pathogenicity of the SN strain bearing the RV G from the pathogenic SB strain. Moreover, the pathogenicity was further increased when both G and M from SB were introduced into SN. Interestingly, the replacement of the G or M gene or both in SN by the corresponding genes of SB was associated with a significant decrease in the rate of viral replication and viral RNA synthesis. In addition, a chimeric SN virus bearing both the M and G genes from SB exhibited more efficient cell-to-cell spread than a chimeric SN virus in which only the G gene was replaced. Together, these data indicate that both G and M play an important role in RV pathogenesis by regulating virus replication and facilitating cell-to-cell spread.

  4. Molecular genetic characterization of rabies virus glycoprotein gene sequences from rabid dogs in Bangkok and neighboring provinces in Thailand, 2013-2014.

    Science.gov (United States)

    Benjathummarak, Surachet; Fa-Ngoen, Chanon; Pipattanaboon, Chonlatip; Boonha, Khwanchit; Ramasoota, Pongrama; Pitaksajjakul, Pannamthip

    2016-05-01

    Because of its association with dogs, rabies virus (RABV) is still endemic in Thailand, where it is a serious public health problem. The genetic characterization of RABV in Thailand is limited. Therefore, in this study, we investigated the molecular epidemiology and genetic diversity of RABV in the endemic area. Viral RNA from 48 brain specimens from rabid dogs, collected in Bangkok and seven neighboring provinces in 2013-2014, was extracted and sequenced. The complete rabies glycoprotein (G) gene sequences (1575 nt) were aligned, and a phylogenetic analysis was performed using the maximum-likelihood method. All of the Thai rabies virus isolates belonged to lyssavirus genotype 1 and clustered in the same lineage as isolates from South East Asia (SEA) and China. The Thai rabies virus isolates formed two distinct clades, THA-1 and THA-2. Clade THA-1 was the predominant clade and could be divided into two subclades, THA-1A and THA-1B. Clade THA-2 was closely associated with human Thai isolates collected in a previous study. The overall mean rate of evolution based on the G gene was approximately 1.56 × 10(-4) substitutions/site/year. The genetic identities among the isolates from Thailand and other SEA countries were >88.4 % at the nucleotide sequence level and 95 % at the amino acid sequence level. The deduced amino acid sequences of the G proteins of the RABV isolates were compared. A single amino acid change (N194T) in subclade THA-1A distinguished the Thai RABV isolates from other RABV isolates. Our results suggest that these Thai dog RABV isolates share a common ancestor with the RABV isolates circulating in the endemic regions of SEA countries and China. Furthermore, there were strong genetic relationship to RABV from Cambodia, Vietnam and Laos. These data extend our understanding of the relatedness and genetic variation of RABV in Thailand.

  5. Arctic Rabies – A Review

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    Prestrud Pål

    2004-03-01

    Full Text Available Rabies seems to persist throughout most arctic regions, and the northern parts of Norway, Sweden and Finland, is the only part of the Arctic where rabies has not been diagnosed in recent time. The arctic fox is the main host, and the same arctic virus variant seems to infect the arctic fox throughout the range of this species. The epidemiology of rabies seems to have certain common characteristics in arctic regions, but main questions such as the maintenance and spread of the disease remains largely unknown. The virus has spread and initiated new epidemics also in other species such as the red fox and the racoon dog. Large land areas and cold climate complicate the control of the disease, but experimental oral vaccination of arctic foxes has been successful. This article summarises the current knowledge and the typical characteristics of arctic rabies including its distribution and epidemiology.

  6. Circulation of the rabies virus in non-hematophagous bats in the city of Rio de Janeiro, Brazil, during 2001-2010

    OpenAIRE

    Claudius Couto Cabral; Ana Carolina Nunes de Morais; Alba Valéria de Almeida Barcelos Dias; Marcela Garcia Araújo; Wildeberg Cal Moreira; Gláucio Luis Mata Mattos

    2012-01-01

    INTRODUCTION: Rabies is one of the most known lethal zoonosis, responsible for 55,000 human deaths per year. It is transmitted to humans mainly by the bite of domestic or wild animals infected with the virus. This paper shows the circulation of this virus in non-hematophagous bats in the City of Rio de Janeiro, Brazil. METHODS: A survey was performed on the number of bats that had been sent for diagnosis by the Seção de Virologia of the Instituto Municipal de Medicina Veterinária Jorge Vaitsm...

  7. 皮卡佐剂狂犬病治疗性疫苗对暴露后实验动物和人体免疫记忆的效果%The effects treated with PICKCa rabies vaccine to mice and beagle dogs infected rabies wild viruses and volunteers immunized with PICKCa rabies vaccine

    Institute of Scientific and Technical Information of China (English)

    林海祥; 徐葛林; 吴杰; 张守峰; 扈荣良; 李烈涛; 刘芳; 张师瑞; 张译

    2016-01-01

    Objective To test the immune therapeutic effects of PICKCa adjuvant rabies vaccine for the post-exposure mice and beagle dogs and immune memory effect for human.Methods For the mice and beagle dogs first to infect with rabies wild virus and then immunize with PICKCa rabies vaccine.For volunteers, first to immunize with PICKCa rabies vaccine after 2.5 years to take peripheral blood mononuclear cell and then to check cells secreted interferon-gwith flow cytometry. Results In 3 independent assays of post-explosure immunization of mice and beagle dogs PICKCa rabies vaccine were much better then commercial adjuvant-free rabies vaccines, the protective rate from 20%-30%to 70%-100%Also, in the assay of cells secreted IFN-γby peripheral blood mononuclear cells from volunteers immunized by PICKCa rabies vaccine the IFN-γcell levels were much higher than control.Conclusions Compared with commercial adjuvant-free rabies vaccines the PICKCa rabies vaccine had significant immune therapeutic effects in the mice and dogs.Also PICKCa rabies vaccine had good immune memory effect in human.%目的:检测皮卡佐剂狂犬病疫苗对暴露后实验动物免疫治疗作用和对人的免疫记忆效果。方法模仿人体暴露后免疫,对小白鼠和Beagle犬进行了先感染狂犬病毒野毒株病毒再用不同狂犬病灭活疫苗免疫,观察保护效果;对犬咬伤志愿者用皮卡佐剂狂犬病疫苗免疫2.5年后分离外周血单个核细胞,用流式细胞仪检测干扰素免疫记忆细胞数量。结果在法国巴斯德研究所、武汉生物制品研究所、军事医学科学院军事兽医研究所三次独立实验结果均显示在没有联合应用抗狂犬病免疫球蛋白的情况下,国内外市售人用狂犬病疫苗保护率为0%~30%,皮卡佐剂狂犬病疫苗保护率为70%~100%,统计学分析有极其显著的差异。暴露后志愿者用皮卡佐剂狂犬病疫苗免疫,2.5年后外周血单个核细胞仍能

  8. AN ELISA SUITABLE FOR THE DETECTION OF RABIES VIRUS ANTIBODIES IN SERUM SAMPLES FROM HUMAN VACCINATED WITH EITHER CELL-CULTURE VACCINE OR SUCKLING-MOUSE-BRAIN VACCINE

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    PIZA Adriana Souza de Toledo

    1999-01-01

    Full Text Available An indirect ELISA for determination of post-vaccination rabies antibody was applied. Purified rabies virus was used as antigen to coat plates, and staphylococcal protein A linked with horseradish peroxidase was used for detecting IgG antibody in human sera. Sera from humans, vaccinated with cell-culture vaccine or suckling-mouse-brain vaccine, were examined. ELISA results were compared to those obtained from the virus neutralization test. The mean and standard deviation of OD were determined for 126 negative sera (pre-vaccination and for 73 sera from vaccinated persons showing antibody titers lower than 0.5 IU/ml. Results were defined as ELISA -positive, -negative or -doubtful. Establishment of a doubtful region reduced the number of sera otherwise classified as positive (false-positive sera. In this way, the sensitivity, specificity and agreement values were respectively 87.5%, 92.4% and 88.5%. No significant differences were observed in these values when the group vaccinated with cell-culture vaccine and the group vaccinated with suckling-mouse-brain vaccine were compared. It was shown that much of the disagreement between the values obtained by neutralization test and ELISA occurred in sera obtained at the beginning of the immunization process, and was probably due to the presence of IgM in the serum samples, detected only by the former test. This ELISA method can be used as a screening test in rabies laboratories regardless of the kind of vaccine used for immunization.

  9. Could the homologous sequence of anti-inflammatory pentapeptide (MLIF) produced by Entamoeba histolytica in the N protein of rabies virus affect the inflammatory process?

    Science.gov (United States)

    Morales, M E; Rico, G; Gómez, J L; Alonso, R; Cortés, R; Silva, R; Giménez, J A; Kretschmer, R; Aguilar-Setién, A

    2006-02-01

    Amebiasis and rabies are public health problems, and they have in common a poor inflammatory effect in the target organs that they affect. In the GenBank, it was found that the anti-inflammatory peptide monocyte locomotion inhibitory factor (MLIF) produced by Entamoeba histolytica homologates 80%, with a fragment of the N protein of the rabies virus. We speculated if the N protein could contribute to the scant inflammatory reaction produced by rabies virus in central nervous system. The N protein was obtained and studied in vitro and in vivo. The N protein, as MLIF, inhibited the respiratory burst in human mononuclear phagocytes (43%, p<0.05), but in contrast to MLIF, it increased chemotaxis and it did not significantly inhibit delayed hypersensitivity skin reaction to 1-chloro-2-4-dinitrobenzene in guinea pigs. Therefore, the full peptide sequence has to be present or it has to be cleaved-free from the large recombinant N protein molecule (55 kDa) to become active.

  10. Spontaneous pneumomediastinum due to paralytic rabies

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    Wuping Wang

    2013-02-01

    Full Text Available Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.

  11. Fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in Brazil.

    Science.gov (United States)

    Appolinário, Camila; Allendorf, Susan Dora; Vicente, Acácia Ferreira; Ribeiro, Bruna Devidé; Fonseca, Clóvis Reinaldo da; Antunes, João Marcelo; Peres, Marina Gea; Kotait, Ivanete; Carrieri, Maria Luiza; Megid, Jane

    2015-01-01

    Rabies virus (RABV) isolated from different mammals seems to have unique characteristics that influence the outcome of infection. RABV circulates in nature and is maintained by reservoirs that are responsible for the persistence of the disease for almost 4000 years. Considering the different pattern of pathogenicity of RABV strains in naturally and experimentally infected animals, the aim of this study was to analyze the characteristics of RABV variants isolated from the main Brazilian reservoirs, being related to a dog (variant 2), Desmodus rotundus (variant 3), crab eating fox, marmoset, and Myotis spp. Viral replication in brain tissue of experimentally infected mouse was evaluated by two laboratory techniques and the results were compared to clinical evolution from five RABV variants. The presence of the RABV was investigated in brain samples by fluorescent antibody test (FAT) and real time polymerase chain reaction (qRT-PCR) for quantification of rabies virus nucleoprotein gene (N gene). Virus replication is not correlated with clinical signs and evolution. The pattern of FAT is associated with RABV replication levels. Virus isolates from crab eating fox and marmoset had a longer evolution period and higher survival rate suggesting that the evolution period may contribute to the outcome. RABV virus variants had independent characteristics that determine the clinical evolution and survival of the infected mice.

  12. Expression and solubilization of insect cell-based rabies virus glycoprotein and assessment of its immunogenicity and protective efficacy in mice.

    Science.gov (United States)

    Ramya, R; Mohana Subramanian, B; Sivakumar, V; Senthilkumar, R L; Sambasiva Rao, K R S; Srinivasan, V A

    2011-10-01

    Rabies is a fatal zoonotic disease of serious public health and economic significance worldwide. The rabies virus glycoprotein (RVG) has been the major target for subunit vaccine development, since it harbors domains responsible for induction of virus-neutralizing antibodies, infectivity, and neurovirulence. The glycoprotein (G) was cloned using the baculovirus expression vector system (BEVS) and expressed in Spodoptera frugiperda (Sf-9) cells. In order to obtain a soluble form of G suitable for experimentation in mice, 18 different combinations of buffers and detergents were evaluated for their ability to solubilize the insect cell membrane-associated G. The combination that involved 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) detergent in lysis buffer 1, formulated with Tris, NaCl, 10% dimethyl sulfoxide (DMSO), and EDTA, gave the highest yield of soluble G, as evidenced by the experimental data. Subsequently, several other parameters, such as the concentration of CHAPS and the duration and temperature of the treatment for the effective solubilization of G, were optimized. The CHAPS detergent, buffered at a concentration of 0.4% to 0.7% (wt/vol) at room temperature (23 to 25°C) for 30 min to 1 h using buffer 1, containing 10% DMSO, resulted in consistently high yields. The G solubilized using CHAPS detergent was found to be immunogenic when tested in mice, as evidenced by high virus-neutralizing antibody titers in sera and 100% protection upon virulent intracerebral challenge with the challenge virus standard (CVS) strain of rabies virus. The results of the mice study indicated that G solubilized with CHAPS detergent retained the immunologically relevant domains in the native conformation, thereby paving the way for producing a cell-free and efficacious subunit vaccine.

  13. Comparison between the Counter Immunoelectrophoresis Test and Mouse Neutralization Test for the Detection of Antibodies against Rabies Virus in Dog Sera

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    Luzia Helena Queiroz da Silva

    2002-03-01

    Full Text Available The detection of rabies antibodies is extremely valuable for epidemiological studies, determination of immune status in man, animals, and for the diagnosis of the disease. Several serological procedures have been described for this purpose. The present study reports a comparison between counterimmunoelectrophoresis test (CIET and mouse neutralization test (MNT in the detection of antibodies against rabies virus from 212 serum samples of vaccinated dogs. The agreement between both techniques was 79.7% and a significative association was demonstrated. The correlation coefficients between MNT and the CIET titers was determined considering 88 samples showing positive results in both techniques [CIET = 2 and MNT = 5 (0.13 IU/ml] and resulted r² = 0.7926 (p < 0.001. The performance of CIET system was technically simple, cheap and rapid, and thereby it could be useful for serological monitoring of dog vaccination campaigns as well as for individual analysis.

  14. Adaptation of a Chinese ferret badger strain of rabies virus to high-titered growth in BHK-21 cells for canine vaccine development.

    Science.gov (United States)

    Liu, Ye; Zhang, Shoufeng; Zhang, Fei; Hu, Rongliang

    2012-12-01

    Rabies virus strain JX08-45CC was derived from a Chinese isolate (JX08-45) by serial passage in the BHK-21 cell line, reaching a titer of 10(8) TCID(50)/mL. JX08-45CC produced rabies in adult mice but was nonpathogenic in dogs after intramuscular injection. A comparison of the entire genomes of JX08-45 and JX08-45CC led to the identification of 17 nucleotide substitutions, resulting in seven amino acid changes in the mature G and L proteins. The immunogenicity of β-propiolactone-inactivated JX08-45CC was similar to the immunogenicity of the live vaccine strains widely used in China. The inactivated vaccine induced antibody responses for more than 6 months and provided full protection from an intramuscular challenge in dogs. JX08-45CC has excellent potential for development as an inactivated vaccine for dogs in China.

  15. Comparación antigénica y de la respuesta inmune en ratones desafiados con virus CVS y aislados «calle» y «fijo»presumiblemente atípicos del virus rábico Antigenic comparison and immune response in challenges mice with virus CVS and "street" and "fixed" isolates presumably atipics of rabies virus

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    P. MARTINEZ

    1999-01-01

    /1091, y en el pasaje Nº 14 para el aislado 85/1068. En la protección conferida por las vacunas hubo diferencias significativas (p Rabies is a disease caused by neurotropic virus which has the capability to infect a wide range of animals and humans. Antigenic analysis of a wide variety of fixed (vaccine strains and street viruses with monoclonal antibodies has revealed considerable antigenic variation among the samples of viruses isolated from different host species, or geographical locations. These marked antigenic variations have potentially serious implications for rabies control strategies. We studied the patterns of "street" and "fixed" rabies virus isolates compared with the prototype Challenge Virus Standard (CVS, using the Fuenzalida-Palacios rabies vaccine and anti-rabies serum standard. Six street rabies virus were used. These were detected and isolated in 1985, at the Public Health Institute of Chile. First, suckling mice were inoculated with street rabies virus 85/423, 85/433, 85/684, 85/882, 85/1068, 85/1091. The detection of rabies virus antigen in CNS tissues was performed with the direct immunofluorescence technique. These positive samples were used for the viral passage in mice. Next, brain tissues from mice experimentally infected with street virus were used for the next intracerebral inoculation. This street rabies virus was fixed. We analysed role of Fuenzalidad-Palacios vaccine in induction of protective immune response against a lethal infection in suckling mice with six street rabies virus ( 85/423, 85/433, 85/684, 85/882, 85/1068 and 85/1091, challenge virus standard (CVS and fixed rabies virus (85/423, 85/433, 85/684, 85/882, 85/1068 and 85/1091. To study the protection of anti-rabies serum, mice were inoculated intracerebrally with preincubated mixtures of anti-rabies serum with virus CVS and anti-rabies serum with fixed rabies virus. The results indicated that the Fuenzalida-Palacios vaccine, experimentally produced only partial protection

  16. An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs.

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    Margit Schnee

    2016-06-01

    Full Text Available Rabies is a zoonotic infectious disease of the central nervous system (CNS. In unvaccinated or untreated subjects, rabies virus infection causes severe neurological symptoms and is invariably fatal. Despite the long-standing existence of effective vaccines, vaccine availability remains insufficient, with high numbers of fatal infections mostly in developing countries. Nucleic acid based vaccines have proven convincingly as a new technology for the fast development of vaccines against newly emerging pathogens, diseases where no vaccine exists or for replacing already existing vaccines. We used an optimized non-replicating rabies virus glycoprotein (RABV-G encoding messenger RNA (mRNA to induce potent neutralizing antibodies (VN titers in mice and domestic pigs. Functional antibody titers were followed in mice for up to one year and titers remained stable for the entire observation period in all dose groups. T cell analysis revealed the induction of both, specific CD4+ as well as CD8+ T cells by RABV-G mRNA, with the induced CD4+ T cells being higher than those induced by a licensed vaccine. Notably, RABV-G mRNA vaccinated mice were protected against lethal intracerebral challenge infection. Inhibition of viral replication by vaccination was verified by qRT-PCR. Furthermore, we demonstrate that CD4+ T cells are crucial for the generation of neutralizing antibodies. In domestic pigs we were able to induce VN titers that correlate with protection in adult and newborn pigs. This study demonstrates the feasibility of a non-replicating mRNA rabies vaccine in small and large animals and highlights the promises of mRNA vaccines for the prevention of infectious diseases.

  17. A VL-linker-VH Orientation Dependent Single Chain Variable Antibody Fragment Against Rabies Virus G Protein with Enhanced Neutralizing Potency in vivo.

    Science.gov (United States)

    Cheng, Yue; Li, Zhuang; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2016-01-01

    Lethal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragment (scFv), which is composed of a variable heavy chain (VH) and variable light chain (VL) connected by a peptide linker, may be developed as alternative to RIG for neutralizing rabies virus (RV). However, our previously constructed scFv (FV57S) with the (NH2) VH-linker-VL (COOH) orientation showed a lower neutralizing potency than its parent RIG. This orientation may inhibit FV57S from refolding into an intact and correct conformation. Therefore, the RFV57S protein with a VL-linker-VH orientation was constructed based on FV57S. A HIS tag was incorporated to aid in purification and detection of RFV57S and FV57S. However, abilities of RFV57S and FV57S to bind with the anti-HIS tag mAb were different. Therefore, a novel direct ELISA was established by utilizing a biotin-labeled truncated glycoprotein of RV. Although with similar stability and in vitro neutralizing potency as FV57S, RFV57S showed enhanced binding ability, affinity and in vivo protective efficacy against lethal dose of RV. Our studies support the feasibility of developing a scFv with reversed orientation and provide a novel method for evaluating the binding ability, stability and affinity of engineered antibodies recognizing linear epitope.

  18. BAT-BORNE RABIES IN LATIN AMERICA

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    Luis E. Escobar

    2015-02-01

    Full Text Available The situation of rabies in America is complex: rabies in dogs has decreased dramatically, but bats are increasingly recognized as natural reservoirs of other rabies variants. Here, bat species known to be rabies-positive with different antigenic variants, are summarized in relation to bat conservation status across Latin America. Rabies virus is widespread in Latin American bat species, 22.5%75 of bat species have been confirmed as rabies-positive. Most bat species found rabies positive are classified by the International Union for Conservation of Nature as “Least Concern”. According to diet type, insectivorous bats had the most species known as rabies reservoirs, while in proportion hematophagous bats were the most important. Research at coarse spatial scales must strive to understand rabies ecology; basic information on distribution and population dynamics of many Latin American and Caribbean bat species is needed; and detailed information on effects of landscape change in driving bat-borne rabies outbreaks remains unassessed. Finally, integrated approaches including public health, ecology, and conservation biology are needed to understand and prevent emergent diseases in bats.

  19. The analysis of VH and VL genes repertoires of Fab library built from peripheral B cells of human rabies virus vaccinated donors.

    Science.gov (United States)

    Houimel, Mehdi

    2014-08-01

    A human combinatorial Fab antibody library was generated from immune repertoire based on peripheral B cells of ten rabies virus vaccinated donors. The analysis of random Fab fragments from the unselected library presented some bias of V gene usage towards IGHV-genes and IGLV-gen families. The screening of the Fab library on rabies virus allowed specific human Fab antibody fragments characterized for their gene encoding sequences, binding and specificities to RV. Genetic analysis of selected Fabs indicated that the IGHV and IGLV differ from the germ-line sequence. At the level of nucleotide sequences, the IGHV and IGLV domains were found to share 74-92% and 90-96% homology with sequences encoded by the corresponding human germ-line genes respectively. IGHV domains are characterized most frequently by IGHV3 genes, and large proportions of the anti-RV heavy chain IGHV domains are obtained following a VDJ recombination process that uses IGHD3, IGHD2, IGHD1 and IGHD6 genes. IGHJ3 and IGHJ4 genes are predominantly used in RV-Fab. The IGLV domains are dominated by IGKV1, IGLV1 and IGLV3 genes. Numerous somatic hypermutations in the RV-specific IGHV are detected, but only limited amino acid replacement in most of the RV-specific IGLV particularly in those encoded by J proximal IGLV or IGKV genes are found. Furthermore, IGHV3-IGKV1, IGHV3-IGVL1, and IGHV3-IGLV3 germ-line family pairings are preferentially enriched after the screening on rabies virus.

  20. Ferret badger rabies origin and its revisited importance as potential source of rabies transmission in Southeast China

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    Liu Ye

    2010-08-01

    Full Text Available Abstract Background The frequent occurrence of ferret badger-associated human rabies cases in southeast China highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. To determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in dogs and ferret badgers. Methods A retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and Anhui provinces in southeast China. The brain tissues from ferret badgers and dogs were assayed by fluorescent antibody test. Rabies virus was isolated and sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were titrated using rabies virus neutralizing antibodies (VNA test. Results The ferret badgers presented a higher percentage of rabies seroconversion than dogs did in the endemic region, reaching a maximum of 95% in the collected samples. Nine ferret badger-associated rabies viruses were isolated, sequenced, and were phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4-99.8% homology within the ferret badger isolates, and 83-89% homology to the dog isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic regions. Conclusions Our data suggest ferret badger-associated rabies has likely formed as an independent enzootic originating from dogs during the long-term rabies infestation in southeast China. The eventual role of FB rabies in public health remains unclear. However, management of ferret badger bites, rabies awareness and control in the related regions should be an immediate need.

  1. Recent data on the epidemiology and prophylaxis of human rabies in France.

    Science.gov (United States)

    Sureau, P

    1990-01-01

    Rabies is an animal disease which is transmitted to man only by accident, most often through the bite (more rarely after scratches or licks of mucosa) of a rabid animal, domestic or wild. A good knowledge of the epizootiology of animal rabies is therefore necessary to establish, on solid grounds, the prophylaxis of human rabies. Inter-human transmission of rabies being an exceptional event which will be considered separately, the epidemiology of human rabies mainly studies the sources and circumstances of human exposure to rabid animals, which differ according to the epizootiology of animal rabies in a given country: either enzootic (or hyperenzootic) canine rabies, or enzootic selvatic rabies. It appears that the risk of human rabies is higher in the first situation for two reasons: (i) rabies viruses show an increased virulence due to numerous serial passages in dogs (viruses with short incubation period) and (ii) high frequency of dog-man contacts due to the high density of both populations.

  2. RABIES IN NIGERIA: A REVIEW OF LITERATURE

    African Journals Online (AJOL)

    boaz

    The domestic dog (Canis familiaris) plays a principal role (accounting for ... Early recognition of the infectivity of the saliva of rabid dogs led ... immunogenicity and their virulent properties 11. .... sustain a bite or wound exposure to rabies virus.

  3. Characterization of a virulent dog-originated rabies virus affecting more than twenty fallow deer (Dama dama) in Inner Mongolia, China.

    Science.gov (United States)

    Zhu, Hongwei; Chen, Xiaoyun; Shao, Xiqun; Ba, Hengxing; Wang, Fengxue; Wang, Hualei; Yang, Yong; Sun, Na; Ren, Jingqiang; Cheng, Shipeng; Wen, Yongjun

    2015-04-01

    Rabies has emerged as a serious problem in the most recent years in northern China. A rabies virus (RABV) isolate, IMDRV-13, was recovered from brain samples of dog-bitten rabid fallow deer (Dama dama) in a farm in Hohhot, Inner Mongolia. We tested the susceptibility of mouse neuroblastoma (MNA) cells and BSR cells as well as that of adult mice to IMDRV-13. The isolate was found to be a virulent isolate with an equivalent pathogenicity index (0.12) and a slight lower neurotropism index (1.07) compared with those of challenge virus standard, CVS-24, which was 0.13 and 1.23, respectively. The complete genome of IMDRV-13 was determined subsequently and found to be 11,924 nucleotides (nt) in length with the same genomic organization as other RABVs. Phylogenetic tree based on complete genome sequences of 43 RABV isolates and strains indicated that IMDRV-13, along with other two isolates in Inner Mongolia, CNM1101C and CNM1104D, clustered within the dog-associated China I clade, which is also the dominant lineage in the current rabies epidemic in China. In addition, sequence analysis of the glycoprotein G identified an amino acid substitution (I338→T338) unique to the IMDRV-13 within antigenic sites III (330-338), this mutation also leads to an additional potential N-glycosylation site (N336), which may represent a useful model to study relationship of N-glycosylation in G protein and specific properties such as pathogenicity or host adaption of RABV.

  4. Caveats in transneuronal tracing with unmodified rabies virus: an evaluation of aberrant results using a nearly perfect tracing technique

    Directory of Open Access Journals (Sweden)

    Tom J.H. Ruigrok

    2016-07-01

    Full Text Available Apart from the genetically engineered, modified, strains of rabies virus (RABV, unmodified ‘fixed’ virus strains of RABV, such as the ‘French’ subtype of CVS11, are used to examine synaptically connected networks in the brain. This technique has been shown to have all the prerequisite characteristics for ideal tracing as it does not metabolically affect infected neurons within the time span of the experiment, it is transferred transneuronally in one direction only and to all types of neurons presynaptic to the infected neuron, number of transneuronal steps can be precisely controlled by survival time and it is easily detectable with a sensitive technique.Here, using the ‘French’ CVS 11 subtype of RABV in Wistar rats, we show that some of these characteristics may not be as perfect as previously indicated. Using injection of RABV in hind limb muscles, we show that RABV-infected spinal motoneurons may already show lysis 1 or 2 days after infection. Using longer survival times we were able to establish that Purkinje cells may succumb approximately 3 days after infection. In addition, some neurons seem to resist infection, as we noted that the number of RABV-infected inferior olivary neurons did not progress in the same rate as other infected neurons. Furthermore, in our hands, we noted that infection of Purkinje cells did not result in expected transneuronal labeling of cell types that are presynaptic to Purkinje cells such as molecular layer interneurons and granule cells. However, these cell types were readily infected when RABV was injected directly in the cerebellar cortex. Conversely, neurons in the cerebellar nuclei that project to the inferior olive did not take up RABV when this was injected in the inferior olive, whereas these cells could be infected with RABV via a transneuronal route. These results suggest that viral entry from the extracellular space depends on other factors or mechanisms than those used for retrograde

  5. Novel vaccines to human rabies.

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    Hildegund C J Ertl

    Full Text Available Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP. In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.

  6. Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe.

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    Thomas F Müller

    Full Text Available In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978-2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution.

  7. A microcarrier cell culture process for propagating rabies virus in Vero cells grown in a stirred bioreactor under fully animal component free conditions.

    Science.gov (United States)

    Rourou, Samia; van der Ark, Arno; van der Velden, Tiny; Kallel, Héla

    2007-05-10

    Rabies virus strain production in Vero cells grown on Cytodex 1 in a 2 L stirred tank bioreactor and in a medium free of components of human or animal origin (VP-SFM) is described. Cell banking procedure in VP-SFM supplemented with an animal components free mixture (10%DMSO+0.1%methylcellulose) was reported and cell growth after revitalization was assessed. Vero cells exhibited growth performances (specific growth rate and cell division number) similar to that obtained in serum containing medium. To design a scalable process that is totally free of animal-derived substances, two proteases: TrypLE Select and Accutase, were assessed as an alternative to trypsin which is routinely used for cell passage. Growth performance of Vero cells grown in VP-SFM and MEM+10% fetal calf serum (FCS) over four passages and subcultivated with either TrypLE Select or Accutase was evaluated. TrypLE Select showed the best performance in terms of specific growth rate and cell division number. Kinetics of cell growth and rabies virus production (LP2061/Vero strain) were investigated in spinner flask and in a 2 L bioreactor. In spinner flask, a maximal cell density level of 1.85x10(6) cells/mL was achieved when the cells were grown in VP-SFM on 2 g/L Cytodex 1. Cell infection experiments conducted at an MOI of 0.3 and without the medium exchange step, typically needed for serum containing rabies virus production, resulted in a maximal virus titer equal to 2x10(7) (Fluorescent Focus Unit) FFU/mL. In stirred tank bioreactor, Vero cell growth in VP-SFM on 3 g/L Cytodex 1 was shown to be sensitive to the aeration mode. Sparging the culture was detrimental for cell growth, whereas cell density level was greatly enhanced when only headspace aeration was used. A cell density level of 2.6x10(6) cells/mL was obtained when the cells were grown on 3g/L Cytodex 1 and in batch culture mode. Cell infection at an MOI of 0.1 without any medium exchange, yielded a maximal rabies virus titer of 2.4x10

  8. Ultrastructure of cranial nerves of rats inoculated with rabies virus Ultraestrutura de nervos cranianos de ratos inoculados com o vírus da raiva

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    Guilberto Minguetti

    1997-01-01

    Full Text Available The V and VII cranial nerves of rats inoculated with rabies virus were studied by electron microscopy. The results were compared with the same cranial nerves of rats inoculated with rabies virus but vaccinated against the disease. The findings are those of axonal degeneration and intense demyelination of the nerves of the group of rats not vaccinated. The vaccinated rats showed some ultrastructural irrelevant alterations when compared with the other group. The degree of ultrastructural alterations found in the group of rats not vaccinated suggests that in rabies severe damage of the cranial nerves occurs and that this may be closely related to the clinical picture of the disease (hydrophobia. Furthermore, as far as the authors know, this has not been considered in the classic descriptions of rabies and it is possible that an immunologic process may take part in the demyelination observed in the present study.Os autores estudaram o quinto e o sétimo nervos cranianos de ratos inoculados com o vírus da raiva. Os resultados foram comparados com os mesmos nervos cranianos de ratos inoculados com o vírus da raiva, porém vacinados contra a doença. Os achados no grupo não vacinado foram de degeneração axonal e intensa desmielinização dos nervos examinados. No grupo vacinado foram encontrados apenas discretas alterações da mielina, sem relevância do ponto de vista patológico. As grandes alterações ultraestruturais encontradas no grupo de ratos não vacinados sugerem que na raiva ocorram acentuadas alterações nos nervos cranianos e que tais alterações devem estar intimamente relacionadas ao quadro clínico da doença (hidrofobia. Além disso, é possível que tais alterações estejam associadas a um processo imunológico responsável também por acometimento sistêmico dos nervos periféricos.

  9. Immunohistochemical evaluation of calbindin expression in mouse brain at different times after rabies virus inoculation.

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    Natalia Lamprea

    2009-11-01

    Full Text Available Introducción: La calbindina (CB es una proteína reguladora del metabolismo del calcio intracelular. Previamente se demostró que la infección con virus fijo de la rabia induce pérdida de la expresión de CB, en el cerebro de ratones en estado terminal de la enfermedad, a los 7-8 días de post-inoculación (p.i. intramuscular. Objetivo: Determinar si la pérdida de expresión de CB se presenta también en etapas tempranas de la infección y si es una consecuencia inmediata a la aparición de antígenos virales en el cerebro. Materiales y métodos: Se inocularon ratones con virus fijo de la rabia, por vía intramuscular, en su extremidad posterior izquierda. Diariamente se tomaron entre 4 y 6 animales infectados y sus respectivos controles, se fijaron por perfusión intracardíaca con paraformaldehído, se extrajeron sus cerebros y se obtuvieron cortes coronales en un vibrátomo. Estos se sometieron a reacciones inmunohistoquímicas para evaluar la presencia de antígenos virales y la expresión de CB. Esta última fue cuantificada mediante densitometría óptica en un microscopio con análisis de imágenes. Resultados: La inmunorreactividad a la rabia fue positiva en el cerebro a partir del día 3 p.i.; se observó primero en neuronas piramidales de la corteza frontal. La inmunotinción para CB no sufrió ninguna alteración cualitativa ni cuantitativa en la corteza cerebral y el estriado hasta el día 6 p.i. Conclusiones: Estos resultados coinciden con los de otros estudios sobre la rabia en los que se han encontrado alteraciones moleculares, metabólicas o fisiopatológicas en el sistema nervioso sólo en la fase terminal de la enfermedad.

  10. A novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus G protein compared to its corresponding single-chain variable antibody fragment.

    Science.gov (United States)

    Li, Zhuang; Cheng, Yue; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2015-12-01

    Fatal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragments (scFv), which are composed of a variable heavy chain (VH) and a variable light chain (VL) connected by a peptide linker, can potentially be used to replace RIG. However, in our previous study, a scFv (scFV57S) specific for the rabies virus (RV) G protein showed a lower neutralizing potency than that of its parent IgG due to lower stability and altered peptide assembly pattern. In monoclonal antibodies, the VH and VL interact non-covalently, while in scFvs the VH is connected covalently with the VL by the artificial linker. In this study, we constructed and expressed two peptides 57VL-JUN-HIS and 57VH-FOS-HA in Escherichia coli. The well-known Fos and Jun leucine zippers were utilized to dimerize VH and VL similarly to the IgG counterpart. The two peptides assembled to form zipFv57S in vitro. Due to the greater similarity in structure with IgG, the zipFv57S protein showed a higher binding ability and affinity resulting in notable improvement of in vitro neutralizing activity over its corresponding scFv. The zipFv57S protein was also found to be more stable and showed similar protective rate as RIG in mice challenged with a lethal dose of RV. Our results not only indicated zipFv57S as an ideal alternative for RIG in PEP but also offered a novel and efficient hetero-dimerization pattern of VH and VL leading to enhanced neutralizing potency.

  11. Variability in seroprevalence of rabies virus neutralizing antibodies and associated factors in a Colorado population of big brown bats (Eptesicus fuscus)

    Science.gov (United States)

    O’Shea, Thomas J.; Bowen, Richard A.; Stanley, Thomas R.; Shankar, Vidya; Rupprecht, Charles E.

    2014-01-01

    In 2001–2005 we sampled permanently marked big brown bats (Eptesicus fuscus) at summer roosts in buildings at Fort Collins, Colorado, for rabies virus neutralizing antibodies (RVNA). Seroprevalence was higher in adult females (17.9%, n = 2,332) than males (9.4%, n = 128; P = 0.007) or volant juveniles (10.2%, n = 738; Pbats. Seroprevalence also increased with age of bat, and varied from 6.2 to 26.7% among adult females at five roosts sampled each year for five years. Seroprevalence of adult females at 17 other roosts sampled for 1 to 4 years ranged from 0.0 to 47.1%. Using logistic regression, the only ranking model in our candidate set of explanatory variables for serological status at first sampling included year, day of season, and a year by day of season interaction that varied with relative drought conditions. The presence or absence of antibodies in individual bats showed temporal variability. Year alone provided the best model to explain the likelihood of adult female bats showing a transition to seronegative from a previously seropositive state. Day of the season was the only competitive model to explain the likelihood of a transition from seronegative to seropositive, which increased as the season progressed. We found no rabies viral RNA in oropharyngeal secretions of 261 seropositive bats or in organs of 13 euthanized seropositive bats. Survival of seropositive and seronegative bats did not differ. The presence of RVNA in serum of bats should not be interpreted as evidence for ongoing rabies infection.

  12. Fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in Brazil

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    Camila Appolinário

    2015-10-01

    Full Text Available ABSTRACTRabies virus (RABV isolated from different mammals seems to have unique characteristics that influence the outcome of infection. RABV circulates in nature and is maintained by reservoirs that are responsible for the persistence of the disease for almost 4000 years. Considering the different pattern of pathogenicity of RABV strains in naturally and experimentally infected animals, the aim of this study was to analyze the characteristics of RABV variants isolated from the main Brazilian reservoirs, being related to a dog (variant 2,Desmodus rotundus (variant 3, crab eating fox, marmoset, and Myotis spp. Viral replication in brain tissue of experimentally infected mouse was evaluated by two laboratory techniques and the results were compared to clinical evolution from five RABV variants. The presence of the RABV was investigated in brain samples by fluorescent antibody test (FAT and real time polymerase chain reaction (qRT-PCR for quantification of rabies virus nucleoprotein gene (N gene. Virus replication is not correlated with clinical signs and evolution. The pattern of FAT is associated with RABV replication levels. Virus isolates from crab eating fox and marmoset had a longer evolution period and higher survival rate suggesting that the evolution period may contribute to the outcome. RABV virus variants had independent characteristics that determine the clinical evolution and survival of the infected mice.

  13. Global epidemiology of canine rabies: past, present, and future prospects

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    Taylor LH

    2015-11-01

    Full Text Available Louise H Taylor,1 Louis H Nel1,21Global Alliance for Rabies Control, Manhattan, KS, USA; 2Department of Microbiology and Plant Pathology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa Abstract: The rabies virus, a public health scourge from ancient times, is currently responsible for an estimated 59,000 human deaths a year, almost all transmitted via dog bites. It causes considerable economic impacts on developing countries, primarily in Africa and Asia, which can least afford these losses. However, despite its almost 100% case fatality rate, canine rabies is a completely preventable disease, and historic examples of canine rabies elimination in the developed world attest to this. Over the last decade, programs based on eliminating the source of the disease from dogs have shown success in reducing the public health burden of canine rabies in developing countries, notably across Latin America, and this has contributed to the growing evidence base necessary to change attitudes toward the feasibility of global canine rabies elimination. More recently, assessments of the current economic burden of canine rabies and the potential cost savings achievable through mass dog vaccinations have been added to this evidence base. Tools and support are available from the international community to help countries move progressively toward canine rabies elimination, and there is optimism that global freedom from canine rabies can be achieved within the next few decades. Keywords: canine rabies, epidemiology, elimination, zoonosis, rabies virus

  14. 现代狂犬病疫苗生产用细胞和毒种:现状和前景%Cells and seed viruses for production of modern rabies vaccines: current situation and prospects

    Institute of Scientific and Technical Information of China (English)

    王月; 黄思佳

    2012-01-01

    A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines.In contrast to the outdated nervous tissue-based techniques for rabies vaccines production,modem techniques of cell culture provide suitable substrates for virus propagation to produce high titer virus and modem high quality rabies vaccine on a large scale.Given the current scenario of only inactivated vaccines for humans,the vaccines prepared from highly cell-adapted and stable,attenuated rabies viruses are ideal candidates in the future.%对全球狂犬病预防控制的一个主要挑战是不能充分供应廉价优质的狂犬病疫苗.基于神经组织生产狂犬病疫苗的技术早已过时,现代细胞培养技术提供了适当的病毒培养基质,可以获得高滴度病毒和大规模生产高质量的现代狂犬病疫苗.目前人用疫苗仅使用灭活疫苗,用高度适应细胞的稳定的减毒狂犬病病毒生产的疫苗将是未来的理想疫苗.

  15. Comparative costs of the Mouse Inoculation Test (MIT) and Virus Isolation in Cell Culture (VICC) for use in rabies diagnosis in Brazil.

    Science.gov (United States)

    Bones, Vanessa C; Gameiro, Augusto H; Castilho, Juliana G; Molento, Carla F M

    2015-05-01

    The decision to use laboratory animals rather than in vitro methods is frequently based on the financial costs involved, so the objective of our study was to compare the costs of performing the Mouse Inoculation Test (MIT) and Virus Isolation in Cell Culture (VICC) for use in rabies diagnosis in Brazil. Based on observations of laboratory routines at the Pasteur Institute, São Paulo, we listed the fixed cost (FC) and variable cost (VC) items necessary to perform both tests. Considering that 200 MITs are equivalent to 350 VICC assays, in terms of facilities and staff-hours needed per month, we calculated, for both tests, the average total cost per sample, the costs of the implementation of the laboratory structure, and the costs of routine use. With regard to absolute values, the total cost was mainly influenced by FC items, as they represented 60% of the cost for the MIT and 86% of the cost for VICC. A sample analysed by the MIT costs around 205% more than one analysed by using VICC. The MIT costs 74% and 406% more than VICC, when implementation costs and routine use per month, respectively, are taken into account. Our results can assist in the resolution of costing disputes that could hinder the replacement of animals for rabies diagnosis in Brazil. The method demonstrated here might also be useful for cost comparisons in other situations where animal use still continues when validated alternatives exist.

  16. Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation -assay-based diagnostic kit.

    Science.gov (United States)

    Mather, Stuart T; Wright, Edward; Scott, Simon D; Temperton, Nigel J

    2014-12-15

    Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses.

  17. Rabies and bats in a rabies-endemic area of southern Africa: application of two commercial test kits for antigen and antibody detection.

    Science.gov (United States)

    Oelofsen, M J; Smith, M S

    1993-09-01

    In southern Africa, isolates of rabies-related viruses (i.e. Duvenhage virus and Lagos bat virus) have been made from insectivorous and frugivorous bats. As no recent formal bat virus survey has been reported in southern Africa, a survey of bats in rabies-endemic areas was undertaken. Five hundred and forty-seven bats (13 species) were collected from 21 localities in the Orange Free State, Lesotho and the northern Cape Province. None of the 190 bat sera tested using the "Trousse Platelia Rage" ELISA kit (Diagnostic Pasteur), had antibodies to rabies virus glycoprotein G. Rabies virus nucleocapsid antigen was also sought for in the brains of 530 bats (13 species) by means of the "Rapid rabies enzyme immunodiagnosis" (RREID) test (Diagnostics Pasteur). No positive results were obtained. These results show that bats are unlikely to play an important role as hosts of rabies in these parts of Africa, although a low rate of infection cannot be excluded.

  18. Purification and on-column refolding of a single-chain antibody fragment against rabies virus glycoprotein expressed in Escherichia coli.

    Science.gov (United States)

    Xi, Hualong; Yuan, Ruosen; Chen, Xiaoxu; Gu, Tiejun; Cheng, Yue; Li, Zhuang; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2016-10-01

    An anti-rabies virus single-chain antibody fragment of an anti-glycoprotein with the VL-linker-VH orientation, designated scFv57RN, was successfully and conveniently prepared in this study. The scFv57RN protein was mainly expressed in inclusion bodies in Escherichia coli. After washing and purification, the inclusion bodies were finally obtained with an on-column refolding procedure. Further purification by gel exclusion chromatography was performed to remove inactive multimers. About 360 mg of final product was recovered from 1 L of bacterial culture. The final product showed a high neutralizing titer of 950 IU/mg to the CVS-11 strain as measured using the rapid fluorescent focus inhibition test. Our study demonstrated a highly efficient method to mass produce scFV57RN with activity from inclusion bodies, which may be applied in the purification of other insoluble proteins.

  19. Vampire Bat Rabies: Ecology, Epidemiology and Control

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    Nicholas Johnson

    2014-04-01

    Full Text Available Extensive surveillance in bat populations in response to recent emerging diseases has revealed that this group of mammals acts as a reservoir for a large range of viruses. However, the oldest known association between a zoonotic virus and a bat is that between rabies virus and the vampire bat. Vampire bats are only found in Latin America and their unique method of obtaining nutrition, blood-feeding or haematophagy, has only evolved in the New World. The adaptations that enable blood-feeding also make the vampire bat highly effective at transmitting rabies virus. Whether the virus was present in pre-Columbian America or was introduced is much disputed, however, the introduction of Old World livestock and associated landscape modification, which continues to the present day, has enabled vampire bat populations to increase. This in turn has provided the conditions for rabies re-emergence to threaten both livestock and human populations as vampire bats target large mammals. This review considers the ecology of the vampire bat that make it such an efficient vector for rabies, the current status of vampire-transmitted rabies and the future prospects for spread by this virus and its control.

  20. Oral rabies vaccination in north america: opportunities, complexities, and challenges.

    Directory of Open Access Journals (Sweden)

    Dennis Slate

    Full Text Available Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV. Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US

  1. Improvement Control System of Rabies in Ukraine

    Science.gov (United States)

    Nychyk, Serhiy; Zhukorskiy, Ostap; Polupan, Ivan; Ivanov, Mykola; Nikitova, Alina

    2013-01-01

    Objective The purpose of the research was to find out the reasons of rabies antropurgisation in Ukraine. Introduction In Ukraine in spite of considerable financial expenses on oral immunization of foxes and parenteral immunization of dogs and cats, it is not succeeded to reach considerable results in the fight with rabies. Unfortunately there was a negative tendency to increasing a part of dogs and cats in the structure of rabies disease which are the main source of rabies in people. Methods Analysis of 228 anamnesis data of rabies infected dogs during 2008–2012. Research of 234 samples of the blood serum from dogs on existence of antibodies to the rabies virus by the ELISA method. Results Analysis of animal morbidity on rabies in Ukraine in period of 2006–2011 found out the changes of structure of morbidity in animal species that means decreasing a part of wild animals (from 49,0 % in 2006 to 38,7 % in 2011) and increasing a part of dogs (from 18,3 % in 2006 to 23,2 % in 2011) and cats (from 19,8 % in 2006 to 25,0 % in 2011) in the general amount of animals which perished from rabies (Fig. 1). A lot of Ukrainian scientists and doctors of veterinary medicine consider that the main reason of spreading the rabies is a great number of homeless animals which factually are the reservoirs of infection in towns and villages. However, in our opinion spreading of rabies shows the insufficient level of measures of control of rabies among home animals. It was confirmed with conducted analysis that only 26 (12,9 %) dogs were stray, others 202 (87,1 %) had owners, but didn’t get necessary protective rabies vaccination. According to Ukrainian instruction “Preventive measures against rabies of animals”, all the dogs must be vaccinated against rabies, but it actually appears it is quite not so. At research of 234 samples of the blood serum of dogs on existence of antibodies to the rabies virus it was determined that the level of population immunity in dogs is 36,6 % in

  2. Learning about Bats and Rabies

    Science.gov (United States)

    ... About CDC.gov . Rabies Rabies Homepage Share Compartir Learning about bats and rabies Most bats don t ... Monday-Friday Closed Holidays cdcinfo@cdc.gov Bats Learning about bats and rabies Coming in contact with ...

  3. Molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the Philippines.

    Science.gov (United States)

    Tohma, Kentaro; Saito, Mariko; Demetria, Catalino S; Manalo, Daria L; Quiambao, Beatriz P; Kamigaki, Taro; Oshitani, Hitoshi

    2016-03-01

    Rabies is endemic in the Philippines and dog bites are a major cause of rabies cases in humans. The rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. Therefore, more effective and feasible strategies for rabies control are urgently required in the country. To control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously had no reported cases. Our molecular epidemiological study suggests that inter-island transmission events can occur; therefore, we further investigated these inter-island transmission using phylogenetic and modeling approaches. We investigate inter-island transmission between Luzon and Tablas Islands in the Philippines. Phylogenetic analysis and mathematical modeling demonstrate that there was a time lag of several months to a year from rabies introduction to initial case detection, indicating the difficulties in recognizing the initial rabies introductory event. There had been no rabies cases reported in Tablas Island; however, transmission chain was sustained on this island after the introduction of rabies virus because of low vaccination coverage among dogs. Across the islands, a rabies control program should include control of inter-island dog transportation and rabies vaccination to avoid viral introduction from the outside and to break transmission chains after viral introduction. However, this program has not yet been completely implemented and transmission chains following inter-island virus transmission are still observed. Local government units try to control dog transport; however, it should be more strictly controlled, and a continuous rabies control program should be implemented to prevent rabies spread even in rabies-free areas.

  4. 78 FR 33798 - Oral Rabies Vaccine Trial; Availability of a Supplemental Environmental Assessment

    Science.gov (United States)

    2013-06-05

    ... rabies from sources in Mexico, the successful control of gray fox rabies virus variant in western Texas... and Plant Health Inspection Service [Docket No. APHIS-2013-0046] Oral Rabies Vaccine Trial; Availability of a Supplemental Environmental Assessment AGENCY: Animal and Plant Health Inspection...

  5. Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling.

    Science.gov (United States)

    Masatani, Tatsunori; Ozawa, Makoto; Yamada, Kentaro; Ito, Naoto; Horie, Masayuki; Matsuu, Aya; Okuya, Kosuke; Tsukiyama-Kohara, Kyoko; Sugiyama, Makoto; Nishizono, Akira

    2016-02-01

    The P protein of rabies virus (RABV) is known to interfere with the phosphorylation of the host IFN regulatory factor 3 (IRF-3) and to consequently inhibit type I IFN induction. Previous studies, however, have only tested P proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of P proteins from street RABV strains or other lyssaviruses on the IRF-3-mediated type I IFN induction system. In this study, we evaluated the inhibitory effect of P proteins from several RABV strains, including fixed and street virus strains and other lyssaviruses (Lagos bat, Mokola and Duvenhage viruses), on IRF-3 signalling. All P proteins tested inhibited retinoic acid-inducible gene-1 (RIG-I)- and TANK binding kinase 1 (TBK1)-mediated IRF-3-dependent IFN-β promoter activities. On the other hand, the P proteins from the RABV street strains 1088 and HCM-9, but not from fixed strains Nishigahara (Ni) and CVS-11 and other lyssaviruses tested, significantly inhibited I-kappa B kinase ϵ (IKKϵ)-inducible IRF-3-dependent IFN-β promoter activity. Importantly, we revealed that the P proteins from the 1088 and HCM-9 strains, but not from the remaining viruses, interacted with IKKϵ. By using expression plasmids encoding chimeric P proteins from the 1088 strain and Ni strain, we found that the C-terminal region of the P protein is important for the interaction with IKKϵ. These findings suggest that the P protein of RABV street strains may contribute to efficient evasion of host innate immunity.

  6. PREPARATION OF MOUSE ANTI-RABIES VIRUS PHOSPHOPROTEIN MONOCLONAL ANTIBODIES AND APPLICATION%狂犬病病毒磷蛋白单抗的制备与应用

    Institute of Scientific and Technical Information of China (English)

    米立娟; 张守峰; 刘晔; 王述超; 扈荣良

    2014-01-01

    Four monoclonal antibodies against Rabies virus phosphoprotein were produced by immunization with Rabies virus strain CVS in BALB/c mice. After fusion, antibodies in the supernatant of the hybrid cells were respectively detected by ELISA test and western-blot method. Four hybrid cells secreting antibody binding to rabies virus , i.e. 1C9, 4B10, 2G12 and4G5 strains. The 1C9 monoclonal lgG antibody was purified by affinity chromatography method and then labeled with FITC. 501 brain samples collected from ferret badgers, bats, dogs and weasels were detected using the labeled 1C9 antibody and FITC-labeled rabies virus N protein-specific monoclonal antibody (made in our laboratory). The results showed that the labeled 1C9 antibody can detect rabies-related lyssaviruses isolated in China including Rabies virus and Irkut virus, however, the N protein-specific monoclonal antibody only can detect Rabies virus. It suggests that the labeled 1C9 antibody can be used as a rabies diagnostic reagent in China.%以灭活的狂犬病病毒CVS株细胞毒免疫BALB/c小鼠,通过间接ELISA法和Western-blot筛选获得针对磷蛋白的单克隆抗体4株:1C9、4B10、2G12、4G5,其中1C9针对氨基端保守表位。以亲和层析法纯化1C9单抗腹水,异硫氰酸荧光黄标记制备荧光抗体。以1C9磷蛋白荧光抗体与本实验室研制的狂犬病核蛋白免疫荧光抗原检测试剂盒,对本实验室收集的501份疑似狂犬病鼬獾、蝙蝠、犬和黄鼬的脑组织样品进行直接免疫荧光平行检测。结果显示,两种检测手段对基因1型狂犬病毒的检出结果完全一致,而蝙蝠源Irkut病毒仅能以磷蛋白单抗1C9检出。本研究成功获得了与我国现有不同基因型狂犬病毒良好反应的抗狂犬病磷蛋白单抗,并应用于狂犬病的直接免疫荧光检测,为狂犬病诊断提供了敏感性和可靠性良好的诊断试剂。

  7. Demonstration of non-infectious hemagglutinating particles of rabies virus and isolation of the hemagglutinin by disruption of the virion with Nonidet P-40.

    Science.gov (United States)

    Arai, Y T; Kondo, A; Suzuki, K

    1976-01-01

    Non-infectious hemagglutinating particles of rabies virus accumulated in the fluid phase of chick embryo cell cultures at 6 days post-infection, though they were undetectable at 4 days. They were characterized as looped filaments resembling viral envelope as revealed by electron microscopy. Another form of hemagglutinin (HAnin) was obtained by solubilization of partially purified virions with Nonidet P-40 (NP-40) followed by successive high speed and CsCl density gradient centrifugations. The density of the isolated HAnin averaged 1.28 g/cm3. SDS-polyacrylamide gel electrophoresis of the HAnin demonstrated that it was mainly composed of a glycoprotein (G) with a molecular weight of 83,000. Electron microscopically, it differed from the above non-infectious hemagglutinating particles, being much smaller in size and showing a star- or rosette-like appearance with a diameter of about 25 nm, composed of a central particle surrounded by particles resembling envelope-spikes. Virus-neutralizing (VN) and hemagglutination inhibiting (HI) antibodies were produced in rabbits immunized with the HAnin isolated from virions.

  8. Rabies virus infection induces type I interferon production in an IPS-1 dependent manner while dendritic cell activation relies on IFNAR signaling.

    Science.gov (United States)

    Faul, Elizabeth J; Wanjalla, Celestine N; Suthar, Mehul S; Gale, Michael; Wirblich, Christoph; Schnell, Matthias J

    2010-07-22

    As with many viruses, rabies virus (RABV) infection induces type I interferon (IFN) production within the infected host cells. However, RABV has evolved mechanisms by which to inhibit IFN production in order to sustain infection. Here we show that RABV infection of dendritic cells (DC) induces potent type I IFN production and DC activation. Although DCs are infected by RABV, the viral replication is highly suppressed in DCs, rendering the infection non-productive. We exploited this finding in bone marrow derived DCs (BMDC) in order to differentiate which pattern recognition receptor(s) (PRR) is responsible for inducing type I IFN following infection with RABV. Our results indicate that BMDC activation and type I IFN production following a RABV infection is independent of TLR signaling. However, IPS-1 is essential for both BMDC activation and IFN production. Interestingly, we see that the BMDC activation is primarily due to signaling through the IFNAR and only marginally induced by the initial infection. To further identify the receptor recognizing RABV infection, we next analyzed BMDC from Mda-5-/- and RIG-I-/- mice. In the absence of either receptor, there is a significant decrease in BMDC activation at 12h post infection. However, only RIG-I-/- cells exhibit a delay in type I IFN production. In order to determine the role that IPS-1 plays in vivo, we infected mice with pathogenic RABV. We see that IPS-1-/- mice are more susceptible to infection than IPS-1+/+ mice and have a significantly increased incident of limb paralysis.

  9. Genetic analysis of glycoprotein genes derived from the rabies virus epidemic in Guangxi%广西流行狂犬病毒糖蛋白基因的遗传性分析

    Institute of Scientific and Technical Information of China (English)

    杨健; 罗廷荣; 张红普; 章民; 李晓宁; 何晓霞; 谢琳娟; 陆专灵; 韦显凯; 唐海波

    2012-01-01

    In order to understand the epidemic trend and genetic variation of rabies disease in Guangxi and to provide relevant prevention and control strategies, the glycoprotein (G) gene sequences, isolated from Guangxi rabies virus strains, were studied and analyzed. [Method]From Oct. 2000 to Oct. 2007, 1569 samples of animal brain tissues collected from 14 cities of Guangxi were used to isolate and detect rabies virus by RT桺CR and Mouse Intracerebral Inoculation Test, then they were sequenced according to procedure. [Result]The results showed that 26 wild strains of rabies were collected from different areas of Guangxi; out of the strains, 23 belonged to dogs, 1 belonged to cattle, 1 belonged to swine, and 1 belonged to cat. The whole length of the nucleotide of rabies virus G gene was 2067 bp, and the open reading frame was 1575 bp, which encoded 524 amino acid. According to homology and evolutionary tree analysis results, the isolated Guangxi rabies virus G genes were divided into three gene-groups, namely groups I (15 strains), II (10 strains), and III (1 strains). The nucleotide homology rates of groups I and II were 97.7-99.9% and 98.0-99.9%, respectively. Amino acid mutation sites of glycoprotein encoded by rabies virus G genes in 26 wild strains were obtained by analyzing the amino acid variation. [Conclusion]There were three groups of rabies virus virulent strains, of which groups I and II were more common. The amino acid variations in each of the three groups were significantly specified.%[目的]通过测定广西流行狂犬病毒糖蛋白(G)基因的全序列,了解广西狂犬病的流行趋势和遗传变异规律,为制定广西狂犬病的防控策略提供科学依据.[方法]2000年10月~2007年10月,从广西14个市采集1569份动物脑组织,经RT-PCR检测及小白鼠脑内接种试验分离狂犬病毒,然后对狂犬病毒G基因进行测序分析.[结果]从广西各地共分离获得26株狂犬病毒野毒株,其中犬23

  10. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Z.Q. [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Greenberg, L. [Centers for Disease Control and Prevention, Atlanta, GA (United States); Ertl, H.C., E-mail: ertl@wistar.upenn.edu [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Rupprecht, C.E. [The Global Alliance for Rabies Control, Manhattan, KS (United States); Ross University School of Veterinary Medicine, Basseterre (Saint Kitts and Nevis)

    2014-02-15

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.

  11. 狂犬病病毒磷蛋白在杆状病毒系统的表达及鉴定%EXPRESSION AND CHARACTERIZATION OF PHOSPHOPROTEIN OF RABIES VIRUS IN BACULOVIRUS

    Institute of Scientific and Technical Information of China (English)

    许运斌; 徐洁萍; 张金阳; 昝洁; 阮系真; 周继勇

    2012-01-01

    为了建立狂犬病毒磷蛋白(phosphoprotein,P)的体外表达系统,本研究将RT-PCR扩增的狂犬病病毒ERA株P蛋白基因克隆于杆状病毒转移载体pFastBacHTA,构建重组质粒pFastBacHTA-P,并转染昆虫细胞Sf9包装形成重组杆状病毒。SDS-PAGE分析显示重组质粒pFastBacHTA-P转染的Sf9细胞中出现了分子量约为42 kDa的蛋白条带,Western blot证实分子量约为42 kDa的蛋白能与抗His的单克隆抗体发生特异性反应,间接免疫荧光(indirect immunofluorescence assay,IFA)分析进一步显示Sf9细胞表达的P蛋白与抗P蛋白单克隆抗体能特异性结合。这些实验证明,狂犬病病毒P蛋白不仅在Sf9细胞中获得表达,而且具有良好的免疫反应性。狂犬病病毒P蛋白杆状病毒表达体系的建立,为蛋白结构的解析和诊断试剂的研制奠定了基础。%To construct an in vitro expression system of phosphoprotein of Rabies virus ERA strain,the phosphoprotein gene was amplified in RT-PCR and cloned into the baculovirus vector pFastBacHTA.The recombinant baculovirus expressing phosphoprotein was obtained by transfecting the resulting plasmid into Sf9 cells.The phosphoprotein expressed in Sf9 cells was detected to be a 42 kDa protein as determined in SDS-PAGE and Western blot using anti-His monoclonal antibody.Furthermore,the expressed phosphoprotein was recognized in immunofluorescence assay using monoclonal antibody against phosphoprotein of Rabies virus.These results confirmed that the phosphoprotein of Rabies virus was expressed in Sf9 cells and retained its immunoreactivity.The expression of phosphoprotein of Rabies virus in baculovirus expression system provided a tool for structural analysis and development of diagnostic reagent for Rabies virus.

  12. Detection of rabies virus antigen in 134 dog brain samples in Lishui%浙江省丽水山区134份犬脑组织狂犬病病毒抗原检测

    Institute of Scientific and Technical Information of China (English)

    雷永良; 梅建华; 陈秀英; 王晓光; 叶碧峰; 柳付明; 叶夏良; 兰进权; 林仁卫; 梅盛华

    2009-01-01

    Objective To investigate the infection status of rabies virus in dogs by detecting the virus antigen in dog brain samples in the mountain area in Lishui, Zhejiang province. Methods A total of 134 brain samples from the sick dogs, the suspected sick dogs and the dogs looking health were taken, and the virus antigen was detected by using direct fluorescent antibody method (DFA). Results Nine samples were positive, accounting for 6.72% (9/134), and eight were from the dogs which looked abnormal and bit people or other dogs causing human or dog rabies. Among 126 brain samples of the dogs looking health, one was positive with the positive rate of 0.79% (1/126). Conclusion It was the first time to use DFA to detect rabies virus in Lishui, which indicated that rabies virus transmitted in dogs in the endemic area and the dog rabies epidemic was in expansion.%目的 对浙江省丽水市山区犬脑组织标本进行狂犬病病毒抗原检测,了解犬狂犬病毒感染状况.方法 收集丽水市山区狂犬病和疑似狂犬病犬以及外观健康犬脑组织标本134份,用直接免疫荧光试验(DFA)检测狂犬病病毒抗原,确定阳性标本.结果 134份犬脑组织标本印片DFA检测9份为阳性,占所检标本的6.72%(9/134),其中外观异常并攻击人/犬导致人或犬间疫情的犬脑组织标本8份,均阳性;外观正常犬脑组织标本共126份,1份阳性,阳性率0.79%(1/126).结论 在丽水市首次用免疫学方法进行狂犬病病毒的实验室检测,狂犬病病毒在丽水山区狂犬病疫区的犬间相互传播,犬狂犬病疫情存在扩散的现象.

  13. Rabies in the arctic fox population, Svalbard, Norway.

    Science.gov (United States)

    Mørk, Torill; Bohlin, Jon; Fuglei, Eva; Åsbakk, Kjetil; Tryland, Morten

    2011-10-01

    Arctic foxes, 620 that were trapped and 22 found dead on Svalbard, Norway (1996-2004), as well as 10 foxes trapped in Nenets, North-West Russia (1999), were tested for rabies virus antigen in brain tissue by standard direct fluorescent antibody test. Rabies antigen was found in two foxes from Svalbard and in three from Russia. Blood samples from 515 of the fox carcasses were screened for rabies antibodies with negative result. Our results, together with a previous screening (1980-1989, n=817) indicate that the prevalence of rabies in Svalbard has remained low or that the virus has not been enzootic in the arctic fox population since the first reported outbreak in 1980. Brain tissues from four arctic foxes (one from Svalbard, three from Russia) in which rabies virus antigen was detected were further analyzed by reverse-transcriptase polymerase chain reaction direct amplicon sequencing and phylogenetic analysis. Sequences were compared to corresponding sequences from rabies virus isolates from other arctic regions. The Svalbard isolate and two of the Russian isolates were identical (310 nucleotides), whereas the third Russian isolate differed in six nucleotide positions. However, when translated into amino acid sequences, none of these substitutions produced changes in the amino acid sequence. These findings suggest that the spread of rabies virus to Svalbard was likely due to migration of arctic foxes over sea ice from Russia to Svalbard. Furthermore, when compared to other Arctic rabies virus isolates, a high degree of homology was found, suggesting a high contact rate between arctic fox populations from different arctic regions. The high degree of homology also indicates that other, and more variable, regions of the genome than this part of the nucleoprotein gene should be used to distinguish Arctic rabies virus isolates for epidemiologic purposes.

  14. Natural Rabies Infection in a Domestic Fowl (Gallus domesticus: A Report from India.

    Directory of Open Access Journals (Sweden)

    Julie Baby

    Full Text Available Rabies is a fatal encephalitis caused by viruses belonging to the genus Lyssavirus of the family Rhabdoviridae. It is a viral disease primarily affecting mammals, though all warm blooded animals are susceptible. Experimental rabies virus infection in birds has been reported, but naturally occurring infection of birds has been documented very rarely.The carcass of a domestic fowl (Gallus domesticus, which had been bitten by a stray dog one month back, was brought to the rabies diagnostic laboratory. A necropsy was performed and the brain tissue obtained was subjected to laboratory tests for rabies. The brain tissue was positive for rabies viral antigens by fluorescent antibody test (FAT confirming a diagnosis of rabies. Phylogenetic analysis based on nucleoprotein gene sequencing revealed that the rabies virus strain from the domestic fowl belonged to a distinct and relatively rare Indian subcontinent lineage.This case of naturally acquired rabies infection in a bird species, Gallus domesticus, being reported for the first time in India, was identified from an area which has a significant stray dog population and is highly endemic for canine rabies. It indicates that spill over of infection even to an unusual host is possible in highly endemic areas. Lack of any clinical signs, and fewer opportunities for diagnostic laboratory testing of suspected rabies in birds, may be the reason for disease in these species being undiagnosed and probably under-reported. Butchering and handling of rabies virus- infected poultry may pose a potential exposure risk.

  15. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    Directory of Open Access Journals (Sweden)

    James E Norton

    Full Text Available We have previously shown that live-attenuated rabies virus (RABV-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1 to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1, on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1. We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV, rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3 focus forming units (ffu/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a

  16. The spatiotemporal expansion of human rabies and its probable explanation in mainland China, 2004-2013.

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    Hong-Wu Yao

    2015-02-01

    Full Text Available Human rabies is a significant public health concern in mainland China. However, the neglect of rabies expansion and scarce analyses of the dynamics have made the spatiotemporal spread pattern of human rabies and its determinants being poorly understood.We collected geographic locations and timeline of reported human rabies cases, rabies sequences and socioeconomic variables for the years 2004-2013, and integrated multidisciplinary approaches, including epidemiological characterization, hotspots identification, risk factors analysis and phylogeographic inference, to explore the spread pattern of human rabies in mainland China during the last decade.The results show that human rabies distribution and hotspots were expanding from southeastern regions to north or west regions, which could be associated with the evolution of the virus, especially the clade I-G. A Panel Poisson Regression analysis reveals that human rabies incidences had significant correlation with the education level, GDP per capita, temperature at one-month lag and canine rabies outbreak at two-month lag.The reduction in the overall human rabies incidence was accompanied by a westward and northward expansion of the circulating region in mainland China. Higher risk of human rabies was associated with lower level of education and economic status. New clades of rabies, especial Clade I-G, played an important role in recent spread. Our findings provide valuable information for rabies control and prevention in the future.

  17. Organization of multisynaptic inputs to the dorsal and ventral dentate gyrus: retrograde trans-synaptic tracing with rabies virus vector in the rat.

    Directory of Open Access Journals (Sweden)

    Shinya Ohara

    Full Text Available Behavioral, anatomical, and gene expression studies have shown functional dissociations between the dorsal and ventral hippocampus with regard to their involvement in spatial cognition, emotion, and stress. In this study we examined the difference of the multisynaptic inputs to the dorsal and ventral dentate gyrus (DG in the rat by using retrograde trans-synaptic tracing of recombinant rabies virus vectors. Three days after the vectors were injected into the dorsal or ventral DG, monosynaptic neuronal labeling was present in the entorhinal cortex, medial septum, diagonal band, and supramammillary nucleus, each of which is known to project to the DG directly. As in previous tracing studies, topographical patterns related to the dorsal and ventral DG were seen in these regions. Five days after infection, more of the neurons in these regions were labeled and labeled neurons were also seen in cortical and subcortical regions, including the piriform and medial prefrontal cortices, the endopiriform nucleus, the claustrum, the cortical amygdala, the medial raphe nucleus, the medial habenular nucleus, the interpeduncular nucleus, and the lateral septum. As in the monosynaptically labeled regions, a topographical distribution of labeled neurons was evident in most of these disynaptically labeled regions. These data indicate that the cortical and subcortical inputs to the dorsal and ventral DG are conveyed through parallel disynaptic pathways. This second-order input difference in the dorsal and ventral DG is likely to contribute to the functional differentiation of the hippocampus along the dorsoventral axis.

  18. A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi [Yisheng Biopharma. Co., Ltd., Beijing (China); Zhang, Shoufeng [Academy of Military Medical Sciences, Changchun (China); Li, Wei [National Center for Safety Evaluation of Drugs, Beijing (China); Hu, Yuchi; Zhao, Jinyan [Beijing Institute for Drug Control, Beijing (China); Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu [Yisheng Biopharma. Co., Ltd., Beijing (China); Hu, Rongliang, E-mail: ronglianghu@hotmail.com [Academy of Military Medical Sciences, Changchun (China); Shao, Hui, E-mail: hui.shao@yishengbio.com [Yisheng Biopharma. Co., Ltd., Beijing (China); Li, Lietao, E-mail: lietao.li@gmail.com [Yisheng Biopharma. Co., Ltd., Beijing (China)

    2016-02-15

    Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

  19. 河南省九株狂犬病毒的糖蛋白基因序列分析%Study on glycoprotein gene sequences of nine rabies virus isolates in Henan Province

    Institute of Scientific and Technical Information of China (English)

    熊成龙; 邵中军; 魏纪东; 居丽雯; 周联娣; 姜庆五

    2010-01-01

    目的 了解河南省狂犬病毒与人用、兽用狂犬病疫苗株在糖蛋白基因核苷酸和氨基酸序列水平上的差异,为有效控制狂犬病疫情提供初步的科学依据.方法 以反转录-半套式聚合酶链反应(RT-heminested-PCR)扩增2006年12月分离自河南省信阳市的9株狂犬病毒街毒株,经纯化、克隆、测序后获得9条糖蛋白基因全长序列,采用生物信息学软件构建基因系统发育树,对糖蛋白基因序列和氨基酸序列进行分析.结果 9株狂犬病毒糖蛋白在核苷酸及氨基酸序列水平上彼此的同源性分别为97.6%~98.9%和99.2%~99.8%;9株病毒与CTN疫苗的同源性最高,其核苷酸及氨基酸同源性分别为85.6%~93.0%和91.9%~92.9%;9株病毒与其他疫苗株相比,其核苷酸及氨基酸同源性分别为80.4%~83.3%和87.7%~92.5%;与已知的基因1型狂犬病毒比较,9株病毒糖蛋白氨基酸序列发生了若干位点的氨基酸取代.结论 9株河南省狂犬病毒街毒株均属基因1型,CTN疫苗株可能为目前我国河南省所流行的狂犬病提供较好的保护效果.%Objective To understand the nucleotide and amino acid differences of glycoprotein gene (G gene) between isolated rabies viruses in Henan Province and rabies vaccine strains used for human and animals. Methods G gene sequences of nine rabies viruses isolated from dogs in Xinyang city of Henan Province in December 2006 were amplified by reverse transcriptase (RT)-heminestedpolymerase chain reaction (PCR), and then were cloned and sequenced. The phylogenetic trees were constructed for analyzing the genetic characteristics of these rabies viruses. Results The homology of G gene among the nine isolates from Henan Province was 97.6% - 98.9% at nucleotide level and 99.2%-99.8% at amino acid level. The similarities between these isolates and CTN vaccine strain were 85.6%-93.0% and 91.9%-92.9% at nucleotide and amino acid level, respectively, which were higher than those

  20. DIAGNOSTIC AND MEDICAL TREATMENT OF RABIES DISEASE IN HEALTH CENTER OF COMMUNITY

    Directory of Open Access Journals (Sweden)

    Raflizar Raflizar

    2012-11-01

    Full Text Available In Indonesia, Rabies is still considered as the most common zoonotic disease. It is not due to the number of death cases but to the number of human cases of human bitten by rabies virus infected animals or suspected ones. Most of human rabies cases caused by dog bites, besides cat and monkey bites. If rabies can be eliminated from dogs, rabies in cats and monkeys can also be eliminated as spontaneous rabies in these two animals are rare. Rabies is caused by an RNA virus from Rhabdowidae Family and it attacks the central nervous system. It is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms in unvaccinated people Diagnose is based on the history of close contacts to infected saliva (via bites or scratches and development of signs and symptoms. The early stage symptoms are fever. malaise, followed by agitation, abnormal behaviours, anxiety, hallucination, progressing to delirium, hypersalivalion, hydrophobia, aerophobia, neurological symptoms such as pharynx spasm. paralysis, seizure, and finally death. Laboratory test to detect rabies virus in saliva can be done by a Reverse transcription followed by Polymerase Cham Reaction (RT/PCR and virus isolation in cultured tissues. Skin biopsies of hair follicles at nape of the neck are exammed for rabies antigen in cutaneous nerves at the base of hair follicles by immunofluoresence staining. The treatment after exposure are cleansing lesion, administering intradermal anti-rabies immunization to accelerate immune response. anti-rabies serum to stop infection process, intravenous and intraventricular ribavirin and alfa interferon, high concentration of ketamine infusion to inhibit rabies virus replication. At last, vaccination is the best prevention. Key words: rabies, RNA-virus, vaccination, diagnosis, treatment

  1. Rabies virus infection induces type I interferon production in an IPS-1 dependent manner while dendritic cell activation relies on IFNAR signaling.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Faul

    Full Text Available As with many viruses, rabies virus (RABV infection induces type I interferon (IFN production within the infected host cells. However, RABV has evolved mechanisms by which to inhibit IFN production in order to sustain infection. Here we show that RABV infection of dendritic cells (DC induces potent type I IFN production and DC activation. Although DCs are infected by RABV, the viral replication is highly suppressed in DCs, rendering the infection non-productive. We exploited this finding in bone marrow derived DCs (BMDC in order to differentiate which pattern recognition receptor(s (PRR is responsible for inducing type I IFN following infection with RABV. Our results indicate that BMDC activation and type I IFN production following a RABV infection is independent of TLR signaling. However, IPS-1 is essential for both BMDC activation and IFN production. Interestingly, we see that the BMDC activation is primarily due to signaling through the IFNAR and only marginally induced by the initial infection. To further identify the receptor recognizing RABV infection, we next analyzed BMDC from Mda-5-/- and RIG-I-/- mice. In the absence of either receptor, there is a significant decrease in BMDC activation at 12h post infection. However, only RIG-I-/- cells exhibit a delay in type I IFN production. In order to determine the role that IPS-1 plays in vivo, we infected mice with pathogenic RABV. We see that IPS-1-/- mice are more susceptible to infection than IPS-1+/+ mice and have a significantly increased incident of limb paralysis.

  2. Detection and analysis of rabies street virus in animals in China%我国各地区动物狂犬病街毒的检测及分析

    Institute of Scientific and Technical Information of China (English)

    徐葛林; 严家新; 张永振; 董关木; 唐建蓉; 杨晓明; 孟胜利; 吴杰; 肖奇友; 周敦金; 朱凤才; 王萍; 王定明; 明平刚

    2008-01-01

    目的 检测我国不同地区动物中狂犬病毒带毒率并分析糖蛋白编码基因序列.方法 El.ISA、免疫荧光法分别检测586份采集自中国不同地区的犬、猫,蝙蝠和野鼠脑标本和16份犬唾液中狂犬病街毒,阳性标本乳鼠颅内接种.并测序.结果 ELISA、免疫荧光法均在犬脑中分离到10株狂犬病街毒,其中贵州省113份犬脑中分离到2株病毒,湖南省62份犬脑中分离到2株病毒,武汉市70份犬脑中分离到2株病毒,江苏省85份犬脑中分离到4株病毒,沈阳市69份犬脑中未分离到狂犬病毒;79份猫脑、100份蝙蝠脑及8份鼠脑中未检出狂犬病街毒,16份犬唾液标本未检出狂犬病毒.在贵州省和武汉市,冬季采集的112份犬脑末检出狂犬病毒.春夏季采集的40份犬脑中,4份阳性.分离的10株狂犬病毒阳性株颅内接种乳鼠后.均发病死亡.所有分离株均属狂犬病毒基因1型,可分为4个亚组.结论 同一地区的狂犬病毒分离株以及相邻省份的狂犬病毒分离株的同源性十分接近,动物样本采集时间与狂犬病毒阳检率有关.%Objective To detect the positive rate of rabies virus in animals of different regions in China and to analyze the sequences of glycoprotein encoding gene.Methods Rabies street viruses were detected in 586 brain samples of dogs,cats,bats,mice and 16 saliva samples of dogs from different regions in China using enzyme-linked immunosorbent assay(ELISA)and immunofluorescent assay (IFA).Positive samples were inoculated intracranially to neonate rats and then sequenced.Results Ten street virus strains were isolated from dog brains using ELISA and IFA,in which 2 positive of 113 in Guizhou Province,2 positive of 62 in Hunan Province,2 positive of 70 in Wuban city,4 positive of 85 in Jiangsu Province,and no positive of 69 in Shenyang city.There was no detectable rabies virus in brains of 79 cats,100 bats,8 mice and in 16 saliva samples.One hundred and twelve brain samples

  3. 浙江省不同宿主来源狂犬病病毒N基因分子特征分析%Sequencing and analysis of N gene of street rabies virus isolated from different hosts in Zhejiang province

    Institute of Scientific and Technical Information of China (English)

    王晓光; 雷永良; 陶晓燕; 李浩; 申辛欣; 于鹏程; 尹翠萍; 孟胜利; 王欣莹

    2014-01-01

    目的 测定浙江省不同宿主(人、鼬獾、犬)来源的狂犬病病毒街毒株N基因序列,分析病毒遗传变异特征及其与流行的关系.方法 采用直接免疫荧光试验和反转录聚合酶链式反应检测狂犬病病毒阳性标本N基因核苷酸序列,利用生物信息学软件分析基因序列和编码蛋白.结果 共获得浙江省2个人源、5个鼬獾源和11个犬源狂犬病病毒街毒株N基因核苷酸序列,18个核苷酸和氨基酸序列同源性在89.7%~ 100.0%和98.4%~ 100.0%,N蛋白一级结构上绝大部分为稳定区域,编码基因的核苷酸变异多为无义突变,系统发育分析显示18个街毒株均属于传统的基因1型.结论 浙江省不同宿主来源狂犬病病毒的流行具有地域性特征,同类宿主动物病毒株或来自同一县域/相邻县域的毒株在地理位置上最为近缘,但人源株病毒更具有复杂性.浙江省狂犬病病毒街毒株的流行具有通过犬向鼬獾和人传播,并在犬、鼬獾中跨区域循环传播的特点.%Objective To elucidate the characteristics of genetic variability and its relationship with prevalence,through sequencing and analysis of N gene among street rabies virus isolated from different hosts (homo sapiens,ferret badger,dog) in Zhejiang province.Methods Samples were screened and confirmed by direct fluorescence assay and reverse transcript PCR.Sequences were analyzed using bio-information software.Results Eighteen street rabies virus strains were identified,including 2 from homo sapiens,5 from ferret badger,and 11 from dog.Similarities of N gene and N protein were calculated to be 89.7%-100.0% and 98.4%-100.0% respectively.Mutations occurred in N gene were almost non-sense mutations.In addition,Data from phylogenetic analysis showed that all these strains could be classified into traditional genotype 1.Conclusion The prevalence of rabies viruses among different hosts in Zhejiang province had certain regional

  4. A new outbreak of fox rabies at the Russian–Mongolian border

    Institute of Scientific and Technical Information of China (English)

    Renat; V.Adelshin; Olga; V.Melnikova; Yulia; N.Trushina; Alexander; D.Botvinkin; Tatyana; I.Borisova; Evgeny; I.Andaev; Dmitry; B.Verzhutsky; Albert; S.Khangazhinov; Sergey; V.Balakhonov

    2015-01-01

    Dear Editor,Lake Baikal and its neighboring territories are an intermediate zone for the"steppe"and"arctic-like"rabies virus lineages in Russia.After the elimination of dog-mediated rabies during the early 1980s,this area remained rabies-free for over 25–30 years.A sudden reappearance of rabies occurred in this zone in the Republic of Buryatia in 2011–2012.A marginal part of the Mongolian steppe penetrates the Siberian taiga forests in this area,and human and animal rabies have been repeatedly recorded in the Republic of Buryatia from the end of the

  5. Rabies in translocated raccoons.

    Science.gov (United States)

    Nettles, V F; Shaddock, J H; Sikes, R K; Reyes, C R

    1979-01-01

    Two raccoons imported from Florida by a North Carolina hunting club were diagnosed as having rabies by fluorescent antibody testing of brain tissue. Although dead on arrival in North Carolina, they could have infected other raccoons in the same shipment which had already been released into the wild. Raccoon rabies has become increasingly important in recent years, but this is the first documented report of rabies presence in hunter-purchased interstate shipments. PMID:443502

  6. Rabbit anti-rabies immunoglobulins production and evaluation.

    Science.gov (United States)

    Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

    2011-04-01

    Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

  7. 稳定表达狂犬病病毒CTN-1V株糖蛋白细胞系的建立%Study on the mammalian cell lines of stable expression glycoprotein of rabies virus CTN-1V strain

    Institute of Scientific and Technical Information of China (English)

    曹守春; 李玉华; 李加; 唐建蓉; 石磊泰; 刘景华; 王云鹏; 俞永新; 董关木

    2013-01-01

    目的 构建能稳定表达狂犬病病毒糖蛋白的CHO细胞系.方法 用RT-PCR法扩增和分离CTN-1V株狂犬病毒糖蛋白基因,测序后克隆入pCDNA5.0FRT载体,构建重组质粒pCDNA5.0FRT-G,之后与POG44质粒共转染CHO细胞,采用潮霉素B抗性筛选,挑选阳性克隆,间接免疫荧光和Western Blot进行稳定表达细胞系的鉴定.结果 经酶切和测序鉴定,获得重组表达质粒pCDNA5.0FRT-G,共转染CHO细胞后,获得肉眼可见阳性细胞克隆,刮取阳性克隆进行传代扩大培养并定义为第2代,经过10代后免疫荧光和Western Blot结果依然阳性.结论 成功建立稳定表达狂犬病病毒糖蛋白的CHO细胞系,为深入研究糖蛋白的功能奠定基础.%Objective To build the mammalian cell line of stable expression of rabies virus glycoprotein.Methods A amplified rabies virus glycoprotein gene of CTN-1V strain by RT-PCR method,and cloned into pCDNA5.0 FRT plasmid.Transfected the recombinant pCDNAS.0 FRT-G plasmid into CHO cells with POG44 together.Selection screens the positive cell with hygromycin B resistance.Identify the cell which stable express rabies virus glycoprotein with indirect immunofluorescence and Western Blot.Results Recombinant expression plasmid pCDNA5.0 FRT-G was successfully reconstruct by identification with enzyme digestion and sequencing.Get the visible positive cell clones,scraping into 96 well,it's the first passage.Subculture with 10 passages,the results of immunofluorescence and Western Blot were still positive.Conclusion Successfully established the stable expression of rabies virus glycoprotein CHO cell lines,and it's helpful to further study on the function of glycoprotein.

  8. Spatio-temporal Analysis of the Genetic Diversity of Arctic Rabies Viruses and Their Reservoir Hosts in Greenland

    DEFF Research Database (Denmark)

    Hanke, Dennis; Freuling, Conrad M.; Fischer, Susanne

    2016-01-01

    arctic RABV full genome sequences from Greenland, Canada, USA (Alaska) and Russia obtained between 1977 and 2014, a description of the historic context in relation to the genetic diversity of currently circulating RABV in Greenland and neighboring Canadian Northern territories has been provided...... containing viruses from both Greenland and Canada. By combining analysis of full length RABV genome sequences and host derived sequences encoding mitochondrial proteins obtained simultaneously from brain tissues of 49 arctic foxes, the interaction of viruses and their hosts was explored in detail...

  9. Modeling the transmission dynamics and control of rabies in China.

    Science.gov (United States)

    Ruan, Shigui

    2017-04-01

    Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Rabid epidemiologies: the emergence and resurgence of rabies in twentieth century South Africa.

    Science.gov (United States)

    Brown, Karen

    2011-01-01

    This article discusses the history of rabies in South Africa since the early twentieth century. It argues that rabies is a zoonotic disease that traverses rural and urban spaces, that transfers itself between wild and domestic animals and remains a potential threat to human life in the region. Scientists discovered an indigenous form of rabies, found primarily in the yellow mongoose, after the first biomedically confirmed human fatalities in 1928. Since the 1950s canine rabies, presumed to have moved southwards from across the Zambezi River, has become endemic also. South Africa is home to a comparatively large number of rabies strains and animal carriers, making it a particularly interesting case study. Environmental changes during the colonial and apartheid periods have helped to explain the increase in rabies cases since the mid-twentieth century. Moreover, developments in the biological and ecological sciences have provided insights into why the rabies virus has become endemic in certain wildlife species.

  11. Host and viral ecology determine bat rabies seasonality and maintenance.

    Science.gov (United States)

    George, Dylan B; Webb, Colleen T; Farnsworth, Matthew L; O'Shea, Thomas J; Bowen, Richard A; Smith, David L; Stanley, Thomas R; Ellison, Laura E; Rupprecht, Charles E

    2011-06-21

    Rabies is an acute viral infection that is typically fatal. Most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e.g., raccoons and foxes). As such, rabies in bats has been largely neglected until recently. Because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including SARS-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. Unfortunately, little is known about maintenance mechanisms for any pathogen in bat populations. We present a mathematical model parameterized with unique data from an extensive study of rabies in a Colorado population of big brown bats (Eptesicus fuscus) to elucidate general maintenance mechanisms. We propose that life history patterns of many species of temperate-zone bats, coupled with sufficiently long incubation periods, allows for rabies virus maintenance. Seasonal variability in bat mortality rates, specifically low mortality during hibernation, allows long-term bat population viability. Within viable bat populations, sufficiently long incubation periods allow enough infected individuals to enter hibernation and survive until the following year, and hence avoid an epizootic fadeout of rabies virus. We hypothesize that the slowing effects of hibernation on metabolic and viral activity maintains infected individuals and their pathogens until susceptibles from the annual birth pulse become infected and continue the cycle. This research provides a context to explore similar host ecology and viral dynamics that may explain seasonal patterns and maintenance of other bat-borne diseases.

  12. Burden of Rabies

    Science.gov (United States)

    ... wild animal acting strangely, report it to animal control. If you or someone in your family is exposed to a rabid animal, rabies can be prevented through a series of shots called rabies post-exposure prophylaxis (PEP) . If you are bitten by any animal (domestic ...

  13. 福建省狂犬病毒街毒株分离鉴定及生物学特性研究%Biological characterizations of street strain of rabies virus in Fujian Province,China

    Institute of Scientific and Technical Information of China (English)

    张建明; 邓艳琴; 王灵岚; 林代华; 杨秀惠; 严延生

    2014-01-01

    In this study ,street trains were isolated from brain of suspected rabid dogs via mouse inoculation technique (MIT) and cell culture inoculation technique (CIT) .Virus was identified by FAT ,RT-PCR and sequencing .Then ,the virus’ biological characteristics were analysed .The TCID50 test results demonstrated that viral titers were not high ,which showed the BHK-21 cells was not the best host cell of rabies viral strain .The LD50 test results showed it was a strong strain of rabies virus .These results laid a strong foundation for rabies laboratory research in Fujian .%目的:分离福建省狂犬病毒街毒株,了解病毒株的生物学特性。方法采集疑似狂犬的脑组织,通过细胞培养和乳鼠脑接种分离狂犬病毒,用直接免疫荧光和RT-PCR等方法进行鉴定,并对病毒的分子生物学特性进行研究。结果从疑似狂犬的脑组织中分离出狂犬病毒,TCID50的测定结果显示,细胞毒滴度不高,病毒株对BHK-21细胞的适应性不强,LD50的测定结果显示,病毒株为狂犬病毒强毒株。结论从福建省家犬中成功分离到狂犬病毒街毒株,为狂犬病的实验室研究奠定基础。

  14. Applications of nanoparticles for DNA based rabies vaccine.

    Science.gov (United States)

    Shah, Muhammad Ali A; Khan, Sajid Umar; Ali, Zeeshan; Yang, Haowen; Liu, Keke; Mao, Lanlan

    2014-01-01

    Rabies is a fatal encephalomyelitis. Most cases occur in developing countries and are transmitted by dogs. The cell culture vaccines as associated with high cost; therefore, have not replaced the unsafe brain-derived vaccines. In the developing countries these brain-derived rabies vaccines still can be seen in action. Moreover, there will be a need for vaccines against rabies-related viruses against which classical vaccines are not always effective. The worldwide incidence of rabies and the inability of currently used vaccination strategies to provide highly potent and cost-effective therapy indicate the need for alternate control strategies. DNA vaccines have emerged as the safest vaccines and best remedy for complicated diseases like hepatitis, HIV, and rabies. A number of recombinant DNA vaccines are now being developed against several diseases such as AIDS and malaria. Therefore, it can be a valuable alternative for the production of cheaper rabies vaccines against its larger spectrum of viruses. In this review we report published data on DNA-based immunization with sequences encoding rabies with special reference to nanotechnology.

  15. Is injecting a finger with rabies immunoglobulin dangerous?

    Science.gov (United States)

    Suwansrinon, Kanitta; Jaijaroensup, Wipaporn; Wilde, Henry; Sitprija, Visith

    2006-08-01

    Treating potentially rabies virus infected wounds requires the injection of rabies immunoglobulin into and around the wounds, followed by vaccination with an approved tissue culture rabies vaccine. A significant number of such bite wounds involves fingers where there is little space for expansion. Injecting immunoglobulin into such areas under pressure may induce a compartment syndrome caused by compromising circulation. We carried out a retrospective review and a prospective study of patients seen with digital bite injuries and found that it is a safe procedure if carried out with care by experienced staff.

  16. [Rabies in Potos flavus identified in Madre de Dios, Peru].

    Science.gov (United States)

    Vargas-Linares, Elena; Romaní-Romaní, Franco; López-Ingunza, Ricardo; Arrasco-Alegre, Juan; Yagui-Moscoso, Martín

    2014-01-01

    The Potos flavus is a nocturnal mammal that lives in neotropical forests from Central America to South America. A study of four cases of rabies in Potos flavus was conducted; these occurred in April 2012 in the Madre de Dios region in Peru and were collected as part of epidemiological surveillance. The analysis performed in the regional reference laboratory of Madre de Dios determined the presence of the rabies virus antigen in three of the brain tissue samples. Results were verified in the Laboratory of Viral Zoonoses of the Peruvian National Institute of Health by direct immunofluorescence. The typification did not identify any of the known variants in bats or dogs. The occurrence of four cases of rabies in Potos flavus adds evidence of the emergence of a new reservoir of the rabies virus previously reported in the same region in 2007.

  17. RDIS: The Rabies Disease Information System.

    Science.gov (United States)

    Dharmalingam, Baskeran; Jothi, Lydia

    2015-01-01

    Rabies is a deadly viral disease causing acute inflammation or encephalitis of the brain in human beings and other mammals. Therefore, it is of interest to collect information related to the disease from several sources including known literature databases for further analysis and interpretation. Hence, we describe the development of a database called the Rabies Disease Information System (RDIS) for this purpose. The online database describes the etiology, epidemiology, pathogenesis and pathology of the disease using diagrammatic representations. It provides information on several carriers of the rabies viruses like dog, bat, fox and civet, and their distributions around the world. Information related to the urban and sylvatic cycles of transmission of the virus is also made available. The database also contains information related to available diagnostic methods and vaccines for human and other animals. This information is of use to medical, veterinary and paramedical practitioners, students, researchers, pet owners, animal lovers, livestock handlers, travelers and many others. The database is available for free http://rabies.mscwbif.org/home.html.

  18. Rabies Vaccine: What You Need to Know

    Science.gov (United States)

    ... high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers should be offered rabies vaccine. • The vaccine should also be considered for: - People ...

  19. Rabies in Kazakhstan.

    Directory of Open Access Journals (Sweden)

    Akmetzhan A Sultanov

    2016-08-01

    Full Text Available Rabies is a neglected zoonotic disease. There is a sparsity of data on this disease with regard to the incidence of human and animal disease in many low and middle income countries. Furthermore, rabies results in a large economic impact and a high human burden of disease. Kazakhstan is a large landlocked middle income country that gained independence from the Soviet Union in 1991 and is endemic for rabies.We used detailed public health and veterinary surveillance data from 2003 to 2015 to map where livestock rabies is occurring. We also estimate the economic impact and human burden of rabies. Livestock and canine rabies occurred over most of Kazakhstan, but there were regional variations in disease distribution. There were a mean of 7.1 officially recorded human fatalities due to rabies per year resulting in approximately 457 Disability Adjusted Life Years (DALYs. A mean of 64,289 individuals per annum underwent post exposure prophylaxis (PEP which may have resulted in an additional 1140 DALYs annually. PEP is preventing at least 118 cases of human rabies each year or possibly as many as 1184 at an estimated cost of $1193 or $119 per DALY averted respectively. The estimated economic impact of rabies in Kazakhstan is $20.9 million per annum, with nearly half of this cost being attributed to the cost of PEP and the loss of income whilst being treated. A further $5.4 million per annum was estimated to be the life time loss of income for fatal cases. Animal vaccination programmes and animal control programmes also contributed substantially to the economic losses. The direct costs due to rabies fatalities of agricultural animals was relatively low.This study demonstrates that in Kazakhstan there is a substantial economic cost and health impact of rabies. These costs could be reduced by modifying the vaccination programme that is now practised. The study also fills some data gaps on the epidemiology and economic effects of rabies in respect to

  20. Caracterização de amostras do vírus da raiva, isoladas nas regiões Norte e Centro-Oeste do Brasil, com anticorpos monoclonais antilissavírus Antigenic characterization of Brazilian rabies virus isolate North and Central West regions of Brazil with anti-lyssavirus monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    H.B.C.R. Batista

    2008-02-01

    Full Text Available The occurrence of rabies virus antigenic variants in North and Central West regions of Brazil was studied using 61 rabies viruses isolated from different species: 30 from domestic dogs, 20 from cattle, four from horses, two from cats, one from a human and four from unidentified species. The isolates were submitted to antigenic analyses by indirect immunofluorescence with a panel of 12 monoclonal antibodies (Mabs to lyssavirus antigens. Antigenic analyses revealed consistent differences between isolates whose natural hosts were dogs and those of haematophagous bats, often isolated from cattle. Three out of four isolates from horses and one from a domestic dog showed patterns of reactivity found only in viruses of insectivorous bats, indicating that non-haematophagous bats do play a unique role in the transmission of the virus to other species.

  1. Rabies in Captive Deer

    Centers for Disease Control (CDC) Podcasts

    2012-04-30

    Dr. Brett Petersen, a medical officer at CDC, discusses rabies in captive deer.  Created: 4/30/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/30/2012.

  2. Travelers' Health: Rabies

    Science.gov (United States)

    ... from rabies in a UK traveller returning from India. Euro Surveill. 2005 Jul;10(30):E050728 5. ... Follow CDC Email Recommend Tweet Post RSS CDC Media Listen Watch YouTube About CDC Employment Newsroom Training/ ...

  3. Rabies in Transplant Recipients

    Centers for Disease Control (CDC) Podcasts

    2016-09-19

    Dr. Richard Franka, a CDC scientist, discusses rabies in organ transplant recipients.  Created: 9/19/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/19/2016.

  4. Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine.

    Science.gov (United States)

    Henderson, Heather; Jackson, Felix; Bean, Kayla; Panasuk, Brian; Niezgoda, Michael; Slate, Dennis; Li, Jianwei; Dietzschold, Bernard; Mattis, Jeff; Rupprecht, Charles E

    2009-11-27

    Oral vaccination is an important part of wildlife rabies control programs. Currently, the vaccinia-rabies glycoprotein recombinant virus is the only oral rabies vaccine licensed in the United States, and it is not effective in skunks. In the current study, captive raccoons and skunks were used to evaluate a vaccine developed by incorporating the rabies virus glycoprotein gene into a canine adenovirus serotype 2 vector (CAV2-RVG). Seven of 7 raccoons orally vaccinated with CAV2-RVG developed virus neutralizing antibodies and survived lethal challenge. Five of 5 and 6 of 6 skunks in 2 experimental groups receiving 10-fold different dilutions of CAV2-RVG developed neutralizing antibodies and survived challenge. The results of this preliminary study suggest that CAV2-RVG stimulates protective immunity against rabies in raccoons and skunks.

  5. Generation and Characterization of an scFv Directed against Site II of Rabies Glycoprotein

    Directory of Open Access Journals (Sweden)

    Shukra M. Aavula

    2011-01-01

    Full Text Available Recombinant antibody phage display technology is a vital tool that facilitates identification of specific binding molecules to a target enabling the rapid generation and selection of high affinity, fully human, or mouse antibody product candidates essentially directed towards disease target appropriate for antibody therapy. In this study, a recombinant single-chain Fv antibody fragment (scFv A11 was isolated from immune spleen cells obtained from mice immunized with inactivated rabies virus (Pasteur strain using standard methodology and was characterized for its specificity towards the rabies virus glycoprotein. Epitope mapping using peptide libraries and truncated glycoprotein polypeptides suggested that A11 bound to the antigenic site II of rabies glycoprotein against which a majority of rabies virus neutralizing antibodies are directed. The use of the above technology could, therefore, allow development of scFvs with different specificities against the rabies glycoprotein as an alternative to the more cumbersome protocols used for the development of monoclonal antibodies.

  6. Antibody levels against rabies among occupationally exposed individuals in a Nigerian University

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    Babasola O. Olugasa

    2010-03-01

    Full Text Available The authors investigated the levels of anti-glycoprotein antibodies against rabies virus in the sera of occupationally exposed humans at the University of Ibadan, Nigeria. A quantitative indirect enzyme-linked immunosorbent assay (ELISA was used to detect rabies virus anti-glycoprotein antibodies in sera from 20 zoological garden workers, 20 veterinarians and 30 clinical veterinary students at the University of Ibadan. The sera were obtained between September 2008 and February 2009. Of these 70 healthy individuals, 29 (41.4% consisting of 15 zoological garden workers (75.0%, 13 veterinarians (65.0% and 1 veterinary student (3.3% were immune to rabies virus (antibody titre >0.5 equivalent units per ml, while 41 (58.6% were not immune. The prevalence of rabies anti-glycoprotein antibody was higher within the older segment of the study population than among the younger veterinary students. Almost all those who had spent at least 10 years on the job had higher levels of rabies vaccination compliance and were immune. Our results indicated that there is low anti-rabies immunity among occupationally exposed individuals at the University of Ibadan. There is a need for a complete course of primary and booster vaccinations of professionals exposed to the rabies virus. The impact of these results on rabies control in Nigeria is discussed.

  7. Pathogenic monitoring and genetic diversity analysis of rabies virus in Yunnan Province%云南省狂犬病病原监测及病毒遗传多样性分析

    Institute of Scientific and Technical Information of China (English)

    杜传海; 张文东; 胡挺松; 赵焕云; 张应国; 范泉水; 张富强; 刘勇

    2013-01-01

    Objective To elucidate the pathogenic distribution and virus genetic diversity of rabies in Yunnan Province between 2006 and 2011. Methods Brain tissues or saliva swab samples were collected from suspected dogs with rabies in different areas in Yunnan Province for pathogenic monitoring between 2006 and 2011. The representative positive samples were selected for cloning and sequencing of the G genes and G-L intergenic regions. Comparison and phylogenic analysis were made between the sequence data of those samples and those of the reference strains. Results The positive samples had been found in 30 counties among 11 districts of Yunnan Province. The virus strains from these positive samples belonged to Serotype Ⅰ and Genotype Ⅰ . There were four different lineages or sub-lineages( China Ⅰ -1, China Ⅰ -2, China Ⅰ -3 , and Thailand )and seven types of genetic structures. Conclusion There is genetic diversity in G gene and G-L intergenic region of rabies virus in Yunnan Province. China Ⅰ -1 becomes the dominant epidemic strain.%目的 阐明2006~2011年期间云南省狂犬病病原分布状况和病毒基因结构特征.方法 2006~2011年期间,在云南省不同地点采集疑似狂犬病犬脑组织样品或唾液拭子样品,开展狂犬病病原监测;选择代表性阳性样品,对G基因、G-L间隔区进行克隆、测序,并与参考毒株序列进行比对及系统发育分析.结果 云南省11个地州30个县检出狂犬病病毒阳性样品,云南省狂犬病病毒均属于血清Ⅰ型和基因Ⅰ型毒株,至少存在4个不同遗传(亚)谱系(China Ⅰ-1、China Ⅰ-2、China Ⅰ-3、Thailand)、7种基因结构类型.结论 云南省狂犬病病毒G基因和G-L间隔区具有遗传多样性,China Ⅰ-1毒株已成为当前流行的优势毒株.

  8. RABIES, PENYEBAB DAN MANAJEMEN PRA-PAJANAN SERTA PASCA-PAJANAN

    Directory of Open Access Journals (Sweden)

    Hemavalli Ragunathan

    2016-03-01

    Full Text Available RABIES, ETIOLOGY,PRE-EXPOSURE AND POST-EXPOSURE MANAGEMENT ABSTRACT Rabies is an acute viral disease that causes fatal encephalomyelitis in virtually all the warm-blooded animals including man. The virus is found in wild and some domestic animals, and is transmitted to other animals and to humans through their saliva (i.e. following bites, scratches, licks on broken skin and mucous membrane. Guidelines throughout worldwide quote that dogs are responsible for about 97% of human rabies, followed by cats (2%, jackals, mongoose and others (1%. The disease is mainly transmitted by the bite of a rabid dog. Keyword: Rabies, Epidemiology, Causes, Management

  9. Assessing the Risk of a Canine Rabies Incursion in Northern Australia

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    Emily G. Hudson

    2017-08-01

    Full Text Available Rabies is a globally distributed virus that causes approximately 60,00 human deaths annually with >99% of cases caused by dog bites. Australia is currently canine rabies free. However, the recent eastward spread of rabies in the Indonesian archipelago has increased the probability of rabies entry into northern Australian communities. In addition, many northern Australian communities have large populations of free-roaming dogs, capable of maintaining rabies should an incursion occur. A risk assessment of rabies entry and transmission into these communities is needed to target control and surveillance measures. Illegal transportation of rabies-infected dogs via boat landings is a high-risk entry pathway and was the focus of the current study. A quantitative, stochastic, risk assessment model was developed to evaluate the risk of rabies entry into north-west Cape York Peninsula, Australia, and rabies introduction to resident dogs in one of the communities via transport of rabies-infected dogs on illegal Indonesian fishing boats. Parameter distributions were derived from expert opinion, literature, and analysis of field studies. The estimated median probability of rabies entry into north-west Cape York Peninsula and into Seisia from individual fishing boats was 1.9 × 10−4/boat and 8.7 × 10−6/boat, respectively. The estimated annual probability that at least one rabies-infected dog enters north-west Cape York Peninsula and into Seisia was 5.5 × 10−3 and 3.5 × 10−4, respectively. The estimated median probability of rabies introduction into Seisia was 4.7 × 10−8/boat, and the estimated annual probability that at least one rabies-infected dog causes rabies transmission in a resident Seisia dog was 8.3 × 10−5. Sensitivity analysis using the Sobol method highlighted some parameters as influential, including but not limited to the prevalence of rabies in Indonesia, the probability of a dog on board an Indonesian

  10. Assessing the Risk of a Canine Rabies Incursion in Northern Australia.

    Science.gov (United States)

    Hudson, Emily G; Brookes, Victoria J; Ward, Michael P

    2017-01-01

    Rabies is a globally distributed virus that causes approximately 60,00 human deaths annually with >99% of cases caused by dog bites. Australia is currently canine rabies free. However, the recent eastward spread of rabies in the Indonesian archipelago has increased the probability of rabies entry into northern Australian communities. In addition, many northern Australian communities have large populations of free-roaming dogs, capable of maintaining rabies should an incursion occur. A risk assessment of rabies entry and transmission into these communities is needed to target control and surveillance measures. Illegal transportation of rabies-infected dogs via boat landings is a high-risk entry pathway and was the focus of the current study. A quantitative, stochastic, risk assessment model was developed to evaluate the risk of rabies entry into north-west Cape York Peninsula, Australia, and rabies introduction to resident dogs in one of the communities via transport of rabies-infected dogs on illegal Indonesian fishing boats. Parameter distributions were derived from expert opinion, literature, and analysis of field studies. The estimated median probability of rabies entry into north-west Cape York Peninsula and into Seisia from individual fishing boats was 1.9 × 10(-4)/boat and 8.7 × 10(-6)/boat, respectively. The estimated annual probability that at least one rabies-infected dog enters north-west Cape York Peninsula and into Seisia was 5.5 × 10(-3) and 3.5 × 10(-4), respectively. The estimated median probability of rabies introduction into Seisia was 4.7 × 10(-8)/boat, and the estimated annual probability that at least one rabies-infected dog causes rabies transmission in a resident Seisia dog was 8.3 × 10(-5). Sensitivity analysis using the Sobol method highlighted some parameters as influential, including but not limited to the prevalence of rabies in Indonesia, the probability of a dog on board an Indonesian fishing boat, and the

  11. Estimativa de validade de um novo método de isolamento de vírus rábico Estimate of the validity of a new method for the isolation of rabies virus

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    Yeda L Nogueira

    2004-04-01

    Full Text Available OBJETIVOS: Nenhum estudo de base populacional foi realizado para mostrar o uso potencial de diagnóstico virológico do vírus rábico. O estudo realizado teve por objetivo estimar parâmetros de acurácia para o isolamento de vírus rábico em célula McCoy, como um método alternativo, e comparar com o uso da célula N2A, considerada método de referência. MÉTODOS: Foi realizado um inquérito em 120 morcegos coletados aleatoriamente, na Mata Atlântica, no Estado de São Paulo. Utilizou-se a reação de imunofluorescência para a detecção do vírus rábico isolado no cérebro desses morcegos, avaliado nos dois sistemas de cultivos celulares. Dois bancos de dados foram formados com os resultados. A análise foi feita com o programa Computer Methods for Diagnosis Tests (CMDT, utilizando a técnica de two-graph-receiver operating characteristic (TG-ROC para obter os parâmetros de sensibilidade e especificidade, além de outros indicadores, tais como eficácia, valor preditivo positivo, valor preditivo negativo e razão de verossimilhança. RESULTADOS: A célula N2A apresentou 90% de sensibilidade e especificidade, enquanto que a célula McCoy obteve 95% para os mesmos parâmetros. Os valores foram baseados em pontos de cortes otimizados para cada uma das células. CONCLUSÕES: Observou-se que a célula McCoy permite obter estimativas de acurácia superiores aos resultados observados com a célula de N2A, representando um método alternativo eficaz no isolamento do vírus rábico.OBJECTIVES: No population-based studies have been conducted to show the potential for the use of virological diagnosis of the rabies virus. The objective of the present study was to estimate accuracy parameters for the isolation of the rabies virus in McCoy cells as an alternative method and to compare this with the use of murine neuroblastoma (N2A cells, which is considered to be a reference method. METHODS: An evaluation was performed on 120 bats collected at

  12. Rabies - epizootiological situation at the territory of Serbia and countries in the region from 2006. to 2012.

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    Maksimović-Zorić Jelena

    2013-01-01

    Full Text Available Rabies is a disease that occurs both in animals and people, with relatively long period of incubation, intense clinical course and fatal ending. Majority of cases of illnes and death in people are caused by the standard rabies virus. According to books of regulations on suppression and eradiction of rabies from 1988. and 2009., each suspected rabies has to be laboratory confirmed. From 2006. to 2012. within the passive surveilance, 3549 samples of brain tissue were examined for the presence of rabies virus. The virus was confirmed in 923 samples by using the method of direct imunofluorescence. From 2006. to 2012. there were diagnosed 192, 160, 233, 181, 104, 43 and 10 positive cases, respectively. For the purpose of rabies eradiction at the territory of the Republic of Serbia, a regional project of oral vaccination of foxes against rabies has been implemented since 2010.Within monitoring of the effectiveness of oral vaccination against rabies which was carried out at the end of 2011. and at the beginning of 2012., there were examined 1385 samples, out of which 11 reacted positively. The virus was dominantly present in the fox population. During 2008. and 2009., a relatively large number of rabid cats was registered, what indicates a transmission of rabies from the fox to the cat population. The incidence of rabies at the territory of Serbia significantly differs from one epizootic area to another. Northern parts of the country (Sombor and Subotica epizootic regions have more favorable situation with only two cases of rabies for the last 7 years. In the period until 2010., in Pozarevac, Novi Sad, Jagodina, Pancevo, Belgrade and Nis epizootic region, a gradual decline in number of positive cases was noticed. International project for oral vaccination of foxes against rabies which has been implemented at the territory of the Republic of Serbia and neighboring countries, influenced a significant reduction of registered rabies cases. [Projekat

  13. Human rabies in Iran.

    Science.gov (United States)

    Farahtaj, Firouzeh; Fayaz, Ahmad; Howaizi, Nader; Biglari, Peyvand; Gholami, Alirez

    2014-10-01

    Like most Asian and African countries, Iran is highly endemic for rabies, which is a preventable disease with the timely utilisation of post-exposure prophylaxis (PEP). With the availability of affordable vaccination in Iran, there are still several rabies deaths which are assumed misdiagnosed or received ineffective PEP. We reviewed the files of 16 human rabies deaths, consisting of two groups: 1, ineffective treatment; and 2, erroneous PEP. Most of the studied cases were male and were from rural areas. Stray dogs were found to be the common biting animal (68.75%). Of the patients, 10/16 (62.5%) who had injuries on their head and/or face demonstrated shorter incubation periods. The incubation period was longer in a 4-year-old boy who sustained injuries in his abdomen and back. All the patients in group 1 received four doses of vaccine and administration of human rabies immune globulin (HRIG), and death occurred with the mean of 49 days after the bite. This mean was 27 days in three patients in group 2, who received vaccine without administration of HRIG. In a total of 1,188,579 cases of PEP given in Iran during: 2002-2011, it is not known whether all PEPs were correctly administered by World Health Organization standards. Extending rabies awareness programmes and timely PEP education in the community in accordance with the implementation of rabies control measures might lead to a decrease in these unfortunate scenarios and heavy financial burden of vaccination required due to the prevalence of rabies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Pathogenicity of different rabies virus isolates and protection test in vaccinated mice Patogenicidade de diferentes isolados do vírus da raiva e teste de proteção em camundongos vacinados

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    Elenice M.S. Cunha

    2010-10-01

    Full Text Available This study was aimed to evaluate and compare the pathogenicity of rabies virus isolated from bats and dogs, and to verify the efficacy of a commercial rabies vaccine against these isolates. For evaluation of pathogenicity, mice were inoculated by the intramuscular route (IM with 500MICLD50/0.03mL of the viruses. The cross-protection test was performed by vaccinating groups of mice by the subcutaneous route and challenged through the intracerebral (IC route. Isolates were fully pathogenic when inoculated by the IC route. When inoculated intramuscularly, the pathogenicity observed showed different death rates: 60.0% for the Desmodus rotundus isolate; 50.0% for dog and Nyctinomops laticaudatus isolates; 40.0% for Artibeus lituratus isolate; 9.5% Molossus molossus isolate; and 5.2% for the Eptesicus furinalis isolate. Mice receiving two doses of the vaccine and challenged by the IC route with the isolates were fully protected. Mice receiving only one dose of vaccine were partially protected against the dog isolate. The isolates from bats were pathogenic by the IC route in mice. However, when inoculated through the intramuscular route, the same isolates were found with different degrees of pathogenicity. The results of this work suggest that a commercial vaccine protects mice from infection with bat rabies virus isolates, in addition to a canine rabies virus isolate.O estudo avaliou e comparou as propriedades patogênicas de cinco isolados do vírus da raiva de morcegos e um isolado do vírus da raiva de cão e analisou a eficácia de vacina comercial contra estes isolados, em camundongos. Para o estudo de patogenicidade camundongos foram inoculados pela via IM com 0,1 mL contendo 500MICLD50/0,03mL das amostras de vírus. Quando inoculados pela via IC, os isolados do vírus da raiva provocaram a morte de 100% dos camundongos. No entanto, 500MICLD50/0,03mL das mesmas amostras, inoculadas pela via IM, ocasionaram mortalidade de: 60,0% quando a amostra

  15. Isolamento do vírus rábico de morcego insetívoro Myotis nigricans Isolation of the rabies virus in a specimen of the insectiverous bat Myotis nigricans

    Directory of Open Access Journals (Sweden)

    Luzia F. A. Martorelli

    1995-04-01

    Full Text Available Relata-se um caso de infecção natural de raiva em morcego insetívoro Myotis nigricans, no Município de Ribeirão Pires, Grande São Paulo (Brasil. O diagnóstico realizou-se através das técnicas de imunofluorescência e inoculação intracerebral em camundongos, do tecido nervoso e da musculatura da região interescapular do morcego.The following is a case study of the natural infection by the rabies virus of an insectiverous bat belonging to the species Myotis nigricans in the municipality of Ribeirão Pires, Greater S. Paulo. Diagnosis was made by means of immunofluorescence and intracerebral innoculation of mice with nervous and intrascapular muscular tissues.

  16. Isolamento do vírus rábico de morcego insetívoro , Lasyurus borealis Rabies virus isolation in insectivorous bat Lasyurus borealis

    Directory of Open Access Journals (Sweden)

    Luzia Fatima Alves Martorelli

    1996-02-01

    Full Text Available Relata-se um caso de raiva em morcego insetívoro, Lasyurus borealis, na região urbana, em bairro residencial, no Município de Jundiaí, SP (Brasil.A case of rabies in an insectivorous bat, Lasyurus borealis , in a residential suburb in an urban area in the southern region of Brazil, is reported.

  17. Predictive spatial dynamics and strategic planning for raccoon rabies emergence in Ohio.

    Directory of Open Access Journals (Sweden)

    Colin A Russell

    2005-03-01

    Full Text Available Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia. Although sporadic cases of rabies have been identified in Ohio since oral rabies vaccine distribution in 1998, the first evidence of a significant breach in this vaccine corridor was not detected until 2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in Ohio from this breach using a stochastic spatial model that was first developed for exploratory data analysis in Connecticut and next used to successfully hind-cast wave-front dynamics of rabies spread across New York. The projections, based on expansion from the Lake County breach, are strongly affected by the spread of rabies by rare, but unpredictable long-distance translocation of rabid raccoons; rabies may traverse central Ohio at a rate 2.5-fold greater than previously analyzed wildlife epidemics. Using prior estimates of the impact of local heterogeneities on wave-front propagation and of the time lag between surveillance-based detection of an initial rabies case to full-blown epidemic, specific regions within the state are identified for vaccine delivery and expanded surveillance effort.

  18. Rabies in Latin America.

    Science.gov (United States)

    Ruiz, Marco; Chávez, Carlo Briones

    2010-04-01

    To review and discuss the available literature for rabies control in Latin America. A literature search was conducted in PubMed through October 2008. Articles in English, Spanish and Portuguese were reviewed. Recent reports indicate that the region is close to achieve the goal of eliminating human rabies transmitted by dogs even though there are some isolated cases reported. However, insectivorous and vampire bats continue to expose humans and animals. These cases have been reported with increasing frequency. Many challenges to the successful eradication of canine and non-canine rabies have been identified: among these are issues related to vaccine supply, the increase in transmission of canine rabies in certain areas, the presence of bat rabies in geographically inaccessible areas and lack of active action at local level. New strategies for systems information, networking and education are needed. Effective decentralization, adequate reallocation of resources, constant active surveillance, active local community participation and aggressive health education, might be some of the strategies that could prove to be helpful. More investment (funding and resources) and a very strong political commitment are needed to be able to eradicate this deadly disease.

  19. Analysis on Nucleoprotein Gene Sequence of 25 Rabies Virus Isolates in Guizhou Province, China%贵州省25株狂犬病病毒核蛋白基因序列分析

    Institute of Scientific and Technical Information of China (English)

    余春; 田克诚; 唐光鹏; 李世军; 王定明; 唐青; 陶晓燕; 李浩; 庄妍; 周敬祝; 王月

    2011-01-01

    To analyze 25 nucleoprotein gene (N gene) sequences of rabies viruses circulating in Guizhou province during 2005~2010, China, and to explore the epidemic characteristics and the probable mutant of rabies in Guizhou Province. Rabies virus RNA in human brain tissues, human saliva, and domestic dog brain tissues derived from different prefectures of Guizhou Province were detected with RT-nested PCR,and the amplified products were then sequenced. Bioinformatics software was used to determine the genetic characteristics of these rabies viruses. The sequences of N gene of 25 Guizhou provincial isolates were identical with homogeny between 97. 5%-99. 3% and 98. 4%- 99. 8% at nucleotide and deduced amino acid level, respectively, while the identities between them and isolated strains from other province of China were 88%~99. 1% and 88% - 99. 7%. There were several amino acid substitutions in the nucleoprotein of 25 Guizhou isolates compared with the known genotype 1 isolates. The analysis of phylogenetic tree of 25 Guizhou isolates was demonstrated to be genetically divided into two groups, indicating that the virus presented a unique characteristics in geographic distribution and in a time dependent-manner. And phylogenetic tree of 25 Guizhou isolates and 7 genotype 1 strains isolated from other Province of China was also divided into two groups, which were further composed of several subgroups, respectively. From these observations, the rabies viruses derived from Guizhou province were still genotype 1. These isolates of rabies virus were diverged from the strains isolated from other provinces in both gene sequences and deduced amino acid sequences, and these divergences were characterized in geographic distribution and in a time-dependent manner.%分析贵州省25株狂犬病病毒的核蛋白基因(N基因)序列,探讨贵州省狂犬病流行特征与狂犬病病毒变异情况.以RT-nested PCR检测来自贵州省2005年至2010年不同地区的病人脑组织、

  20. Feasibility of reducing rabies immunoglobulin dosage for passive immunization against rabies: results of In vitro and In vivo studies.

    Science.gov (United States)

    Madhusudana, Shampur Narayan; Ashwin, Belludi Yajaman; Sudarshan, Sampada

    2013-09-01

    Passive immunization is a crucial parameter for prevention of human rabies. Presently as World Health Organization (WHO) strongly advocates local infiltration of rabies immunoglobulin in and around the bite wound, we feel that there is no basis for calculating the dose of immunoglobulin based on body weight. Keeping this in view we conducted both in vitro and in vivo studies to know whether the dose of immunoglobulin can be reduced and still obtain complete neutralization of the virus. In vitro neutralization studies were conducted using CVS strain of virus and BHK 21 cells. In vivo experiments were conducted in 4 weeks old Swiss albino mice by initial challenge with CVS followed by infiltration with increasing dilutions of either human rabies immunoglobulin (HRIG) and equine rabies immunoglobulin (ERIG). In vitro studies showed that a dose of 100 FFD 50 of CVS was neutralized by increasing dilution of both HRIG and ERIG and 100% neutralization was observed with HRIG and ERIG in as low quantities as 0.025 IU. In mice studies there was 100% survival of mice infiltrated with 0.025 IU of both HRIG and ERIG compared with 100% mortality in mice infiltrated with normal saline. These results suggest that it is possible to reduce the dose of rabies immunoglobulins by at least 16 times the presently advocated dose. These findings needs to be further evaluated using larger animal models and street viruses prevalent in nature but cannot serve as recommendations for use of RIG for passive immunization in humans.

  1. 狂犬病毒糖蛋白重组的新城疫病毒诱导人胃癌 SGC 细胞自噬%The rabies virus glycoprotein recombinated Newcastle disease virus induce the human stomachal adenocarcinoma autophagy

    Institute of Scientific and Technical Information of China (English)

    王穆彬; 严玉兰; 张志坚; 赵英海; 李米; 步雪峰

    2015-01-01

    目的:观察狂犬病毒糖蛋白重组的新城疫病毒(rabies virus glycoprotein recombinated Newcastle disease vi-rus,rL-RVG)及野生型新城疫病毒(Newcastle disease virus,NDV)对胃癌 SGC 细胞自噬的影响。方法:将 SGC 细胞随机分为3组,rl-RVG 组(转染 rl-RVG)、NDV 组(转染 NDV)、对照组(转染 PBS),24 h 后观察细胞的形态变化,评价病毒对细胞的影响。用免疫双标记和免疫印迹法鉴定病毒感染是否成功;蛋白质印迹检测各组细胞自噬相关蛋白 LC3及 Beclin1的表达;透射电镜观察细胞内超微结构的变化和自噬体的形成。结果:病毒感染细胞24 h 后, rl-RVG 组及 NDV 组细胞皱缩明显,且 rl-RVG 组较 NDV 组变化明显,对照组无明显变化;rl-RVG 组和 NDV 组细胞LC3及 Beclin1蛋白表达较对照组明显升高(P <0.05),且 rl-RVG 组明显高于 NDV 组(P <0.05);rl-RVG 组及NDV 组出现的自噬体明显多于对照组,且 rl-RVG 组较 NDV 组明显增多(P <0.05)。结论:rL-RVG 较 NDV 更易引起胃癌 SGC 细胞的自噬。%Objective:To observe the autophagy of the human gastric cancer SGC infected by rabies virus glycoprotein recombinated Newcastle disease virus(rL-RVG)or wild type Newcastle disease virus (NDV).Methods:The cells were divided into three groups at random,the rL-RVG group(infected with rL-RVG),the NDV group(infected with NDV),and the control group(infected with PBS).The mor-phology of SGC cells after infected 24 hours were monitored by microscope.The infected cells were ana-lysed with immunofluorescence,the total proteins get from the cells infected with or without virus were analysed with western blotting,and the ultrastructural of SGC was observed by transmission electron mi-croscope.Results:After infected 24 hours,there was a significantly morphologic changes in the rL-RVG group and the NDV group,and the cells were shrink,the rL-RVG group changes

  2. Vírus da raiva em quirópteros naturalmente infectados no Estado de São Paulo, Brasil Rabies virus in naturally infected bats in the State of São Paulo, Southeastern Brazil

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    Karin Corrêa Scheffer

    2007-06-01

    Full Text Available OBJETIVO: Identificar as espécies de morcegos envolvidas na manutenção do ciclo da raiva, verificar a distribuição do vírus da raiva em tecidos e órgãos de morcegos e os períodos de mortalidade dos camundongos inoculados. MÉTODOS: A positividade para o vírus da raiva foi avaliada por imunofluorescência direta em morcegos de municípios do Estado de São Paulo, de abril de 2002 a novembro de 2003. A distribuição do vírus nos morcegos foi avaliada pela inoculação de camundongos e infecção de células N2A, com suspensões a 20% preparadas a partir de fragmentos de diversos órgãos e tecidos, além de cérebro e glândula salivar. A mortalidade dos camundongos foi observada diariamente, após inoculação intracerebral. RESULTADOS: Dos 4.393 morcegos pesquisados, 1,9% foram positivos para o vírus da raiva, pertencentes a dez gêneros, com predomínio de insetívoros. A média do período máximo de mortalidade dos camundongos pós-inoculação a partir de cérebros e glândulas salivares de morcegos hematófagos foi de 15,33±2,08 dias e 11,33±2,30 dias; insetívoros, 16,45±4,48 dias e 18,91±6,12 dias; e frugívoros, 12,60±2,13 dias e 15,67±4,82 dias, respectivamente. CONCLUSÕES: As espécies infectadas com o vírus da raiva foram: Artibeus lituratus, Artibeus sp., Myotis nigricans, Myotis sp., Eptesicus sp., Lasiurus ega, Lasiurus cinereus, Nyctinomops laticaudatus, Tadarida brasiliensis, Histiotus velatus, Molossus rufus, Eumops sp. e Desmodus rotundus. A pesquisa de vírus em diferentes tecidos e órgãos mostrou-se que os mais apropriados para o isolamento foram cérebro e glândulas salivares.OBJECTIVE: To identify the species of bats involved in maintaining the rabies cycle; to investigate the distribution of the rabies virus in the tissues and organs of bats and the time taken for mortality among inoculated mice. METHODS: From April 2002 to November 2003, bats from municipalities in the State of São Paulo were

  3. Emergence of rabies in the Gauteng Province, South Africa: 2010–2011

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    Claude T. Sabeta

    2013-02-01

    Full Text Available Canine rabies is enzootic throughout Sub-Saharan Africa, including the Republic of South Africa. Historically, in South Africa the coastal provinces of KwaZulu-Natal and Eastern Cape were most affected. Alarmingly, outbreaks of canine rabies have been increasingly reported in the past decade from sites where it has previously been under control. From January 2010 to December 2011, 53 animal rabies cases were confirmed; these were mostly in domestic dogs from southern Johannesburg, which was previously considered to be rabies free. In addition, one case was confirmed in a 26-month old girl who had been scratched by a pet puppy during this period. The introduction of rabies into Gauteng Province was investigated through genetic analysis of rabies positive samples confirmed during the outbreak period. In addition, the nucleotide sequences of incidental cases reported in the province for the past ten years were also included in the analysis. It was found that the recent canine rabies outbreak in the Gauteng Province came from the introduction of the rabies virus from KwaZulu-Natal, with subsequent local spread in the susceptible domestic dog population of southern Johannesburg. The vulnerability of the province was also highlighted through multiple, dead-end introductions in the past ten years. This is the first report of a rabies outbreak in the greater Johannesburg area with evidence of local transmission in the domestic dog population.

  4. Emergence of rabies in the Gauteng Province, South Africa: 2010–2011

    Directory of Open Access Journals (Sweden)

    Claude T. Sabeta

    2013-04-01

    Full Text Available Canine rabies is enzootic throughout Sub-Saharan Africa, including the Republic of South Africa. Historically, in South Africa the coastal provinces of KwaZulu-Natal and Eastern Cape were most affected. Alarmingly, outbreaks of canine rabies have been increasingly reported in the past decade from sites where it has previously been under control. From January 2010 to December 2011, 53 animal rabies cases were confirmed; these were mostly in domestic dogs from southern Johannesburg, which was previously considered to be rabies free. In addition, one case was confirmed in a 26-month old girl who had been scratched by a pet puppy during this period. The introduction of rabies into Gauteng Province was investigated through genetic analysis of rabies positive samples confirmed during the outbreak period. In addition, the nucleotide sequences of incidental cases reported in the province for the past ten years were also included in the analysis. It was found that the recent canine rabies outbreak in the Gauteng Province came from the introduction of the rabies virus from KwaZulu-Natal, with subsequent local spread in the susceptible domestic dog population of southern Johannesburg. The vulnerability of the province was also highlighted through multiple, dead-end introductions in the past ten years. This is the first report of a rabies outbreak in the greater Johannesburg area with evidence of local transmission in the domestic dog population.

  5. Enhanced diagnosis of rabies and molecular evidence for the transboundary spread of the disease in Mozambique.

    Science.gov (United States)

    Coetzer, Andre; Anahory, Iolanda; Dias, Paula T; Sabeta, Claude T; Scott, Terence P; Markotter, Wanda; Nel, Louis H

    2017-03-24

    Rabies is a neglected zoonotic disease with veterinary and public health significance, particularly in Africa and Asia. The current knowledge of the epidemiology of rabies in Mozambique is limited because of inadequate sample submission, constrained diagnostic capabilities and a lack of molecular epidemiological research. We wanted to consider the direct, rapid immunohistochemical test (DRIT) as an alternative to the direct fluorescent antibody (DFA) for rabies diagnosis at the diagnostic laboratory of the Central Veterinary Laboratory (CVL), Directorate of Animal Science, Maputo, Mozambique. Towards this aim, as a training exercise at the World Organisation for Animal Health (OIE) Rabies Reference Laboratory in South Africa, we performed the DRIT on 29 rabies samples from across Mozambique. With the use of the DRIT, we found 15 of the 29 samples (52%) to be negative. The DRIT-negative samples were retested by DFA at the OIE Rabies Reference Laboratory, as well as with an established real-time Polymerase chain reaction, confirming the DRIT-negative results. The DRIT-positive results (14/29) were retested with the DFA and subsequently amplified, sequenced and subjected to phylogenetic analyses, confirming the presence of rabies RNA. Molecular epidemiological analyses that included viruses from neighbouring countries suggested that rabies cycles within Mozambique might be implicated in multiple instances of cross-border transmission. In this regard, our study has provided new insights that should be helpful in informing the next steps required to better diagnose, control and hopefully eliminate rabies in Mozambique.

  6. Advances in Diagnosis of Rabies

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    Shankar B.P.

    2009-04-01

    Full Text Available Rabies is a major zoonosis for which diagnostic techniques have been standardised internationally. Laboratory techniques are preferably conducted on central nervous system (CNS tissue removed from the cranium. Agent identification is preferably done using the fluorescent antibody test. A drop of purified immunoglobulin previously conjugated with fluorescein isothiocyanate is added to an acetone-fixed brain tissue smear, preferably made from several parts of the brain, including the hippocampus, cerebellum and medulla oblongata. For a large number of samples, as in an epidemiological survey, the immunoenzyme technique can provide rapid results (the rapid rabies enzyme immunodiagnosis. FAT provides a reliable diagnosis in 98-100% of cases for all genotypes if a potent conjugate is used, while RREID detects only genotype 1 virus. Infected neuronal cells have been demonstrated by histological tests and these procedures will reveal aggregates of viral material (the Negri bodies in the cytoplasm of neurones. However, the sensitivity of histological techniques is much less than that of immunological methods, especially if there has been some autolysis of the specimen. Consequently, histological techniques can no longer be recommended. As a single negative test on fresh material does not rule out the possibility of infection, inoculation tests, or other tests, should be carried out simultaneously. Newborn or 3-4-week-old mice are inoculated intracerebrally with a pool of several CNS tissues, including the brain stem, and then kept under observation for 28 days. For any mouse that dies between 5 and 28 days, the cause of death should be confirmed by FAT. Alternatively, a monolayer culture of susceptible cells is inoculated with the same material as used for mice. FAT carried out after appropriate incubation will demonstrate the presence or absence of viral antigen. Wherever possible, virus isolation in cell culture should replace mouse inoculation tests

  7. GAMBARAN DISTRIBUSI RABIES DI KABUPATEN SIKKA PROVINSI NUSA TENGGARA TIMUR 2004-2008

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    Fridolina Mau

    2013-09-01

    Full Text Available AbstractRabies has long been known as one of the major public healht problems in Sikka district, East Nusa Tenggara Province,Indonesia. Flores is an isolated preveiously rabies- free. It started with the importation of three dogs from rabies endemicSulawesi in September 1997. The rabies virus is present in the saliva of infected animals; all warm-blooded animals aresusceptible to rabies, and some may serve as natural reservoirs of the virus. Rabies is still a problem for world healthincluding Indonesia. Data of deathcase of rabies (lyssa in Indonesia register 125 cases each year. Rabies in Indonesia is aserious health problem because almost fatal after clinical symptom of the disease with death rate of 100%. Since 2004 toDecember 2009 rabies spread to 24 provinces in East Nusa Tenggara Province. Number of cases due to bite of a mad dogwas 16.000 cases. The aim of this study is to know distribution of rabies casse and the main control measures isimmunizing dogs. Tipe of this study is cross sectional. The result of this study showed the improvement in the last five years(2004 until August 2008 of the occurences of dog bite in cases and human deaths highest in 128 cases (32,48% incommunity health centers Waipare and population dog highest in Kewapante subdistrict 7213 (26,27% although thecoverage of immunization was very low that was 2523 (10,77% out of 6210 population. In average the dog bite casesoccurred in April.Key Word; Description, Distribution, Rabies

  8. Use of infrared thermography to detect signs of rabies infection in raccoons (Procyon lotor).

    Science.gov (United States)

    Dunbar, Mike R; MacCarthy, Kathleen A

    2006-12-01

    Infrared thermography was evaluated as a technique to determine if raccoons (Procyon lotor) experimentally infected with rabies virus could be differentiated from noninfected raccoons. Following a 10-day adjustment period, raccoons (n = 6) were infected with a virulent rabies street strain raccoon variant by injection into the masseter muscle at a dose of 2 x 10(4) tissue-culture infectious dose (TCID50) in 0.2 ml (n = 4) or 10(5) TCID50 in 1 ml (n = 2). Five of the six raccoons developed prodromal signs of rabies 17 to 22 days postinoculation (PI) and distinctive clinical signs of furious rabies between 19 and 24 days PI. At the time of euthanasia, which occurred 2 days after the onset of clinical signs of rabies, these five raccoons tested positive for rabies virus in brain tissue. Infrared thermal images of each raccoon were recorded twice daily during the preinoculation and PI periods. No apparent differences were identified among thermal temperatures compared among days for the eye, average body surface, and body temperature recorded from subcutaneous implants throughout the experiment for any of the six raccoons. However, increases in infrared surface temperature of the noses and differences in the visual thermal images of the noses were detected when animals began showing clinical signs of rabies. Differences were detected among the mean infrared nose temperatures for the disease progression intervals (F3.12 = 70.03, P raccoons in the infectious stage and capable of exhibiting clinical signs of rabies.

  9. Memorial I.Rabi

    CERN Multimedia

    Schopper,H

    1988-01-01

    Le DG H.Schopper ainsi que Norman Ramsey et le DG de l'Unesco rendent hommage à Isidor Rabi, grand scientifique et humaniste (1929-1988).Cette rencontre est organisée ensemble avec le Cern et l'Unesco.

  10. Rabies: Questions and Answers

    Science.gov (United States)

    ... be tested for rabies if possible. Call animal control or a wildlife conservation officer for help in capturing the bat ... Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) formulate the ... reactions to this vaccine are mild, such as sore- ...

  11. Management and modeling approaches for controlling raccoon rabies: The road to elimination.

    Science.gov (United States)

    Elmore, Stacey A; Chipman, Richard B; Slate, Dennis; Huyvaert, Kathryn P; VerCauteren, Kurt C; Gilbert, Amy T

    2017-03-01

    Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (PEP) annually. Previous rabies variant elimination in raccoons (Canada), foxes (Europe), and dogs and coyotes (United States) demonstrates that elimination of the raccoon variant from the eastern US is feasible, given an understanding of rabies control costs and benefits and the availability of proper tools. Also critical is a cooperatively produced strategic plan that emphasizes collaborative rabies management among agencies and organizations at the landscape scale. Common management strategies, alone or as part of an integrated approach, include the following: oral rabies vaccination (ORV), trap-vaccinate-release (TVR), and local population reduction. As a complement, mathematical and statistical modeling approaches can guide intervention planning, such as through contact networks, circuit theory, individual-based modeling, and others, which can be used to better understand and predict rabies dynamics through simulated interactions among the host, virus, environment, and control strategy. Strategies derived from this ecological lens can then be optimized to produce a management plan that balances the ecological needs and program financial resources. This paper discusses the management and modeling strategies that are currently used, or have been used in the past, and provides a platform of options for consideration while developing raccoon rabies virus elimination strategies in the US.

  12. Management and modeling approaches for controlling raccoon rabies: The road to elimination.

    Directory of Open Access Journals (Sweden)

    Stacey A Elmore

    2017-03-01

    Full Text Available Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (PEP annually. Previous rabies variant elimination in raccoons (Canada, foxes (Europe, and dogs and coyotes (United States demonstrates that elimination of the raccoon variant from the eastern US is feasible, given an understanding of rabies control costs and benefits and the availability of proper tools. Also critical is a cooperatively produced strategic plan that emphasizes collaborative rabies management among agencies and organizations at the landscape scale. Common management strategies, alone or as part of an integrated approach, include the following: oral rabies vaccination (ORV, trap-vaccinate-release (TVR, and local population reduction. As a complement, mathematical and statistical modeling approaches can guide intervention planning, such as through contact networks, circuit theory, individual-based modeling, and others, which can be used to better understand and predict rabies dynamics through simulated interactions among the host, virus, environment, and control strategy. Strategies derived from this ecological lens can then be optimized to produce a management plan that balances the ecological needs and program financial resources. This paper discusses the management and modeling strategies that are currently used, or have been used in the past, and provides a platform of options for consideration while developing raccoon rabies virus elimination strategies in the US.

  13. Rabies diagnosis and serology in bats from the State of São Paulo, Brazil

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    Marilene Fernandes de Almeida

    2011-04-01

    Full Text Available INTRODUCTION: Bats are one of the most important reservoirs and vectors of the rabies virus in the world. METHODS: From 1988 to 2003, the Zoonosis Control Center in São Paulo City performed rabies diagnosis on 5,670 bats by direct immunofluorescent test and mouse inoculation test. Blood samples were collected from 1,618 bats and the sera were analyzed using the rapid fluorescent focus inhibition test to confirm rabies antibodies. RESULTS: Forty-four (0.8% bats were positive for rabies. The prevalence of rabies antibodies was 5.9% using 0.5IU/ml as a cutoff. Insectivorous bats (69.8% and bats of the species Molossus molossus (51.8% constituted the majority of the sample; however, the highest prevalence of antibodies were observed in Glossophaga soricina (14/133, Histiotus velatus (16/60, Desmodus rotundus (8/66, Artibeus lituratus (5/54, Nyctinomops macrotis (3/23, Tadarida brasiliensis (3/48, Carollia perspicillata (3/9, Eumops auripendulus (2/30, Nyctinomops laticaudatus (2/16, Sturnira lilium (2/17 and Eumops perotis (1/13. The prevalence of rabies antibodies was analyzed by species, food preference and sex. CONCLUSIONS: The expressive levels of antibodies associated with the low virus positivity verified in these bats indicate that rabies virus circulates actively among them.

  14. Molecular epidemiology of rabies in bat-eared foxes (Otocyon megalotis) in South Africa.

    Science.gov (United States)

    Sabeta, C T; Mansfield, K L; McElhinney, L M; Fooks, A R; Nel, L H

    2007-10-01

    A panel of 124 rabies viruses from wildlife host species (principally the bat-eared fox, Otocyon megalotis) and domestic carnivore species were collected between 1980 and 2005 from a region of South Africa associated with endemic bat-eared fox rabies. We have studied the molecular epidemiology of bat-eared fox rabies by virtue of nucleotide sequence analyses of PCR amplicons specific to the variable G-L intergenic region as well as the conserved nucleoprotein gene of each of the rabies viruses in this South African panel. Although it was demonstrated that all of these viruses were very closely related, they could be segregated into two major phylogenetic groups. The data presented in this paper complement antigenic and surveillance data on rabies in this host species in South Africa. Most importantly our data support a hypothesis that the bat-eared fox independently maintains rabies cycles in specific geographical loci. This is the first molecular epidemiological investigation describing rabies transmission dynamics in this wildlife carnivore host species in South Africa.

  15. The phylogeography of rabies in Grenada, West Indies, and implications for control.

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    Ulrike Zieger

    2014-10-01

    Full Text Available In Grenada, West Indies, rabies is endemic, and is thought to be maintained in a wildlife host, the small Indian mongoose (Herpestes auropunctatus with occasional spillover into other hosts. Therefore, the present study was undertaken to improve understanding of rabies epidemiology in Grenada and to inform rabies control policy. Mongooses were trapped island-wide between April 2011 and March 2013 and examined for the presence of Rabies virus (RABV antigen using the direct fluorescent antibody test (dFAT and PCR, and for serum neutralizing antibodies (SNA using the fluorescent antibody virus neutralization test (FAVN. An additional cohort of brain samples from clinical rabies suspects submitted between April 2011 and March 2014 were also investigated for the presence of virus. Two of the 171 (1.7% live-trapped mongooses were RABV positive by FAT and PCR, and 20 (11.7% had SNAs. Rabies was diagnosed in 31 of the submitted animals with suspicious clinical signs: 16 mongooses, 12 dogs, 2 cats and 1 goat. Our investigation has revealed that rabies infection spread from the northeast to the southwest of Grenada within the study period. Phylogenetic analysis revealed that the viruses from Grenada formed a monophyletic clade within the cosmopolitan lineage with a common ancestor predicted to have occurred recently (6-23 years ago, and are distinct from those found in Cuba and Puerto Rico, where mongoose rabies is also endemic. These data suggest that it is likely that this specific strain of RABV was imported from European regions rather than the Americas. These data contribute essential information for any potential rabies control program in Grenada and demonstrate the importance of a sound evidence base for planning interventions.

  16. Assessment of knowledge, attitude and practice of dog owners to canine rabies in Wukari metropolis, Taraba State, Nigeria.

    Science.gov (United States)

    Ameh, Veronica O; Dzikwi, Asabe A; Umoh, Jarlath U

    2014-06-12

    Canine rabies is endemic and occurs throughout the year in all parts of Nigeria. A descriptive cross sectional study was designed to assess knowledge, attitude and practice of dog owners towards rabies, to check for the presence of rabies antigens in brain tissue of dogs slaughtered for human consumption and to assess rabies vaccination coverage of dogs in Wukari. Structured questionnaires were prepared and administered to 200 dog owners by face to face interview. The questionnaire sought information on demographic characteristics of the dog owners, their association with dogs, knowledge, attitude and practice of dog owners towards rabies. Associations between demographic variables and knowledge, attitude or practice scores were assessed using chi(2) analysis. Also, 188 brain samples from slaughtered dogs were analysed for presence of rabies antigen using direct fluorescent antibody test. Fifteen (7.89%) had rabies antigen. Record files and vaccination certificates of dogs presented to the State Veterinary Hospital Wukari were assessed for anti rabies vaccination coverage. Out of the 200 dog owners, only 26 (13%) knew that rabies virus can be found in nervous tissue, 121 (60.5%) were aware that rabies can be spread through the saliva of a rabid animal, but majority of respondents 172 (86%) did not know the age for first vaccination of dogs against rabies. Dog owners who were civil servants were 4.8 times more likely to have good knowledge (OR=4.84, 95% CI on OR 1.09-21.44) than those of other occupation groups. Positive attitude towards rabies increased with increase in age of dog owners, with respondents within the age group 20-30 years more likely to have negative attitude than those over 40 years. Civil servants were 9.8 times more likely to have good practice than other occupation groups. Rabies antigen was detected in 7.98% of slaughtered dogs. Out of 8370 dogs presented to the hospital between January 2003 and December 2012, only 1128 (13.50%) received anti

  17. Complete genome and molecular epidemiological data infer the maintenance of rabies among kudu (Tragelaphus strepsiceros in Namibia.

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    Terence P Scott

    Full Text Available Rabies in kudu is unique to Namibia and two major peaks in the epizootic have occurred since it was first noted in 1977. Due to the large numbers of kudu that were affected, it was suspected that horizontal transmission of rabies occurs among kudu and that rabies was being maintained independently within the Namibian kudu population - separate from canid cycles, despite geographic overlap. In this study, it was our aim to show, through phylogenetic analyses, that rabies was being maintained independently within the Namibian kudu population. We also tested, through complete genome sequencing of four rabies virus isolates from jackal and kudu, whether specific mutations occurred in the virus genome due to host adaptation. We found the separate grouping of all rabies isolates from kudu to those of any other canid species in Namibia, suggesting that rabies was being maintained independently in kudu. Additionally, we noted several mutations unique to isolates from kudu, suggesting that these mutations may be due to the adaptation of rabies to a new host. In conclusion, we show clear evidence that rabies is being maintained independently in the Namibian kudu population - a unique phenomenon with ecological and economic impacts.

  18. Anisotropic Rabi model

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    Qiong-Tao Xie

    2014-06-01

    Full Text Available We define the anisotropic Rabi model as the generalization of the spin-boson Rabi model: The Hamiltonian system breaks the parity symmetry; the rotating and counterrotating interactions are governed by two different coupling constants; a further parameter introduces a phase factor in the counterrotating terms. The exact energy spectrum and eigenstates of the generalized model are worked out. The solution is obtained as an elaboration of a recently proposed method for the isotropic limit of the model. In this way, we provide a long-sought solution of a cascade of models with immediate relevance in different physical fields, including (i quantum optics, a two-level atom in single-mode cross-electric and magnetic fields; (ii solid-state physics, electrons in semiconductors with Rashba and Dresselhaus spin-orbit coupling; and (iii mesoscopic physics, Josephson-junction flux-qubit quantum circuits.

  19. 贵州省狂犬病病毒糖蛋白基因序列特征分析%Characteristic of glycoprotein gene sequences of rabies virus in Guizhou Province

    Institute of Scientific and Technical Information of China (English)

    李世军; 田克诚; 唐光鹏; 余春; 王定明; 唐青; 陶晓燕; 李浩; 庄妍; 周敬祝; 王月

    2012-01-01

    To study the characteristic of glycoprotein gene sequence of rabies virus in Guizhou Province in recent years and provide scientific basis for effective control and prevention of rabies,RT-PCR assay were used to detect human and dog brain tissues derived from different prefectures of Guizhou.The amplification products were sequenced and analyzed with bioinformatics software.The results showed that the full-length G gene sequences of 8 positive samples were obtained by RT-PCR amplification,sequencing and splicing.The homology of eight G gene sequences from Guizhou Province were between 87.4% -99.9% and 83.3.%- 100% on nucleotide and deduced amino acid level,respectively,and the highest homology were found with the genotype 1 strains ( 86.5 %- 87.0% for nucleotide and 83.3 %- 100 % for amino acid) among genotype 1- 7 representative strains.Besides,phylogenetic analysis based on the G gene indicated that the relationship of 8 strains derived from Guizhou were closest to genotype 1 Lyssavirus,and the strains of Guizhou were very close to the strains come from Hubei,Hunan,Anhui,Guangxi,Jiangsu provinces and Shanghai,except for GZ01 and GZ09.Moreover,GZ09 were evolutionarily closed to the strains come from Malaysia and Thailand,while the remaining sequences were closed to the strain of Indonesia.This study confirmed on the G gene level that rabies virus epidemic strains circulated in Guizhou Province in recent years belonged to rabies virus genotype 1 and the evolutionary relationship with reported strains come from different provinces of China and different countries were revealed in this study.It will provide scientific basis for effective control and prevention of human and animal rabies in Guizhou Province.%目的 分析贵州省狂犬病病毒的糖蛋白基因(G基因)序列特征,为狂犬病的有效预防和控制提供科学依据.方法 以RT- PCR扩增贵州省近年来不同地区的人和犬狂犬病病毒阳性脑组织标本狂犬病病

  20. Human Rabies with Initial Manifestations that Mimic Acute Brachial Neuritis and Guillain-Barré Syndrome.

    Science.gov (United States)

    Mader, Edward C; Maury, Joaquin S; Santana-Gould, Lenay; Craver, Randall D; El-Abassi, Rima; Segura-Palacios, Enrique; Sumner, Austin J

    2012-01-01

    Human rabies can be overlooked in places where this disease is now rare. Its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a Guillain-Barré syndrome (GBS) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (ABN). A 19-year-old Mexican, with no past health problems, presented with a two-day history of left shoulder, arm, and chest pain. He arrived in Louisiana from Mexico five days prior to admission. Of particular importance is the absence of a history of rabies exposure and immunization. On admission, the patient had quadriparesis, areflexia, and elevated protein in the cerebrospinal fluid, prompting a diagnosis of GBS. However, emerging neurological deficits pointed towards acute encephalitis. Rabies was suspected on hospital day 11 after common causes of encephalitis (eg, arboviruses) have been excluded. The patient tested positive for rabies IgM and IgG. He died 17 days after admission. Negri bodies were detected in the patient's brain and rabies virus antigen typing identified the vampire bat as the source of infection. Rabies should be suspected in every patient with a rapidly evolving GBS-like illness-even if there is no history of exposure and no evidence of encephalitis on presentation. The patient's ABN-like symptoms may be equivalent to the pain experienced by rabies victims near the inoculation site.

  1. Influence of oral rabies vaccine bait density on rabies seroprevalence in wild raccoons.

    Science.gov (United States)

    Sattler, Andrew C; Krogwold, Roger A; Wittum, Thomas E; Rupprecht, Charles E; Algeo, Timothy P; Slate, Dennis; Smith, Kathleen A; Hale, Robert L; Nohrenberg, Gary A; Lovell, Charles D; Niezgoda, Mike; Montoney, Andrew J; Slemons, Richard D

    2009-11-27

    The effect of different oral rabies vaccine (ORV) bait densities (75, 150, and 300 baits/km(2)) on the seroprevalence of rabies virus neutralizing antibodies (RVNAs) in raccoons (Procyon lotor) was assessed at a 15% seroprevalence difference threshold in rural areas of northeast Ohio. Results (n=588 raccoons) indicated that seropositivity for RVNAs was associated with both bait density and bait campaign frequency. Associations were not detected for raccoon gender, age, or macro-habitat. The odds of being seropositive were greater for raccoons originating from 300 bait/km(2) treatment areas relative to those coming from the 75 bait/km(2) areas (odds ratio [OR]=4.4, probability [P]raccoons between sequential, semi-annual campaigns, yet cumulative ORV campaigns were associated with gradual increases in seroprevalence.

  2. Rabies Outbreaks and Vaccination in Domestic Camels and Cattle in Northwest China.

    Science.gov (United States)

    Liu, Ye; Zhang, He-Ping; Zhang, Shou-Feng; Wang, Jin-Xiang; Zhou, Hai-Ning; Zhang, Fei; Wang, Yu-Mei; Ma, Long; Li, Nan; Hu, Rong-Liang

    2016-09-01

    In contrast to many countries where rabies has been well controlled in humans and livestock, even in wildlife, rabies is still endemic in almost regions of China. In Northwest China, rabies transmitted by stray dogs and wild foxes has caused heavy economic losses to local herdsmen, as well as causing numbers of human cases. In this study, as part of an investigation of ways to prevent rabies epidemics in livestock, we report an analysis of domestic cattle and camel rabies cases in Ningxia Hui (NHAR) and Inner Mongolia Autonomous Region (IMAR) and the immune efficacy of canine inactivated rabies vaccines in these animals. We found that rabies viruses from these animals are closely related to dog-hosted China I and fox-associated China III lineages, respectively, indicating that the infections originated from two different sources (dogs and wild foxes). As well as the previously reported Arctic and Arctic-related China IV lineage in IMAR, at least three separate phylogenetic groups of rabies virus consistently exist and spread throughout Northwest China. Since there is no licensed oral vaccine for wild foxes and no inactivated vaccine for large livestock, local canine inactivated vaccine products were used for emergency immunization of beef and milk cattle and bactrian (two-humped) camels in local farms. Compared with a single injection with one (low-efficacy) or three doses (high-cost), a single injection of a double dose of canine vaccine provided low-price and convenience for local veterinarians while inducing levels of virus neutralizing antibodies indicative of protection against rabies for at least 1 year in the cattle and camels. However, licensed vaccines for wildlife and large domestic animals are still needed in China.

  3. The sensitivity and specificity of two PCR assays for detecting rabies virus%两种PCR方法检测狂犬病毒的敏感性和特异性比较

    Institute of Scientific and Technical Information of China (English)

    马莉珍; 柯雪梅; 肖建鹏; 陈清

    2011-01-01

    目的 比较Nested-PCR和SYBR Green Ⅰ Real-Time PCR两种方法检测狂犬病毒的敏感性、特异性和时效性.方法 对10倍连续稀释的狂犬病毒(疫苗株)核酸样品,采用Nested-PCR和SYBR Green Ⅰ Real-Time PCR方法进行平行检测,比较两种方法的敏感性:同时以登革热2型病毒、诺如病毒、星状病毒、EV71和乙型脑炎病毒核酸对两种方法的特异性进行评价.结果 SYBR Green Ⅰ Real-Time PCR方法可检测出2.3×106 copies/μl核酸分子,与NestedPCR方法相比,敏感度提高10倍.两种检测方法的特异性均好,与登革热2型病毒、诺如病毒、星状病毒、EV71和乙型脑炎病毒核酸均无交叉反应.SYBR Green Ⅰ Real-Time PCR方法检测花费3 h,检测时间比Nested-PCR方法节省2 h.结论 与Nested-PCR相比,SYBR Green Ⅰ Real-Time PCR是相对高效的检测狂犬病毒的方法.%Objective The aim of the study was to compare the sensitivity, specificity and time-consuming of Nested-PCR and SYBR Green I Real-Time PCR assays for detecting rabies virus (RABV). Methods A series of 10-fold dilutions of a RABV (vaccine strain) DNA was used for detection of the sensitivity of the Nested-PCR and SYBR Green I Real-Time PCR assays. EV71, Dengue type 2 virus, Norovirus, Astrovirus and Japanese encephalitis virus (JEV) were used to test the specificity of the assays. Results Sensitivity of SYBR Green I Real-Time PCR assay was 2.3×106 copies/μl which were 10 times more sensitive than that of Nested-PCR assay. There was no crossing-reaction with Dengue type 2 virus, Astrovirus,Norovirus, EV71 and JEV. The time-consuming of the SYBR Green I real-time PCR amplification was about 3 hours, 2 hours shorter than Nested-PCR. Conclusion For detection of Rabies Virus, SYBR Green I Real-Time PCR is a more sensitive and rapid assay compared with Nested-PCR.

  4. Excessive libido in a woman with rabies.

    OpenAIRE

    Dutta, J. K.

    1996-01-01

    Rabies is endemic in India in both wildlife and humans. Human rabies kills 25,000 to 30,000 persons every year. Several types of sexual manifestations including excessive libido may develop in cases of human rabies. A laboratory proven case of rabies in an Indian woman who manifested excessive libido is presented below. She later developed hydrophobia and died.

  5. Bats, emerging infectious diseases, and the rabies paradigm revisited

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    Ivan V. Kuzmin

    2011-06-01

    Full Text Available The significance of bats as sources of emerging infectious diseases has been increasingly appreciated, and new data have been accumulated rapidly during recent years. For some emerging pathogens the bat origin has been confirmed (such as lyssaviruses, henipaviruses, coronaviruses, for other it has been suggested (filoviruses. Several recently identified viruses remain to be ‘orphan’ but have a potential for further emergence (such as Tioman, Menangle, and Pulau viruses. In the present review we summarize information on major bat-associated emerging infections and discuss specific characteristics of bats as carriers of pathogens (from evolutionary, ecological, and immunological positions. We also discuss drivers and forces of an infectious disease emergence and describe various existing and potential approaches for control and prevention of such infections at individual, populational, and societal levels.

  6. In-Depth Characterization of Live Vaccines Used in Europe for Oral Rabies Vaccination of Wildlife

    Science.gov (United States)

    Cliquet, Florence; Picard-Meyer, Evelyne; Mojzis, Miroslav; Dirbakova, Zuzana; Muizniece, Zita; Jaceviciene, Ingrida; Mutinelli, Franco; Matulova, Marta; Frolichova, Jitka; Rychlik, Ivan; Celer, Vladimir

    2015-01-01

    Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release. PMID:26509266

  7. In-Depth Characterization of Live Vaccines Used in Europe for Oral Rabies Vaccination of Wildlife.

    Directory of Open Access Journals (Sweden)

    Florence Cliquet

    Full Text Available Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.

  8. Fox- and raccoon-dog–associated rabies outbreaks in northern China

    Institute of Scientific and Technical Information of China (English)

    Ye; Liu; Shoufeng; Zhang; Jinghui; Zhao; Fei; Zhang; Nan; Li; Hai; Lian; Wurengege; Shiyu; Guo; Rongliang; Hu

    2014-01-01

    <正>Dear Editor,Rabies is a generally fatal disease caused by the rabies virus(RABV),and is transmitted mainly by Carnivora and Chiroptera(Fooks A R,et al.,2014;Tao X,et al.,2013).In China,stray dogs and some wild animals(e.g.,Chinese ferret badgers,foxes,and raccoon dogs)are the principal reservoirs for RABV(Hu R L,et al.,2009).Historically,rabies in wild foxes and raccoon dogs(Nyctereutes procyonoides)was recorded in the early

  9. Bioinformatics of glycoprotein of virus strain for production of rabies vaccine for human use in China%我国人用狂犬病疫苗株病毒糖蛋白生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    李加; 曹守春; 石磊泰; 唐建蓉; 田宏; 高向东; 董关木

    2012-01-01

    Objective To sequence the glycoprotein (G) genes of virus strains 4aGV, CTN-1V and PV2061 for production of rabies vaccine for human use in China, and analyze their bioinformatics. Methods The G genes of strains 4aGV, CTN-1V and PV2061 were amplified by RT-PCR and inserted into vector Pgem-T respectively. The constructed recombinant plasmids were transformed to E. Coli DH5a, and positive clones were screened and sequenced. The glycoprotein of three strains were analyzed for homology by using DNAstar MegAlign software, and for structure and potential B cell epitope by using AntheProt5. 0 and DNAstar Protean software. Results All the three strains were rabies virus genotype I , of which the homologies of gene sequences encoding G region and ORF of G region were 76. 0% ~ 88. 4% and 84. 4% ~ 91. 5% respectively, while those of amino acid sequences were 90. 5% ~ 92. 2%. Potential signal peptide structures existed in the amino acids at first 19 sites of glycoprotein of the three strains. However, the amino acid at site 19 contained the potential signal peptide breakage sites of glycoprotein of all the three strains, while that a t site 17 contained the potential signal peptide breakage site of strain 4aGV. Potential hydrophobic regions consisting of foldaway helixes were observed in amino acids at sites 463 ~ 476, 464 ~ 475 and 463 ~ 475 of strains 4aGV, CTN-1V and PV2061 respectively, which were judged as typical transmembrane regions. The proportions of α-helix in amino acid residues of glycoprotein of strains 4aGV, CTN-1V and PV2061 were 30%, 31% and 39%, while those of β-sheets were 28%. 30% and 41%, and those of β coil were 29%, 30% and 41%, respectively. Meanwhile, the sites and numbers of potential B cell antigen epitopes of glycoprotein of the three strains were similar. Conclusion The bioinformatics of glycoprotein of three rabies vaccine virus strains were analyzed, which provided a support for perfecting the standard for quality control of virus strains for

  10. Rabies vaccination for international travelers.

    Science.gov (United States)

    Gautret, Philippe; Parola, Philippe

    2012-01-05

    Rabies prevention in travelers is a controversial issue. According to experts, the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveler, the rabies endemicity and access to appropriate medical care in the country of destination. However, no detailed information is available regarding the last two determinants in many regions. Twenty-two cases of rabies were reported in tourists, expatriates and migrant travelers over the last decade, including three cases following short-term travel of no more than two weeks. Studies on rabies post-exposure prophylaxis (PEP) in travelers show that overall, 0.4% (range 0.01-2.3%) of travelers have experienced an at-risk bite per month of stay in a rabies-endemic country, while 31% of expatriates and 12% of tourists were vaccinated against rabies before traveling. The main reason cited by travelers for not being vaccinated is the cost of the vaccine. The majority of patients who sustained a high risk injury was not vaccinated against rabies before traveling and were not properly treated abroad. From available studies, the following risk factors for injuries sustained from potentially rabid animals may be identified: traveling to South-East Asia, India or North Africa, young age, and traveling for tourism. The duration of travel does not appear to be a risk factor. It should be noted that "at-risk activities" have not been addressed in these studies. Detailed rabies distribution maps and information on the availability of rabies biologics are urgently needed in order to identify those travelers who need pre-travel vaccination. Meanwhile, cost-minimization of rabies pre-exposure vaccination may be achieved in several ways, notably by using the intra-dermal method of vaccination.

  11. Acute flaccid paralysis due to rabies

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    J B Ghosh

    2009-01-01

    Full Text Available Two clinical forms of rabies are recognize: i a furious form associated with classical signs of excitation or phobic symptoms, ii Dumb rabies (paralytic rabies characterized by progressive paralysis without an initial furious phase wherein distinction from Guillain-Barrι Syndrome may be difficult. Paralytic rabies is more common in persons who have received postexposure vaccination. We report here the diagnostic dilemma of two cases of acute flaccid paralysis due to rabies.

  12. Rabies vaccination campaigns in dogs and cats, and rabies positivity in bats, from 2004 to 2014, in Campinas, São Paulo, Brazil.

    Science.gov (United States)

    Rodrigues, Ricardo Conde Alves; Zuben, Andrea Paula Bruno von; Lucca, Tosca de; Reichmann, Maria de Lourdes Aguiar Bonadia

    2017-01-01

    to describe the results of rabies vaccination campaigns in dogs and cats from 2004 to 2009 and from 2012 to 2014, and the positivity for rabies in bats from 2004 to 2014, in Campinas-SP, Brazil. a descriptive study was carried out with secondary data from the Zoonoses Surveillance Unit. there was a marked reduction in the number of vaccinated dogs, from 105,764 (2004) to 65,561 (2014), with vaccine coverage below 80%, except in 2004; there was little oscillation in the number of vaccinated cats, from 10,212 (2004) to 9,522 (2014), with vaccine coverage below 80%, except in 2014; 4,464 bats were collected by passive surveillance, 2.17% of them were positive for rabies. the low vaccine coverage in dogs and cats and the circulation of the virus in bats imposes the need for improvement in surveillance actions, in order to prevent cases of human rabies.

  13. Elimination of Dog-Mediated Human Rabies Deaths by 2030: Needs Assessment and Alternatives for Progress Based on Dog Vaccination.

    Science.gov (United States)

    Wallace, Ryan M; Undurraga, Eduardo A; Blanton, Jesse D; Cleaton, Julie; Franka, Richard

    2017-01-01

    Rabies imposes a substantial burden to about half of the world population. The World Health Organization (WHO), World Organization for Animal Health, and the Food and Agriculture Organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. This could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. Here, we focused on the resources needed for the elimination of dog rabies virus by 2030. Drawing from multiple datasets, including national dog vaccination campaigns, rabies literature, and expert opinion, we developed a model considering country-specific current dog vaccination capacity to estimate the years and resources required to achieve dog rabies elimination by 2030. Resources were determined based on four factors: (a) country development status, (b) dog vaccination costs, (c) dog rabies vaccine availability, and (d) existing animal health workers. Our calculations were based on the WHO's estimate that vaccinating 70% of the dog population for seven consecutive years would eliminate rabies. If dog rabies vaccine production remains at 2015 levels, we estimate that there will be a cumulative shortage of about 7.5 billion doses to meet expected demand to achieve dog rabies elimination. We estimated a present cost of $6,300 million to eliminate dog rabies in all endemic countries, equivalent to a $3,900 million gap compared to current spending. To eliminate dog rabies, the vaccination workforce may suffice if all public health veterinarians in endemic countries were to dedicate 3 months each year to dog rabies vaccination. We discuss implications of potential technology improvements, including population management, vaccine price reduction, and increases in dog-vaccinating capacities. Our results highlight the resources needed to achieve elimination of dog-mediated human rabies deaths by 2030. As exemplified by multiple successful disease

  14. Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies

    Science.gov (United States)

    Rupprecht, Charles; Kuzmin, Ivan; Meslin, Francois

    2017-01-01

    Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies. Africa is the likely home to the ancestors of taxa residing within the Genus Lyssavirus, Family Rhabdoviridae. Diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. In terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species today, but for unknown reasons. All mammals are believed to be susceptible to rabies virus infection. Besides reservoirs among the Chiroptera, meso-carnivores also serve as major historical hosts and are represented among the canids, raccoons, skunks, mongooses, and ferret badgers.  Perpetuating as a disease of nature with the mammalian central nervous system as niche, host breadth alone precludes any candidacy for true eradication. Despite having the highest case fatality of any infectious disease and a burden in excess of or comparative to other major zoonoses, rabies remains neglected. Once illness appears, no treatment is proven to prevent death. Paradoxically, vaccines were developed more than a century ago, but the clear majority of human cases are unvaccinated. Tens of millions of people are exposed to suspect rabid animals and tens of thousands succumb annually, primarily children in developing countries, where canine rabies is enzootic. Rather than culling animal populations, one of the most cost-effective strategies to curbing human fatalities is the mass vaccination of dogs. Building on considerable progress to date, several complementary actions are needed in the near future, including a more harmonized approach to viral taxonomy, enhanced de-centralized laboratory-based surveillance, focal pathogen discovery and characterization, applied pathobiological research for therapeutics, improved estimates of canine populations at risk, actual production of required

  15. Epidemiological and clinical features of human rabies cases in Bali 2008-2010

    Directory of Open Access Journals (Sweden)

    Susilawathi Ni M

    2012-04-01

    Full Text Available Abstract Background Previously thought to be rabies free, Bali experienced an outbreak of animal and human rabies cases in November 2008. We describe the epidemiological and clinical data of human rabies cases occurring in the first two years of the outbreak. Methods We analysed the patient records of all rabies cases from the Sanglah General Hospital in Denpasar, and district hospitals in Buleleng and Tabanan. A conventional reverse transcriptase polymerase chain reaction was developed to detect the rabies virus genome in saliva, corneal swabs, and ante- and post-mortem cerebrospinal fluid (CSF. Results There were 104 human rabies cases in Bali during November 2008-November 2010. Patients' mean age was 36.6 years (range 3-84 years; SD 20.7, most were male (56.7%, and originated from rural districts. Almost all (92% cases had a history of dog bite. Only 5.8% had their wounds treated and received an anti-rabies vaccine (ARV after the bite incident. No patients received rabies immunoglobulin (RIG. The estimated time from dog bite to the onset of signs and symptoms was 110.4 days (range 12-720 days; SD 118.2. The mean length of medical care until death was 21.8 hours (range 1-220 hours; SD 32.6. Less than 50% of patients had prodromal symptoms. The most frequent prodromal symptom was pain or paraesthesia at the bite site (37.6%. The two most common central nervous system infection signs were agitation (89.2% and confusion (83.3%. Signs of autonomic nervous system dysfunction included hydrophobia (93.1%, hypersalivation (88.2%, and dyspnea (74.4%. On admission, 22 of 102 patients (21.6% showed paralytic manifestations, while the rest (78.4% showed furious rabies manifestations. The case-fatality rate was 100%. The rabies virus genome was detected in 50 of 101 patients (49.5% with the highest detection rate from post-mortem CSF samples. Conclusions Rabies is a major public health problem in Bali. Human fatalities occur because of a lack of knowledge

  16. First human rabies case in French Guiana, 2008: epidemiological investigation and control.

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    Jean-Baptiste Meynard

    Full Text Available BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species, closely related to those circulating in hematophagous bats (mainly Desmodus rotundus in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.

  17. Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru.

    Directory of Open Access Journals (Sweden)

    Ricardo Castillo-Neyra

    2017-03-01

    Full Text Available Canine rabies was reintroduced to the city of Arequipa, Peru in March 2015. The Ministry of Health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in Arequipa's complex urban environment, putting the city's 1 million inhabitants at risk of infection. The proximate driver of canine rabies in Arequipa is low dog vaccination coverage. Our objectives were to qualitatively assess barriers to and facilitators of rabies vaccination during mass campaigns, and to explore strategies to increase participation in future efforts.We conducted 8 focus groups (FG in urban and peri-urban communities of Mariano Melgar district; each FG included both sexes, and campaign participants and non-participants. All FG were transcribed and then coded independently by two coders. Results were summarized using the Social Ecological Model. At the individual level, participants described not knowing enough about rabies and vaccination campaigns, mistrusting the campaign, and being unable to handle their dogs, particularly in peri-urban vs. urban areas. At the interpersonal level, we detected some social pressure to vaccinate dogs, as well as some disparaging of those who invest time and money in pet dogs. At the organizational level, participants found the campaign information to be insufficient and ill-timed, and campaign locations and personnel inadequate. At the community level, the influence of landscape and topography on accessibility to vaccination points was reported differently between participants from the urban and peri-urban areas. Poor security and impermanent housing materials in the peri-urban areas also drives higher prevalence of guard dog ownership for home protection; these dogs usually roam freely on the streets and are more difficult to handle and bring to the vaccination points.A well-designed communication campaign could improve knowledge about canine rabies. Timely messages

  18. Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru.

    Science.gov (United States)

    Castillo-Neyra, Ricardo; Brown, Joanna; Borrini, Katty; Arevalo, Claudia; Levy, Michael Z; Buttenheim, Alison; Hunter, Gabrielle C; Becerra, Victor; Behrman, Jere; Paz-Soldan, Valerie A

    2017-03-01

    Canine rabies was reintroduced to the city of Arequipa, Peru in March 2015. The Ministry of Health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in Arequipa's complex urban environment, putting the city's 1 million inhabitants at risk of infection. The proximate driver of canine rabies in Arequipa is low dog vaccination coverage. Our objectives were to qualitatively assess barriers to and facilitators of rabies vaccination during mass campaigns, and to explore strategies to increase participation in future efforts. We conducted 8 focus groups (FG) in urban and peri-urban communities of Mariano Melgar district; each FG included both sexes, and campaign participants and non-participants. All FG were transcribed and then coded independently by two coders. Results were summarized using the Social Ecological Model. At the individual level, participants described not knowing enough about rabies and vaccination campaigns, mistrusting the campaign, and being unable to handle their dogs, particularly in peri-urban vs. urban areas. At the interpersonal level, we detected some social pressure to vaccinate dogs, as well as some disparaging of those who invest time and money in pet dogs. At the organizational level, participants found the campaign information to be insufficient and ill-timed, and campaign locations and personnel inadequate. At the community level, the influence of landscape and topography on accessibility to vaccination points was reported differently between participants from the urban and peri-urban areas. Poor security and impermanent housing materials in the peri-urban areas also drives higher prevalence of guard dog ownership for home protection; these dogs usually roam freely on the streets and are more difficult to handle and bring to the vaccination points. A well-designed communication campaign could improve knowledge about canine rabies. Timely messages on where and

  19. Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru

    Science.gov (United States)

    Brown, Joanna; Borrini, Katty; Arevalo, Claudia; Levy, Michael Z.; Buttenheim, Alison; Hunter, Gabrielle C.; Becerra, Victor; Behrman, Jere; Paz-Soldan, Valerie A.

    2017-01-01

    Background Canine rabies was reintroduced to the city of Arequipa, Peru in March 2015. The Ministry of Health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in Arequipa’s complex urban environment, putting the city’s 1 million inhabitants at risk of infection. The proximate driver of canine rabies in Arequipa is low dog vaccination coverage. Our objectives were to qualitatively assess barriers to and facilitators of rabies vaccination during mass campaigns, and to explore strategies to increase participation in future efforts. Methodology/Principal findings We conducted 8 focus groups (FG) in urban and peri-urban communities of Mariano Melgar district; each FG included both sexes, and campaign participants and non-participants. All FG were transcribed and then coded independently by two coders. Results were summarized using the Social Ecological Model. At the individual level, participants described not knowing enough about rabies and vaccination campaigns, mistrusting the campaign, and being unable to handle their dogs, particularly in peri-urban vs. urban areas. At the interpersonal level, we detected some social pressure to vaccinate dogs, as well as some disparaging of those who invest time and money in pet dogs. At the organizational level, participants found the campaign information to be insufficient and ill-timed, and campaign locations and personnel inadequate. At the community level, the influence of landscape and topography on accessibility to vaccination points was reported differently between participants from the urban and peri-urban areas. Poor security and impermanent housing materials in the peri-urban areas also drives higher prevalence of guard dog ownership for home protection; these dogs usually roam freely on the streets and are more difficult to handle and bring to the vaccination points. Conclusions A well-designed communication campaign could improve

  20. Evolutionary history of rabies in Ghana.

    Directory of Open Access Journals (Sweden)

    David T S Hayman

    Full Text Available Rabies virus (RABV is enzootic throughout Africa, with the domestic dog (Canis familiaris being the principal vector. Dog rabies is estimated to cause 24,000 human deaths per year in Africa, however, this estimate is still considered to be conservative. Two sub-Saharan African RABV lineages have been detected in West Africa. Lineage 2 is present throughout West Africa, whereas Africa 1a dominates in northern and eastern Africa, but has been detected in Nigeria and Gabon, and Africa 1b was previously absent from West Africa. We confirmed the presence of RABV in a cohort of 76 brain samples obtained from rabid animals in Ghana collected over an eighteen-month period (2007-2009. Phylogenetic analysis of the sequences obtained confirmed all viruses to be RABV, belonging to lineages previously detected in sub-Saharan Africa. However, unlike earlier reported studies that suggested a single lineage (Africa 2 circulates in West Africa, we identified viruses belonging to the Africa 2 lineage and both Africa 1 (a and b sub-lineages. Phylogeographic Bayesian Markov chain Monte Carlo analysis of a 405 bp fragment of the RABV nucleoprotein gene from the 76 new sequences derived from Ghanaian animals suggest that within the Africa 2 lineage three clades co-circulate with their origins in other West African countries. Africa 1a is probably a western extension of a clade circulating in central Africa and the Africa 1b virus a probable recent introduction from eastern Africa. We also developed and tested a novel reverse-transcription loop-mediated isothermal amplification (RT-LAMP assay for the detection of RABV in African laboratories. This RT-LAMP was shown to detect both Africa 1 and 2 viruses, including its adaptation to a lateral flow device format for product visualization. These data suggest that RABV epidemiology is more complex than previously thought in West Africa and that there have been repeated introductions of RABV into Ghana. This analysis

  1. The role of viral evolution in rabies host shifts and emergence

    Science.gov (United States)

    Mollentze, Nardus; Biek, Roman; Streicker, Daniel G

    2014-01-01

    Despite its ability to infect all mammals, Rabies virus persists in numerous species-specific cycles that rarely sustain transmission in alternative species. The determinants of these species-associations and the adaptive significance of genetic divergence between host-associated viruses are poorly understood. One explanation is that epidemiological separation between reservoirs causes neutral genetic differentiation. Indeed, recent studies attributed host shifts to ecological factors and selection of ‘preadapted’ viral variants from the existing viral community. However, phenotypic differences between isolates and broad scale comparative and molecular evolutionary analyses indicate multiple barriers that Rabies virus must overcome through adaptation. This review assesses various lines of evidence and proposes a synthetic hypothesis for the respective roles of ecology and evolution in Rabies virus host shifts. PMID:25064563

  2. Human rabies in rural Bangladesh.

    Science.gov (United States)

    Hossain, M; Ahmed, K; Bulbul, T; Hossain, S; Rahman, A; Biswas, M N U; Nishizono, A

    2012-11-01

    Rabies is a major public health problem in Bangladesh, where most of the population live in rural areas. However, there is little epidemiological information on rabies in rural Bangladesh. This study was conducted in 30 upazilas (subdistricts) covering all six divisions of the country, to determine the levels of rabies and animal bites in Bangladesh. The total population of these upazilas was 6 992 302. A pretested questionnaire was used and data were collected by interviewing the adult members of families. We estimated that in Bangladesh, 166 590 [95% confidence interval (CI) 163 350-170 550] people per year are bitten by an animal. The annual incidence of rabies deaths in Bangladesh was estimated to be 1·40 (95% CI 1·05-1·78)/100 000 population. By extrapolating this, we estimated that 2100 (95% CI 1575-2670) people die annually from rabies in Bangladesh. More than three-quarters of rabies patients died at home. This community-based study provides new information on rabies epidemiology in Bangladesh.

  3. Rabies and Risk to Travelers

    Centers for Disease Control (CDC) Podcasts

    2007-10-01

    Each year over 55,000 people die because of rabies, mostly from being bitten by rabid dogs. Over half of all rabies infections occur in children under the age of 15 who live in developing countries, but travelers are not immune. This podcast discusses some of the activities that put travelers at risk for rabies and describes ways to prevent infection.  Created: 10/1/2007 by National Center for the Prevention, Detection and Control of Infectious Diseases (NCPDCID).   Date Released: 10/5/2007.

  4. Rabies, canine distemper, and canine parvovirus exposure in large carnivore communities from two Zambian ecosystems.

    Science.gov (United States)

    Berentsen, Are R; Dunbar, Mike R; Becker, Matthew S; M'soka, Jassiel; Droge, Egil; Sakuya, Nicholas M; Matandiko, Wigganson; McRobb, Rachel; Hanlon, Cathleen A

    2013-09-01

    Disease transmission within and among wild and domestic carnivores can have significant impacts on populations, particularly for threatened and endangered species. We used serology to evaluate potential exposure to rabies virus, canine distemper virus (CDV), and canine parvovirus (CPV) for populations of African lions (Panthera leo), African wild dogs (Lycaon pictus), and spotted hyenas (Crocuta crocuta) in Zambia's South Luangwa National Park (SLNP) and Liuwa Plain National Park (LPNP) as well as community lands bordering these areas. In addition, domestic dogs in the study region were evaluated for exposure to CDV and rabies. We provide the first comprehensive disease exposure data for these species in these ecosystems. Twenty-one lions, 20 hyenas, 13 wild dogs, and 38 domestic dogs were sampled across both regions from 2009 to 2011. Laboratory results show 10.5% of domestic dogs, 5.0% of hyenas, and 7.7% of wild dogs sampled were positive for CDV exposure. All lions were negative. Exposure to CPV was 10.0% and 4.8% for hyenas and lions, respectively. All wild dogs were negative, and domestic dogs were not tested due to insufficient serum samples. All species sampled were negative for rabies virus neutralizing antibodies except lions. Forty percent of lions tested positive for rabies virus neutralizing antibodies. Because these lions appeared clinically healthy, this finding is consistent with seroconversion following exposure to rabies antigen. To our knowledge, this finding represents the first ever documentation of rabies virus neutralizing antibodies consistent with rabies exposure that did not lead to clinical disease in free-ranging African lions from this region. With ever-increasing human pressure on these ecosystems, understanding disease transmission dynamics is essential for proper management and conservation of these carnivore species.

  5. Pengetahuan Masyarakat Tentang Rabies Dalam Upaya Bali Bebas Rabies

    Directory of Open Access Journals (Sweden)

    I Nyoman Suartha

    2012-02-01

    Full Text Available This study aims to determine the level of public knowledge about rabies in an effort to Balirabies-free. The data were collected from three villages namely Kukuh in Tabananregency, Jagapati in Badung regency, and Seraya in Karangasem regency. The mentiontotal of responden are 991 people. Data were collected using questionnaire. Results showedthat respondents who do not know about the news that rabies has been in outbreak in Balias much as 33.3%. The sources of information about the disease of rabies came from themedia (TV, newspapers, radio as much as 44%, and 31% from health extension program.First aid to do if bitten by a dog was wash wound with soap (80%, but there were alsoresponden who do not care for themself (4%. Most responden would go to health centerfor treatment (85% if they were bitten by rabies dogs. But , there were also few respondenwho take no care and do nothing (7%. Public knowledge about the clinical symptoms of rabies was still low (53%, and as much as 39% of respondents did not know the signs ofrabies. Knowing of report place if there was an event of rabies or finding a dog with rabieswas to the head of the village (41%, to the Department of Animal Husbandry (39% andnot reporting 4%. The conclusion of this study is the public knowledge about the disease ofrabies is moderate.

  6. 贵州省狂犬病病毒流行毒株与疫苗毒株糖蛋白基因差异研究%Study on the differences of glycoprotein gene between rabies virus epidemic strains from Guizhou province and vaccine strains

    Institute of Scientific and Technical Information of China (English)

    李世军; 田克诚; 唐光鹏; 余春; 王定明; 唐青; 陶晓燕; 李浩; 庄妍; 周敬祝; 王月

    2012-01-01

    Objective To study the differences of glycoprotein gene (G gene) between rabies virus epidemic strains of Guizhou province in recent years and vaccine strains,and to provide scientific basis for the development of rabies vaccine and establishment of effective control and prevention measures.Methods RT-PCR assay was used to amplify the G gene of rabies positive brain tissues samples of human and dog derived from Guizhou province in recent years.The amplification products were sequenced and comparatively analyzed with that of vaccine strains by using bioinformatics software.Results Eight full-length G gene sequences were obtained by RT-PCR amplification,sequencing and splicing.The homogeny of G gene between 8 epidemic strains of Guizhou province and 9 vaccine strains were 82.0%-94.1% and 87.6%-97.5% on nucleotide and deduced amino acid level,respectively,and the highest homogeny were found with the human vaccine strain CTN (87.0%-94.1% for nucleotide and 93.7.%-97.5% for amino acid) among the 6 human rabies vaccine strains,while highest homogeny were found with strain Flury (83.9%-84.6% for nucleotide and 91.1%-93.0% for amino acid) among the three animal vaccine strains.Besides,among the 8 epidemic strains from Guizhou province,strain GZ09 collected in the year of 2005 was of the highest homogeny with human rabies vaccine strain CTN and animal rabies vaccine strain Flury,while strain GZ30 collected in the year of 2010 was of lowest homogeny with human rabies vaccine strain CTN and animal rabies vaccine strain Flury.Moreover,phylogenetic analysis based on the G gene indicated that the relationship of 8 epidemic strains derived from Guizhou,the 9 vaccine strains and genotype 1 Lyssavirus were clustered to a same branch.Vaccine strain CTN among the 9 vaccine strains was closest to the 8 epidemic strains,and the other 8 vaccine strains were relatively more distant from the epidemic strains of Guizhou province.In addition,phylogenetic analysis

  7. 狂犬病毒糖蛋白衍生物作为靶脑载体初探%New Brain Delivery Vector: Rabies Virus Glycoprotein-derived Peptide

    Institute of Scientific and Technical Information of China (English)

    王逸麟; 付爱玲

    2011-01-01

    血脑屏障( blood-brain barrier,BBB)阻碍了具有治疗潜力的大分子化合物从外周组织进入脑内.为了寻找一种高效、快速通过BBB的靶向性载体,实验通过罗丹明B标记的狂犬病毒糖蛋白衍生肽(RDP)注射入昆明小鼠体内,并于15 min、5h取大脑、脊髓及肝、肾等外周组织,冷冻切片观察其在体内的分布,并通过构建pET28 a-RDP-luciferase重组质粒,结果发现融合蛋白能快速地穿过血脑屏障分布于中枢神经系统,为治疗中枢神经系统的药物开发提供新的思路.%Blood-brain barrier (BBB) prevents the transport pathway of potential macromolecular protein from blood to brain in order to find an efficient brain delivery vector, the rhodamine B labeled rabies virus glycoprotein-derived peptide (RDP)is applied to inject Kunming mice, and 15 min or 5 h take the brain, spinal cord, liver, kidney and so on. Frozen sections were observed the distribution. The RDP gene and luciferase gene were fused to the pET28a plasmid. The fusion protein can cross the BBB and distributed in the central nervous system rapidly. RDP can be used in future engineering of therapeutic fusion proteins for BBB drug delivery.

  8. Rabies in travelers.

    Science.gov (United States)

    Gautret, Philippe; Parola, Philippe

    2014-03-01

    Most cases of rabies in travelers are associated with dog bites and occur in adults who are commonly migrants. The incidence of injuries to travelers caused by potentially rabid animals is approximately 0.4 % per month of stay. Dogs account for 51 % of cases, but nonhuman primates are the leading animals responsible for injuries in travelers returning from Southeast Asia. Travel to Southeast Asia, India and North Africa, young age, and traveling for tourism are risk factors for potential exposure. More than 70 % of travelers are not immunized prior to departing and do not receive adequate care when injured. The intradermal vaccination route has been proven economical, safe and immunogenic in travelers. The immunity provided by the three-dose series is long-lasting and should be considered an investment for future travel. Abbreviated schedules may be used for last-minute travelers.

  9. [A new approach to postexposure treatment of rabies by complex of immuno- and chemotherapy in belarus].

    Science.gov (United States)

    Mishaeva, N P; Votiakov, V I; Titov, L P; Naralenkov, V A; Nekhaĭ, M R; Sinkevich, V V; Kurlukov, A I; Gorbunov, V A

    2013-01-01

    A method for preventive treatment of rabies with a complex of immuno- and chemotherapeutics was developed. Rifampicin was used a an etiotropic drug. In the experiments on laboratory animals infected with fixed and street strains of rabies virus it was shown to prolong the incubation period and to increase the survival rate. The protective mechanisms of rifampicin against rabies should be associated with inhibition of RNA transcription, as well as immunomodulating function of macrophages, dendritic cells, B- and T-cells. Since 1992, after the approval of the Ministry of Health of Belarus rifampicin is used in complex with antirabic vaccine for postexposure treatment of rabies in people after severe bites by infected animals (wolves, foxes, dogs). For an 18-year period (1992-2009) of integrated application of chemo- and immunotherapy in Belarus there was not registered any case of hydrophobia in people even after the heaviest wolf bites, incompatible with life (penetrating injuries of the skull, scalping, multiple bites).

  10. Calbindin distribution in cortical and subcortical brain structures of normal and rabies-infected mice.

    Science.gov (United States)

    Torres-Fernández, Orlando; Yepes, Gloria E; Gómez, Javier E; Pimienta, Hernán J

    2005-10-01

    Rabies has been an enigmatic disease of the nervous system because microscopic findings in the brain tissue are not paralleled by the severity of the clinical illness. The calcium binding protein calbindin (CB) is a neuronal marker of great interest in neuroanatomy and neuropathology. CB-ir neurons in the striatum and cerebral cortex are gabaergic cells. In the present work CB-immunoreactivity was evaluated in brains of normal and rabies-infected mice. Rabies infection caused loss of CB-immunostaining in the cortical supragranular layers as well as in the striatum. Loss of CB in the brains of mice infected with rabies virus can produce impairment in Ca++ homeostasis and in the gabaergic neurotransmission.

  11. Immunogenicity and efficacy of two rabies vaccines in wild-caught, captive raccoons.

    Science.gov (United States)

    Brown, L J; Rosatte, R C; Fehlner-Gardiner, C; Knowles, M K; Bachmann, P; Davies, J C; Wandeler, A; Sobey, K; Donovan, D

    2011-01-01

    The immunogenicity and efficacy of two rabies vaccines in wild-caught, captive raccoons (Procyon lotor) were investigated. Raccoons were fed Ontario Slim (OS) baits containing a recombinant vaccinia virus-rabies glycoprotein (VRG) oral rabies vaccine, or they were given an intramuscular (IM) injection of IMRAB(®) 3 rabies vaccine. Blood samples collected before treatment and from weeks 1 to 16 posttreatment were assessed for the presence of rabies virus antibody (RVA). There were significantly more positive responders in the group that received an IM injection of IMRAB 3 (18/27) than in the group that consumed VRG in OS baits (VRG-OS; 4/ 26). There were no significant associations among age, sex, and seroconversion. Of those animals that mounted a humoral immune response to vaccination, RVA was first detected between weeks 1 and 5, with the majority of initial seroconversions detectable at week 2. A subsample of 50 raccoons (19 VRG-OS, 18 IMRAB 3, and 13 controls) from the longitudinal serology study was challenged with live raccoon variant rabies virus 442 days after initial treatment. There were significantly more survivors in the group that received IMRAB 3 (13/18) than in the VRG-OS (5/19) or control (2/13) groups. All 15 raccoons that demonstrated a serologic response survived challenge regardless of treatment. Of the 35 raccoons with no detectable serologic response, 30 (86%) succumbed to rabies virus infection (14/15 VRG-OS, 5/7 IMRAB 3, and 11/13 controls).

  12. A comparative approach between heterologous prime-boost vaccination strategy and DNA vaccinations for rabies.

    Science.gov (United States)

    Borhani, Kiandokht; Ajorloo, Mehdi; Bamdad, Taravat; Mozhgani, Sayed Hamid Reza; Ghaderi, Mostafa; Gholami, Ali Reza

    2015-04-01

    Rabies is a widespread neurological zoonotic disease causing significant mortality rates, especially in developing countries. Although a vaccine for rabies is available, its production and scheduling are costly in such countries. Advances in recombinant DNA technology have made it a good candidate for an affordable vaccine. Among the proteins of rabies virus, the Glycoprotein (RVG) has been the major target for new vaccine development which plays the principal role in providing complete protection against RV challenge. The aim of this study is to produce recombinant RVG which could be a DNA vaccine candidate and to evaluate the efficiency of this construct in a prime-boost vaccination regimen, compared to commercial vaccine. Cloning to pcDNA3.1(+) and expression of rabies virus glycoprotein gene in BSR cell  line were performed followed by SDS-PAGE and Western blot analysis of the expressed glycoprotein. The resulting genetic construct was used as a DNA vaccine by injecting 80 µg of the plasmid to MNRI mice twice. Prime-Boost vaccination strategy was performed using 80 µg plasmid construct as prime dose and the second dose of an inactivated rabies virus vaccine. Production of rabies virus neutralizing antibody (RVNA) titers of the serum samples were determined by RFFIT. In comparisons between heterologous prime-boost vaccination strategy and DNA vaccinations, the potency of group D that received Prime-Boost vaccine with the second dose of pcDNA3.1(+)-Gp was enhanced significantly compared to the group C which had received pcDNA3.1(+)-Gp as first injection. In this study, RVGP expressing construct was used in a comparative approach between Prime-Boost vaccination strategy and DNA vaccination and compared with the standard method of rabies vaccination. It was concluded that this strategy could lead to induction of acceptable humoral immunity.

  13. Faktor-Faktor Risiko Rabies pada Anjing di Bali (RISK FACTORS ANALYSIS FOR RABIES INDOGS IN BALI

    Directory of Open Access Journals (Sweden)

    I Nyoman Dibia

    2015-10-01

    Full Text Available The efforts to eradicate rabies in Bali have been done for more than three years. However, therabiescases is still spreading. Thus, rabies virus continues to infect humans. A case-control study wasconducted to identify the risk factors associated with rabid dog in Bali. Cases were defined as dogsconfirmed having rabies by direct fluorescent antibody test (dFAT. Determination of sample amount ineach district was taken proportionally and samples were taken by using simple random sampling. A totalof 51 rabid dog cases between 2010 and 2011 and 102 uninfected rabies dogs as control were used in thisstudy. Possible associated factors were obtained by doing questionnaire. The data were subsequentlyanalyzed using chi-square (X2 and odds-ratio (OR for possible association, which were ultimately analyzedby means of logistic regression to build up of model. This study revealed that factors associated with rabiddog were the status of rabies vaccination (X2= 55.538; P= 0.000; OR= 19.133; 95% CI= 8.015rabies=1| x = - 4.413 + 3.919 (status of rabies vaccination + 3.457(contact with other dog. This study is expected to be used as a reference in order to improve rabies controleffectiveness in Bali.

  14. A presumptive case of Human rabies: a rare survived case in rural Ghana

    Directory of Open Access Journals (Sweden)

    Paschal Awingura Apanga

    2016-11-01

    Full Text Available Rabies remains endemic in Ghana and continues to pose a major public health threat to humans and animals with nearly hundred percent (100% case fatality rate in humans. We report of a presumptive case of human rabies whose survival was a rare occurrence in rural Ghana. Lessons from this case study provides a critically needed focus in helping improve rabies surveillance and case management in Ghana. We report of the survival of a 36 year old man who developed clinical rabies three weeks after he was bitten by his dog while restraining the dog with a chain. Prior to this he did not observe any abnormal or rabid behaviour in the dog. Following the bite, he did not immediately resort to hospital treatment, but rather to traditional application of herbs to the laceration he sustained after the bite. Reason given for not seeking immediate hospital treatment was that the dog was not rabid and lack of funds to seek hospital care. However, he began to show symptoms consistent with rabies virus infection after 10 days and was subsequently rushed to the hospital by relatives. At the hospital, he was administered human immune tetanus immunoglobulin, diazepam, ceftriaxone, paracetamol and intravenous fluids. No rabies vaccine was administered. Six days after commencing treatment patient became well, showed no signs of confused state of mind, hydrophobia nor photophobia. He was discharged home after 13 days of commencing treatment. This study provides insight on a presumptive case of Human rabies case that survived despite non-administration of rabies vaccine during esposure. It also exposes the weaknesses in the health and veterinary systems in rural Ghana regarding rabies surveillance and case management.

  15. How Can You Prevent Rabies in Animals?

    Science.gov (United States)

    ... 2008 Rabies in Wild Animals, 1958-2008 Rabid Raccoons Reported in the United States, 2008 Rabid Skunks ... 2009 Rabies in Wild Animals, 1959-2009 Rabid Raccoons Reported in the United States during 2009 Rabid ...

  16. Rabies: What Care Will I Receive?

    Science.gov (United States)

    ... March 1, 2010: Assessing Haitian Patients, Immigrants, and Refugees for Rabies Selection Criteria for Milwaukee Protocol August ... of the risk of rabies, bite wounds can cause serious injury such as nerve or tendon laceration ...

  17. Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae

    Directory of Open Access Journals (Sweden)

    Reaves Erik J

    2012-05-01

    Full Text Available Abstract Background Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP. To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus. Methods Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R and observed for >130 days. Oral and blood samples were collected and analyzed. Results Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D. was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429. No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody. Discussion This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically

  18. A conceptual model for the impact of climate change on fox rabies in Alaska, 1980-2010.

    Science.gov (United States)

    Kim, B I; Blanton, J D; Gilbert, A; Castrodale, L; Hueffer, K; Slate, D; Rupprecht, C E

    2014-02-01

    The direct and interactive effects of climate change on host species and infectious disease dynamics are likely to initially manifest\\ at latitudinal extremes. As such, Alaska represents a region in the United States for introspection on climate change and disease. Rabies is enzootic among arctic foxes (Vulpes lagopus) throughout the northern polar region. In Alaska, arctic and red foxes (Vulpes vulpes) are reservoirs for rabies, with most domestic animal and wildlife cases reported from northern and western coastal Alaska. Based on passive surveillance, a pronounced seasonal trend in rabid foxes occurs in Alaska, with a peak in winter and spring. This study describes climatic factors that may be associated with reported cyclic rabies occurrence. Based upon probabilistic modelling, a stronger seasonal effect in reported fox rabies cases appears at higher latitudes in Alaska, and rabies in arctic foxes appear disproportionately affected by climatic factors in comparison with red foxes. As temperatures continue a warming trend, a decrease in reported rabid arctic foxes may be expected. The overall epidemiology of rabies in Alaska is likely to shift to increased viral transmission among red foxes as the primary reservoir in the region. Information on fox and lemming demographics, in addition to enhanced rabies surveillance among foxes at finer geographic scales, will be critical to develop more comprehensive models for rabies virus transmission in the region.

  19. A molecular epidemiological study of rabies epizootics in kudu (Tragelaphus strepsiceros in Namibia

    Directory of Open Access Journals (Sweden)

    Nel Louis H

    2006-01-01

    Full Text Available Abstract Background A panel of 37 rabies virus isolates were collected and studied, originating mainly from the northern and central regions of Namibia, between 1980 and 2003. Results These virus isolates demonstrated a high degree of genetic similarity with respect to a 400 bp region of the nucleoprotein gene, with the virus isolates originating from kudu antelope (n = 10 sharing 97.2–100% similarity with jackal isolates, and 97–100% similarity with those isolated from domestic dogs. Phylogenetic analysis suggested that these viruses were all of the canid rabies biotype of southern Africa. The viruses from kudu were closely associated with jackal isolates (n = 6, bat-eared fox isolates (n = 2 and domestic dog isolates (n = 2 at the genetic level and identical at the amino acid level, irrespective of the year of isolation. Conclusion These data suggest that jackal and kudu may form part of the same epidemiological cycle of rabies in Namibian wildlife, and might demonstrate the close-relationship between rabies virus strains that circulate within Namibia and those that circulate between Namibia and its neighbouring countries such as Botswana and South Africa.

  20. 广西玉林市2005-2012年狂犬病病原学监测及病毒N基因特征分析%Surveillance of rabies virus and the N gene analysis in Yulin City, Guangxi, from 2005 to 2012

    Institute of Scientific and Technical Information of China (English)

    周开姣; 陈敏玫; 谭毅; 莫兆军; 莫毅

    2015-01-01

    Objective To analyze the surveillance results of rabies virus in Yulin City and the genetic characteristics of the rabies virus N gene. Methods Dog brain samples and saliva specimens from clinical cases were collected in Yulin City during 2005-2012 and were detected. The N gene of rabies virus were sequenced and their homology and phylogenetic analysis were compared. Results 728 samples of dog brain were collected and 7 of them (0.96% ) were positive for rabies virus by both DFA and RT-PCR testing, while 51.52% (17/33) of saliva samples were positive by RT-PCR method. The full length of 11 N gene sequences were acquired from 5 dog and 6 clinical cases, and their nucleotide similarities were 94.7%-100.0% . When compared with previously reported isolate strain in Guangxi (GX01) the nucleotide similarities were 94.5%-98.4%, and the newly identified strains in this study showed the highest similarity (94.6%-99.7%) with CTN vaccine strain. The phylogenetic analysis showed that dog virus strains were very close to the clinical case strains, and they belonged to the same branch in genotype I. Conclusion Rabies virus infections from 17 clinical cases and 7 dogs in Yulin were identified by molecular detection, and these rabies virus strains belonged to genotype I. The main factor of rabies widely spreading with high incidence in this area is the rabies virus continuously circulating in the dogs.%目的:分析2005—2012年广西玉林市狂犬病病原学监测结果及病毒N基因遗传变异特征,为狂犬病防控提供科学依据。方法2005—2012年在广西玉林市采集犬脑组织及临床诊断人狂犬病病例的唾液进行病原学检测,检测阳性标本进行N基因核苷酸序列测定、同源性比较和种系发生分析。结果共采集、检测外观健康犬脑组织728份、临床诊断人狂犬病病例唾液33份,RT-PCR检测阳性率分别为0.96%(7/728)和51.52%(17/33)。获得5条犬源、6条人源狂犬病病

  1. Sequencing and analysis of the complete genome of two wild-type strains of rabies virus isolated from dogs%两株犬源狂犬病病毒街毒株全基因组序列测定与分析

    Institute of Scientific and Technical Information of China (English)

    齐瑛琳; 金宏丽; 赵丽丽; 王化磊; 赵平森; 付玉; 涂长春; 杨松涛; 夏咸柱

    2011-01-01

    Objective In order to ascertain the prevalence and diversity of rabies viruses in China, two wild-type strains of rabies virus were isolated by intracerebral inoculation of mouse pups with homogenate samples. Methods The genomes of two isolates were amplified by RT-PCR with series of specified primers and cloned into pEASY-Blunt vectors. The recombinant plasmids were sequenced and the obtained sequences of virus were processed and assembled with Seqman software from DNAstar. Results Analysis of the diversity of the viral genomes, amino acid residues, and functional sites revealed that the genomes of the two rabies viruses (TJD04 and TJD05) have the same nucleotide length (11924 nts). The two genomes had similar nucleotides and amino acid residues and were homologous to Rhabdoviridae Lyssavirus according to BLAST and multi-sequence alignment. Both viruses had a genome with 5 ORFs, start and stop sites of genes were highly conserved, and both coded for the same number of amino acids. Compared to reference rabies viruses, the two viruses had little variation in terms of coded protein sequences but did vary in terms of the main functional sites of genes. The phylogenic tree showed that both viruses were type I genes and the viruses were highly homologous to the rabies strain BD06 from China. Both isolates were closely related evolutionarily and differed from other strains of the rabies virus from China (BD06). Conclusion Data showed that two isolates were probably natural wild-type forms of the rabies virus particular to China.%目的 对2株犬源狂犬病病毒街毒株全基因组测序,了解国内狂犬病病毒的流行和变异情况.方法 采用乳鼠脑内接种方法分离2株天津地区狂犬病病毒街毒株,RT-PCR扩增病毒DNA覆盖全基因组12个相互重叠的基因片段,PCR产物平端克隆后进行全基因组核苷酸序列测定,然后对其分子变异和进化特点进行分析.进行两分离株的序列相似性、氨基酸同源性、

  2. Rabies in Costa Rica: Documentation of the Surveillance Program and the Endemic Situation from 1985 to 2014

    Science.gov (United States)

    Brugger, Katharina; Sancho Vargas, Victor Hugo; González, Rocío; Aguilar, Olga; León, Bernal; Tichy, Alexander; Firth, Clair L.; Rubel, Franz

    2016-01-01

    Abstract This is the first comprehensive epidemiological analysis of rabies in Costa Rica. We characterized the occurrence of the disease and demonstrated its endemic nature in this country. In Costa Rica, as in other countries in Latin America, hematophagous vampire bats are the primary wildlife vectors transmitting the rabies virus to cattle herds. Between 1985 and 2014, a total of 78 outbreaks of bovine rabies was reported in Costa Rica, with documented cases of 723 dead cattle. Of cattle outbreaks, 82% occurred between 0 and 500 meters above sea level, and seasonality could be demonstrated on the Pacific side of the country, with significantly more outbreaks occurring during the wet season. A total of 1588 animal samples, or an average of 55 samples per year, was received by the veterinary authority (SENASA) for rabies diagnostic testing at this time. Of all samples tested, 9% (143/1588) were positive. Of these, 85.6% (125/1588) were from cattle; four dogs (0.3% [4/1588]) were diagnosed with rabies in this 30-year period. Simultaneously, an extremely low number (n = 3) of autochthonous rabies cases were reported among human patients, all of which were fatal. However, given the virus' zoonotic characteristics and predominantly fatal outcome among both cattle and humans, it is extremely important for healthcare practitioners and veterinarians to be aware of the importance of adequate wound hygiene and postexpositional rabies prophylaxis when dealing with both wild and domestic animal bites. PMID:26982168

  3. Immunogenicity and efficacy of an in-house developed cell-culture derived veterinarian rabies vaccine.

    Science.gov (United States)

    Kallel, Héla; Diouani, Mohamed Fethi; Loukil, Houssem; Trabelsi, Khaled; Snoussi, Mohamed Ali; Majoul, Samy; Rourou, Samia; Dellagi, Koussay

    2006-05-29

    The efficiency of an inactivated tissue culture rabies vaccine produced on BHK-21 cells, according to an in-house developed process, was evaluated and compared to a commercial cell-tissue culture vaccine (Rabisin). Fifteen experimental dogs from local common breed were duly conditioned during a quarantine period, then vaccinated via the subcutaneous route with 1 ml of either the tissue culture vaccine developed in-house or the commercial vaccine Rabisin. The immune response of each dog was monitored for 162 days. Serum-neutralizing antibodies titers to rabies virus were determined by the rapid fluorescent focus inhibition test (RFFIT) which confirmed the strong response of dogs to both vaccines except one dog in the Rabisin group. The dogs were then challenged in the masseter muscle with a rabies street virus of canine origin. All vaccinated dogs except the single dog in the Rabisin group that failed to respond to the vaccine, survived the challenge. In contrast, 80% of animals in the control non-vaccinated group, developed rabies and died. A field vaccine trial was also conducted: 1,000 local dogs living in field conditions received one subcutaneous dose of the locally developed vaccine. Serum neutralizing antibody titers to rabies virus was determined by RFFIT at days 0, 60 and 360. Mean rabies neutralizing antibody titers were equal to 0.786, 3.73 and 1.55 IU/ml, respectively. The percentage of dogs with a neutralizing rabies antibody titer higher than the 0.5 IU/ml mandated WHO threshold, was 30%, 91.4% and 87.5% at day 0, 2 months and 1 year post-vaccination, respectively. These data demonstrate the efficiency of the in-house developed vaccine produced on BHK-21 cells in both experimental and field conditions and support its use in dog mass vaccination campaigns.

  4. Bat Rabies in France: A 24-Year Retrospective Epidemiological Study

    Science.gov (United States)

    Picard-Meyer, Evelyne; Robardet, Emmanuelle; Arthur, Laurent; Larcher, Gérald; Harbusch, Christine; Servat, Alexandre; Cliquet, Florence

    2014-01-01

    Since bat rabies surveillance was first implemented in France in 1989, 48 autochthonous rabies cases without human contamination have been reported using routine diagnosis methods. In this retrospective study, data on bats submitted for rabies testing were analysed in order to better understand the epidemiology of EBLV-1 in bats in France and to investigate some epidemiological trends. Of the 3176 bats submitted for rabies diagnosis from 1989 to 2013, 1.96% (48/2447 analysed) were diagnosed positive. Among the twelve recognised virus species within the Lyssavirus genus, two species were isolated in France. 47 positive bats were morphologically identified as Eptesicus serotinus and were shown to be infected by both the EBLV-1a and the EBLV-1b lineages. Isolation of BBLV in Myotis nattereri was reported once in the north-east of France in 2012. The phylogenetic characterisation of all 47 French EBLV-1 isolates sampled between 1989 and 2013 and the French BBLV sample against 21 referenced partial nucleoprotein sequences confirmed the low genetic diversity of EBLV-1 despite its extensive geographical range. Statistical analysis performed on the serotine bat data collected from 1989 to 2013 showed seasonal variation of rabies occurrence with a significantly higher proportion of positive samples detected during the autumn compared to the spring and the summer period (34% of positive bats detected in autumn, 15% in summer, 13% in spring and 12% in winter). In this study, we have provided the details of the geographical distribution of EBLV-1a in the south-west of France and the north-south division of EBLV-1b with its subdivisions into three phylogenetic groups: group B1 in the north-west, group B2 in the centre and group B3 in the north-east of France. PMID:24892287

  5. Factors associated with dog rabies immunisation status in Bamako, Mali.

    Science.gov (United States)

    Mauti, S; Traoré, A; Hattendorf, J; Schelling, E; Wasniewski, M; Schereffer, J L; Zinsstag, J; Cliquet, F

    2017-01-01

    We conducted a cross-sectional survey in Bamako, Mali, to determine for the first time the seroprevalence of rabies virus antibodies in the dog population and people's knowledge, attitudes and practices (KAP) towards the disease and its control. Antibody detection was done with the fluorescent antibody virus neutralisation (FAVN) test, with a positivity threshold of 0.25IU/ml. We visited 2956 households in 2010 and 2011 and found 379 dogs in 279 households. Data were collected on 279 dog-owning households, on 1017 non-dog-owning households and on 311 dogs. A serum or plasma sample was collected from 98 dogs. For 26 dogs we had sufficient data to describe the antibody decline over time after rabies vaccination using a quadratic regression. Ninety percent of interviewed persons (95% CI: 85%-91%) knew about rabies. The majority of interviewees knew that rabies is transmitted from dogs to humans, and some of the characteristic clinical signs seen in rabid dogs (change of behaviour, biting, salivation) could be listed by the majority. When asked how people behave regarding a rabid dog, killing the animal was the most frequent answer (>70%). Most (65% of the non-dog-owners and 81% of the dog-owners) were aware that vaccination of dogs can prevent rabies, but only a minority of dog-owners could answer correctly at what age the dog should get a first rabies vaccination (i.e. at 3 months). There was also strong consensus among dog-owners that it is better to protect their dog from becoming rabid by vaccinating it rather than needing to treat a bitten person. Forty-five percent (n=306; 95% CI 38%-52%) of dogs were reported as vaccinated against rabies at least once, but less than half of these (59/136) had a valid vaccination card. When asked for reasons for non-vaccination, cost was the most frequent reason at 31% (95% CI: 21%-43%), while general negligence was mentioned by 15% (95% CI: 10%-24%). Approximately one third of dog-owners would not pay for vaccination. To reach

  6. Raccoon dog rabies surveillance and post-vaccination monitoring in Lithuania 2006 to 2010

    Directory of Open Access Journals (Sweden)

    Zienius Dainius

    2011-11-01

    Full Text Available Abstract Background Oral rabies vaccination (ORV in rabies infected regions should target the primary rabies vector species, which in Lithuania includes raccoon dogs as well as red foxes. Specific investigations on ORV in raccoon dogs are needed e.g. evaluation of vaccine effectiveness under field conditions. The objective of the current study was to investigate the efficacy of the ORV programme 2006-2010 in Lithuania by examining the number of rabies cases and estimating the prevalences of a tetracycline biomarker (TTC and rabies virus antibodies in raccoon dogs. Methods From 2006 to 2010, 12.5 million rabies vaccine-baits were distributed by aircraft. Baiting occurred twice per year (spring and autumn, targeting raccoon dogs and red foxes in a 63,000 km2 area of Lithuania. The mandibles of raccoon dogs found dead or killed in the vaccination area were analyzed by fluorescence microscopy for the presence of the TTC. Rabies virus sera neutralizing anti-glycoprotein antibody titres were determined using an indirect ELISA method and seroconversion (> 0.5 EU/ml rates were estimated. Results During the study period, 51.5% of raccoon dog mandibles were positive for TTC. 1688 of 3260 tested adults and 69 of 175 tested cubs were TTC positive. Forty-seven percent of raccoon dog serum samples were positive for rabies virus antibodies. 302 of 621 investigated adults and 33 of 95 investigated cubs were seropositive. In the same time 302 of 684 and 43 of 124 tested samples were TTC and ELISA positive in spring; whereas 1455 of 2751 and 292 of 592 tested samples were TTC and ELISA positive in autumn. There was a positive correlation between the number of TTC and antibody positive animals for both adult and cub groups. Conclusions ORV was effective in reducing the prevalence of rabies in the raccoon dog population in Lithuania. The prevalence of rabies cases in raccoon dogs in Lithuania decreased from 60.7% in 2006-2007 to 6.5% in 2009-2010.

  7. Preparation and preliminary use of a gold immuno-chromatography assay to detect the rabies virus%狂犬病毒胶体金检测试纸的制备及初步应用

    Institute of Scientific and Technical Information of China (English)

    王铁成; 杨松涛; 王承宇; 高玉伟; 侯小强; 邹啸环; 黄耕; 夏咸柱

    2009-01-01

    Objective To develop a rapid, convenient, and specific method of immunochromatography assay (ICA) to detect the rabies virus(RV) in clinical specimens from naturally infected dogs. Methods Colloidal gold was prepared through deoxidization of trisodium citrate, and anti-RV monoclonal antibody labeled with colloidal gold was used as a detector. Anti-RV polyclonal antibody and sheep anti-mouse IgG were blotted on a nitrocellulose membrane for test and control lines, respectively. Results Colloidal gold test strips revealed a positive reaction to 15 mouse brains infected with RV, and results of FAT were the same. Reactions to CDV, CPV, CCV and healthy mouse brains were negative. Conclusion Colloidal gold test strips rapidly, conveniently and specifically detect RV, so these strips are suited to clinical diagnosis of RV.%目的 利用胶体金免疫层析技术建立一种快速、简便、特异的狂犬病毒检测方法. 方法 采用柠檬酸三钠还原法制备胶体金标记鼠抗狂犬病毒单克隆抗体,包被于结合释放垫处,分别利用纯化的兔抗狂犬病毒多克隆抗体和羊抗鼠IgG包被检测线及质控线,组装胶体金检测试纸. 结果 制备的狂犬病毒胶体金试纸对15个接种狂犬病毒乳鼠脑组织的检测均为阳性,与FAT结果一致;对犬瘟热病毒、犬细小病毒及犬冠状病毒细胞培养液及9个狂犬病毒阴性乳鼠脑处理液的检测均为阴性. 结论 用制备的狂犬病毒胶体金试纸检测狂犬病毒快速、简便、特异,具有良好的临床应用前景.

  8. Concomitant administration of GonaCon™ and rabies vaccine in female dogs (Canis familiaris) in Mexico.

    Science.gov (United States)

    Vargas-Pino, Fernando; Gutiérrez-Cedillo, Verónica; Canales-Vargas, Erick J; Gress-Ortega, Luis R; Miller, Lowell A; Rupprecht, Charles E; Bender, Scott C; García-Reyna, Patricia; Ocampo-López, Juan; Slate, Dennis

    2013-09-13

    Mexico serves as a global model for advances in rabies prevention and control in dogs. The Mexican Ministry of Health (MMH) annual application of approximately 16 million doses of parenteral rabies vaccine has resulted in significant reductions in canine rabies during the past 20 years. One collateral parameter of rabies programs is dog population management. Enhanced public awareness is critical to reinforce responsible pet ownership. Surgical spaying and neutering remain important to prevent reproduction, but are impractical for achieving dog population management goals. GonaCon™, an anti-gonadotropin releasing hormone (GnRH) vaccine, was initially tested in captive female dogs on the Navajo Nation, 2008. The MMH led this international collaborative study on an improved formulation of GonaCon™ in captive dogs with local representatives in Hidalgo, Mexico in 2011. This study contained 20 bitches assigned to Group A (6 control), Group B (7 GonaCon™), and Group C (7 GonaCon™ and rabies vaccine). Vaccines were delivered IM. Animals were placed under observation and evaluated during the 61-day trial. Clinically, all dogs behaved normally. No limping or prostration was observed, in spite of minor muscle atrophy post-mortem in the left hind leg of dogs that received GonaCon™. Two dogs that began the study pregnant give birth to healthy pups. Dogs that received a GonaCon™ injection had macro and microscopic lesions consistent with prior findings, but the adverse injection effects were less frequent and lower in intensity. Both vaccines were immunogenic based on significant increases in rabies virus neutralizing antibodies and anti-GnRH antibodies in treatment Groups B and C. Simultaneous administration of GonaCon™ and rabies vaccine in Group C did not affect immunogenicity. Progesterone was suppressed significantly in comparison to controls. Future studies that monitor fertility through multiple breeding cycles represent a research need to determine the

  9. 狂犬病病毒抗体竞争ELISA检测方法的建立及初步应用%Development and Preliminary Application of Competitive ELISA Method for Rabies Virus Antibody

    Institute of Scientific and Technical Information of China (English)

    王伟伟; 王远征; 张国强; 马昱

    2011-01-01

    Objective To develop a competitive ELBA method for rabies virus (RV) antibody and use for determination of antibody levels after immunization with of rabies vaccines prepared from various virus strains. Methods NIH mice were immunized with the antigens of commercial rabies vaccine prepared with various strains, and the obtained immune sera were determined for antibody titer by using the EIA plate coated with the antigens of various vaccine strains. The antigen diversity was analyzed by cross neutralization test of antigens and antibodies of various strains, based on which the EIA plate was coated with antigens of various strains mixed at different ratios to determine positive serum samples, and the results were compared with those by rapid fluorescent focus inhibition test (RFFTT) to determine the coating antigen, and a competitive ELISA method for RV antibody was developed, of which the optimal quantitative detection range and sensitivity were determined by plotting a standard curve, the cut-off value was determined, and the specificity, precision, accuracy and stability were verified. Serum samples were determined by the developed method, and the results were compared with those by other commercial kits for RV antibody to analyze the consistence and correlation. Results The coating pattern was optimized as mixing the antigens from AG and CTN-1 strains at a ratio of 4 : 1. After optimization, the linear detection range of the developed kit for antibody titer was 535. 00 - 33. 44 mlU/ml (r > 0. 99), while the minimum detection limit and cut-off value were 8. 36 mlU/ml and 0. 735 mill respectively. All the detection results of human serum albumin, tetanus positive serum, HBsAg positive serum and diphtheria positive quality control serum by the developed method were negative. The inter-variation coefficient of detection result by the developed method was 6. 68% ~ 7. 84%, while the recovery rate was 97. 25% ~ 104. 50%. The detection results by the developed kit after

  10. The Importance of Wild Canids in the Epidemiology of Rabies in Northeast Brazil: A Retrospective Study.

    Science.gov (United States)

    Cordeiro, R de A; Duarte, N F H; Rolim, B N; Soares Júnior, F A; Franco, I C F; Ferrer, L L; Almeida, C P; Duarte, B H; de Araújo, D B; Rocha, M F G; Brilhante, R S N; Favoretto, S R; Sidrim, J J C

    2016-09-01

    Rabies is an endemic disease in Brazil, where it is considered a serious public health problem. Although the number of human and dog-transmitted cases has declined in recent decades, rabies in wildlife has emerged considerably. Among the sylvatic animals, wild canids have been considered important hosts of the rabies virus. We performed a retrospective study of reported cases of rabies in wild canids and human victims in Ceará state (Northeast Brazil) during 2003 to 2013. Information was provided by governmental laboratories involved in rabies detection and by the Ministry of Health. From January 2003 to December 2013, a total of 11 931 animal samples were examined for rabies. Positivity were detected in 438 samples (3.67%), of which 229 (52.28%) were domestic animals, 105 (23.97%) wild canids and 104 (23.74%) other wild animals (bats, marmosets and raccoons). Approximately 33% of wild canids surveyed (n = 317) were positive for rabies. During the studied period, a total of 1923 attacks on humans by wild canids were registered. Males (n = 1405) were more affected than females (n = 520; 72.98% versus 27.01%), and the median age of all cases was 36.5 years. Injuries to individuals up to 19 years old corresponded to approximately 30% (n = 565) of all cases. Most of the victims lived in rural areas (72.46%; n = 1395), and the majority showed bites (81.13%; n = 1677) or scratches (12.23%; n = 253). Injuries were considered profound (52.1%; n = 1003), superficial (40.91; n = 788) or multiple with severe laceration (6.98%; n = 134). Only 1300 (67.53%) victims were enrolled for the complete rabies post-exposure prophylaxis scheme. Data from the present study confirm that wild canids are important hosts of rabies virus in northeastern Brazil and jeopardize rabies control in this area. Local authorities should focus their efforts in education of health professionals. In addition, strategies should be formulated to preserve wildlife.

  11. Protect Your Family from Rabies

    Science.gov (United States)

    ... series of shots called rabies post-exposure prophylaxis (PEP). If you are bitten by any animal (domestic or wild), immediately wash the wound well with soap and water and see a healthcare provider. Contact animal control if you are bitten by an animal, to ...

  12. Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil

    Directory of Open Access Journals (Sweden)

    Santos Hamilton P

    2008-11-01

    Full Text Available Abstract Background Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil. Methods Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil. Results In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers. Conclusion This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.

  13. What Is the Rabies Risk for My Pet?

    Science.gov (United States)

    ... March 1, 2010: Assessing Haitian Patients, Immigrants, and Refugees for Rabies Selection Criteria for Milwaukee Protocol August ... with rabies and have not been known to cause rabies among humans in the United States. Bites ...

  14. Identification and sequencial analysis on rabies virus isolated from a donkey%1株驴源狂犬病毒的分离鉴定及N、G基因序列分析

    Institute of Scientific and Technical Information of China (English)

    解庭波; 俞华; 吴杰; 黄思佳; 徐葛林; 严家新; 余滨; 周敦金

    2012-01-01

    目的 对武汉市汉南区新分离的1株驴源狂犬病毒(RABV)街毒株的N、G基因进行遗传学分析,比较其与近年来湖北省及周边地区分离的代表性街毒株以及人用和兽用狂犬病疫苗病毒株之间的差异.方法 以直接免疫荧光法检测驴脑组织中的RABV,并将驴脑海马组织研磨后接种乳鼠,观察其发病情况,采用双抗体夹心ELISA法检测驴脑组织及发病乳鼠脑组织悬液中的RABV,然后提取发病乳鼠脑组织RNA,利用RT-PCR扩增RABV的N、G基因,测序后进行遗传学分析.结果 在驴脑组织及发病乳鼠脑组织中检出RABV,该病毒株与近年来湖北省及周边地区分离的代表性街毒株以及国内外人用和兽用狂犬病疫苗病毒株相比,N、G基因核苷酸序列的同源性分别为85.7%~99.1%和82.2%~99.7%,推导的氨基酸序列同源性分别为95.6%-99.8%和87.8%~99.4%,与国内分离街毒株核苷酸和氨基酸的同源性高于疫苗株,且与国内疫苗株CTN-181的同源性要高于国外疫苗株.结论 该病毒株鉴定为驴源RABV,与湖北省及周边地区分离的代表性街毒株及中国人用狂犬病疫苗株CTN-181处于同一个亚群,有较近的系统进化关系.%Objective To identify and analyze the genetic characteristics of nucleoprotein (N) and glycoprotein (G) genes of rabies virus (RABV) isolated from a donkey in Wuhan.N gene and G gene of the virus were compared with other representative street strains isolated around Hubei areas as well as the vaccine strains used in China and abroad.Methods RABV in brain tissue of a donkey was detected by direct immunofluorescent method and then inoculated in suckling mice to observe the incidence of rabies.Brain samples of the donkey and infected suckling mice were detected by ELISA.The N gene and G gene fragment of the isolated RABV were amplified by RT-PCR and cloned into pMD18-T vector for sequencing and genetic analysis.Results RABVs were detected in

  15. Compendium of animal rabies prevention and control, 2008: National Association of State Public Health Veterinarians, Inc. (NASPHV).

    Science.gov (United States)

    2008-04-18

    Rabies is a fatal viral zoonosis and a serious public health problem. The disease is an acute, progressive encephalitis caused by a lyssavirus. Although the United States has been declared free of canine rabies virus variant transmission, multiple viral variants are maintained in wild mammal populations, and there is always a risk of reintroduction of canine rabies. All mammals are believed to be susceptible to the disease, and for purposes of this document, use of the term "animal" refers to mammals. The recommendations in this compendium serve as a basis for animal rabies-prevention and -control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies-control program. This document is reviewed annually and revised as necessary. The most current version replaces all previous versions. These recommendations do not supersede state and local laws or requirements. Principles of rabies-prevention and -control are detailed in Part I; recommendations for parenteral vaccination procedures are presented in Part II; and all animal rabies vaccines licensed by the U. S. Department of Agriculture (USDA) and marketed in the United States are listed in Part III.

  16. Effects of gamma radiation immunogenicity of ribonucleoprotein (RNPs) of rabies virus and purification of anti-RNPs antibodies for diagnosis; Efeitos da radiacao gama na imunogenicidade das ribonucleoproteinas (RNPs) do virus da raiva e purificacao de anticorpos anti-RNPs para diagnostico

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Ana Elena Boamorte da

    2010-07-01

    The World Health Organization recommends the direct immunofluorescence test for laboratory diagnosis and serological evaluation of rabies. To achieve this test, fluorescent anti-ribo nucleoproteins (RNPs) conjugates, produced from purified IgGs of RNP-immunized animals are employed. The aims of the present study were: investigate the effects of gamma radiation on the immunogenicity of RNPs, as well as to compare two chromatographic methodologies for the purification of anti-RNPs immunoglobulins. Sera from animals immunized with either native or irradiated RNPs were compared by direct immunofluorescence and immuno enzymatic assays. Our results indicate that the animals immunized with irradiated antigen requested a lower number of doses to reach high antibody titers. The immunofluorescence assays indicated that the conjugates produced with the anti-irradiated RNPs IgGs showed similar specificity to its anti-native counterpart, but with a higher definition of the virus inclusions. The purification methods were compared by Bradford and electrophoresis assays. According to the results, we concluded that the affinity-based process resulted in higher yields, lower execution time, and higher purity of the antibodies. (author)

  17. Estimating the global burden of endemic canine rabies

    National Research Council Canada - National Science Library

    Hampson, Katie; Coudeville, Laurent; Lembo, Tiziana; Sambo, Maganga; Kieffer, Alexia; Attlan, Michaël; Barrat, Jacques; Blanton, Jesse D; Briggs, Deborah J; Cleaveland, Sarah; Costa, Peter; Freuling, Conrad M; Hiby, Elly; Knopf, Lea; Leanes, Fernando; Meslin, François-Xavier; Metlin, Artem; Miranda, Mary Elizabeth; Müller, Thomas; Nel, Louis H; Recuenco, Sergio; Rupprecht, Charles E; Schumacher, Carolin; Taylor, Louise; Vigilato, Marco Antonio Natal; Zinsstag, Jakob; Dushoff, Jonathan

    2015-01-01

    ... of how much this preventable disease costs endemic countries. We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework...

  18. Discrepancies in data reporting for rabies, Africa.

    Science.gov (United States)

    Nel, Louis H

    2013-04-01

    Human rabies is an ancient disease but in modern times has primarily been associated with dog rabies-endemic countries of Asia and Africa. From an African perspective, the inevitable and tragic consequences of rabies require serious reflection of the factors that continue to drive its neglect. Established as a major disease only after multiple introductions during the colonial era, rabies continues to spread into new reservoirs and territories in Africa. However, analysis of reported data identified major discrepancies that are indicators of poor surveillance, reporting, and cooperation among national, international, and global authorities. Ultimately, the absence of reliable and sustained data compromises the priority given to the control of rabies. Appropriate actions and changes, in accordance to the One Health philosophy and including aspects such as synchronized, shared, and unified global rabies data reporting, will not only be necessary, but also should be feasible.

  19. Evaluation of Cases with Rabies Risk Presenting to Emergency Department

    Directory of Open Access Journals (Sweden)

    Fevzi Yilmaz

    2013-10-01

    Full Text Available Aim: All around the world 10-12 million people/year receive rabies prophylaxis. Rabies is an acute fatal central nervous system viral enfection. The virus can infect all warm-blooded animals and almost in all cases the enfection results with fatal encephalitis. The aim of this study is to determine the demographic characteristics of cases with rabies risk exposures and behind this to emphasise the significance of cooperation between the institutions to perform effective and accurate treatment. Material and Method: This study was performed with retrospective analysis of 1429 cases who attended to Emergency Department of Diyarbakir Goverment Hospital between January 2007-2010 for animal bites and exposures with the risk of rabies. Statistical analysis of data was performed SPSS V16 pocket programme. Data were defined as frequency and %. For statistical analysis Chi-Square and Fischer exact test was used. A value of P<0.05 was accepted statistically significant. Results: A total of 1055 (73.8% were male, 374 (26.2% were female and the mean age was 21.75 ± 16.9 (6 months-87 years. The major group in children was 6-11 years old and 651 (% 45.5 of the cases attended to hospital were under 18 years old. The vast majority (39.3% in adults were between 19-49 years. In our study 808 (56.5% of the cases  were bitten, 597 (41.8% of the cases  were scrabbled by the animal and 24 (1.7%of them  had indirect contact with the animal Both of them were taken into prophylactic vaccination programme (p<0.05. The vast majority of animal bites were dog (67%  and cat (28%. 3 doses of Human diploid cell vaccine-HDCV were administered to 1001 (70% of the patients and 5 doses to 428 (30% of patients. Human rabies immune globulin-HRIG were administered to 475 (33,3% of the patients in addition to vaccine. Discussion:  In our region rabies risk exposure is an important public health problem. Public oriented education should be given about attending to health care

  20. Spatial expansions and travelling waves of rabies in vampire bats

    Science.gov (United States)

    Valderrama, William; Streicker, Daniel G.

    2016-01-01

    A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs.

  1. Real-time PCR analysis of dog cerebrospinal fluid and saliva samples for ante-mortem diagnosis of rabies.

    Science.gov (United States)

    Saengseesom, Wachiraporn; Mitmoonpitak, Channarong; Kasempimolporn, Songsri; Sitprija, Visith

    2007-01-01

    The use of a 10-day observation to determine whether a dog is rabid is standard practice. This study was conducted in order to look for evidence of rabies vius in saliva and cerebrospinal fluid (CSF) of suspected live rabid dogs at the time of quarantine by using a SYBR Green real-time RT-PCR based assay for the detection of rabies virus RNA. Saliva and CSF of dogs were collected once on the day of admission for the 10-day quarantine. All test dogs were or became ill and died of rabies within the observation period. Thirteen of 15 dogs (87%) had saliva samples that were positive for rabies RNA. Two dogs with furious rabies had negative saliva samples. Positive CSF samples were found in 4 of 15 dogs (27%) whose saliva samples were positive. The time from sample collection to result was less than 5 hours. Because virus may be absent or present at very low level in both clinical fluids, samples taken for ante-mortem diagnosis cannot definitively rule out rabies.

  2. Rabies molecular virology, diagnosis, prevention and treatment

    Directory of Open Access Journals (Sweden)

    Yousaf Muhammad

    2012-02-01

    Full Text Available Abstract Rabies is an avertable viral disease caused by the rabid animal to the warm blooded animals (zoonotic especially human. Rabies occurs in more than 150 countries and territories. According to an estimation by WHO, almost 55,000 people die because of rabies every year. The Dogs are the major reason behind this, approximately 99% human deaths caused by dog's bites. Developing and under developing countries, both are the victims of rabies. With the post-exposure preventive regimes, 327,000 people can prevent this disease annually. The current article mainly covers the genome, virology, symptoms, epidemiology, diagnostic methods, and the high risk countries around the globe.

  3. The quantum Rabi model: solution and dynamics

    Science.gov (United States)

    Xie, Qiongtao; Zhong, Honghua; Batchelor, Murray T.; Lee, Chaohong

    2017-03-01

    This article presents a review of recent developments on various aspects of the quantum Rabi model. Particular emphasis is given on the exact analytic solution obtained in terms of confluent Heun functions. The analytic solutions for various generalisations of the quantum Rabi model are also discussed. Results are also reviewed on the level statistics and the dynamics of the quantum Rabi model. The article concludes with an introductory overview of several experimental realisations of the quantum Rabi model. An outlook towards future developments is also given.

  4. Rabies molecular virology, diagnosis, prevention and treatment

    Science.gov (United States)

    2012-01-01

    Rabies is an avertable viral disease caused by the rabid animal to the warm blooded animals (zoonotic) especially human. Rabies occurs in more than 150 countries and territories. According to an estimation by WHO, almost 55,000 people die because of rabies every year. The Dogs are the major reason behind this, approximately 99% human deaths caused by dog's bites. Developing and under developing countries, both are the victims of rabies. With the post-exposure preventive regimes, 327,000 people can prevent this disease annually. The current article mainly covers the genome, virology, symptoms, epidemiology, diagnostic methods, and the high risk countries around the globe. PMID:22348291

  5. Rabies: Rare Human Infection - Common Questions.

    Science.gov (United States)

    Willoughby, Rodney E

    2015-12-01

    Rabies is an acute, rapidly progressive encephalitis that is almost always fatal. Prophylaxis is highly effective but economics limits disease control. The mechanism of death from rabies is unclear. It is poorly cytopathic and poorly inflammatory. Rabies behaves like an acquired metabolic disorder. There may be a continuum of disease severity. History of animal bite is rare. The diagnosis is often missed. Intermittent encephalopathy, dysphagia, hydrophobia and aerophobia, and focal paresthesias or myoclonic jerks suggest rabies. Laboratory diagnosis is cumbersome but sensitive. Treatment is controversial but survivors are increasingly reported, with good outcomes in 4 of 8 survivors.

  6. The quantum Rabi model: solution and dynamics

    CERN Document Server

    Xie, Qiongtao; Batchelor, Murray T; Lee, Chaohong

    2016-01-01

    This article presents a review of recent developments on various aspects of the quantum Rabi model. Particular emphasis is given on the exact analytic solution obtained in terms of confluent Heun functions. The analytic solutions for various generalisations of the quantum Rabi model are also discussed. Results are also reviewed on the level statistics and the dynamics of the quantum Rabi model. The article concludes with an introductory overview of several experimental realisations of the quantum Rabi model. An outlook towards future developments is also given.

  7. Neutralizing Antibody Response after Intramuscular Purified Vero Cell Rabies Vaccination (PVRV in Iranian Patients with Specific Medical Conditions.

    Directory of Open Access Journals (Sweden)

    Pooneh Rahimi

    Full Text Available Post exposure prophylaxis using one of the WHO-approved vaccines is the method of choice for preventing rabies. Abnormal immune function in patients with some specific medical conditions, such as pregnancy, chronic hepatitis B virus infection, different types of cancers like lymphoma, diabetes I and II, corticosteroid consumption by patients with rheumatoid arthritis and lupus erythematosus, could impair the immunologic response to various vaccines. The immune response to rabies vaccination has never been examined in patients with any of these described medical conditions. This study purposed to evaluate the neutralyzing antibody response after vaccination with purified Vero cell rabies vaccine (PVRV according to the WHO-recommended Post-Exposure Prophylaxis (PEP "ESSEN" regimen.Thirty healthy volunteers and 50 volunteers with different medical conditions who were exposed to a suspected rabid animal in the 2nd or 3rd category of exposure received 5 doses of PVRV under the ESSEN protocol. Three blood samples were collected on days 0 (before the first dose, 14, and 35. The anti-rabies antibody titer was measured using the Rapid Fluorescent Foci Inhibition Test (RFFIT and an ELISA Bio-Rad, Platelia, Rabies II kit.All subjects reached NAb titers above 0.5 IU/ml by day 14 after vaccination. On day 35 (1 week after receiving the last rabies vaccine, anti-rabies antibodies were in the protective level (>0.5 IU/ml in both groups. There was no statistically significant difference in anti-rabies antibody response due to the type of exposure (category 2 or 3, and successful seroconversion was confirmed in both groups.In conclusion, the ESSEN protocol using the PVRV vaccine is sufficient for rabies prophylaxis in patients with specific medical conditions.

  8. Rabies encephalitis in a child: a failure of rabies post exposure prophylaxis?

    Science.gov (United States)

    Tinsa, Faten; Borgi, Aida; Jahouat, Imen; Boussetta, Khadija

    2015-01-01

    Rabies remains a serious public health problem in many developing countries. The diagnosis is easy when a non-immunised patient presents with hydrophobia and hypersalivation after a bite by a known rabid animal but more difficult when a patient presents atypical symptoms after having received rabies postexposure prophylaxis. Rabies postexposure prophylaxis failure is rare. We report a case of a 6-year-old boy who presented febrile seizure with agitation and cerebellar signs, without hydrophobia or hypersalivation, 17 days after a dog bite. Despite four doses of rabies vaccine and immunoglobulin, he died. Diagnostic confirmation of rabies encephalitis was made in post mortem on brain biopsies by fluorescent antibody technique.

  9. Rabi N. Bhattacharya selected papers

    CERN Document Server

    Waymire, Edward

    2016-01-01

    This volume presents some of the most influential papers published by Rabi N. Bhattacharya, along with commentaries from international experts, demonstrating his knowledge, insight, and influence in the field of probability and its applications. For more than three decades, Bhattacharya has made significant contributions in areas ranging from theoretical statistics via analytical probability theory, Markov processes, and random dynamics to applied topics in statistics, economics, and geophysics. Selected reprints of Bhattacharya’s papers are divided into three sections: Modes of Approximation, Large Times for Markov Processes, and Stochastic Foundations in Applied Sciences. The accompanying articles by the contributing authors not only help to position his work in the context of other achievements, but also provide a unique assessment of the state of their individual fields, both historically and for the next generation of researchers. Rabi N. Bhattacharya: Selected Papers will be a valuable resource for yo...

  10. Control of terrestrial animal rabies in Anne Arundel County, Maryland, after oral vaccination of raccoons (1998-2007).

    Science.gov (United States)

    Horman, Joseph T; Shannon, Kyle V; Simpson, E Marie; Burja, Thomas M; Fey, Robert H; Smith, Jeremy J; Phillips, Frances B

    2012-09-15

    To evaluate the effectiveness of an oral rabies vaccination (ORV) project conducted from 1998 through 2007 in Anne Arundel County, Md, for the control of rabies in terrestrial animals. Retrospective analysis of surveillance data (1997 through 2007). Free-ranging raccoons (Procyon lotor) and other terrestrial mammals. Vaccinia-rabies glycoprotein recombinant virus oral rabies vaccine-bait units were distributed annually by aircraft and ground teams targeting free-ranging raccoons. Approximately 2 to 4 weeks following the vaccine-bait placement, raccoons were live trapped, sedated, processed, and then released. Serologic samples were tested for the presence of rabies virus-neutralizing antibodies (RVNAs). Bait acceptance was estimated by analysis of tetracycline biomarking of sampled teeth. Rabies incidence was determined by the passive identification of rabid terrestrial animals. The incidence of rabies in terrestrial animals decreased 92% between 1997 (the year prior to the start of the ORV project) and 2007. The mean RVNA prevalence across all years was 33% among trapped raccoons in areas baited with a fish meal polymer bait type, whereas the mean bait acceptance was 30%. Adult raccoons had a seropositivity rate twice that of juvenile raccoons, whereas the bait acceptance rate between adults and juveniles did not differ significantly. For areas baited with a coated sachet bait, adults and juveniles had the same seroprevalence. Juveniles had better seroprevalence when the annual campaign started in September and October, compared with August. The ORV project contributed to a significant decrease in annual incidence of terrestrial animal rabies in Anne Arundel County, Md, during the 10-year project period. For fish meal polymer baits, juvenile raccoons accessed bait at the same rate as adult raccoons but had a significantly lower prevalence of RVNAs. For coated sachet baits, seroprevalence was the same in both age groups. The time of year the bait distribution

  11. On the interference of clinical outcome on rabies transmission an perpetuation

    Directory of Open Access Journals (Sweden)

    PE Brandão

    2009-01-01

    Full Text Available Rabies is a viral zoonotic infectious disease that affects mammals and is caused by genotypes/species of the Lyssavirus genus (Rhabdoviridae, Mononegavirales, with the genotype 1 (classic rabies virus - RABV being the most prevalent. Despite continuous efforts, rabies is still an incurable disease that causes thousands of deaths amongst humans worldwide. Due to a wide range of hosts and the different evolutionary paths of RABV in each host, several host-specific variants have arisen in an ongoing process. The result of RABV replication in nervous tissues may lead to two opposite clinical outcomes, i.e., paralytic/dumb form and encephalitic/furious one. The paralytic form creates dead-end hosts mainly amongst herbivores, while the furious form of the disease allows for augmented transmission when manifested in gregarious carnivores, as their natural aggressive behavior is accentuated by the disease itself. The aim of this article is to propose a theoretical model intended to explore how the rabies virus intrinsically modulates the immune system of different host classes, the pathological changes that the virus causes in these animals and how these elements favor its own perpetuation in nature, thus providing a basis for better prediction of the patterns this disease may present.

  12. Potential cost savings with terrestrial rabies control

    Directory of Open Access Journals (Sweden)

    Cherry Bryan

    2007-04-01

    Full Text Available Abstract Background The cost-benefit of raccoon rabies control strategies such as oral rabies vaccination (ORV are under evaluation. As an initial quantification of the potential cost savings for a control program, the collection of selected rabies cost data was pilot tested for five counties in New York State (NYS in a three-year period. Methods Rabies costs reported to NYS from the study counties were computerized and linked to a human rabies exposure database. Consolidated costs by county and year were averaged and compared. Results Reported rabies-associated costs for all rabies variants totalled $2.1 million, for human rabies postexposure prophylaxes (PEP (90.9%, animal specimen preparation/shipment to laboratory (4.7%, and pet vaccination clinics (4.4%. The proportion that may be attributed to raccoon rabies control was 37% ($784,529. Average costs associated with the raccoon variant varied across counties from $440 to $1,885 per PEP, $14 to $44 per specimen, and $0.33 to $15 per pet vaccinated. Conclusion Rabies costs vary widely by county in New York State, and were associated with human population size and methods used by counties to estimate costs. Rabies cost variability must be considered in developing estimates of possible ORV-related cost savings. Costs of PEPs and specimen preparation/shipments, as well as the costs of pet vaccination provided by this study may be valuable for development of more realistic scenarios in economic modelling of ORV costs versus benefits.

  13. Isidor I. Rabi and CERN

    Science.gov (United States)

    Krige, John

    2005-06-01

    Isidor I. Rabi (1898 1988) is the acknowledged “father of CERN,” today one of the most important particle-physics laboratories in the world. I explore his motives for promoting the idea in 1950 that Western Europe should build a “Brookhaven” with national governments replacing universities. I unravel the many ways in which a major accelerator facility in Geneva, Switzerland, could both stimulate European science and serve the interests of the American scientific community. Rabi was careful to avoid giving any official support to steps then under way in Europe to build a research reactor, even though Brookhaven National Laboratory on Long Island, New York, had one from the outset. I suggest that his main motive for doing so was that he wanted West Germany to be part of the collaborative venture. Rabi was well aware of the foreign-policy objectives of the U.S. State Department in the European theater in 1950, and he wanted to situate politically the new research center in the framework of the Marshall Plan for the postwar reconstruction of the continent, “remaking the Old World in the image of the New.”

  14. Isidor I Rabi and CERN

    CERN Document Server

    Krige, Gerhard John

    2005-01-01

    Isidor I. Rabi (1898-1988) is the acknowledged "father of CERN", today one of the most important particle-physics laboratories in the world. I explore his motives for promoting the idea in 1950 that Western Europe should build a "Brookhaven" with national governments replacing universities. I unravel the many ways in which a major accelerator facility in Geneva, Switzerland, could both stimulate European science and serve the interests of the American scientific community. Rabi was careful to avoid giving any official support to steps then under way in Europe to build a research reactor, even though Brookhaven National Laboratory on Long Island, New York, had one from the outset. I suggest that his main motive for doing so was that he wanted West Germany to be part of the collaborative venture. Rabi was well aware of the foreign-policy objectives of the U.S. State Department in the European theater in 1950, and he wanted to situate politically the new research center in the framework of the Marshall Plan for ...

  15. 2006-2009年北京市丰台区犬只狂犬病病毒抗体效价调查分析%Surveillance of rabies virus antibody level in domestic dogs in Fengtai District, Beijing during 2006- 2009

    Institute of Scientific and Technical Information of China (English)

    路静; 朱祥宇; 王迎; 李益琛; 杜小燕; 陈振文; 王超

    2012-01-01

    为了摸清当前社会犬只的狂犬病免疫状况,我们从2006年起连续4年对北京市丰台区城区和4个乡镇社会犬只的狂犬病病毒抗体效价进行了抽样调查。所采集的犬只血清样品共4776份,采用免疫荧光中和试验法检测其血清狂犬病病毒抗体效价并做统计分析。结果显示,有68.1%的免疫接种犬的抗体滴度为阳性,未免疫犬有16.4%为阳性(P〈0.01);在城区和乡镇间,免疫接种覆盖率分别为81.7%和27.6%(P〈0.01);在大型犬和小型犬间,免疫接种率有较大差异,分别为69.5%和39.3%(P〈0.01)。虽然北京市狂犬病的发生率和病死率多年来都控制在0.02/100000以下,但从犬只免疫接种率来看,4年中任何1年的接种率都没有超过WHO规定的70%的标准,分别为55.0%、53.8%、67.4%和54.4%,提示免疫接种率较低,存在狂犬病发作的风险。调查结果还显示城区免疫阳性犬数量是乡镇的2.5倍;在疫苗的接种率和狂犬病病毒抗体效价方面,城区也好于乡镇,说明加强农村地区犬只免疫接种率是今后狂犬病预防的重要工作内容。调查还发现,免疫过的小型犬数量是大型犬的1.68倍,究其原因,一方面是因为城区绝大多数犬都是小型犬,普遍接受免疫接种;而在乡镇,大多数犬是中大型犬,而且漏免率较高。调查结果提示:北京市应加强对农村地区犬只的免疫接种,尤其要提高对中大型犬的免疫接种率。%In order to clarify the general control of rabies in domestic dogs,the authors investigated the rabies antibody level in the dogs raised in urban and 4 rural satellite towns in Fengtai District,Beijing from 2006 to 2009. All of 4776 samples were collected,rabies virus neutralization antibody (VNA) titers were detected by fluorescent antibody virus neutralization method. The results showed that

  16. Rabies diagnosis for developing countries.

    Directory of Open Access Journals (Sweden)

    Salome Dürr

    Full Text Available BACKGROUND: Canine rabies is a neglected disease causing 55,000 human deaths worldwide per year, and 99% of all cases are transmitted by dog bites. In N'Djaména, the capital of Chad, rabies is endemic with an incidence of 1.71/1,000 dogs (95% C.I. 1.45-1.98. The gold standard of rabies diagnosis is the direct immunofluorescent antibody (DFA test, requiring a fluorescent microscope. The Centers for Disease Control and Prevention (CDC, Atlanta, United States of America developed a histochemical test using low-cost light microscopy, the direct rapid immunohistochemical test (dRIT. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the dRIT in the Chadian National Veterinary Laboratory in N'Djaména by testing 35 fresh samples parallel with both the DFA and dRIT. Additional retests (n = 68 in Chad, n = 74 at CDC by DFA and dRIT of stored samples enhanced the power of the evaluation. All samples were from dogs, cats, and in one case from a bat. The dRIT performed very well compared to DFA. We found a 100% agreement of the dRIT and DFA in fresh samples (n = 35. Results of retesting at CDC and in Chad depended on the condition of samples. When the sample was in good condition (fresh brain tissue, we found simple Cohen's kappa coefficient related to the DFA diagnostic results in fresh tissue of 0.87 (95% C.I. 0.63-1 up to 1. For poor quality samples, the kappa values were between 0.13 (95% C.I. -0.15-0.40 and 0.48 (95% C.I. 0.14-0.82. For samples stored in glycerol, dRIT results were more likely to agree with DFA testing in fresh samples than the DFA retesting. CONCLUSION/SIGNIFICANCE: The dRIT is as reliable a diagnostic method as the gold standard (DFA for fresh samples. It has an advantage of requiring only light microscopy, which is 10 times less expensive than a fluorescence microscope. Reduced cost suggests high potential for making rabies diagnosis available in other cities and rural areas of Africa for large populations for which a capacity for

  17. Rabies in the U.S.

    Science.gov (United States)

    ... if I receive treatment outside the United States? Veterinarians What to do with an animal that has bitten a person Caring for animals with potential exposure Clinical signs of rabies in animals Vaccines Rabies Vaccines Licensed and Marketed in the U.S., ...

  18. Rabies: Diagnosis in Animals and Humans

    Science.gov (United States)

    ... with a low probability of rabies such as dogs, cats, and ferrets, observation periods (10 days) may be appropriate to rule out the risk of potential human rabies exposure. Consultation with a local or state health official following a potential exposure can help determine ...

  19. Spatial control of rabies on heterogeneous landscapes.

    Directory of Open Access Journals (Sweden)

    Colin A Russell

    Full Text Available Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV. In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics.

  20. Rabies in Asia: the classical zoonosis.

    Science.gov (United States)

    Wilde, Henry; Hemachudha, Thiravat; Wacharapluesadee, Supaporn; Lumlertdacha, Boonlert; Tepsumethanon, Veera

    2013-01-01

    Rabies remains a constant threat to humans throughout much of Asia. The dog is the main reservoir and vector with wildlife playing a very minor role. No Asian country or region has been declared rabies free by WHO in over two decades and there is evidence of canine rabies spread to new regions during the past 10 years. We now have the knowledge and technology to control canine rabies. The main barrier in managing this costly endemic is lack of motivation by authorities to address this issue along with regional inability of public health and livestock (agriculture) officials to tackle this issue in cooperation and coordination. Rabies is one of the first recognized zoonoses and a model for a true "One Health" management goal where human; veterinary, and government officials must work together in harmony to defeat this disease.

  1. Avaliação da vacina anti-rábica ERA, frente a variantes antigênicas do vírus da raiva, em diferentes períodos pós-imunização Evaluation of the ERA antirabies vaccine against antigenic variants of rabies virus in different post-immunization periods

    Directory of Open Access Journals (Sweden)

    Cláudia C. Cordeiro

    1990-12-01

    Full Text Available Avaliou-se, em camudongos, os níveis de proteção conferidos por uma vacina anti-rábica atenuada, preparada em cultura de tecido renal a partir da amostra ERA, frente a diferentes variantes antigênicas dos vírus da raiva. Utilizaram-se dois esquemas de vacinação, representados por uma única dose e por 6 doses aplicadas em dias alternados. Os diferentes camundogos dos grupos experimentais foram desafiados, em diversos períodos pós-imunização (15, 30, 60 e 120 dias, com variantes procedentes de cães (São Paulo e Nigéria, de morcego (DR-19 e Pernambuco, de raposa (Rio Grande do Norte e CVS "Challenge Virus Standard". Os resultados obtidos permitiram constatar que a vacina ERA foi eficaz contra todas as variantes de rua e silváticas do vírus rábico, independentemente do esquema vacinal. Contra as cepas adaptadas no laboratório DR-19 e CVS, quando aplicada em uma única dose, sua eficácia foi menor do que quando aplicada em 6 doses.Protection levels of an attenuated antirabies vaccine, of ERA origin, prepared in Kidney tissue culture, were evaluated in mice. Two schemes of vaccination were utilized: a single dose and 6 doses on alternate days. Animals of different experimental groups were challenged at 15, 30, 60 and 120 days post-immunization with six antigenic variants of rabies virus: strains of dog origin (S. Paulo, Brazil and Nigéria, vampire origin (DR-19 and Pernambuco, Brazil, fox origin (Rio Grande do Norte,Brazil, and CVS (Challenge Virus Standard. The results showed the effectiveness of the ERA vaccine against all antigenic variants of street and sylvatic rabies virus, independently of the vaccination scheme. Against the laboratory strains (DR-19 and CVS the ERA vaccine was less effective, mainly in the groups vaccinated with a single dose.

  2. 浙江省野生动物鼬獾狂犬病毒全基因组序列测定分析%Complete genome sequencing and analyses of rabies viruses isolated from wild animals (Chinese Ferret-Badger) in Zhejiang province

    Institute of Scientific and Technical Information of China (English)

    雷永良; 王晓光; 柳付明; 陈秀英; 叶碧峰; 梅建华; 兰进权; 唐青

    2009-01-01

    目的 测定浙江省分离的2株野生动物鼬獾狂犬病毒株全基因组序列,从分子水平进行遗传变异特征分析,了解狂犬病毒在浙江省的流行和变异情况.方法 RT-PCR测定鼬獾狂犬病毒株全基因组核苷酸序列,并进行基因序列和编码蛋白相似性比较及种系发生分析.结果 测序获得2株鼬獾狂犬病毒全基因组核苷酸序列信息:基因组全长11 923 nts,leader长58 nts,由5个编码区组成:NP(1353 nts)、PP(894 nts)、MP(609 nts)、GP(1575 nts)、LP(6386 nts),N-P-M-G间隔序列长2、5、5 nts;G-L基因间伪基因ψ长423 nts;trailer长70 nts.核酸BLAST及多序列比对显示,浙江省鼬獾狂犬病毒株全基因组序列的组成和结构符合弹状病毒科狂犬病毒属特征;鼬獾病毒株负链RNA基因组5个基因编码氨基酸的长度没有变异,编码区基因没有发生重组,编码蛋白仅表现较少的序列变化,多数只发生碱基的替代;中国病毒株之间特别是同种动物狂犬病毒之间各个基因区域核苷酸与氨基酸序列相似性最高,鼬獾狂犬病毒基因组序列相似性在氨基酸水平明显高于核苷酸水平,蛋白质编码基因的核苷酸变异大多属于同义突变.结论 鼬獾狂犬病毒与研究中选择的代表性疫苗株或者街毒株的变异位点和变异类型相似,多序列相似性比较和N基因种系发生分析显示,鼬獾狂犬病毒均属于基因1型,具有中国地域性特点,2株野生动物鼬獾狂犬病毒极有可能是存在于自然界中固有的街毒株.%Objective Based on sequencing the full-length genomes of two Chinese Ferret-Badger, we analyzed the properties of rabies viruses genetic variation in molecular level to get information on prevalence and variation of rabies viruses in Zhejiang,and to enrich the genome database of rabies viruses street swains isolated from Chinese wildlife.Methods Overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to

  3. Titulação de anticorpos contra o vírus da raiva em cães, em Campo Grande, MS, na Campanha Anti-Rábica de 2003 Rabies virus antibody titers in dogs in Campo Grande, Mato Grosso do Sul State, during the anti-rabies campaign, 2003

    Directory of Open Access Journals (Sweden)

    Leonardo Rigo

    2006-12-01

    Full Text Available Para avaliar a resposta imune em cães, que compareceram a Campanha de Vacinação Anti-Rábica Animal de 2003, foram analisados 333 soros caninos, coletados nos diversos postos de vacinação. Verificou-se que 51,1% dos animais não possuíam títulos protetores. Não foi encontrada associação entre aplicação de vacina e maior número de vacinações, com maior título imunitário.To assess the immune response in dogs attended during the 2003 anti-rabies animal vaccination campaign, 333 serum samples collected at different vaccination posts were analyzed. It was found that 51.1% of the animals did not have protective titers. No correlation was found between vaccine application or multiple vaccinations and higher immune titers.

  4. Molecular epidemiology of rabies in Colombia 1994-2005 based on partial nucleoprotein gene sequences.

    Science.gov (United States)

    Páez, Andrés; Velasco-Villa, Andrés; Rey, Gloria; Rupprecht, Charles E

    2007-12-01

    One hundred and twenty-four rabies viruses (RABV) were isolated from humans and eight species of mammals in Colombia during 1994-2005. To determine the genetic and reservoir-associated diversity cDNA fragments encoding 88 amino acids at the carboxyl terminus of the nucleoprotein were sequenced and used in phylogenetic analyses. Eight genetic lineages (GL) were characterized. GL1, GL2 and GL3 consisted of dog-associated antigenic variant (AV) 1 RABV, isolated in the centre-east, north and southwest of Colombia, respectively. GL1 is apparently extinct in Colombia. The GL4 were AV3, AV8 and non-determined (ND) AV viruses associated with hematophagous bats. The GL5 and GL6 consisted of AV4 viruses. GL6 isolate was found associated with Tadarida brasiliensis bats. GL5 segregated independently. The GL7 and GL8 segregated independently within clades associated with colonial insectivorous and solitary bats, respectively. Both of these were represented by NDAV viruses. Viruses isolated from humans grouped within GL2, GL3 and GL4, which in turn corresponded to AV1, 3, 8 and ND. Dogs and D. rotundus are the two major rabies reservoirs and vectors in Colombia. Insectivorous bats may also be important rabies reservoirs but spillovers to other species are rare. Our data were consistent with previous studies in which partial Psi, G and L gene sequences were analyzed. Our results confirmed the existence of RABV of unclassified AV in Colombia.

  5. Role of Apoptosis in Rabies Viral Encephalitis: A Comparative Study in Mice, Canine, and Human Brain with a Review of Literature

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    M. S. Suja

    2011-01-01

    Full Text Available To evaluate the role of apoptosis in rabies encephalitis in humans and canines infected with wild-type street virus, in comparison with rodent model infected with street and laboratory passaged CVS strain, we studied postmortem brain tissue from nine humans, six canines infected with street rabies virus, and Swiss albino mice inoculated intramuscularly (IM and intracerebrally (IC with street and CVS strains. Encephalitis and high rabies antigen load were prominent in canine and human brains compared to rodents inoculated with street virus. Neuronal apoptosis was detectable only in sucking mice inoculated with CVS strain and minimal in street virus inoculated mice. In a time point study in suckling mice, DNA laddering was noted only terminally (7 days p.i. following IC inoculation with CVS strain but not with street virus. In weanling and adult mice, apoptosis was restricted to inflammatory cells and absent in neurons similar to human and canine rabies-infected brains. Absence of neuronal apoptosis in wild-type rabies may facilitate intraneuronal survival and replication while apoptosis in inflammatory cells prevents elimination of the virus by abrogation of host inflammatory response.

  6. Barriers to innovation in human rabies prophylaxis and treatment: A causal analysis of insights from key opinion leaders and literature.

    Science.gov (United States)

    van de Burgwal, L H M; Neevel, A M G; Pittens, C A C M; Osterhaus, A D M E; Rupprecht, C E; Claassen, E

    2017-03-20

    Rabies is an essentially 100% fatal, zoonotic disease, caused by Lyssaviruses. Currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (PrEP and PEP). Still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural Asia and Africa, due to the inaccessibility of prophylaxis and non-existence of treatment. Despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innovation receives relatively little attention compared to other neglected tropical diseases (NTDs). As such, the lag of innovation in human rabies prophylaxis and treatment cannot be explained by limited return on investment alone. Strategies countering rabies-specific innovation barriers are important for the acceleration of innovation in human rabies prophylaxis and treatment. Barriers throughout society, science, business development and market domains were identified through literature review and 23 semi-structured interviews with key opinion leaders worldwide. A subsequent root cause analysis revealed causal relations between innovation barriers and a limited set of root causes. Finally, prioritization by experts indicated their relative importance. Root causes, which are fundamental to barriers, were aggregated into four types: market and commercial, stakeholder collaboration, public health and awareness, and disease trajectory. These were found in all domains of the innovation process and thus are relevant for all stakeholders. This study identifies barriers that were not previously described in this specific context, for example the competition for funding between medical and veterinary approaches. The results stress the existence of barriers beyond the limited return on investment and thereby explain why innovation in human rabies medication is lagging behind NTDs with a lower burden of disease. A re-orientation on the full spectrum of barriers that hinder innovation in

  7. Development and validation of a quantitative competitive ELISA for potency testing of equine anti rabies sera with other potential use.

    Science.gov (United States)

    Korimbocus, Jehanara; Dehay, Nicolas; Tordo, Noël; Cano, François; Morgeaux, Sylvie

    2016-06-14

    In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab')2 fragments produced from Equine Rabies Immunoglobulin (F(ab')2 - ERIGs). According to international regulation, quality control of F(ab')2 - ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab')2 - ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab')2 - ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r=0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Potential economic benefits of eliminating canine rabies.

    Science.gov (United States)

    Shwiff, Stephanie; Hampson, Katie; Anderson, Aaron

    2013-05-01

    Although canine rabies has been eliminated from industrialized countries, infected dogs remain the primary source of human and livestock exposures in Asia, Africa and much of South America. Human deaths are the most important direct economic impact of canine rabies, followed by livestock losses and the cost of PEP, while expenses associated with dog vaccination and control are major indirect impacts. The global burden of rabies disproportionately affects Asia, which experiences more than half of human rabies deaths and approximately 65% of livestock losses, and performs more than 90% of postexposure prophylaxis (PEP). Africa is second to Asia in terms of human deaths and livestock losses, but administers the least number of PEPs of the three regions. Recent experience in Latin America shows that efforts to reduce human deaths from rabies through expanded dog vaccination and improved access to PEP result in significant monetary savings. The elimination of canine rabies would lead to major economic benefits in developing countries that are often the least capable of dealing with the disease. This article forms part of a symposium in Antiviral Research on the elimination of canine rabies. Published by Elsevier B.V.

  9. Safety and immunogenicity of Ontario Rabies Vaccine Bait (ONRAB) in the first us field trial in raccoons (Procyon lotor).

    Science.gov (United States)

    Slate, Dennis; Chipman, Richard B; Algeo, Timothy P; Mills, Samuel A; Nelson, Kathleen M; Croson, Christopher K; Dubovi, Edward J; Vercauteren, Kurt; Renshaw, Randall W; Atwood, Todd; Johnson, Shylo; Rupprecht, Charles E

    2014-07-01

    In 2011, we conducted a field trial in rural West Virginia, USA to evaluate the safety and immunogenicity of a live, recombinant human adenovirus (AdRG1.3) rabies virus glycoprotein vaccine (Ontario Rabies Vaccine Bait; ONRAB) in wild raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). We selected ONRAB for evaluation because of its effectiveness in raccoon rabies management in Ontario and Quebec, Canada, and significantly higher antibody prevalence rates in raccoons compared with a recombinant vaccinia-rabies glycoprotein (V-RG) vaccine, Raboral V-RG®, in US-Canada border studies. Raccoon rabies was enzootic and oral rabies vaccination (ORV) had never been used in the study area. We distributed 79,027 ONRAB baits at 75 baits/km(2) mostly by fixed-wing aircraft along parallel flight lines at 750-m intervals. Antibody prevalence was significantly higher at 49.2% (n=262) in raccoons after ONRAB was distributed than the 9.6% (n=395) before ORV. This was the highest antibody prevalence observed in raccoons by US Department of Agriculture Wildlife Services for areas with similar management histories evaluated before and after an initial ORV campaign at 75 baits/km(2) with Raboral V-RG. Tetracycline biomarker (TTCC) was significantly higher among antibody-positive raccoons after ONRAB baiting and was similar among raccoons before ORV had been conducted, an indication of vaccine-induced rabies virus-neutralizing antibody production following consumption of bait containing TTCC. Skunk sample size was inadequate to assess ONRAB effects. Safety and immunogenicity results supported replication of this field trial and led to a recommendation for expanded field trials in 2012 to evaluate safety and immunogenicity of ground-distributed ONRAB at 150 baits/km(2) in residential and commercial habitats in Ohio, USA and aerially distributed ONRAB at 75 baits/km(2) in rural habitats along US-Quebec border.

  10. Rabies antibody levels in pregnant women and their newborns after rabies post-exposure prophylaxis

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    Ahmad Fayaz

    2012-01-01

    Full Text Available Background: Rabies is a fatal infectious disease and rabies post-exposure prophylaxis is the method of choice for prevention of human rabies.Case series: We report rabies antibody levels in cord blood and also in serum of pregnant women who were bitten by suspected animals to rabies and were immunized by purified Vero cell rabies vaccine (PVRV and Human Rabies immunoglobulin (HRIG serum. During the years of 2007-2010, six pregnant women by the age range of 22-35 years were admitted in treatment and prevention of rabies center in Pasture institute of Iran, in Tehran. Among them two cases were at first trimester, one at second trimester and three at third trimester of conception. The interval between biting with delivery was 5-265 days (mean 121 days.Conclusion: Results of immunoglobulin illustrate that levels of rabies antibody in maternal sera with the fetus are not equal and uniform but it is proved that baby will find efficient immunity as well with minimum protective level of 0.5 IU/ml in all cases except a newborn whom had been born just 5 days after the mother’s immunization and in a shorter time than the appropriate immunization of the mother who had received her second vaccination courses.

  11. [Rabies Tissue Culture Infection Test as an Alternative for the Mouse Inoculation Test

    Science.gov (United States)

    Zanoni, R.; Hörnlimann, B.; Wandeler, A. I.; Kappeler, A.; Kipfer, R.; Peterhans, E.

    1990-01-01

    Rabies has disappeared from large parts of Switzerland. Due to systematic oral fox-vaccination campaings that started in 1987, cases of rabies in wild and domestic animals have been confined to the western frontier with France in the last three years. Nevertheless, some cases of severe exposition of man by rabid or rabies-suspect animals still occur. Rabies can be diagnosed in brain smears of infected animals with high specificity and sensitivity by a direct immunofluorescence method. According to WHO recommendations, negative results are to be confirmed in cases of a human exposition by intracerebral inoculation of brain suspensions in three-weeks-old mice. This method has an excellent sensitivity and is able to detect false-negative results in immunofluorescence, which occur in a very small percentage (0.043%). The disadvantage of this confirmatory assay is the sacrification of relatively high numbers of mice (in the Swiss rabies center about 1,300 animals each year), and the long time required for a final diagnosis: 7-20 days in positive, 21 days in negative cases. The cultivation of virus from brain suspensions on a mouse neuroblastoma cell line is a tempting alternative to the mouse inoculation test. This method usually provides a conclusive diagnosis within a few days. However, in our hands it showed in preliminary experiments an unsatisfactory sensitivity (80.7%). The necessity to carry out strict reproducibility controls in this assay has to be emphasized. Further work must be invested in the improvement of the rabies tissue culture infection test and a careful long-term comparison with the mouse inoculation test will be necessary before the mouse inoculation test can be replaced.

  12. Comparison of pathogenic domains of rabies and African rabies-related lyssaviruses and pathogenicity observed in mice

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    Joe Kgaladi

    2013-03-01

    Full Text Available Several lyssavirus species occur in Africa (Rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus, displaying a high sequence diversity between isolates belonging to the same species. There is limited information about comparative pathogenesis of these African lyssaviruses and this precludes authoritative opinion on the potential public and veterinary health impact. In this study, an analysis of representative African lyssaviruses attempted to correlate viral genomic sequence similarities and differences with the corresponding pathogenic profiles observed in mice. The study demonstrated that the virus isolates evaluated could be lethal to mice when introduced intramuscularly and that different isolates of the same lyssavirus species differ in their virulence. Using real-time polymerase chain reaction (PCR, viral RNA was detected in brain tissue, but no viral RNA was detected in the salivary glands or blood of mice that succumbed to infection. Comparison of known pathogenic domains indicated that pathogenicity is likely to be dependent on multiple domains. Cumulatively, our results re-emphasised the realisation that the pathogenicity of a lyssavirus species cannot be deduced based on studies of only a single isolate of the species or a single pathogenic domain.

  13. Expression of the miR-200 family in the brain of mice infected with the rabies virus and prediction of miR-200 family target genes%microRNA-200家族在狂犬病病毒感染鼠脑组织中的表达及其靶基因预测

    Institute of Scientific and Technical Information of China (English)

    赵丽丽; 赵平森; 齐瑛琳; 杨玉蛟; 赵永坤; 郑学星; 王化磊; 王铁成; 黄耕

    2013-01-01

    目的 检测microRNA-200(miR-200)家族在感染狂犬病病毒鼠脑中的表达水平,预测相关靶基因,为miR-200家族靶基因的生物学验证提供数据支持,为研究miR-200家族在狂犬病病毒感染过程中的调节机制和生物学功能奠定理论基础. 方法 利用MicroRNA基因芯片技术检测miR-200家族在感染狂犬病病毒鼠脑组织中的表达水平,并对其进行qRT-PCR验证;利用TargetScan、MicroCosm Targets和miRarnada等3个数据库预测miR-200的靶基因,并对靶基因进行功能和信号转导通路富集分析. 结果 与对照组相比,miR-200在感染狂犬病病毒的小鼠脑组织中表达水平显著下降,预测的靶基因有3 154个,靶基因主要参与细胞周期、细胞因子受体结合、细胞代谢、高分子代谢和生物学调节等生物学功能(P<0.01).参与的信号通路主要有JAK-STAT信号通路、TCR信号传导通路、轴突引导、蛋白质泛素化、Wnt信号通路、TGF-β信号通路和癌症等信号通路(P<0.05). 结论 miR-200家族在感染狂犬病病毒的鼠脑组织中表达水平显著下降,预测的靶基因在相关免疫应答中起重要作用,也可能与狂犬病病毒的感染和致病性有关.%Objectives To provide corroborating data for biological determination of the target genes of the miR-200 family by investigating the expression of the miR-200 family in the brain of mice infected with the rabies virus and predicting related target genes in order to lay the foundation for the regulatory mechanisms and biological function of the miR-200 family in rabies virus infection. Methods The expression of the miR-200 family was studied in the brains of mice infected with rabies using an miRNA microarray assay. These data were verified by quantitative real-time PCR. Tar-getScan, MicroCosm Targets, and miRanda were used to predict target genes of the miR-200 family. Target genes identified by all 3 approaches were subjected to GO analysis and KEGG

  14. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  15. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  16. Field trial with oral vaccination of dogs against rabies in the Philippines

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    De Leon Renato

    2001-11-01

    Full Text Available Abstract Background The potential role of oral vaccination of dogs against rabies in the Philippines was investigated in terms of safety and efficacy. Methods Prior to the vaccination campaign, a house-to-house survey was carried out to collect data on the dog population in the study area, the coastal village of Mindoro. During the vaccination campaign all households were visited again, and all dogs encountered (>2 months old were, if possible, vaccinated. Furthermore, 14 dogs vaccinated were bled on different occasions. Results During the survey, a total of 216 dogs were counted, and none of these animals had previously been vaccinated against rabies. Only 17 dogs could be restrained and subsequently vaccinated directly by the vaccinators. Another 126 dogs were offered a local-made boiled intestine bait, containing a capsule filled with 3.0 ml SAD B19 (107.9 FFU/ml. The bait acceptance rate of dogs offered a bait was 96.1%. The vaccination coverage of the dog population (> 2 months old estimated by the number of animals vaccinated directly and the number of dogs that accepted a bait and subsequently punctured the vaccine container was 76%. Fifteen and 29 days after the vaccination campaign 6 and 10 dogs (n = 14 had rabies virus neutralizing antibody titres of ≥ 0.5 IU/ml, respectively. No unintentional contacts of nontarget species, including humans, with the vaccine virus were reported. Conclusions The results of the campaign show that oral vaccination of dogs against rabies is a promising supplementary method in dog rabies control in the Philippines.

  17. Dog Ecology and Dog Rabies Control

    OpenAIRE

    Wandeler, A I; Budde, A.; Capt, S.; Kappeler, A.; Matter, H.

    2017-01-01

    Dog populations, like other populations, depend on the availability of resources (food, water, and shelter). Humans either make available or deliberately withhold resources for varying proportions of dog populations. Dog-keeping practices and the duties of responsible ownership vary with the cultural setting. Dog populations often attain densities that allow the species to be a main host of rabies. The epidemiology of dog rabies is not well understood, despite the easy access to dog populatio...

  18. Heterogeneity of Rabies Vaccination Recommendations across Asia

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    Philippe Buchy

    2017-07-01

    Full Text Available Asian countries bear the greatest burden of the disease, with a majority (59% of rabies-related deaths occurring in Asia. In order to promote best practices, we summarized national human vaccination guidelines across this region, to highlight differences and similarities and to discuss the aspects that would benefit from updates. National management guidelines for rabies were retrieved from various sources to extract information on rabies pre- and post-exposure prophylaxis (PrEP, and PEP, booster vaccination, and route of administration. Rabies guidelines recommendations for wound management and PrEP across Asia are broadly aligned to the World Health Organization (WHO guidelines. For PEP, the 5-dose Essen, and the 4-dose Zagreb are the regimens of choice for intramuscular (IM, and the Thai Red Cross regimen for intradermal (ID, administration. Several national guidelines have yet to endorse ID vaccine administration. Most guidelines recommend rabies immunoglobulin in category III exposures. Booster recommendations are not included in all guidelines, with limited clarity on booster requirement across the spectrum of risk of rabies exposure. In conclusion, national recommendations across Asian countries differ and while some guidelines are closely aligned to the WHO recommendations, resource-saving ID administration and use of rational abbreviated schedules have yet to be endorsed.

  19. Efficient In Vitro and In Vivo Activity of Glyco-Engineered Plant-Produced Rabies Monoclonal Antibodies E559 and 62-71-3.

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    Tsepo Lebiletsa Tsekoa

    Full Text Available Rabies is a neglected zoonotic disease that has no effective treatment after onset of illness. However the disease can be prevented effectively by prompt administration of post exposure prophylaxis which includes administration of passive immunizing antibodies (Rabies Immune Globulin, RIG. Currently, human RIG suffers from many restrictions including limited availability, batch-to batch inconsistencies and potential for contamination with blood-borne pathogens. Anti-rabies monoclonal antibodies (mAbs have been identified as a promising alternative to RIG. Here, we applied a plant-based transient expression system to achieve rapid, high level production and efficacy of the two highly potent anti-rabies mAbs E559 and 62-71-3. Expression levels of up to 490 mg/kg of recombinant mAbs were obtained in Nicotiana benthamiana glycosylation mutants by using a viral based transient expression system. The plant-made E559 and 62-71-3, carrying human-type fucose-free N-glycans, assembled properly and were structurally sound as determined by mass spectrometry and calorimetric density measurements. Both mAbs efficiently neutralised diverse rabies virus variants in vitro. Importantly, E559 and 62-71-3 exhibited enhanced protection against rabies virus compared to human RIG in a hamster model post-exposure challenge trial. Collectively, our results provide the basis for the development of a multi-mAb based alternative to RIG.

  20. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  1. Evaluation of standard reagents for radial-immunodiffusion assays. In vitro control of rabies vaccines

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    MICELI Graciela S.

    2000-01-01

    Full Text Available The RID assay is one of the in vitro methods used for in-process control in the production of rabies vaccines for veterinary use. It has been shown to be very useful for determining antigen concentration in the final bulk product. The work presented in this paper, including the production and standardization of candidate standard reagents for use in the Radial Immunodiffusion Assay (RID was carried out at the Pan American Institute for Food Protection and Zoonoses (INPPAZ/PAHO/WHO. The study was completed with the cooperation of the Faculty of Veterinary Sciences, National University of La Plata (NULP, Argentina, where the validation of the proposed standards and the quality control of samples from 28 different batches of rabies vaccines produced with Pasteur strain rabies virus (PV in BHK cells were performed. The activity of the vaccines was determined by in vivo (NIH and in vitro (RIDassays. The results of the candidate reagents for the reagent standardization tests showed stability, sensitivity and reproducibility. The Relative Potency the 1.2 between the problem vaccines and the reference vaccine was estimated by variance and regression analysis. The results of our validation study show that the INPPAZ (PAHO/WHO is capable of producing and distributing the above-mentioned standard reagents, as well as of providing support for the incorporation of the RID technique (sensitive, rapid and inexpensive to the laboratories that manufacture rabies vaccines in Latin America and the Caribbean.

  2. Kinetics of rabies antibodies as a strategy for canine active immunization

    Science.gov (United States)

    2014-01-01

    Background Rabies, a zoonosis found throughout the globe, is caused by a virus of the Lyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil. Findings During 12 months we evaluated the active immunity of dogs first vaccinated (booster shot at 30 days after first vaccination) against rabies using the Fuenzalida-Palácios modified vaccine in the urban area of Botucatu city, São Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (≥0.5 IU/mL) for 360 days after the first vaccination whereas 51.5% during all the study period. Conclusions The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30 days after the first and the third dose at 180 days after the first for the maintenance of protective titers during 12 months. PMID:26413082

  3. Avanços na pesquisa da raiva Advances in rabies research

    Directory of Open Access Journals (Sweden)

    Pedro Manuel Leal Germano

    1994-02-01

    Full Text Available Fez-se revisão sobre os recentes avanços na pesquisa da raiva resultantes do progresso tecnológico das ciências biológicas, em especial a biologia molecular e a engenharia genética. Enfatizam-se os novos conhecimentos sobre as características e propriedades do virus rábico, sobre a patogenia e imunologia da infecção, bem como o desenvolvimento de novas técnicas de diagnóstico e de avaliação de imunógenos. Destacam-se, na epidemiologia, a importância da identificação de cepas imunogenicamente distintas do virus rábico, e na imunoprofilaxia, a produção de vacinas altamente imunogênicas.Recent advances in research into rabies, based on the technological process of the biological sciences mainly molecular biology and genetic engineering, are mentioned. The current knowledge of the characteristics, properties pathogeny and immunology of the rabies views is presented, as well as the development of new diagnostic and vaccine evaluation techniques. The epidemiological importance of the identification of different immunogenic rabies virus strains and the role in immunoprophylaxis of the production of highly immunogenic vaccines, are set out.

  4. Sudden onset unilateral sensorineural hearing loss after rabies vaccination.

    Science.gov (United States)

    Okhovat, Saleh; Fox, Richard; Magill, Jennifer; Narula, Antony

    2015-12-15

    A 33-year-old man developed profound sudden onset right-sided hearing loss with tinnitus and vertigo, within 24 h of pretravel rabies vaccination. There was no history of upper respiratory tract infection, systemic illness, ototoxic medication or trauma, and normal otoscopic examination. Pure tone audiograms (PTA) demonstrated right-sided sensorineural hearing loss (thresholds 90-100 dB) and normal left-sided hearing. MRI internal acoustic meatus, viral serology (hepatitis B, C, HIV and cytomegalovirus) and syphilis screen were normal. Positive Epstein-Barr virus IgG, viral capsid IgG and anticochlear antibodies (anti-HSP-70) were noted. Initial treatment involved a course of high-dose oral prednisolone and acyclovir. Repeat PTAs after 12 days of treatment showed a small improvement in hearing thresholds. Salvage intratympanic steroid injections were attempted but failed to improve hearing further. Sudden onset sensorineural hearing loss (SSNHL) is an uncommon but frightening experience for patients. This is the first report of SSNHL following rabies immunisation in an adult.

  5. Phylodynamics of vampire bat-transmitted rabies in Argentina.

    Science.gov (United States)

    Torres, C; Lema, C; Dohmen, F Gury; Beltran, F; Novaro, L; Russo, S; Freire, M C; Velasco-Villa, A; Mbayed, V A; Cisterna, D M

    2014-05-01

    Common vampire bat populations distributed from Mexico to Argentina are important rabies reservoir hosts in Latin America. The aim of this work was to analyse the population structure of the rabies virus (RABV) variants associated with vampire bats in the Americas and to study their phylodynamic pattern within Argentina. The phylogenetic analysis based on all available vampire bat-related N gene sequences showed both a geographical and a temporal structure. The two largest groups of RABV variants from Argentina were isolated from northwestern Argentina and from the central western zone of northeastern Argentina, corresponding to livestock areas with different climatic, topographic and biogeographical conditions, which determined their dissemination and evolutionary patterns. In addition, multiple introductions of the infection into Argentina, possibly from Brazil, were detected. The phylodynamic analysis suggests that RABV transmission dynamics is characterized by initial epizootic waves followed by local enzootic cycles with variable persistence. Anthropogenic interventions in the ecosystem should be assessed taking into account not only the environmental impact but also the potential risk of disease spreading through dissemination of current RABV lineages or the emergence of novel ones associated with vampire bats. © 2014 John Wiley & Sons Ltd.

  6. Rabies Exposure: When Should I Seek Medical Attention?

    Science.gov (United States)

    ... Rabies Share Compartir When should I seek medical attention? Were you exposed to rabies? What materials can ... with soap and water. See your doctor for attention for any trauma due to an animal attack ...

  7. Predicted Spatial Spread of Canine Rabies in Australia

    National Research Council Canada - National Science Library

    Johnstone-Robertson, Simon P; Fleming, Peter J. S; Ward, Michael P; Davis, Stephen A

    2017-01-01

    ... for the spread of canine rabies in the currently rabies-free wild dog population of Australia. The introduction of a sub-clinically infected dog from Indonesia is a distinct possibility, as is t...

  8. Rabies: What If I Receive Treatment Outside the United States?

    Science.gov (United States)

    ... Exposure at a Softball Tournament September 9, 2006: Horse Stabled in Tennessee Tested Positive for Rabies May ... In addition, unpurified anti-rabies serum of equine origin might still be used in some countries where ...

  9. Rabies exposures, post-exposure prophylaxis and deaths in a region of endemic canine rabies.

    Directory of Open Access Journals (Sweden)

    Katie Hampson

    Full Text Available Thousands of human deaths from rabies occur annually despite the availability of effective vaccines following exposure, and for disease control in the animal reservoir. Our aim was to assess risk factors associated with exposure and to determine why human deaths from endemic canine rabies still occur.Contact tracing was used to gather data on rabies exposures, post-exposure prophylaxis (PEP delivered and deaths in two rural districts in northwestern Tanzania from 2002 to 2006. Data on risk factors and the propensity to seek and complete courses of PEP was collected using questionnaires. Exposures varied from 6-141/100,000 per year. Risk of exposure to rabies was greater in an area with agropastoralist communities (and larger domestic dog populations than an area with pastoralist communities. Children were at greater risk than adults of being exposed to rabies and of developing clinical signs. PEP dramatically reduced the risk of developing rabies (odds ratio [OR] 17.33, 95% confidence interval [CI] 6.39-60.83 and when PEP was not delivered the risks were higher in the pastoralist than the agro-pastoralist area (OR 6.12, 95% CI 2.60-14.58. Low socioeconomic class and distance to medical facilities lengthened delays before PEP delivery. Over 20% of rabies-exposed individuals did not seek medical treatment and were not documented in official records and <65% received PEP. Animal bite injury records were an accurate indicator of rabies exposure incidence.Insufficient knowledge about rabies dangers and prevention, particularly prompt PEP, but also wound management, was the main cause of rabies deaths. Education, particularly in poor and marginalized communities, but also for medical and veterinary workers, would prevent future deaths.

  10. Molecular Characterization of Viral G Gene in Emerging and Re-emerging Areas of Rabies in China, 2007 to 2011

    Institute of Scientific and Technical Information of China (English)

    Shu-Lin Lang; Xiao-Yan Tao; Zhen-Yang Guo; Qing Tang; Hao Li; Cui-Ping Yin; Ying Li; Guo-Dong Liang

    2012-01-01

    In recent years (2007 to 2011),although the overall number of rabies cases in China has decreased,there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low incidence of rabies.To investigate the origin and the factors affecting the spread of rabies in China,specimens were collected from 2007 to 2011 from provinces with emerging and re-emerging cases and tested for the presence of the rabies virus.Positive specimens were combined with sequences from GenBank to perform comparisons of homology and functional sites,and to carry out phylogenetic analyses.Out of these regions,five provinces had 9positive specimens from canine and cattle,and 34 canine or human specimens were obtained from previously high-incidence provinces.Complete sequences of G gene were obtained for these samples.Homology of the sequences of these 43 specimens was 87%-100% at the nucleotide level and 93.7% -100% at the amino acid level.These G gene sequences were combined with reference sequence from GenBank and used to construct a phylogenetic tree.The results showed that 43 specimens were all assigned to China clade I and clade Ⅱ,with all specimens from emerging and re-emerging areas placed within clade I.Specimens isolated from Shanxi and Inner Mongolia in 2011 were distinct from previously-isolated local strains and had closer homology to strains from Hebei,Beijing and Tianjin whereas new isolates from Shanghai were tightly clustered with strains isolated in the 1990s.Finally,Shaanxi isolates were clustered with strains from adjacent Sichuan.Our results suggest that the rabies cases in emerging and re-emerging areas in China in the last 5 years are a consequence of the epidemic spreading from of neighboring provinces and regions experiencing a serious epidemic of rabies.

  11. IMMUNE RESPONSE AND COST ANALYSIS OF INTRADERMAL RABIES VACCINATION FOR POST-EXPOSURE PROPHYLAXIS REGIMEN IN HUMAN

    Directory of Open Access Journals (Sweden)

    N. S. Budayanti

    2014-01-01

    Full Text Available BackgroundThe outbreak of rabies in human in Bali-Indonesia is causing an extraordinary pressure for the government in providing adequate doses of anti-rabies vaccine for post-exposure prophylaxis (PEP. Here, we directly compare the immune response and benefit of the intradermal (ID protocol for rabies vaccine delivery with the intramuscular (IM route. Methods: Sixty health workers who were willing to participate in this study have been randomly selected and grouped into ID, IM, and control groups, each with 20 volunteers. The Thai Red Cross ID- and Zangreb IM-protocols have been applied to the respective group. The sera of the volunteers were collected at day 0, week 1, week 3, week 4, month 3, month 6, month 9, and month 12 after the first vaccination. Anti-rabies virus IgG was detected using PlateliaTM Rabies II Kit (Bio-Rad. Results: Anti-rabies IgG could be detected in the ID-group at one week. The ID-vaccine delivery induced a slightly higher maximum antibody titer compared to IM, though not statistically significant (p>0.05. ID vaccination caused less adverse reactions and produces longer lasting protective immune response.  Cost minimization analysis (CMA on the provincial and national PEP data in 2009-2011 shows that the ID-delivery will reduce the total cost for a completed regimen by USD 28.5, and would have saved the Indonesian government budget approximately USD 3.6 and 4.3 million for complete regimens in Bali and Indonesia, respectively. Conclusion: The ID administration of anti-rabies vaccine induces a similar immune response compared to that of intramuscular injection. It also produces longer lasting protective immune response. It offers additional advantages of potential net cost savings as well as decreasing the pressure on vaccine availability due to the high number of dog bite cases.

  12. Landscape genetics of raccoons (Procyon lotor) associated with ridges and valleys of Pennsylvania: implications for oral rabies vaccination programs.

    Science.gov (United States)

    Root, J Jeffrey; Puskas, Robert B; Fischer, Justin W; Swope, Craig B; Neubaum, Melissa A; Reeder, Serena A; Piaggio, Antoinette J

    2009-12-01

    Raccoons are the reservoir for the raccoon rabies virus variant in the United States. To combat this threat, oral rabies vaccination (ORV) programs are conducted in many eastern states. To aid in these efforts, the genetic structure of raccoons (Procyon lotor) was assessed in southwestern Pennsylvania to determine if select geographic features (i.e., ridges and valleys) serve as corridors or hindrances to raccoon gene flow (e.g., movement) and, therefore, rabies virus trafficking in this physiographic region. Raccoon DNA samples (n = 185) were collected from one ridge site and two adjacent valleys in southwestern Pennsylvania (Westmoreland, Cambria, Fayette, and Somerset counties). Raccoon genetic structure within and among these study sites was characterized at nine microsatellite loci. Results indicated that there was little population subdivision among any sites sampled. Furthermore, analyses using a model-based clustering approach indicated one essentially panmictic population was present among all the raccoons sampled over a reasonably broad geographic area (e.g., sites up to 36 km apart). However, a signature of isolation by distance was detected, suggesting that widths of ORV zones are critical for success. Combined, these data indicate that geographic features within this landscape influence raccoon gene flow only to a limited extent, suggesting that ridges of this physiographic system will not provide substantial long-term natural barriers to rabies virus trafficking. These results may be of value for future ORV efforts in Pennsylvania and other eastern states with similar landscapes.

  13. Dog-Mediated Human Rabies Death, Haiti, 2016

    OpenAIRE

    Ryan M Wallace; Etheart, Melissa D.; Doty, Jeff; Monroe, Ben; Crowdis, Kelly; Augustin, Pierre Dilius; Blanton, Jesse; Fenelon, Natael

    2016-01-01

    Haiti has experienced numerous barriers to rabies control over the past decades and is one of the remaining Western Hemisphere countries to report dog-mediated human rabies deaths. We describe the circumstances surrounding a reported human rabies death in 2016 as well as barriers to treatment and surveillance reporting.

  14. Hypersexuality in a 28-year-old woman with rabies.

    Science.gov (United States)

    Senthilkumaran, Subramanian; Balamurgan, Namasivayam; Sweni, Shah; Menezes, Ritesh G; Thirumalaikolundusubramanian, Ponniah

    2011-12-01

    Unusual clinical presentations of rabies are well known. A case of rabies is reported in a 28-year-old female who presented with features of increased sexual desire and heightened sexual arousal without provocation. Health care providers should be aware that marked changes in sexual behavior may be related to infection due to rabies.

  15. Response to a Rabies Epidemic, Bali, Indonesia, 2008–2011

    Science.gov (United States)

    Hampson, Katie; Girardi, Janice; Hiby, Elly; Knobel, Darryn; Mardiana, Wayan; Townsend, Sunny; Scott-Orr, Helen

    2013-01-01

    Emergency vaccinations and culling failed to contain an outbreak of rabies in Bali, Indonesia, during 2008–2009. Subsequent island-wide mass vaccination (reaching 70% coverage, >200,000 dogs) led to substantial declines in rabies incidence and spread. However, the incidence of dog bites remains high, and repeat campaigns are necessary to eliminate rabies in Bali. PMID:23632033

  16. Evaluation of a Direct Rapid Immunohistochemical Test (dRIT) for Rapid Diagnosis of Rabies in Animals and Humans

    Institute of Scientific and Technical Information of China (English)

    Shampur Narayan Madhusudana; Sundaramurthy Subha; Ullas Thankappan; Yajaman Belludi Ashwin

    2012-01-01

    Presently the gold standard diagnostic technique for rabies is the direct immunofluorescence assay (dFA) which is very expensive and requires a high level of expertise.There is a need for more economical and user friendly tests,particularly for use in developing countries.We have established one such test called the direct rapid immunohistochemical test (dRIT) for diagnosis of rabies using brain tissue.The test is based on capture of rabies nucleoprotein (N) antigen in brain smears using a cocktail of biotinylated monoclonal antibodies specific for the N protein and color development by streptavidin peroxidase-amino ethyl carbazole and counter staining with haematoxollin.The test was done in parallel with standard FAT dFA using 400 brain samples from different animals and humans.The rabies virus N protein appears under light microscope as reddish brown particles against a light blue background.There was 100 % correlation between the results obtained by the two tests.Also,interpretation of results by dRIT was easier and only required a light microscope.To conclude,this newly developed dRIT technique promises to be a simple,cost effective diagnostic tool for rabies and will have applicability in field conditions prevalent in developing countries.

  17. Rates of viral evolution are linked to host geography in bat rabies.

    Directory of Open Access Journals (Sweden)

    Daniel G Streicker

    Full Text Available Rates of evolution span orders of magnitude among RNA viruses with important implications for viral transmission and emergence. Although the tempo of viral evolution is often ascribed to viral features such as mutation rates and transmission mode, these factors alone cannot explain variation among closely related viruses, where host biology might operate more strongly on viral evolution. Here, we analyzed sequence data from hundreds of rabies viruses collected from bats throughout the Americas to describe dramatic variation in the speed of rabies virus evolution when circulating in ecologically distinct reservoir species. Integration of ecological and genetic data through a comparative bayesian analysis revealed that viral evolutionary rates were labile following historical jumps between bat species and nearly four times faster in tropical and subtropical bats compared to temperate species. The association between geography and viral evolution could not be explained by host metabolism, phylogeny or variable selection pressures, and instead appeared to be a consequence of reduced seasonality in bat activity and virus transmission associated with climate. Our results demonstrate a key role for host ecology in shaping the tempo of evolution in multi-host viruses and highlight the power of comparative phylogenetic methods to identify the host and environmental features that influence transmission dynamics.

  18. Avaliação de três cepas de vírus rábico, antigenicamente distintas, em camundongos: II - Estudo da disseminação viral por diferentes órgãos Evaluation of three antigenically different rabies virus strains in mice: II -Study of the viral dissemination in different organs

    Directory of Open Access Journals (Sweden)

    Pedro Manuel Leal Germano

    1988-12-01

    Full Text Available Estudou-se, comparativamente, o grau de disseminação de três cepas de vírus rábico, duas de origem de cão, Jales e Nigéria, e uma de origem de morcego, DR 19, com perfis antigênicos do nucleocapside distintos. Estas cepas foram inoculadas por via intramuscular, na face interna da coxa, em dois grupos de camundongos, com 21 e 28 dias de idade. Os animais foram mantidos em observação por um período total de 30 dias, e dos animais vitimados pela infecção, foram coletados diferentes órgãos, músculo lingual, coração, pulmão, rim e fígado, além do cérebro e da medula espinal, para avaliar-se o grau de disseminação de cada cepa viral, através da prova de imunofluorescência direta (IFD. Os resultados obtidos evidenciaram que os decalques de cérebro e de medula espinal apresentaram total concordância na prova de IFD, constatando-se as maiores diferenças com as cepas Jales e Nigéria, situando-se a cepa DR 19, intermediariamente, a estas duas. O músculo lingual foi o órgão que apresentou maior freqüência de positividade para ambos os grupos etários e para as três cepas virais.A study was conducted to compare three strains of rabies virus, two of them, Jales and Nigeria, isolated from dogs, and the other DR 19, from vampire bats, with different nucleo-capside antigenic characteristics. These strains were intramuscularly inoculated in the inner side of the thigh of 21 and 28 day-old mice. The animals were observed for 30 days and different organs: brain, spinal cord, tongue, heart, lung, kidney and liver were collected from the animals which died of rabies for the dissemination study by the immunofluorescent antibody technique (IFA. This technique showed complete agreement between brain and spinal cord. The greatest differences in dissemination were observed between Jales and Nigeria strains. The results observed for the DR 19 strain were situated between those of the two dog strains. The greates degree of dissemination

  19. Human exposure to potential rabies virus transmitters in Olinda, State of Pernambuco, between 2002 and 2006 Exposição humana a potenciais transmissores do vírus rábico em Olinda, Estado de Pernambuco, entre 2002 e 2006

    Directory of Open Access Journals (Sweden)

    Filipe Dantas-Torres

    2007-12-01

    Full Text Available The aim of the present study was to evaluate the data on human exposure to potential rabies virus transmitters in Olinda, State of Pernambuco, Brazil. Data from 7,062 patients who underwent antirabies prophylactic treatment in Olinda between 2002 and 2006 were analyzed. As expected, dogs and cats were involved in most of the cases; i.e. 82.3 and 16.3%, respectively. Attacks by nonhuman primates, bats and other species (unspecified were also reported. Among the 7,062 patients who underwent antirabies treatment, 582 patients abandoned the treatment, either by indication from the health unit (195 or by their own decision (387. In conclusion, this study has indicated that prophylaxis for human rabies in this urban area will require a multifaceted approach, including health education, post-exposure prophylaxis, systematic vaccination for dogs and cats, and possibly selective control over wild animals such as hematophagous bats.O objetivo deste estudo foi avaliar os dados sobre a exposição humana a potenciais transmissores do vírus rábico em Olinda, Pernambuco, Brasil. Foram analisados dados de 7.062 pacientes submetidos ao tratamento anti-rábico em Olinda entre 2002 e 2006. Como esperado, cães e gatos estiveram envolvidos na maioria dos casos; isto é, 82,3 e 16,3%, respectivamente. Ataques por primatas não-humanos, morcegos e outras espécies (não especificadas também foram relatadas. Dos 7.062 pacientes submetidos ao tratamento anti-rábico, 582 abandonaram o tratamento, seja por indicação da unidade de saúde (195 ou por decisão própria (387. Concluindo, esse estudo indica que a profilaxia da raiva humana nessa área urbana irá requer uma abordagem multifacetada, incluindo educação em saúde, profilaxia pós-exposição, vacinação sistemática de cães e gatos e, eventualmente, o controle seletivo de animais silvestres, tais como morcegos hematófagos.

  20. The Formation of the Eastern Africa Rabies Network: A Sub-Regional Approach to Rabies Elimination

    Directory of Open Access Journals (Sweden)

    Emily G Pieracci

    2017-07-01

    Full Text Available Abstract: International rabies networks have been formed in many of the canine-rabies endemic regions around the world to create unified and directed regional approaches towards elimination. The aim of the first sub-regional Eastern Africa rabies network meeting, which included Kenya, Ethiopia, Tanzania, Rwanda, and Uganda, was to discuss how individual country strategies could be coordinated to address the unique challenges that are faced within the network. The Stepwise Approach towards Rabies Elimination and the Global Dog Rabies Elimination Pathway tool were used to stimulate discussion and planning to achieve the elimination of canine-mediated human rabies by 2030. Our analysis estimated a total dog population of 18.3 million dogs in the Eastern Africa region. The current dog vaccination coverage was estimated to be approximately 5% (915,000 dogs, with an estimated 4910 vaccinators available. Assuming that every vaccinator performs rabies vaccination, this equated to each vaccinator currently vaccinating 186 dogs per year, whilst the target would be to vaccinate 2609 dogs every year for the community to reach 70% coverage. In order to achieve the World Health Organization-recommended 70% vaccination coverage, an additional 11 million dogs need to be vaccinated each year, pointing to an average annual shortfall of $ 23 million USD in current spending to achieve elimination by 2030 across the region. Improved vaccination efficiency within the region could be achieved by improving logistics and/or incorporating multiple vaccination methods to increase vaccinator efficiency, and could serve to reduce the financial burden associated with rabies elimination. Regional approaches to rabies control are of value, as neighboring countries can share their unique challenges while, at the same time, common approaches can be developed and resource-saving strategies can be implemented.

  1. Dog bites in humans and estimating human rabies mortality in rabies endemic areas of Bhutan.

    Directory of Open Access Journals (Sweden)

    Tenzin

    2011-11-01

    Full Text Available BACKGROUND: Dog bites in humans are a public health problem worldwide. The issues of increasing stray dog populations, rabies outbreaks, and the risk of dogs biting humans have been frequently reported by the media in Bhutan. This study aimed to estimate the bite incidence and identify the risk factors for dog bites in humans, and to estimate human deaths from rabies in rabies endemic south Bhutan. METHODS: A hospital-based questionnaire survey was conducted during 2009-2010 among dog bites victims who visited three hospitals in Bhutan for anti-rabies vaccine injection. Decision tree modeling was used to estimate human deaths from rabies following dog bite injuries in two rabies endemic areas of south Bhutan. RESULTS: Three hundred and twenty four dog bite victims were interviewed. The annual incidence of dog bites differed between the hospital catchment areas: 869.8 (95% CI: 722.8-1022.5, 293.8 (240-358.2 and 284.8 (251.2-323 per 100,000 people in Gelephu, Phuentsholing and Thimphu, respectively. Males (62% were more at risk than females (P<0.001. Children aged 5-9 years were bitten more than other age groups. The majority of victims (71% were bitten by stray dogs. No direct fatal injury was reported. In two hospital areas (Gelephu and Phuentsholing in south Bhutan the annual incidence of death from rabies was 3.14 (95% CI: 1.57-6.29 per 100,000 population. The decision tree model predicted an equivalent annual incidence of 4.67 (95% CI: 2.53-7.53 deaths/100,000 population at risk. In the absence of post exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69-25.14 deaths/year in these two areas. CONCLUSIONS: Increased educational awareness of people about the risk of dog bites and rabies is necessary, particularly for children in rabies endemic areas of Bhutan.

  2. Dogs Entering the United States from Rabies-Endemic Countries, 2011-2012.

    Science.gov (United States)

    Sinclair, J R; Washburn, F; Fox, S; Lankau, E W

    2015-08-01

    International dog imports pose a risk because of the potential movement of disease agents, including the canine rabies virus variant which has been eliminated from the United States since 2007. US regulations require a rabies vaccination certificate for dogs arriving from rabies-endemic countries, but permit the importation of dogs that have not been adequately immunized against rabies, provided that the dogs are confined under conditions that restrict their contact with humans and other animals until they have been immunized. CDC Form 75.37, 'Notice to Owners and Importers of Dogs', explains the confinement requirements and serves as a binding confinement agreement with the importer. In this evaluation, we describe the characteristics of unimmunized dogs imported into the United States over a 1-year period based upon dog confinement agreements recorded at the Centers for Disease Control and Prevention (CDC) quarantine stations. Confinement agreements were issued for nearly 2800 unimmunized dogs that entered the United States during 1 June 2011-31 May 2012, the majority of which travelled to the United States by air and without any seasonal pattern in import volume. Over 60% of these animals were puppies dogs arrived from 81 countries, with the majority arriving from North America or Europe. Dogs placed on confinement agreements had final destinations in 49 states. California, New York, Texas, Washington and Florida received the largest number of dogs on confinement agreements. These results (which do not reflect human travel or US dog ownership data) suggest that a large portion of unimmunized dogs arrive from rabies-endemic countries for commercial, shelter and rescue purposes. Further evaluation and key stakeholder involvement are needed to assess whether the current dog importation regulations are an adequate compromise between the benefits and risks of dog importation.

  3. Experimental observation of Rabi oscillations in photonic lattices.

    Science.gov (United States)

    Shandarova, Ksenia; Rüter, Christian E; Kip, Detlef; Makris, Konstantinos G; Christodoulides, Demetrios N; Peleg, Or; Segev, Mordechai

    2009-03-27

    We demonstrate spatial Rabi oscillations in optical waveguide arrays. Adiabatic transitions between extended Floquet-Bloch modes associated with different bands are stimulated by periodic modulation of the photonic lattice in the propagation direction. When the stimulating modulation also carries transverse momentum, the transition becomes indirect, equivalent to phonon-assisted Rabi oscillations. In solid state physics such indirect Rabi oscillations necessitate coherent phonons and hence they have never been observed. Our experiments suggest that phonon-assisted Rabi oscillations are observable also with Bose-Einstein condensates, as well as with other wave systems-where coherence can be maintained for at least one period of the Rabi oscillation.

  4. Oral rabies vaccination of raccoons and striped skunks with ONRAB® baits: multiple factors influence field immunogenicity.

    Science.gov (United States)

    Mainguy, Julien; Rees, Erin E; Canac-Marquis, Pierre; Bélanger, Denise; Fehlner-Gardiner, Christine; Séguin, Guylaine; Larrat, Sylvain; Lair, Stéphane; Landry, François; Côté, Nathalie

    2012-10-01

    Multiple control methods have been used in North America to manage the spread of rabies caused by the raccoon (Procyon lotor) rabies virus variant (RRVV). Recently, oral vaccination with ONRAB(®) vaccine baits, which contain an adenovirus rabies glycoprotein recombinant, has been made available as an additional tool for rabies control. Our objectives were to estimate rabies antibody prevalence in wild-caught raccoons and striped skunks (Mephitis mephitis), and identify factors influencing the probability of being antibody positive at the individual level in these species, following oral rabies vaccination (ORV) campaigns in which ONRAB was distributed aerially in 2007-2009 in southern Québec, Canada. Following the aerial distribution of 43-155 ONRAB baits/km(2), the annual percentages of antibody-positive raccoons and skunks varied between 35% and 56% and 11% and 17%, respectively. In raccoons, the probability of being antibody positive was positively associated with age and density of ONRAB distributed, and influenced by the number of previous ORV campaigns conducted. Conversely, this probability was negatively associated with estimated abundance of raccoons in the trapping cell and proportion of residential areas near the raccoon capture location. None of the variables examined explained variation in the probability of being antibody positive in skunks. Our results indicate that the ONRAB density applied during ORV campaigns should be adjusted to account for variations in raccoon population density and presence of residential areas to increase the likelihood of creating an effective immunological barrier against RRVV. The high percentage of juvenile raccoons (annual mean =45 ± 3 [SE]%) and skunks (66 ± 2%) captured during post-ORV monitoring suggests that ORV campaigns should be conducted at least annually to account for the recruitment of naïve individuals into the populations. In Québec, the increasing use of ONRAB coincided with the elimination of rabies

  5. Polaritonic Rabi and Josephson Oscillations.

    Science.gov (United States)

    Rahmani, Amir; Laussy, Fabrice P

    2016-07-25

    The dynamics of coupled condensates is a wide-encompassing problem with relevance to superconductors, BECs in traps, superfluids, etc. Here, we provide a unified picture of this fundamental problem that includes i) detuning of the free energies, ii) different self-interaction strengths and iii) finite lifetime of the modes. At such, this is particularly relevant for the dynamics of polaritons, both for their internal dynamics between their light and matter constituents, as well as for the more conventional dynamics of two spatially separated condensates. Polaritons are short-lived, interact only through their material fraction and are easily detuned. At such, they bring several variations to their atomic counterpart. We show that the combination of these parameters results in important twists to the phenomenology of the Josephson effect, such as the behaviour of the relative phase (running or oscillating) or the occurence of self-trapping. We undertake a comprehensive stability analysis of the fixed points on a normalized Bloch sphere, that allows us to provide a generalized criterion to identify the Rabi and Josephson regimes in presence of detuning and decay.

  6. Vampire bat-transmitted rabies in cattle.

    Science.gov (United States)

    Arellano-Sota, C

    1988-01-01

    A short history of bovine paralytic rabies in the Americas is given. Based on information from the Animal Health Yearbook--a cooperative publication of the Food and Agriculture Organization (FAO), the World Health Organization (WHO), and the International Office of Epizootics (OIE)--a comparison is made of the epidemiology of the disease in 1968, 1978, and 1985. An important reduction in the number of cases of rabies was observed in some countries (Bolivia, Brazil, Guatemala, Mexico, Nicaragua, and Panama), mainly as a result of the use of effective vaccines that are now available and of the application of new technology to reduce the vampire bat population, the vector of the disease in cattle. The trials performed in Argentina and Mexico in the 1960s and 1970s provide enough evidence that many vaccines will protect cattle against bovine paralytic rabies. Results of these trials are presented.

  7. Immunopathology of rabies infection in mice selected for high or low acute inflammatory reaction

    Directory of Open Access Journals (Sweden)

    S. M. Achkar

    2007-01-01

    Full Text Available Rabies is a severe and lethal disease that produces a slight inflammatory response during the infection process. We analyzed the immunopathological mechanisms that occur in the central nervous system (CNS using mice genetically selected for maximal or minimal acute inflammatory reaction (AIRmax or AIRmin. As viral samples, we adopted the antigenic variant 3 (AgV3 of rabies virus from hematophagous bats and a fixed virus strain (PV1 43/3. Titration of specific antibodies was performed using enzyme-linked immunosorbent assay (ELISA. We observed a slight increase in IgG and IgG1 isotypes in infected AIRmax mice. Incubation period, determined by intracerebral inoculation with 100 LD50, was 6-7 days for PV1 43/4 strain and 9-10 days for AgV3. No difference in viral replication was noticed between AIRmax and AIRmin mice. Mortality was 100% with both viral strains. Histopathological analysis of brains and spinal cords showed inflammatory foci in all regions of the CNS. No differences were noticed in the number of neutrophils. Negri bodies were observed in practically all sites analyzed. Results suggested that inflammatory reaction is not a determining factor in the susceptibility to rabies infection.

  8. The changing landscape of rabies epidemiology and control

    Directory of Open Access Journals (Sweden)

    Sarah Cleaveland

    2014-04-01

    Full Text Available Over the past 20 years, major progress has been made in our understanding of critical aspects of rabies epidemiology and control. This paper presents results of recent research, highlighting methodological advances that have been applied to burden of disease studies, rabies epidemiological modelling and rabies surveillance. These results contribute new insights and understanding with regard to the epidemiology of rabies and help to counteract misperceptions that currently hamper rabies control efforts in Africa. The conclusion of these analyses is that the elimination of canine rabies in Africa is feasible, even in wildlife-rich areas, through mass vaccination of domestic dogs and without the need for indiscriminate culling to reduce dog population density. Furthermore, the research provides valuable practical insights that support the operational planning and design of dog vaccination campaigns and rabies surveillance measures.

  9. Bovine herpesvirus type 5 (BHV-5) in a calf with rabies Herpesvírus bovino tipo 5 (BHV-5) em bovino infectado pelo vírus da raiva

    OpenAIRE

    Spilki,Fernando R.; Ana C. Franco; Teixeira,Marjorie B.; Esteves, Paulo A; Rejane Schaefer; Eduardo Schmidt; Lemos,Ricardo A.; Roehe, Paulo M.

    2003-01-01

    The brain of an one year old male calf which died with signs of neurological disease was submitted to the laboratory for rabies diagnosis. Microscopical findings included moderate mielitis, mild meningoencephalitis with perivascular cell cuffing and Negri inclusion bodies in Purkinje cells of the cerebellum. Rabies virus infection was further confirmed by the direct fluorescent antibody test as well as by mouse inoculation. In addition, a herpesvirus was isolated from brain tissues. The isola...

  10. RABIES IN UKRAINE: EPIDEMIOLOGICAL AND EPIZOOTIC SITUATION, MEANS FOR PREVENTIVE AND THERAPEUTIC IMMUNIZATION

    Directory of Open Access Journals (Sweden)

    Lavrik A.,

    2013-06-01

    Full Text Available Epidemiological and epizootic situations of rabies in Ukraine were analyzed. Active centers of animal rabies formed in many areas where 2016 persons were attacked by animals (mostly dogs suspected on rabies during 2011 year. Characteristics of preparates on rabies prevention, and basic methods of analyzing the specific activity of rabies vaccines were described.

  11. The canonical form of the Rabi hamiltonian

    CERN Document Server

    Szopa, M; Ceulemans, A; Szopa, Marek; Mys, Geert; Ceulemans, Arnout

    1996-01-01

    The Rabi Hamiltonian, describing the coupling of a two-level system to a single quantized boson mode, is studied in the Bargmann-Fock representation. The corresponding system of differential equations is transformed into a canonical form in which all regular singularities between zero and infinity have been removed. The canonical or Birkhoff-transformed equations give rise to a two-dimensional eigenvalue problem, involving the energy and a transformational parameter which affects the coupling strength. The known isolated exact solutions of the Rabi Hamiltonian are found to correspond to the uncoupled form of the canonical system.

  12. Dynamical properties of the Rabi model

    Science.gov (United States)

    Hu, Binglu; Zhou, Huili; Chen, Shujie; Xianlong, Gao; Wang, Kelin

    2017-02-01

    We study the dynamical properties of the quantum Rabi model using a systematic expansion method. Based on the observation that the parity symmetry of the Rabi model is kept during evolution of the states, we decompose the initial state and the time-dependent one into positive and negative parity parts expanded by superposition of the coherent states. The evolutions of the corresponding positive and the negative parities are obtained, in which the expansion coefficients in the dynamical equations are known from the derived recurrence relation.

  13. Raiva em morcegos Artibeus lituratus em Montes Claros, Estado de Minas Gerais Rabies in Artibeus lituratus bats in Montes Claros, State of Minas Gerais

    Directory of Open Access Journals (Sweden)

    Nídia Francisca de Figueiredo Carneiro

    2009-08-01

    Full Text Available Apresentam-se os primeiros isolamentos do vírus da raiva em morcegos frugívoros, espécie Artibeus lituratus em Montes Claros, Minas Gerais. Diagnosticou-se através da reação de imunofluorescência direta, prova biológica e tipificação viral. Embora a raiva canina esteja controlada na cidade, o vírus rábico continua circulante em morcegos na área urbana.The first isolation of the rabies virus in frugivorous bats of the species Artibeus lituratus in Montes Claros, State of Minas Gerais, is presented. The diagnosis was obtained through the direct immunofluorescence reaction, biological tests and viral profiling. Although canine rabies is under control in this city, the rabies virus continues to circulate in bats in the urban area.

  14. Carnivore rabies: ecological and evolutionary aspects / La rabbia nei Carnivori: aspetti ecologici ed evolutivi

    Directory of Open Access Journals (Sweden)

    Alexander Wandeler

    1991-07-01

    Full Text Available Abstract Populations of a number of species of the order Carnivora sustain independent rabies epidemics in different parts of the world. These main hosts are all small to medium size (0.4 - 20 kg omnivores, scavenging, and foraging on small vertebrates, invertebrates, fruit, and refuse produced by humans. They reach highest population densities in and near human settlements. High intrinsic population growth rates allow rapid recoveries of populations decimated by persecution or disease. The rabies virus is very uniform, so strains circulating in different host populations can be distinguished by the use of monoclonal antibodies. Rabies virus strains and their hosts have to be coadapted in order to allow their prolonged coexistence. The coadapted (or coevolved? traits are pathogenicity, cell specificity (including species specificity, length of incubation period, duration and magnitude of virus excretion, duration and symptoms of clinical illness, per capita population growth rate of the host, its use of resources (habitat use, social organization and behaviour, and mortality factors other than rabies. These virus and host properties determine rates of infectious contacts and all other epidemiological parameters such as incidence, prevalence, morbidity, and mortality rates. Riassunto Diverse specie di Carnivori mantengono indipendentemente epidemie di rabbia in varie parti del mondo. Questi Carnivori sono tutti di piccola o media taglia (0,4 - 20 kg; sono onnivori, spazzini, e si alimentano di piccoli vertebrati, invertebrati, frutti e di vari rifiuti antropici. Essi raggiungono le densità più elevate nelle aree ubane e suburbane. I1 loro elevato tasso di crescita consente una rapida ripresa delle popolazioni decimate dagli abbattimenti o dalle malattie. Il virus della rabbia è molto uniforme, così che i diversi ceppi presenti nelle popolazioni ospite, possono essere distinti con l'impiego degli anticorpi

  15. Comparing ONRAB® AND RABORAL V-RG® oral rabies vaccine field performance in raccoons and striped skunks, New Brunswick, Canada, and Maine, USA.

    Science.gov (United States)

    Fehlner-Gardiner, Christine; Rudd, Robert; Donovan, Dennis; Slate, Dennis; Kempf, Libby; Badcock, Jacqueline

    2012-01-01

    Control of rabies in mesocarnivore reservoirs through oral rabies vaccination (ORV) requires an effective vaccine bait. Oral rabies vaccine performance in the field may be affected by a variety of factors, including vaccine bait density and distribution pattern, habitat, target species population density, and the availability of competing foods. A field study in which these covariates were restricted as much as possible was conducted along the international border of the state of Maine (ME), USA, and the province of New Brunswick (NB), Canada, to compare the performance of two oral rabies vaccines in raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). RABORAL V-RG(®) (vaccinia-rabies glycoprotein recombinant oral vaccine in fishmeal-coated sachet) or ONRAB(®) (adenovirus-rabies glycoprotein recombinant oral vaccine in Ultralite bait matrix) were distributed in ME and NB, respectively, by fixed-wing aircraft at a density of 75 baits/km(2) along parallel flight lines spaced 1.0 km apart. Sera were collected from live-trapped raccoons and skunks 5-7 wk post-ORV and assayed to determine antibody prevalence in each area. Duplicate serum samples were provided blind to two different laboratories for analyses by rabies virus serum neutralization assays (at both laboratories) and a competitive enzyme-linked immunosorbent assay (at one laboratory). There was no significant difference in the proportion of antibody-positive animals determined by the three serologic methods, nor was there a significant difference between ONRAB and RABORAL V-RG in the proportion of antibody-positive striped skunks observed post-ORV. In contrast, the proportion of antibody-positive raccoons was significantly higher in the ONRAB- versus the RABORAL V-RG-baited areas (74% vs. 30%; χ(2)=89.977, df=5, Praccoon rabies control.

  16. Antibody response of cattle to vaccination with commercial modified live rabies vaccines in Guatemala.

    Science.gov (United States)

    Gilbert, Amy; Greenberg, Lauren; Moran, David; Alvarez, Danilo; Alvarado, Marlon; Garcia, Daniel L; Peruski, Leonard

    2015-01-01

    Vampire bat rabies is a public and animal health concern throughout Latin America. As part of an ecological study of vampire bat depredation on cattle in southern Guatemala, we conducted a vaccine seroconversion study among three dairy farms. The main objectives of this cross sectional and cohort study were to understand factors associated with bat bites among cattle, to determine whether unvaccinated cattle had evidence of rabies virus exposure and evaluate whether exposure was related to bat bite prevalence, and to assess whether cattle demonstrate adequate seroconversion to two commercial vaccines used in Guatemala. In 2012, baseline blood samples were collected immediately prior to intramuscular inoculation of cattle with one of two modified live rabies vaccines. Post vaccination blood samples were collected 13 and 393 days later. Sera were tested for rabies virus neutralizing antibodies (rVNA) by the rapid fluorescent focus inhibition test (RFFIT). Across two years of study, 36% (254/702) of inspected cattle presented gross evidence of vampire bat bites. Individual cattle with a bat bite in 2012 were more likely have a bat bite in 2013. Prior to vaccination, 12% (42/350) of cattle sera demonstrated rVNA, but bite status in 2012 was not associated with presence of rVNA. Vaccine brand was the only factor associated with adequate rVNA response of cattle by day 13. However, vaccine brand and rVNA status at day 13 were associated with an adequate rVNA titer on day 393, with animals demonstrating an adequate titer at day 13 more likely to have an adequate titer at day 393. Our findings support stable levels of vampire bat depredation and evidence of rVNA in unvaccinated cattle. Brand of vaccine may be an important consideration impacting adequate rVNA response and long-term maintenance of rVNA in cattle. Further, the results demonstrate that initial response to vaccination is associated with rVNA status over one year following vaccination.

  17. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the preceding...

  18. Fano resonance Rabi splitting of surface plasmons.

    Science.gov (United States)

    Liu, Zhiguang; Li, Jiafang; Liu, Zhe; Li, Wuxia; Li, Junjie; Gu, Changzhi; Li, Zhi-Yuan

    2017-08-14

    Rabi splitting and Fano resonance are well-known physical phenomena in conventional quantum systems as atoms and quantum dots, arising from strong interaction between two quantum states. In recent years similar features have been observed in various nanophotonic and nanoplasmonic systems. Yet, realization of strong interaction between two or more Fano resonance states has not been accomplished either in quantum or in optical systems. Here we report the observation of Rabi splitting of two strongly coupled surface plasmon Fano resonance states in a three-dimensional plasmonic nanostructure consisting of vertical asymmetric split-ring resonators. The plasmonic system stably supports triple Fano resonance states and double Rabi splittings can occur between lower and upper pairs of the Fano resonance states. The experimental discovery agrees excellently with rigorous numerical simulations, and is well explained by an analytical three-oscillator model. The discovery of Fano resonance Rabi splitting could provide a stimulating insight to explore new fundamental physics in analogous atomic systems and could be used to significantly enhance light-matter interaction for optical sensing and detecting applications.

  19. Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Charles Rupprecht

    2017-02-01

    Full Text Available Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies. Africa is the likely home to the ancestors of taxa residing within the Genus Lyssavirus, Family Rhabdoviridae. Diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. In terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species today, but for unknown reasons. All mammals are believed to be susceptible to rabies virus infection. Besides reservoirs among the Chiroptera, meso-carnivores also serve as major historical hosts and are represented among the canids, raccoons, skunks, mongooses, and ferret badgers.  Perpetuating as a disease of nature with the mammalian central nervous system as niche, host breadth alone precludes any candidacy for true eradication. Despite having the highest case fatality of any infectious disease and a burden in excess of or comparative to other major zoonoses, rabies remains neglected. Once illness appears, no treatment is proven to prevent death. Paradoxically, vaccines were developed more than a century ago, but the clear majority of human cases are unvaccinated. Tens of millions of people are exposed to suspect rabid animals and tens of thousands succumb annually, primarily children in developing countries, where canine rabies is enzootic. Rather than culling animal populations, one of the most cost-effective strategies to curbing human fatalities is the mass vaccination of dogs. Building on considerable progress to date, several complementary actions are needed in the near future, including a more harmonized approach to viral taxonomy, enhanced de-centralized laboratory-based surveillance, focal pathogen discovery and characterization, applied pathobiological research for therapeutics, improved estimates of canine populations at risk, actual

  20. 安徽省2011年新分离的19株狂犬病病毒的N基因序列分析%Sequence analysis on N genes of 19 rabies virus strains isolated from Anhui Province, China in 2011

    Institute of Scientific and Technical Information of China (English)

    吴杰; 解庭波; 黄思佳; 沈智俊; 王月; 朱理业; 曹明华; 刘红; 徐葛林

    2013-01-01

    目的 对安徽省2011年新分离的19株狂犬病病毒(Rabies virus,RABV)的N基因进行序列分析,并比较其与代表性RABV街毒株及疫苗株之间的差异.方法 采集安徽省淮北地区狗肉市场的犬脑组织121份,伤人犬脑组织10份,采用直接免疫荧光法和双抗体夹心ELISA法检测RABV抗原,并通过颅内接种昆明乳鼠进一步鉴定毒株;RT-PCR扩增分离病毒的N基因,与pMD18-T载体连接测序后,与代表性RABV街毒株及疫苗株的N基因序列进行比对,并进行遗传学分析.结果 在送检的131份犬脑组织样品中检出RABV阳性19株,其中伤人犬脑组织阳性率为90%,狗肉市场犬脑组织阳性率为8.26%.19株RABV N基因核苷酸序列同源性为97.5%~99.7%,推导的氨基酸序列同源性为98.7% ~ 100%;与代表性人用和兽用RABV疫苗株相比,N基因核苷酸序列同源性为85.4% ~ 89.9%,推导的氨基酸序列同源性为94.9%~99.1%,核苷酸序列的变异主要为同义突变.分离的19株RABV在系统进化树上高度聚集,与以往国内分离的代表性街毒株系统进化关系较近,在同一个分支(HN10除外)与我国疫苗株CTN-181株亲缘关系最近,处于同—个亚群.结论 从安徽省伤人犬和狗肉市场的犬脑组织中成功分离并鉴定了19株RABV,这些病毒株均属于基因Ⅰ型RABV,且具有地域性特征.本研究对特定区域RABV的流行及监测具有一定的意义.%Objective To analyze the sequence of N genes of 19 rabies virus (RABV) strains isolated from Anhui Province, China in 2011 as well as its difference with other representative street strains and vaccine strains. Methods The brain tissues of 10 dogs biting people and 121 dogs from dog meat market in Huaibei District, Anhui Province were collected, and detected for RABV antigen by direct immunofluorescent assay , then further identified by intracranial inoculation to Kunming suckling mice. The N gene of RABV was amplified by RT

  1. Regulatory systems for prevention and control of rabies, Japan.

    Science.gov (United States)

    Takahashi-Omoe, Hiromi; Omoe, Katsuhiko; Okabe, Nobuhiko

    2008-09-01

    Japan is one of the few rabies-free countries. Although 3 imported cases of human rabies were seen in 1970 and 2006, no other cases have been reported for approximately 50 years. The elimination of rabies in Japan is attributed to not only its geographic isolation but also to effective prevention and control measures, such as registration and vaccination of domestic dogs, required quarantine of susceptible imported animals, and national plans of action based on scientific research. Countermeasures against rabies have been upgraded; an improved management system for domestic dogs under the amended Enforcement Regulations of the Rabies Prevention Law has been in effect since April 2007. The latest regulatory systems for preventing and controlling rabies provide an effective model for elimination of the disease worldwide.

  2. Canine Rabies: A Looming Threat to Public Health

    Directory of Open Access Journals (Sweden)

    Sigfrido Burgos-Cáceres

    2011-09-01

    Full Text Available Rabies is an acute, fatal viral disease that infects domestic and wild animals and is transmissible to humans. Worldwide, rabies kills over 55,000 people every year. The domestic dog plays a pivotal role in rabies transmission. Domestic dogs are not only part of our daily lives but also of our immediate surroundings, and this is reflected in the rise in pet dog ownership in developed and developing countries. This is important given that more frequent exposures and interactions at the animal-human interface increases the likelihood of contracting zoonotic diseases of companion animals. Despite existing vaccines and post-exposure prophylactic treatment, rabies remains a neglected disease that is poorly controlled throughout much of the developing world, particularly Africa and Asia, where most human rabies deaths occur. It is believed that with sustained international commitments, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.

  3. Rabies in Saudi Arabia: a need for epidemiological data

    Directory of Open Access Journals (Sweden)

    Ziad A. Memish

    2015-05-01

    Full Text Available Rabies is endemic in animals in the Arabian Peninsula. Although Saudi Arabia is the largest country in the Peninsula, little has been published about the rabies situation in the country. A total of 11 069 animal bites to humans were reported during 2007–2009, and 40 animals suspected of rabies were examined for rabies infection from 2005 through 2010. Results suggest that animal-related injuries in Saudi Arabia remain a public health problem, with feral dogs accounting for the majority of bites to humans and for the majority of animals found to be rabid. Over the last 10 years, no confirmed human rabies case has been reported. More detailed information about the epidemiology of animal bites and that of animal rabies in Saudi Arabia would be of great interest, notably to provide a basis on which vaccination recommendations could be made for the numerous international travellers visiting the country.

  4. Population Dynamics of Owned, Free-Roaming Dogs: Implications for Rabies Control.

    Directory of Open Access Journals (Sweden)

    Anne Conan

    2015-11-01

    Full Text Available Rabies is a serious yet neglected public health threat in resource-limited communities in Africa, where the virus is maintained in populations of owned, free-roaming domestic dogs. Rabies elimination can be achieved through the mass vaccination of dogs, but maintaining the critical threshold of vaccination coverage for herd immunity in these populations is hampered by their rapid turnover. Knowledge of the population dynamics of free-roaming dog populations can inform effective planning and implementation of mass dog vaccination campaigns to control rabies.We implemented a health and demographic surveillance system in dogs that monitored the entire owned dog population within a defined geographic area in a community in Mpumalanga Province, South Africa. We quantified demographic rates over a 24-month period, from 1st January 2012 through 1st January 2014, and assessed their implications for rabies control by simulating the decline in vaccination coverage over time. During this period, the population declined by 10%. Annual population growth rates were +18.6% in 2012 and -24.5% in 2013. Crude annual birth rates (per 1,000 dog-years of observation were 451 in 2012 and 313 in 2013. Crude annual death rates were 406 in 2012 and 568 in 2013. Females suffered a significantly higher mortality rate in 2013 than males (mortality rate ratio [MRR] = 1.54, 95% CI = 1.28-1.85. In the age class 0-3 months, the mortality rate of dogs vaccinated against rabies was significantly lower than that of unvaccinated dogs (2012: MRR = 0.11, 95% CI = 0.05-0.21; 2013: MRR = 0.31, 95% CI = 0.11-0.69. The results of the simulation showed that achieving a 70% vaccination coverage during annual campaigns would maintain coverage above the critical threshold for at least 12 months.Our findings provide an evidence base for the World Health Organization's empirically-derived target of 70% vaccination coverage during annual campaigns. Achieving this will be effective even in

  5. Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans.

    Directory of Open Access Journals (Sweden)

    Thomas Müller

    Full Text Available As the demand for rabies post-exposure prophylaxis (PEP treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP conditions. Unique combinations (cocktails were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of lyssaviruses except for lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of

  6. The Relevance of Rabies to Today’s Military

    Science.gov (United States)

    2012-01-01

    dog bites.6 Rabies has been known since ancient times, with the fi rst basic treatment for rabies demonstrated by Louis Pasteur in 1885. Still, as...Afghanistan. This history and the symptoms led to the suspicion of rabies, which triggered specifi c test- ing at Wadsworth Center, the New York State...equine encephalomyelitis, and St. Louis encephalitis. The various Army veterinary 6 http://www.cs.amedd.army.mil/amedd_journal.aspx laboratories across

  7. Postexposure Treatment and Animal Rabies, Ontario, 1958-2000

    Science.gov (United States)

    Nunan, Christopher P.; Honig, Janet M.; Ball, David G. A.; Hauschildt, Peggy; LeBer, Charles A.

    2002-01-01

    This paper investigates the relationship between animal rabies and postexposure treatment (PET) in Ontario by examining the introduction of human diploid cell vaccine (HDCV) in 1980 and the initiation of an oral rabies vaccination program for wildlife in 1989. Introducing HDCV led to an immediate doubling of treatments. Both animal rabies and human treatments declined rapidly after the vaccination program was introduced, but human treatments have leveled off at approximately 1,000 per year. PMID:11897079

  8. Current status and control of rabies in Perú

    OpenAIRE

    2007-01-01

    Rabies is an endemic disease of Peru, that appears in two cycles, one urban related with transmission by dog, and another wild caused mainly by vampires bats bite. Most of human cases of the last decades they have been by urban rabies, nevertheless the used measures of control (canine vaccine campaigns, vaccine production, identification of biting dog, opportune attention of the victim and surveillance and notification system) they have managed to reduce the incidence of canine rabies and ...

  9. Molecular Characterization of China Human Rabies Vaccine Strains

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan Tao; Na Han; Zhenyang Guo; Qing Tang; Simon Rayner; Guodong Liang

    2013-01-01

    To understand the molecular characteristics of China human rabies vaccine strains,we report the full-length genome of the aG strain and present a comprehensive analysis of this strain and almost all available lyssavirus genomes (58 strains) from GenBank (as of Jan 6,2011).It is generally considered that the G protein plays a predominant role in determining the pathogenicity of the virus,to this end we predicted the tertiary structure of the G protein of aG strain,CTN 181 strain and wild type strain HN 10 based on the crystal structure of Vesicular stomatitis virus (VSV) G.The predicted RABV G structure has a similar topology to VSV G and the ectodomain can be divided into 4 distinct domains DI-DIV.By mapping the characterized mutations to this structure between China vaccine strains and their close street strains,we speculate that the G303(P-H) mutations of CTN181 and HN10 causing D Ⅱ 3D change may be associated with the attenuated virulence in both strains.Specifically,the two signature mutations (G165P and G231P) in the aG strain are withinβsheets,suggesting that both sites are of structural importance.

  10. Identification of Animal Rabies in Inner Mongolia and Analysis of the Etiologic Characteristics

    Institute of Scientific and Technical Information of China (English)

    YIN Jing Feng; LIANG Guo Dong; WANG Feng Long; WANG Jin Ling; TANG Qing; DING Yu Lin; TAO XiaoYan; LI Hao; SONG Miao; GUO ZhenYang; SHEN Xin Xin

    2014-01-01

    Objective To perform pathological observation and etiological identification of specimens collected from dairy cows, beef cattle and dogs which were suspected of rabies in Inner Mongolia in 2011, and analyze their etiological characteristics. Methods Pathological observation was conducted on the brain specimens of three infected animals with Hematoxylin-Eosin staining, followed by confirmation using immunofluorescence and nested RT-PCR methods. Finally, phylogenetic analysis was conducted using the virus N gene sequence amplified from three specimens. Results Eosinophilic and cytoplasmic inclusion bodies were seen in neuronal cells of the CNS; and rabies non-characteristic histopathological changes were also detected in the CNS. The three brain specimens were detected positive. N gene nucleotide sequence of these three isolates showed distinct sequence identity, therefore they fell into different groups in the phylogenetic analysis. N gene in the cow and dog had higher homology with that in Hebei isolate, but that in the beef cattle had higher homology with that in Mongolian lupine isolate and Russian red fox isolate. Conclusion Rabies were observed in the dairy cow, beef cattle and canine in the farm in Inner Mongolia, in 2011, which led to a different etiologic characteristics of the epidemic situation.

  11. 狂犬病病毒CTN-181减毒株在豚鼠颌下腺的繁殖动态及其低毒力克隆株的筛选研究%Study on the attenuated rabies virus CTN-181 in the submandibular gland of guinea pigs and the low virulence clones from the submandibular gland

    Institute of Scientific and Technical Information of China (English)

    石磊泰; 邹剑; 俞永新; 王玲; 曹守春; 董关木; 李玉华

    2015-01-01

    目的 了解狂犬病病毒减毒株CTN-181在豚鼠颌下腺的繁殖动态并获得毒力更低的病毒纯化克隆株.方法 将CTN-181经刚离乳豚鼠颈部皮下注射,分别于1、2、3和4d取颌下腺分离狂犬病病毒,测定各天次颌下腺内的病毒滴度.用滴度高的病毒液进行下一次豚鼠颌下腺传代,连续传3代.将第3代颌下腺传代的病毒液在BHK21细胞上进行空斑试验,挑选单个病毒克隆,以3周龄小鼠脑内接种测病毒毒力.筛选对小鼠不致病的克隆株进一步测定其对乳鼠的脑内毒力,并以乳鼠脑内传代和豚鼠颌下腺传代检测其遗传稳定性.结果 CTN-181在豚鼠颌下腺能短暂轻度繁殖,通过颌下腺传代后病毒毒力明显有回升.获得19个病毒克隆,不同克隆病毒的毒力不同,为0~3.16 lg LD50;3株脑内无致病力的克隆株对乳鼠的毒力亦有减弱;乳鼠脑内和颌下腺回传后毒力无回升返祖,即传代后的病毒对小鼠均无致病力.结论 CTN-181母株对3周龄小鼠仍存在低水平毒力,经豚鼠颌下腺传代后毒力十分不稳定.筛选到的3株克隆病毒较其母株的毒力更低,遗传稳定性更高,更适合作为狂犬病兽用口服疫苗候选株.%Objective To understand the stability of an attenuated rabies virus strain CTN-181 and to obtain more attenuated and stable virus strains from the CTN-181 strain.Methods The CTN-181 virus was inoculated into the submandibular glands of guinea pigs subcutaneously.The glands were harvested on day 1,2,3 and 4 after inoculation,then the virus contents and virulence in 3-week mice were evaluated.Three generations of the submandibular gland passage were made and the gland virus sample from the third passage of the guinea pigs was used for plaque cloning.Plaque clone viruses were tested for their neurovirulence in 3-week mice or suckling mice,and the attenuation stability was performed by inoculation passage in suckling mice and submandibular gland passages

  12. The History of Rabies in Trinidad: Epidemiology and Control Measures

    Directory of Open Access Journals (Sweden)

    Janine F. R. Seetahal

    2017-07-01

    Full Text Available Vampire bat-transmitted rabies was first recognized in Trinidad during a major outbreak reported in 1925. Trinidad is the only Caribbean island with vampire bat-transmitted rabies. We conducted a literature review to describe the changing epidemiology of rabies in Trinidad and give a historical perspective to rabies prevention and control measures on the island. The last human case of rabies occurred in 1937 and although no case of canine-transmitted rabies was reported since 1914, sporadic outbreaks of bat-transmitted rabies still occur in livestock to date. Over the last century, seven notable epidemics were recorded in Trinidad with the loss of over 3000 animals. During the 1950s, several measures were effectively adopted for the prevention and control of the disease which led to a significant reduction in the number of cases. These measures include: vampire bat population control, livestock vaccination, and animal surveillance. However, due to lapses in these measures over the years (e.g., periods of limited vampire control and incomplete herd vaccination, epidemics have occurred. In light of the significant negative impact of rabies on animal production and human health, rabies surveillance in Trinidad should be enhanced and cases evaluated towards the design and implementation of more evidence-based prevention and control programs.

  13. Rabi-vibronic resonance with large number of vibrational quanta

    OpenAIRE

    Glenn, R.; Raikh, M. E.

    2011-01-01

    We study theoretically the Rabi oscillations of a resonantly driven two-level system linearly coupled to a harmonic oscillator (vibrational mode) with frequency, \\omega_0. We show that for weak coupling, \\omega_p \\ll \\omega_0, where \\omega_p is the polaronic shift, Rabi oscillations are strongly modified in the vicinity of the Rabi-vibronic resonance \\Omega_R = \\omega_0, where \\Omega_R is the Rabi frequency. The width of the resonance is (\\Omega_R-\\omega_0) \\sim \\omega_p^{2/3} \\omega_0^{1/3} ...

  14. A Semi-quantitative Serological Method to Assess the Potency of Inactivated Rabies Vaccine for Veterinary Use

    Institute of Scientific and Technical Information of China (English)

    Ye Liu; Shoufeng Zhang; Fei Zhang; Rongliang Hu

    2012-01-01

    Potency is one of the most important indexes of inactivated vaccines.A number of methods have been established to assay the potency,of which the NIH test and single-dose mouse protection test are the "prescribed methods".Here,we report a method to semi-quantitatively assay the potency of an inactivated rabies vaccine,which uses fewer animals and takes less time to complete.Depending on the quality requirements of a vaccine(e.g.minimum potency),a rabies reference vaccine is,for example,diluted to the minimum potency,and 50 μL of the dilution is taken to inoculate 10 mice.The same amount of the test rabies vaccine is inoculated into another 10 mice.After two weeks,all mice are bled and serum samples are assayed for viral neutralizing antibody by the fluorescent antibody virus neutralization(FAVN) test.By comparing the median and interquartile range of antibody titers of the reference vaccine with those of the test vaccine,the test vaccine potency can be semi-quantitatively judged as to whether it is in accord with the required quality.The reliability of this method was also confirmed in dogs.The procedure can be recommended for batch potency testing during inactivated rabies vaccine production.

  15. CLINICAL KNOWLEDGE AND ATTITUDES OF CLINICIANS TOWARD RABIES CAUSED BY ANIMAL BITES

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    2013-12-01

    Full Text Available ABSTRACT: INTRODUCTION : Rabies is a zoonotic disease that is typically transmitted through bites from infected animals. The majority of reported cases involve wild animals like bats , raccoons and skunks , but domesticated animals like dogs and cats are also a risk. Humans are equ ally susceptible to the rabies virus if bitten by an infected animal. Once the symptoms have appeared , Rabies is always fatal. Death usually occurs less than a week after the onset of signs. METHODOLOGY: A cross - sectional study was conducted in which all th e doctors including JRs , Interns , PG students and SRs and Consultants in the department of Surgery , Medicine , Pediatrics and Emergency Medical Officers were taken . Selection was done on the basis of consent to participate in the study by doctors of the var ious departments handling or required to handle dog /animal bite cases. RESULTS : It can be seen that only 76.92% knew all the Reservoirs of Rabies infection , and the difference in knowledge of senior doctor , 43(41.34 is comparable to junior doctors , 37(35. 57 and the difference is statistically not significant. Regarding different Modes ofTransmission , 90.38% had correct knowledge. The Junior doctors , i.e , 39(37.50 had correct answer whereas , 55(52.88 senior doctors i.e all answered correctlywhich is sta tistically significant . CONCLUSION: There is an apparent lack of awareness among doctors regarding appropriate animal wound management and vaccine administration. Reorientation programmes and continued medical education (CME for the medical practitioners are required to highlight WHO guidelines regarding treatment of animal bite

  16. Fatal rabies despite post-exposure prophylaxis

    Directory of Open Access Journals (Sweden)

    D G Deshmukh

    2011-01-01

    Full Text Available Only sporadic reports of failure of post-exposure prophylaxis for rabies exist in the published literature. We are reporting such a case in a 3-year-old boy. The child had Category III dog bite on his right thigh. He presented with progressive ascending paralysis, finally developing quadriplegia and respiratory paralysis. Typical hydrophobia and aerophobia were absent. He received four doses of antirabies cell culture vaccine. He did not receive antirabies immunoglobulin. The boy succumbed on the 23 rd day of the dog bite. Diagnosis of rabies was confirmed in the laboratory by demonstration of Negri bodies, direct fluorescent antibody test and reverse transcriptase-polymerase chain reaction either on impression smear of brain or a piece of brain taken during autopsy.

  17. Analytical solutions for the Rabi model

    CERN Document Server

    Yu, Lixian; Liang, Qifeng; Chen, Gang; Jia, Suotang

    2012-01-01

    The Rabi model that describes the fundamental interaction between a two-level system with a quantized harmonic oscillator is one of the simplest and most ubiquitous models in modern physics. However, this model has not been solved exactly because it is hard to find a second conserved quantity besides the energy. Here we present a unitary transformation to map this unsolvable Rabi model into a solvable Jaynes-Cummings-like model by choosing a proper variation parameter. As a result, the analytical energy spectrums and wavefunctions including both the ground and the excited states can be obtained easily. Moreover, these explicit results agree well with the direct numerical simulations in a wide range of the experimental parameters. In addition, based on our obtained energy spectrums, the recent experimental observation of Bloch-Siegert in the circuit quantum electrodynamics with the ultrastrong coupling can be explained perfectly. Our results have the potential application in the solid-state quantum information...

  18. Geographical Analysis for Detecting High-Risk Areas for Bovine/Human Rabies Transmitted by the Common Hematophagous Bat in the Amazon Region, Brazil

    Science.gov (United States)

    Begot, Alberto L.; Ramos, Ofir de S.

    2016-01-01

    Background The common hematophagous bat, Desmodus rotundus, is one of the main wild reservoirs of rabies virus in several regions in Latin America. New production practices and changed land use have provided environmental features that have been very favorable for D. rotundus bat populations, making this species the main transmitter of rabies in the cycle that involves humans and herbivores. In the Amazon region, these features include a mosaic of environmental, social, and economic components, which together creates areas with different levels of risk for human and bovine infections, as presented in this work in the eastern Brazilian Amazon. Methodology We geo-referenced a total of 175 cases of rabies, of which 88% occurred in bovines and 12% in humans, respectively, and related these cases to a number of different geographical and biological variables. The spatial distribution was analyzed using the Kernel function, while the association with independent variables was assessed using a multi-criterion Analytical Hierarchy Process (AHP) technique. Findings The spatiotemporal analysis of the occurrence of rabies in bovines and humans found reduction in the number of cases in the eastern state of Pará, where no more cases were recorded in humans, whereas high infection rates were recorded in bovines in the northeastern part of the state, and low rates in the southeast. The areas of highest risk for bovine rabies are found in the proximity of rivers and highways. In the case of human rabies, the highest concentration of high-risk areas was found where the highway network coincides with high densities of rural and indigenous populations. Conclusion The high-risk areas for human and bovine rabies are patchily distributed, and related to extensive deforested areas, large herds of cattle, and the presence of highways. These findings provide an important database for the generation of epidemiological models that could support the development of effective prevention

  19. [Evolution of human anti-rabies vaccines from Pasteur to the present].

    Science.gov (United States)

    Barme, M; Tsiang, H

    1995-05-01

    Since the first immunization of man against rabies in 1885 by Louis Pasteur, antirabies vaccine has been continuously improved. Treatment failures, clinical infections by the fixed virus, neuroparalytic accidents in connection with myelin were progressively eliminated. Vaccines can be standardized and accurately controlled. After the original spinal cord, adult or newborn animals brains, embryonated eggs, primary tissue cultures, diploid and permanent cell lines have been used for the vaccine production. Today, safe and potent vaccines are available. New products might be developed from the technology of genetic recombinants.

  20. Fast Quantum Rabi Model with Trapped Ions

    Science.gov (United States)

    Moya-Cessa, Héctor M.

    2016-12-01

    We show how to produce a fast quantum Rabi model with trapped ions. Its importance resides not only in the acceleration of the phenomena that may be achieved with these systems, from quantum gates to the generation of nonclassical states of the vibrational motion of the ion, but also in reducing unwanted effects such as the decay of coherences that may appear in such systems.

  1. Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses

    DEFF Research Database (Denmark)

    Schandock, Franziska; Riber, Camilla Frich; Röcker, Annika

    2017-01-01

    . This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure...

  2. World Rabies Day campaign in the Philippines.

    Science.gov (United States)

    Medina, Danellie Joy O; Jayme, Sarah I; Amparo, Anna Charinna B; Cresencio, Rubina O; Lopez, Emelinda L; Baquilod, Mario S; Hernandez, Leda M; Villalon, Ernesto E S; Nel, Louis D

    2016-01-01

    Rabies is a fatal disease, claiming the lives of around 59,000 people annually worldwide. It is considered a neglected and underreported disease leading to inadequate support from governments. Apart from dog vaccination and proper animal bite management, an integral part of a successful rabies control program is community education. The Philippine government conducts an extensive nationwide annual World Rabies Day (WRD) celebration as part of its community education. Strong inter-sectoral collaboration at the national level is a key factor for the success of WRD, capitalizing on the partners' strengths to mobilize various sectors. Strategies include the National WRD Celebration and releasing national government memorandums. An invitation letter campaign was initiated, encouraging stakeholders to register their activities. Banners were given as an incentive for those who registered. Mass and social media were also utilized to promote WRD. Registered WRD events held in the Philippines rose from 10 events in 2012, to 37 events in 2013, to 66 events in 2014 and 76 events in 2015. The individual activities involved veterinary services and information, communication, and education (IEC) activities. Nine unique WRD IEC activities are highlighted in this paper. Promotion of WRD through social media was also utilized in recent years. More news items were published online than those printed in newspapers and aired on television. The campaign's success underlines the value of a national government-led program. The national rabies program sets the agenda for priority activities including the WRD campaign. Its capacity to allocate funds for the program also denotes stability which is beneficial for local program implementers. Different segments of society were tapped through various strategies. The campaign's flexibility allowed for a large range of activities and presented opportunities for expanding partnerships and integration with others interventions for its sustainability

  3. Excitonic Doppler-Rabi Oscillations in a Moving Organic Slab

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    It is theoretically shown that excitonic Doppler-Rabi oscillations can occur in an organic slab moving along the axis of a high-Q cavity. Due to the √N enhancement of the vacuum Rabi frequency, this effect can be more easily observed than that in a moving two-level atom.

  4. What Are the Signs and Symptoms of Rabies?

    Science.gov (United States)

    ... if I receive treatment outside the United States? Veterinarians What to do with an animal that has bitten a person Caring for animals with potential exposure Clinical signs of rabies in animals Vaccines Rabies Vaccines Licensed and Marketed in the U.S., ...

  5. Eliminating canine rabies: the role of public-private partnerships.

    Science.gov (United States)

    Taylor, Louise

    2013-05-01

    Canine rabies has been eliminated from industrialized countries, but infected dogs remain the principal source of human infections in the developing world. Despite the availability of effective tools for prevention and post-exposure prophylaxis, canine rabies inflicts a heavy burden on the poorest people of Africa, Asia and Latin America, resulting in more than 60,000 deaths each year. Public-private partnerships offer a new approach to the challenge of eliminating canine rabies in the developing world, by bringing together stakeholders to share responsibilities and reduce costs. The leading partnership for rabies control, the Partners for Rabies Prevention, is an informal international group that includes representatives of major health organizations (WHO, PAHO, FAO, OIE), the European Commission, universities, nongovernmental organizations, the human and animal health industries, and private global health institutions. This article describes how the Partners for Rabies Prevention is working toward the global elimination of canine rabies. It forms part of a symposium in Antiviral Research on the elimination of canine rabies.

  6. Rabies in Captive Deer, Pennsylvania, USA, 2007–2010

    Science.gov (United States)

    Tack, Danielle M.; Longenberger, Allison; Simeone, Aliza; Moll, Mària E.; Deasy, Marshall P.; Blanton, Jesse D.; Rupprecht, Charles E.

    2012-01-01

    Since January 2007, a total of 11 rabid deer from 4 deer farms have been identified in 2 neighboring Pennsylvania counties. Vaccination of deer against rabies, decreasing wildlife animal contact with deer, and education of deer farmers may prevent further cases of rabies in captive deer and exposures to humans. PMID:22260956

  7. Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

    Directory of Open Access Journals (Sweden)

    Touihri Leila

    2012-12-01

    Full Text Available Abstract Background During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV or distemper virus (CDV after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. Methods We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES domain. Results The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The

  8. Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine

    Science.gov (United States)

    Asgary, Vahid; Shoari, Alireza; Baghbani-Arani, Fahimeh; Sadat Shandiz, Seyed Ataollah; Khosravy, Mohammad Sadeq; Janani, Alireza; Bigdeli, Razieh; Bashar, Rouzbeh; Cohan, Reza Ahangari

    2016-01-01

    Background Green synthesis of nanoparticles by plant extracts plays a significant role in different applications. Recently, several studies were conducted on the use of nanoparticles as adjuvant. The main aim of this study was to evaluate green synthesized silver nanoparticles (AgNPs) as adjuvant in rabies veterinary vaccine and compare the results with the existing commercially available alum adjuvant. Materials and methods In the current study, AgNPs were prepared by the reduction of aqueous silver nitrate by leaf extract of Eucalyptus procera. The formation of AgNPs was confirmed by ultraviolet (UV)–visible spectrophotometer, scanning electron microscopy, dynamic light scattering, and X-ray diffraction analysis. Then, different amounts of AgNPs (200 µg, 400 µg, 600 µg, and 800 µg) were added to 1 mL of inactivated rabies virus. The loaded vaccines (0.5 mL) were injected intraperitoneally into six Naval Medical Research Institute mice in each group on days 1 and 7. On the 15th day, the mice were intracerebrally challenged with 0.03 mL of challenge rabies virus (challenge virus strain-11, 20 lethal dose [20 LD50]), and after the latency period of rabies disease in mice (5 days), the mice were monitored for 21 days. Neutralizing antibodies against rabies virus were also investigated using the rapid fluorescent focus inhibition test method. The National Institutes of Health test was performed to determine the potency of optimum concentration of AgNPs as adjuvant. In vitro toxicity of AgNPs was assessed in L929 cell line using MTT assay. In addition, in vivo toxicity of AgNPs and AgNPs-loaded vaccine was investigated according to the European Pharmacopeia 8.0. Results AgNPs were successfully synthesized, and the identity was confirmed by UV–visible spectrophotometry and X-ray diffraction analysis. The prepared AgNPs were spherical in shape, with an average size of 60 nm and a negative zeta potential of −14 mV as determined by dynamic light scattering

  9. Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine.

    Science.gov (United States)

    Asgary, Vahid; Shoari, Alireza; Baghbani-Arani, Fahimeh; Sadat Shandiz, Seyed Ataollah; Khosravy, Mohammad Sadeq; Janani, Alireza; Bigdeli, Razieh; Bashar, Rouzbeh; Cohan, Reza Ahangari

    2016-01-01

    Green synthesis of nanoparticles by plant extracts plays a significant role in different applications. Recently, several studies were conducted on the use of nanoparticles as adjuvant. The main aim of this study was to evaluate green synthesized silver nanoparticles (AgNPs) as adjuvant in rabies veterinary vaccine and compare the results with the existing commercially available alum adjuvant. In the current study, AgNPs were prepared by the reduction of aqueous silver nitrate by leaf extract of Eucalyptus procera. The formation of AgNPs was confirmed by ultraviolet (UV)-visible spectrophotometer, scanning electron microscopy, dynamic light scattering, and X-ray diffraction analysis. Then, different amounts of AgNPs (200 µg, 400 µg, 600 µg, and 800 µg) were added to 1 mL of inactivated rabies virus. The loaded vaccines (0.5 mL) were injected intraperitoneally into six Naval Medical Research Institute mice in each group on days 1 and 7. On the 15th day, the mice were intracerebrally challenged with 0.03 mL of challenge rabies virus (challenge virus strain-11, 20 lethal dose [20 LD50]), and after the latency period of rabies disease in mice (5 days), the mice were monitored for 21 days. Neutralizing antibodies against rabies virus were also investigated using the rapid fluorescent focus inhibition test method. The National Institutes of Health test was performed to determine the potency of optimum concentration of AgNPs as adjuvant. In vitro toxicity of AgNPs was assessed in L929 cell line using MTT assay. In addition, in vivo toxicity of AgNPs and AgNPs-loaded vaccine was investigated according to the European Pharmacopeia 8.0. AgNPs were successfully synthesized, and the identity was confirmed by UV-visible spectrophotometry and X-ray diffraction analysis. The prepared AgNPs were spherical in shape, with an average size of 60 nm and a negative zeta potential of -14 mV as determined by dynamic light scattering technique. The highest percentage of viability was

  10. All-optical coherent control of vacuum Rabi oscillations

    CERN Document Server

    Bose, Ranojoy; Choudhury, Kaushik Roy; Solomon, Glenn S; Waks, Edo

    2014-01-01

    When an atom strongly couples to a cavity, it can undergo coherent vacuum Rabi oscillations. Controlling these oscillatory dynamics quickly relative to the vacuum Rabi frequency enables remarkable capabilities such as Fock state generation and deterministic synthesis of quantum states of light, as demonstrated using microwave frequency devices. At optical frequencies, however, dynamical control of single-atom vacuum Rabi oscillations remains challenging. Here, we demonstrate coherent transfer of optical frequency excitation between a single quantum dot and a cavity by controlling vacuum Rabi oscillations. We utilize a photonic molecule to simultaneously attain strong coupling and a cavity-enhanced AC Stark shift. The Stark shift modulates the detuning between the two systems on picosecond timescales, faster than the vacuum Rabi frequency. We demonstrate the ability to add and remove excitation from the cavity, and perform coherent control of light-matter states. These results enable ultra-fast control of atom...

  11. Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control

    Directory of Open Access Journals (Sweden)

    Tiziana Lembo

    2011-01-01

    Full Text Available Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this “incurable wound” persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination.

  12. [10 years' of production and use of human rabies immunoglobulin in Yugoslavia].

    Science.gov (United States)

    Romić, M; Tomović, O; Medić, P; Pelević, S; Sindić, M; Popović, M; Gligorović, V; Bogdanović, G; Mitrović, M; Petrović, M; Stankov, S; Lazarević-Ivanc, L; Lalosević, V; Lalosević, D

    2001-01-01

    Application of the rabies immunoglobuline is a compulsory part of the prophylaxis of rabies in all severe, transdermal lesions caused by rabies infected animals. Sylvatic rabies has spread in the past few years throughout the whole Yugoslavia, and human cases of rabies have also been reported in other East European countries. In order to achieve the highest level of rabies prophylaxis, apart from postinfective rabies vaccination, it is necessary to provide passive immunization using specific antibodies against rabies. After successful immunization of the young, healthy volunteers in 1990, National Blood Transfusion Institute, in cooperation with the Pasteur Institute from Novi Sad, prepared the first quantities of immunized plasma by plasmapheresis procedure and human rabies immunoglobuline. Without national production, sufficient quantities of human rabies immunoglobuline could not be provided, since the price on the world market is rather high (over $1000 per patient).

  13. Inactivation of Viruses by Benzalkonium Chloride

    Science.gov (United States)

    Armstrong, J. A.; Froelich, E. J.

    1964-01-01

    Benzalkonium chloride (as Roccal or Zephiran) was found to inactivate influenza, measles, canine distemper, rabies, fowl laryngotracheitis, vaccinia, Semliki Forest, feline pneumonitis, meningopneumonitis, and herpes simplex viruses after 10 min of exposure at 30 C or at room temperature. Poliovirus and encephalomyocarditis virus were not inactivated under the same conditions. It was concluded that all viruses tested were sensitive except members of the picorna group. The literature was reviewed. PMID:4288740

  14. Species determination of Brazilian mammals implicated in the epidemiology of rabies based on the control region of mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Pedro Carnieli Junior

    Full Text Available Identification of animals that are decomposing or have been run over or burnt and cannot be visually identified is a problem in the surveillance and control of infectious diseases. Many of these animals are wild and represent a valuable source of information for epidemiologic research as they may be carriers of an infectious agent. This article discusses the results obtained using a method for identifying mammals genetically by sequencing their mitochondrial DNA control region. Fourteen species were analyzed and identified. These included the main reservoirs and transmitters of rabies virus, namely, canids, chiroptera and primates. The results prove that this method of genetic identification is both efficient and simple and that it can be used in the surveillance of infectious diseases which includes mammals in their epidemiologic cycle, such as rabies.

  15. Species determination of Brazilian mammals implicated in the epidemiology of rabies based on the control region of mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Pedro Carnieli Junior

    2008-12-01

    Full Text Available Identification of animals that are decomposing or have been run over or burnt and cannot be visually identified is a problem in the surveillance and control of infectious diseases. Many of these animals are wild and represent a valuable source of information for epidemiologic research as they may be carriers of an infectious agent. This article discusses the results obtained using a method for identifying mammals genetically by sequencing their mitochondrial DNA control region. Fourteen species were analyzed and identified. These included the main reservoirs and transmitters of rabies virus, namely, canids, chiroptera and primates. The results prove that this method of genetic identification is both efficient and simple and that it can be used in the surveillance of infectious diseases which includes mammals in their epidemiologic cycle, such as rabies.

  16. PROTECTION OF MAN AGAINST RABIES AFTER EXPOSURE PAST HISTORY - PRESENT STATE AND THE FUTURE OUTLOOK

    Directory of Open Access Journals (Sweden)

    M. Bahmanyar

    1974-11-01

    Full Text Available After a period of at least 2000 years that rabies existed. on earth and its clinical symptoms were clearly defined, even before Christ, the first basic"nand precise knowledge about this fatal disease of man and animals was advocated by Zinke in 1804. The discovery of the domesticated rabbit as a convenient laboratory animal for the study and the diagnosis of the disease by Galtier in 1879 and the outstanding finding by Raux in 1881 concerning the neurotropism of the agent of the disease and the intracerebral route of inoculation by which prompt transmission could be established, paved the way for Pasteur and his colleagues for their world-known discovery of protecting animals and man against this disease. The vaccine produced and administered by Pasteur himself and numerous other types of vaccines always prepared with the same Pasteur's historical and modified virus which he named "fixed virus" were endeavours in the way of improving the safety and the antieenicitv of the products to fight a hundred per cent fatal illness. The evolution of these efforts during the past 90 years, since Pasteur's first attempt to protect an exposed individual against rabies crowned by outstanding and vcrv promising results are discussed.

  17. High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

    Science.gov (United States)

    Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

    2013-08-28

    Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine.

  18. The quantization of the Rabi Hamiltonian

    Science.gov (United States)

    Vandaele, Eva R. J.; Arvanitidis, Athanasios; Ceulemans, Arnout

    2017-03-01

    The Rabi Hamiltonian addresses the proverbial paradigmatic case of a two-level fermionic system coupled to a single bosonic mode. It is expressed by a system of two coupled first-order differential equations in the complex field, which may be rewritten in a canonical form under the Birkhoff transformation. The transformation gives rise to leapfrog recurrence relations, from which the eigenvalues and eigenvectors could be obtained. The interesting feature of this approach is that it generates integer quantum numbers, which rationalize the spectrum by relating the solutions to the Juddian baselines. The relationship with Braak’s integrability claim (Braak 2011 Phys. Rev. Lett. 107 100401) is discussed.

  19. Perfil antigênico do vírus da raiva isolado de diferentes espécies de morcegos não hematófagos da Região de Presidente Prudente, Estado de São Paulo Antigen profile of rabies virus isolated from different species of non-hematophagous bats in the region of Presidente Prudente, State of São Paulo

    Directory of Open Access Journals (Sweden)

    Avelino Albas

    2009-02-01

    Full Text Available O Laboratório de Virologia Clínica e Molecular do Instituto de Ciências Biomédicas da Universidade de São Paulo, utilizando-se da técnica de anticorpos monoclonais, tipificou 18 amostras de vírus rábico provenientes de morcegos não hematófagos de várias espécies provenientes da Região de Presidente Prudente, SP, Brasil. Destas amostras, 15 (82,3% foram definidas como variante 3 (compatível com amostras isoladas de morcegos Desmodus rotundus e 3 (16,7% como variante 4 (compatível com amostras isoladas de morcegos Tadarida brasiliensis.Using the monoclonal antibody technique, the Clinical and Molecular Virology Laboratory of the Institute of Biomedical Sciences of the University of São Paulo typed 18 rabies virus samples from non-hematophagous bats of several species from the region of Presidente Prudente, SP, Brazil. Among these samples, 15 (82.3% were defined as variant 3 (compatible with samples isolated from Desmodus rotundus bats and three (16.7% as variant 4 (compatible with samples isolated from Tadarida brasiliensis bats.

  20. [Technical guideline for human rabies prevention and control (2016)].

    Science.gov (United States)

    Zhou, H; Li, Y; Chen, R F; Tao, X Y; Yu, P C; Cao, S C; Li, L; Chen, Z H; Zhu, W Y; Yin, W W; Li, Y H; Wang, C L; Yu, H J

    2016-02-01

    In order to promote the prevention and control programs on rabies in our country, to regulate the prevention and disposition of rabies and to reduce the deaths caused by rabies, the Chinese Center for Disease Control and Prevention has organized a panel of experts, in the reference with Guidelines issued by WHO, American Advisory Committee on Immunization Practices, and the latest research progress from home and abroad, and compiled this document-"Technical Guidelines for Human Rabies Prevention and Control (2016)". The Guidelines conducted a systematic review on the etiology, clinical characteristics, laboratory diagnosis, epidemiology of rabies and provided evidence on varieties, mechanisms, effects, side-effects and security of rabies vaccine, as well as on other preparations on passive immunity of its kind, on methods related to prevention and disposition of exposure etc, finally to have come up with the recommendation on the above mentioned various techniques. The guidelines will be used by staff working on prevention and control of rabies from the Center for Disease Control and Prevention at all levels, from the departments of outpatient and divisions of infection and emergency control in all the medical institutions. The guideline will be updated and revised, following the research progress from home and abroad.

  1. Mokola virus infection : description of recent South African cases and a review of the virus epidemiology : case report

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    B.F. Von Teichman

    1998-07-01

    Full Text Available Five cases of Mokola virus, a lyssavirus related to rabies, are described. The cases occurred in cats from the East London, Pinetown and Pietermaritzburg areas of South Africa from February 1996 to February 1998. Each of the cats was suspected of being rabid and their brains were submitted for laboratory confirmation. Four of the cases were positive, but with atypical fluorescence, and 1 was negative. Mokola virus infection was identified by anti-lyssavirus nucleocapsid monoclonal antibody typing. As in rabies cases, the predominant clinical signs were of unusual behaviour. Aggression was present, but only during handling. Four of the 5 cats had been vaccinated for rabies, which is consistent with other studies that show that rabies vaccination does not appear to protect against Mokola virus. Since Mokola may be confused with rabies, the incidence of Mokola virus may be more common in Africa than is currently reported. As human infections may be fatal, the emergence of this virus is a potential threat to public health.

  2. Rabies Control: Could Innovative Financing Break the Deadlock?

    Science.gov (United States)

    Welburn, Susan C.; Coleman, Paul G.; Zinsstag, Jakob

    2017-01-01

    The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries but remain major causes of ill-health and mortality in over 80 countries across Africa, Asia, and Latin America. The nature of neglect for the NZDs has been ascribed, in part, to underreporting resulting in an underestimation of their global burden that, together with a lack of advocacy, downgrades their relevance to policy-makers and funding agencies. While this may be the case for many NZDs, for rabies this is not the case. The global burden estimates for rabies (931,600 DALYs) more than justify prioritizing rabies control building on the strong advocacy platforms, functioning at local, regional, and global levels (including the Global Alliance for Rabies Control), and commitments from WHO, OIE, and FAO. Simple effective tools for rabies control exist together with blueprints for operationalizing control, yet, despite elimination targets being set, no global affirmative action has been taken. Rabies control demands activities both in the short term and over a long period of time to achieve the desired cumulative gains. Despite the availability of effective vaccines and messaging tools, rabies will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. While rabies control is usually perceived as a public good, public private partnerships could prove equally effective in addressing endemic rabies through harnessing social investment and demonstrating the cost-effectiveness of control. It is acknowledged that greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably. In the shadows of resource and institutional limitations in the veterinary sector in low- and middle-income countries, sufficient funding is required so that top-down interventions

  3. Modelling of Rabies Transmission Dynamics Using Optimal Control Analysis

    Directory of Open Access Journals (Sweden)

    Joshua Kiddy K. Asamoah

    2017-01-01

    Full Text Available We examine an optimal way of eradicating rabies transmission from dogs into the human population, using preexposure prophylaxis (vaccination and postexposure prophylaxis (treatment due to public education. We obtain the disease-free equilibrium, the endemic equilibrium, the stability, and the sensitivity analysis of the optimal control model. Using the Latin hypercube sampling (LHS, the forward-backward sweep scheme and the fourth-order Range-Kutta numerical method predict that the global alliance for rabies control’s aim of working to eliminate deaths from canine rabies by 2030 is attainable through mass vaccination of susceptible dogs and continuous use of pre- and postexposure prophylaxis in humans.

  4. Rabies Control: Could Innovative Financing Break the Deadlock?

    Science.gov (United States)

    Welburn, Susan C; Coleman, Paul G; Zinsstag, Jakob

    2017-01-01

    The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries but remain major causes of ill-health and mortality in over 80 countries across Africa, Asia, and Latin America. The nature of neglect for the NZDs has been ascribed, in part, to underreporting resulting in an underestimation of their global burden that, together with a lack of advocacy, downgrades their relevance to policy-makers and funding agencies. While this may be the case for many NZDs, for rabies this is not the case. The global burden estimates for rabies (931,600 DALYs) more than justify prioritizing rabies control building on the strong advocacy platforms, functioning at local, regional, and global levels (including the Global Alliance for Rabies Control), and commitments from WHO, OIE, and FAO. Simple effective tools for rabies control exist together with blueprints for operationalizing control, yet, despite elimination targets being set, no global affirmative action has been taken. Rabies control demands activities both in the short term and over a long period of time to achieve the desired cumulative gains. Despite the availability of effective vaccines and messaging tools, rabies will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. While rabies control is usually perceived as a public good, public private partnerships could prove equally effective in addressing endemic rabies through harnessing social investment and demonstrating the cost-effectiveness of control. It is acknowledged that greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably. In the shadows of resource and institutional limitations in the veterinary sector in low- and middle-income countries, sufficient funding is required so that top-down interventions

  5. Immune response after rabies oral immunization in mice

    Directory of Open Access Journals (Sweden)

    Camila Sloboda Pacheco da Silva

    2013-12-01

    Full Text Available The objective of this study was to formulate an anti-rabies oral vaccine from the cell culture vaccine PV TECPAR to elicit the production of antibodies against the rabies in mice. A vaccine was developed using 10(7.5 DL50/0.03 ml viral antigens homogenised in lanovaseline to facilitate oral administration. Mice were vaccinated two times for seroconversion. Sera of the vaccinated mice showed a higher level of antibody production than the control group. These results could be used to direct the development of an anti-rabies oral vaccine.

  6. Sufficient virus-neutralizing antibody in the central nerve system improves the survival of rabid rats

    Directory of Open Access Journals (Sweden)

    Liao Pi-Hung

    2012-06-01

    Full Text Available Abstract Background Rabies is known to be lethal in human. Treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (CNS signs. The blood–brain barrier (BBB is a complex functional barrier that may compromise the therapeutic development in neurological diseases. The goal of this study is to determine the change of BBB integrity and to assess the therapeutic possibility of enhancing BBB permeability combined with passive immunity in the late stage of rabies virus infection. Methods The integrity of BBB permeability in rats was measured by quantitative ELISA for total IgG and albumin levels in the cerebrospinal fluid (CSF and by exogenously applying Evans blue as a tracer. Western blotting of occludin and ZO-1, two tight junction proteins, was used to assess the molecular change of BBB structure. The breakdown of BBB with hypertonic arabinose, recombinant tumor necrosis factor-alpha (rTNF-γ, and focused ultrasound (FUS were used to compare the extent of BBB disruption with rabies virus infection. Specific humoral immunity was analyzed by immunofluorescent assay and rapid fluorescent focus inhibition test. Virus-neutralizing monoclonal antibody (mAb 8-10E was administered to rats with hypertonic breakdown of BBB as a passive immunotherapy to prevent the death from rabies. Results The BBB permeability was altered on day 7 post-infection. Increased BBB permeability induced by rabies virus infection was observed primarily in the cerebellum and spinal cord. Occludin was significantly decreased in both the cerebral cortex and cerebellum. The rabies virus-specific antibody was not strongly elicited even in the presence of clinical signs. Disruption of BBB had no direct association with the lethal outcome of rabies. Passive immunotherapy with virus-neutralizing mAb 8-10E with the hypertonic breakdown of BBB prolonged the survival of rabies virus-infected rats. Conclusions We demonstrated

  7. Controlling rabies through a multidisciplinary, public health system in Trujillo, La Libertad, Peru.

    Science.gov (United States)

    Seneschall, Charlotte; Luna-Farro, Maria

    2013-10-01

    Rabies remains endemic in Peru. In 1983, Latin America and the Caribbean promised to eliminate canine-transmitted rabies from the continent. This led to Peru introducing a multidisciplinary public health system for controlling and managing rabies across the country. The system consists of mass canine vaccination campaigns, post exposure prophylaxis and monitoring aggressor animals for signs of rabies. The Peruvian city of Trujillo, La Libertad, is an urban area where dogs are the principal reservoir for rabies. The disease burden of rabies in Trujillo, La Libertad is currently minimal, with no rabies cases in humans for over 10 years, and only three canine cases. No human deaths due to rabies have occurred for several decades. From this it can be inferred that antirabies systems such as this do have real effects in reducing cases of human rabies at a grass roots level.

  8. Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

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    Meltzer Martin I

    2010-05-01

    Full Text Available Abstract Background In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP, often in inappropriate circumstances. Methods We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario. Results The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing, estimated to have less than 1 in 1,000,000 (0.000001 risk of transmission. Conclusions Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.

  9. Viral surveillance on rabies in Hunan province,in 2006%湖南省2006年狂犬病病原学监测

    Institute of Scientific and Technical Information of China (English)

    戴德芳; 张红; 刘运芝; 刘富强; 唐青; 李浩; 陶晓燕

    2008-01-01

    Objective To understand the source and distribution of rabies virus(RV)in Hunan province with viral surveillance in order to provide scientific measures for prevention and control on rabies.Methods Brain samples from healthy-looking domestic dogs were collected in the agricultural markets at the dist6cLs of high.middle,and lOW incidence rates and detected by direct Immunofluorescence assay (DFA).Positive samples would be further detected by RT-PCR and the surveillance samples were detected bv RT.PCR.The positive samples detected bv RT-PCR were sequenced with N gene.Results The infection rate of thosc healthy-looking domestic dogs with rabies virus was 2.78%in Hunan province in 2005.23 positive samples’N gene were sequenced and their similarities were 88.8%-100.0%.The results indicated that Hunan rabies virus N gene aberrance was mainly synonymous aberrance and did not CKITy obvious regional characteristics.The rabies virus were circulating among different districts in Hunan province,and the neighboring provinces such as Guizhou,Hubei,GuangxiComparison of immunity to measles between floating and local population,Jiangsu and Henan.There were no positive samples detected in salivary,blood and urine samples.There was one positive sample detected in two skin samples.Conclusion There are dogs infected with rabies virus found in Hunan province and this study showed that rabies virus detected in Hunan had a close genetic relationship with those rabies idcntified in other provinces,suggesting that study on the immunity and management of dog related rabies should be strengthened.%目的 了解湖南省狂犬病病毒的分布及来源,从病原学角度分析该省狂犬病疫情高发的原因.方法 采集湖南省人间狂犬病高、中、低疫区市售家犬脑组织及疑似病例、病犬标本,用直接免疫荧光法(DFA)和RT-PCR检测狂犬病病毒,RT-PCR阳性标本进行狂犬病病毒N基因片段核苷酸序列分析. 结果 外观正常犬脑

  10. 我国狂犬病流行毒株JX08-45适应细胞培养后的生物学特性%Biological characteristics of cell culture-adapted rabies virus isolate JX08-45

    Institute of Scientific and Technical Information of China (English)

    刘晔; 房丽君; 赵敬慧; 张守峰; 张菲; 扈荣良

    2012-01-01

    encoding region of G protein were also popular in other cell-adapted strains such as CVS-11, CTN-1, Nishigahara, SAG2, Flury-LEP and SRV9. The death rate of mice challenged i.e. with strain JX08-45CC at a titer of not less than 107 TCIDso/ml were 100%, while that at a titer of 102 ~ 106 TCID50/ml was 20% ~ 80%. However, the death of mice challenged i.m. with the strain at a titer of 105 ~ 108 TCID50/ml was 10% ~ 70%. Both the incubation periods of the strain in mice challenged by intracerebral and peripheral routes were 7 ~ 9 d, and the mice died 24 ~ 48 h after onset. The neutralizing antibody titer induced by strain JXO8-45CC showed no significant difference with those by strains CVS-11, ERA and SRV, (P > 0. 05). Only one mutation of amino acid was distributed in region L protein. Conclusion The biological characteristics including genome sequence, virulence and immunogenicity of rabies virus strain JXO8-45CC were identified, which laid a foundation of development of candidate strains for rabies vaccine for animal use with independent intellectual property rights in China.

  11. Compendium of animal rabies prevention and control, 2000. National Association of State Public Health Veterinarians, Inc.

    Science.gov (United States)

    2000-07-14

    The purpose of this Compendium is to provide rabies information to veterinarians, public health officials, and others concerned with rabies prevention and control. These recommendations serve as the basis for animal rabies-control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies-control program. This document is reviewed annually and revised as necessary. Immunization procedure recommendations are contained in Part I; all animal rabies vaccines licensed by the United States Department of Agriculture (USDA) and marketed in the United States are listed in Part II; Part III details the principles of rabies control.

  12. Compendium of Animal Rabies Prevention and Control, 2001. National Association of State Public Health Veterinarians, Inc.

    Science.gov (United States)

    2001-05-25

    The purpose of this compendium is to provide rabies information to veterinarians, public health officials, and others concerned with rabies prevention and control. These recommendations serve as the basis for animal rabies-control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies-control program. This document is reviewed annually and revised as necessary. Vaccination procedure recommendations are contained in Part I; all animal rabies vaccines licensed by the United States Department of Agriculture (USDA) and marketed in the United States are listed in Part II; Part III details the principles of rabies control.

  13. Compendium of Animal Rabies Control, 1999. National Association of State Public Health Veterinarians, Inc.

    Science.gov (United States)

    1999-04-02

    The purpose of this Compendium is to provide information on rabies control to veterinarians, public health officials, and others concerned with rabies control. These recommendations serve as the basis for animal rabies-control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies-control program. This document is reviewed annually and revised as necessary. Immunization procedure recommendations are contained in Part I; all animal rabies vaccines licensed by the United States Department of Agriculture (USDA) and marketed in the United States are listed in Part II; Part III details the principles of rabies control.

  14. Control of canine rabies in developing countries: key features and animal welfare implications.

    Science.gov (United States)

    Aréchiga Ceballos, N; Karunaratna, D; Aguilar Setién, A

    2014-04-01

    Over 90% of human deaths from rabies worldwide are caused by dog bites. Mass vaccination, along with the effective control of dog populations, has been used successfully in industrialised countries to control this disease. A lower success rate in developing countries is due to a number of factors, including vaccination campaigns that do not cover a sufficient number of animals or reach all communities, and a wide biodiversity that increases the number of reservoirs of the rabies virus. Educational programmes are needed, which focus on the commitment involved when acquiring a domestic animal, stating clearly what is required to provide it with a good quality of life. New technologies developed in the industrialised world will not always be successful in less developed countries. Approaches must be adapted to the particular conditions in each country, taking cultural and socio-economic issues into account. Authorities must promote research on dog population dynamics, the development of non-invasive methods to control dog populations and the most efficient, stable and low-cost options for vaccination. Under the One Health model, it is hoped that dog-transmitted human rabies will be accorded high priority as a zoonosis by human health authorities, international authorities and donor agencies to support ambitious eradication goals, particularly those being set in South-East Asia. Well-designed and adequately resourced vaccination programmes, based on the World Organisation for Animal Health (OIE) guidelines, will have significant animal welfare benefits, due to the availability of improved vaccines (in terms of efficacy, duration of immunity, ease of administration and lower cost), advances in dog population management and the more widespread implementation of the OIE Guidelines on Stray Dog Control. Animal welfare benefits include not only the elimination of pain and suffering caused by the clinical disease itself, but also the avoidance of the indirect impact of

  15. SOSIALISASI PENYAKIT RABIES PADA SISWA SLTA DI DESA BEBANDEM KARANGASEM

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    Dharmawan. N. S.

    2012-10-01

    Full Text Available This Community Service was conducted on October 23rd. 2010 in Bebandem village, Karangasem regency in the form of socialization of rabies on senior high school students. The aim of this program was to give knowledge, clinical symptoms, transmission, and prevention of the rabies diseases. There were 50 participants who came from representatives of each class. Twenty-eight (56% participants reported that at their house, they have dogs and cats, mostly (50% have not been vaccinated. The activity runs smoothly and as planned. Socialization of rabies diseases has improved the understanding of all participants. At the end of the event, most of them (90% reported that they were satisfied and there are 48 (96% participants are interested in becoming a volunteer to join to inform