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Sample records for rabies virus populations

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

    Directory of Open Access Journals (Sweden)

    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. Re-emergence of rabies virus maintained by canid populations in Paraguay.

    Science.gov (United States)

    Amarilla, A C F; Pompei, J C A; Araujo, D B; Vázquez, F A; Galeano, R R; Delgado, L M; Bogado, G; Colman, M; Sanabria, L; Iamamoto, K; Garcia, R; Assis, D; Recalde, R; Martorelli, L F; Quiñones, E; Cabello, A; Martini, M; Cosivi, O; Durigon, E L; Favoretto, S R

    2018-02-01

    Paraguay has registered no human cases of rabies since 2004, and the last case in dogs, reported in 2009, was due to a variant maintained in the common vampire bat "Desmodus rotundus". In 2014, a dog was diagnosed as positive for rabies with aggression towards a boy and all required measures of control were successfully adopted. Epidemiological investigation revealed that the dog was not vaccinated and had been attacked by a crab-eating fox, "zorro" (Cerdocyon thous). The sample was diagnosed by the Official Veterinary Service of the Country and sent to the Center on Rabies Research from the University of São Paulo, Brazil, for antigenic and genetic characterization. A second sample from a dog positive for rabies in the same region in 2015 and 11 samples from a rabies outbreak from Asuncion in 1996 were also characterized. The antigenic profile of the samples, AgV2, was compatible with one of the variants maintained by dogs in Latin America. In genetic characterization, the samples segregated in the canine (domestic and wild species)-related group in an independent subgroup that also included samples from Argentina. These results and the epidemiology of the case indicate that even with the control of rabies in domestic animals, the virus can still circulate in wildlife and may be transmitted to domestic animals and humans, demonstrating the importance of continuous and improved surveillance and control of rabies, including in wild species, to prevent outbreaks in controlled areas. © 2017 Blackwell Verlag GmbH.

  3. 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.

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

    Science.gov (United States)

    Nouvellet, Pierre; Donnelly, Christl A; De Nardi, Marco; Rhodes, Chris J; De Benedictis, Paola; Citterio, Carlo; Obber, Federica; Lorenzetto, Monica; Pozza, Manuela Dalla; Cauchemez, Simon; Cattoli, Giovanni

    2013-01-01

    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.

  5. Rabies and Canine Distemper Virus Epidemics in the Red Fox Population of Northern Italy (2006–2010)

    Science.gov (United States)

    De Benedictis, Paola; Citterio, Carlo; Obber, Federica; Lorenzetto, Monica; Pozza, Manuela Dalla; Cauchemez, Simon; Cattoli, Giovanni

    2013-01-01

    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. PMID:23630599

  6. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies...

  7. 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... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing... administration. (iii) Observe all animals for signs of rabies until scheduled time to sacrifice. If animals show...

  8. Rabies.

    Science.gov (United States)

    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.? 2013.

  9. Transcriptional mapping of rabies virus in vivo

    International Nuclear Information System (INIS)

    Flamand, A.; Delagneau, J.F.

    1978-01-01

    Synthesis of the proteins of rabies virus was studied in hamster cell infected with uv-irradiated virus. The uv target size of genes L, N, M 1 , and M 2 was measured during primary transcription. Except for N, the target size of the remaining genes was considerably larger than that of their physical sizes. The data fit the hypothesis that four genes occupy a single transcriptional unit and that transcription of rabies virus proceeds in the order N, M 1 , M 2 , and L

  10. Molecular diversity of rabies viruses associated with bats in Mexico and other countries of the Americas.

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    Velasco-Villa, Andrés; Orciari, Lillian A; Juárez-Islas, Víctor; Gómez-Sierra, Mauricio; Padilla-Medina, Irma; Flisser, Ana; Souza, Valeria; Castillo, Amanda; Franka, Richard; Escalante-Mañe, Maribel; Sauri-González, Isaias; Rupprecht, Charles E

    2006-05-01

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

  11. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus

    OpenAIRE

    Faber, Milosz; Li, Jianwei; Kean, Rhonda B.; Hooper, D. Craig; Alugupalli, Kishore R.; Dietzschold, Bernhard

    2009-01-01

    Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage r...

  12. [Viruses and bats: rabies and Lyssavirus].

    Science.gov (United States)

    Tordo, N; Marianneau, M Ph

    2009-01-01

    Recent emerging zoonoses (hemorrhagic fevers due to Ebola or Marburg virus, encephalitis due to Nipah virus, severe acute respiratory syndrome due to SRAS virus...) outline the potential of bats as vectors for transmission of infectious disease to humans. Such a potential is already known for rabies encephalitis since seven out of the eight genotypes of Lyssavirus are transmitted by bats. In addition, phylogenetic reconstructions indicate that Lyssavirus have evolved in chiropters before their emergence in carnivores. Nevertheless, carnivores remain the most critical vectors for public health, in particular dogs that are originating 55.000 rabies deaths per year, essentially in developing countries. Rabies control in carnivores by parenteral (dog) or oral (wild carnivores) vaccination is efficacious and campaigns start to be more widely applied. On the other hand, rabies control in bat still remains non realistic, particularly as the pathogenicity of bat Lyssavirus for bats is still under debate, suggesting that a "diplomatic relationship" between partners would have arisen from a long term cohabitation. While comparing the interactions that humans and bats establish with Lyssavirus, scientists try to understand the molecular basis ofpathogenicity in man, a indispensable prerequisite to identify antiviral targets in a perspective of therapy.

  13. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

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

    2017-04-15

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we 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 protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to 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. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

  14. [Differences on geographic distribution of rabies virus lineages in China].

    Science.gov (United States)

    Wang, Q; Li, M L; Chen, Y; Wang, B; Tao, X Y; Zhu, W Y

    2018-04-10

    Objective: To study the lineages of rabies virus and the epidemic characteristics in different provincial populations of China, to provide information for the development of control and prevention measures in each respective provinces. Methods: Full length N and G genes and full-genome of epidemic strains of rabies virus collected in China were downloaded from GenBank and combined with newly sequenced strains by our lab. Each strain was classified under six lineages of China rabies by constructing phylogenetic trees based on the N or G sequences. Numbers of strains and lineages in each province were counted and compared. Results: Six lineages (China Ⅰ-Ⅵ) were prevalent in China, with 4 found in Yunnan and Hunan. In 6 provinces, including Henan and Fujian, 3 lineages were found. In 8 provinces, including Shanghai and Jiangxi, 2 lineages were found Only 1 lineage, were found in Beijing, Tianjin and other 12 provinces. the China Ⅰ, was the dominant one in 25 provinces. In recent years, China Ⅲ had been found in wild animals and spread over livestock in Inner Mongolia and Xinjiang areas. Qinghai and Tibet had been influenced by China Ⅳ, which also been found in wild animals of Inner Mongolia and Heilongjiang. Conclusion: There had been obvious differences in lineages and strain numbers of rabies virus identified in different provinces in China.

  15. Experimental infection of Artibeus intermedius with a vampire bat rabies virus.

    Science.gov (United States)

    Obregón-Morales, Cirani; Aguilar-Setién, Álvaro; Perea Martínez, Leonardo; Galvez-Romero, Guillermo; Martínez-Martínez, Flor Olivia; Aréchiga-Ceballos, Nidia

    2017-06-01

    Experimental infection of Artibeus intermedius, the great fruit-eating bat, was performed with vampire bat rabies isolates. Bats (n=35) were captured in the wild and quarantined prior to experimental infection. No rabies antibodies were detected by rapid fluorescent focus inhibition test (RFFIT) prior to infection. Three doses of rabies virus (RV) and three different routes of infection were used. One out of 35 bats died without showing any clinical signs at day 14 and was positive for rabies. None of the 34 other bats showed clinical signs for rabies, but high antibody titers were detected post-inoculation, suggesting either innate immune response to the vampire bat rabies virus or possible pre-exposure to RV and inoculation leading to a booster effect. Rabies virus was detected by hemi-nested RT-PCR (hnRT-PCR) in the brain (n=3), stomach (n=1) of bats that were negative by immunofluorescence and that survived rabies infection. The bat that died on day 14 was positive by hnRT-PCR on the brain, heart and liver. These results suggest that either previous non-lethal exposure to RV or natural low susceptibility to vampire bat viruses somehow protected Artibeus intermedius from clinical rabies infection leading to a marginal lethality effect on this bats species population in the wild. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Antigenic analysis of some Nigerian street rabies virus using ...

    African Journals Online (AJOL)

    The authors studied 12 street rabies virus isolates from 3 states of Nigeria using both the anti-nucleocapsid and anti-glycoprotein monoclonal antibodies and cross-protection tests. It was observed that all the viruses were rabies having divergent antigenic presentation. Also noticed was an antigenic shift when the viruses ...

  18. The origin and phylogeography of dog rabies virus

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    Bourhy, Hervé; Reynes, Jean-Marc; Dunham, Eleca J.; Dacheux, Laurent; Larrous, Florence; Huong, Vu Thi Que; Xu, Gelin; Yan, Jiaxin; Miranda, Mary Elizabeth G.; Holmes, Edward C.

    2012-01-01

    Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV. PMID:18931062

  19. Evolutionary History and Phylogeography of Rabies Viruses Associated with Outbreaks in Trinidad

    OpenAIRE

    Seetahal, Janine F. R.; Velasco-Villa, Andres; Allicock, Orchid M.; Adesiyun, Abiodun A.; Bissessar, Joseph; Amour, Kirk; Phillip-Hosein, Annmarie; Marston, Denise A.; McElhinney, Lorraine M.; Shi, Mang; Wharwood, Cheryl-Ann; Fooks, Anthony R.; Carrington, Christine V. F.

    2013-01-01

    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 varia...

  20. Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife

    Directory of Open Access Journals (Sweden)

    Susan M. Moore

    2017-07-01

    Full Text Available Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV of wildlife reservoir populations for decades to control circulation of rabies virus in free-ranging hosts. There remains much debate about the levels of rabies antibodies (and the assays to measure them that confer resistance to rabies virus. In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, are examined as correlates of protection against lethal rabies infection in captive challenge settings. Analysis of our studies suggests that, though serum neutralization test results are expected to reflect in vivo protection, the blocking enzyme linked immunosorbent assay (ELISA result at Day 28 was a better predictor of survival. ELISA kits may have an advantage of greater precision and ability to compare results among different studies and laboratories based on the inherent standardization of the kit format. This paper examines current knowledge and study findings to guide meaningful interpretation of serology results in oral baiting monitoring.

  1. 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; Prabies 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.

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

    OpenAIRE

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

    2017-01-01

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant ...

  3. Medium-term cryopreservation of rabies virus samples

    Directory of Open Access Journals (Sweden)

    Tereza D'avila de Freitas Aguiar

    2013-12-01

    Full Text Available Introduction The cryopreservation of rabies virus has been described in detail in the literature. To date, little information is available on the use of cryoprotective agents for cold preservation of this virus, and the available data focus only on short-term virus preservation. In this study, we investigated the medium-term cryopreservation of samples of rabies virus using different cryopreservation protocols. Methods The cryopreservation protocols for the rabies virus samples were performed at -20°C and were divided according to the variables of time and cryoprotectant type used. The laboratory tests (intracerebral inoculation of mice, viral titration and direct immunofluorescence were performed at regular intervals (360 and 720 days to assess the viability of the viral samples according to the different preservation techniques used. Results After 1 year of cryopreservation, the fluorescence intensity of intracellular corpuscles of the rabies virus and the median survival time of the mice differed between the positive controls and the treatments with the cryoprotectants. After 2 years, most of the samples subjected to the cryopreservation protocols (including the controls did not produce fluorescence. However, the virus samples exposed to the cryoprotectant sucrose (68% solution responded positively in the direct immunofluorescence assay and in the intracerebral inoculation of the mice. Conclusions Medium-term cryopreservation of the rabies virus inactivates the viral sample. However, the cryoprotectant agent sucrose (68% produces a preservative effect in cryopreserved rabies virus samples.

  4. Evaluation of a rapid immunodiagnostic test kit for rabies virus.

    Science.gov (United States)

    Kang, BoKyu; Oh, JinSik; Lee, ChulSeung; Park, Bong-Kyun; Park, YoungNam; Hong, KyungSoo; Lee, KyungGi; Cho, ByungKi; Song, DaeSub

    2007-10-01

    A rapid immunodiagnostic test kit for rabies virus detection was evaluated using 51 clinical samples and 4 isolates of rabies virus. The quick detection of rabies virus under field conditions may be helpful in determining if post-exposure prophylaxis is needed, thereby avoiding unnecessary treatments, as well as undue economic burden. There are several widely used diagnostic methods for rabies, including fluorescent antibody tests, reverse transcription polymerase chain reaction, and electron microscopy; however, these methods include time-consuming, intricate, and costly procedures. The rapid immunodiagnostic test was able to detect rabies virus in clinical samples, including brain tissue and saliva, in addition to 10(3.2) 50% lethal dose (LD(50))/mL cell-adapted rabies virus. The assay was not cross-reactive with non-rabies virus microbes. When the performance of the rapid immunodiagnostic test was compared to a fluorescent antibody test, the rapid immunodiagnostic test had a sensitivity of 91.7% and specificity of 100% (95.8% CI).

  5. Rabies: Questions and Answers

    Science.gov (United States)

    Rabies: Questions and Answers Information about the disease and vaccines What causes rabies? Rabies is caused by a virus. The virus invades ... nervous system and disrupts its functioning. How does rabies spread? The rabies virus is transmitted in the ...

  6. Characterization of rabies virus from a human case in Nepal.

    Science.gov (United States)

    Pant, G R; Horton, D L; Dahal, M; Rai, J N; Ide, S; Leech, S; Marston, D A; McElhinney, L M; Fooks, A R

    2011-04-01

    Rabies is endemic throughout most of Asia, with the majority of human cases transmitted by domestic dogs (Canis familiaris). Here, we report a case of rabies in a 12-year-old girl in the Lalitpur district of Nepal that might have been prevented by better public awareness and timely post-exposure prophylaxis. Molecular characterization of the virus showed 100% identity over a partial nucleoprotein gene sequence to previous isolates from Nepal belonging to the 'arctic-like' lineage of rabies virus. Sequence analysis of both partial nucleoprotein and glycoprotein genes showed differences in consensus sequence after passage in vitro but not after passage in vivo.

  7. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus.

    Science.gov (United States)

    Faber, Milosz; Li, Jianwei; Kean, Rhonda B; Hooper, D Craig; Alugupalli, Kishore R; Dietzschold, Bernhard

    2009-07-07

    Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.

  8. Phylogenetic analysis and victim contact tracing of rabies virus from humans and dogs in Bali, Indonesia.

    Science.gov (United States)

    Mahardika, G N K; Dibia, N; Budayanti, N S; Susilawathi, N M; Subrata, K; Darwinata, A E; Wignall, F S; Richt, J A; Valdivia-Granda, W A; Sudewi, A A R

    2014-06-01

    The emergence of human and animal rabies in Bali since November 2008 has attracted local, national and international interest. The potential origin and time of introduction of rabies virus to Bali is described. The nucleoprotein (N) gene of rabies virus from dog brain and human clinical specimens was sequenced using an automated DNA sequencer. Phylogenetic inference with Bayesian Markov Chain Monte Carlo (MCMC) analysis using the Bayesian Evolutionary Analysis by Sampling Trees (BEAST) v. 1.7.5 software confirmed that the outbreak of rabies in Bali was caused by an Indonesian lineage virus following a single introduction. The ancestor of Bali viruses was the descendant of a virus from Kalimantan. Contact tracing showed that the event most likely occurred in early 2008. The introduction of rabies into a large unvaccinated dog population in Bali clearly demonstrates the risk of disease transmission for government agencies and should lead to an increased preparedness and efforts for sustained risk reduction to prevent such events from occurring in future.

  9. Survey of bat populations from Mexico and Paraguay for rabies.

    Science.gov (United States)

    Sheeler-Gordon, L L; Smith, J S

    2001-07-01

    A mammalian survey was conducted in Mexico (October 1994-January 1996) and in Paraguay (August 1996-March 1997); a complete specimen was collected for each bat in the survey, including primary voucher specimen, ectoparasites, karyotype, and various frozen tissues. The surveys combined provided 937 brain samples (65 bat species) for rabies diagnosis. One male Lasiurus ega, collected in Paraguay, tested positive for the rabies virus (overall prevalence rate of 0.1%). Nucleotide sequence from a 300 bp region of the rabies nucleoprotein gene was compared with sequence obtained from representative rabies virus samples in the repository at the Centers for Disease Control and Prevention (Atlanta, Georgia, USA). Rabies virus extracted from the brain material of L. ega differed by only one nucleotide from a 300 bp consensus sequence (>99% homology) derived from samples for the variant of rabies virus transmitted by Lasiurus cinereus. Lasiurus ego differed by approximately 15% for the variant transmitted by Desmodus rotundus. Phylogenetic analysis found no evidence to suggest L. ego is a reservoir for rabies antigenic variant 6. The most likely explanation for rabies in L. ega was infection following contact with a rabid L. cinereus.

  10. Protective Effect of Different Anti-Rabies Virus VHH Constructs against Rabies Disease in Mice

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Lamoral, Sophie; Hultberg, Anna; Rommelaere, Heidi; Wittelsberger, Angela; Callewaert, Filip; Stohr, Thomas; Meerschaert, Kris; Ottevaere, Ingrid; Stortelers, Catelijne; Vanlandschoot, Peter; Kalai, Michael; Van Gucht, Steven

    2014-01-01

    Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable

  11. Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals.

    Science.gov (United States)

    Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C

    2004-09-03

    Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.

  12. 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.

  13. Generation and characterization of P gene-deficient rabies virus

    International Nuclear Information System (INIS)

    Shoji, Youko; Inoue, Satoshi; Nakamichi, Kazuo; Kurane, Ichiro; Sakai, Takeo; Morimoto, Kinjiro

    2004-01-01

    Rabies virus (RV) deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient (def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus-infected cells that did not express the P protein. However, we found that the def-P virus had the ability to perform primary transcription (by the virion-associated polymerase) in the infected host without de novo P protein synthesis. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody (VNA) and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine

  14. Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

    Science.gov (United States)

    Zhou, Ming; Wang, Lei; Zhou, Songqin; Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F

    2015-11-17

    Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

  15. Rabies Virus Transmission in Solid Organ Transplantation, China, 2015-2016.

    Science.gov (United States)

    Chen, Shuilian; Zhang, Heng; Luo, Meiling; Chen, Jingfang; Yao, Dong; Chen, Faming; Liu, Ruchun; Chen, Tianmu

    2017-09-01

    We report rabies virus transmission among solid organ transplantation recipients in Changsha, China, in 2016. Two recipients were confirmed to have rabies and died. Our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies.

    OpenAIRE

    Bentley, Emma; Ali, Ruqiyo; Horton, Daniel; Corti, Davide; Banyard, Ashley; Fooks, Anthony; Wright, Edward

    2017-01-01

    Rabies viruses have the highest case fatality rate of any known virus and are responsible for an estimated 60,000 deaths each year. This is despite the fact that there are highly efficacious vaccines and post-exposure prophylaxis available. However, while it is assumed these biologics provide protection against all rabies virus isolates, there are certain subdivisions of RABV lineages, such as within the Arctic-like RABV (AL rabies virus lineage, where data is limited and thus the potency of ...

  18. [Production of monoclonal antibodies against a wild strain of rabies virus].

    Science.gov (United States)

    Akacem, O; Benmansour, A; Coulon, P; Brahimi, M; Benhassine, M

    1992-01-01

    Production of monoclonal antibodies against a wild strain of rabies virus. Cell fusion of SP 2/O, a murine myeloma against a wild strain of rabies virus has originated five monoclonal antibodies (M.A.) specific for virus nucleocapsid , one M.A. specific for virus glycoprotein and one M.A. specific for a viral membrane protein.

  19. Rabies

    Science.gov (United States)

    E F G H I J K L M N O P Q R S T U V W X Y Z Rabies Raccoon People are exposed to rabies when they to the local health department. Rabies is almost always fatal once clinical symptoms appear. To confirm the victim's risk of being exposed to rabies, a decision must be made to either test or quarantine

  20. Persepsi Masyarakat Terhadap Penyakit Rabies

    OpenAIRE

    Retna Siwi Padmawati, I Made Kerta Duana Nida Ul Hasanat

    2011-01-01

    Background: Rabies is a viral disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals, and human. The rabies virus infects the central nervous system, ultimately causing disease in the brain and death. Rabies in Bali was firstly discovered in Badung District. Rabies was transferred by dog bite. Bali has enourmous dog population, the number reach approximately 540.000 animals or about 96 animals per square kilometer. Meanwhile, domesticated dog population onl...

  1. Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: Fine mapping and escape mutant analysis

    NARCIS (Netherlands)

    Marissen, W.E.; Kramer, R.A.; Rice, A.; Weldon, W.C.; Niezgoda, M.; Faber, M.; Slootstra, J.W.; Meloen, R.H.; Clijsters-van der Horst, M.; Visser, T.J.; Jongeneelen, M.; Thijsse, S.; Throsby, M.; Kruif, de J.; Rupprecht, C.E.; Dietzschold, B.; Goudsmit, J.; Bakker, A.B.H.

    2005-01-01

    Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We

  2. Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: fine mapping and escape mutant analysis

    NARCIS (Netherlands)

    Marissen, Wilfred E.; Kramer, R. Arjen; Rice, Amy; Weldon, William C.; Niezgoda, Michael; Faber, Milosz; Slootstra, Jerry W.; Meloen, Rob H.; Clijsters-van der Horst, Marieke; Visser, Therese J.; Jongeneelen, Mandy; Thijsse, Sandra; Throsby, Mark; de Kruif, John; Rupprecht, Charles E.; Dietzschold, Bernhard; Goudsmit, Jaap; Bakker, Alexander B. H.

    2005-01-01

    Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We

  3. Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review.

    Science.gov (United States)

    Maki, Joanne; Guiot, Anne-Laure; Aubert, Michel; Brochier, Bernard; Cliquet, Florence; Hanlon, Cathleen A; King, Roni; Oertli, Ernest H; Rupprecht, Charles E; Schumacher, Caroline; Slate, Dennis; Yakobson, Boris; Wohlers, Anne; Lankau, Emily W

    2017-09-22

    RABORAL V-RG ® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control

  4. Molecular Diagnosis of Classical Rabies Virus in Polar Foxes in Greeenland

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Strandbygaard, Bertel

    Classical rabies virus continues to circulate in polar foxes in Greenland. Within the last 5 years more than 30 animals, mainly polar foxes have been tested positive for rabies. In this study, brain samples from this period were assessed for the presence of rabies viral RNA using molecular...

  5. Ifit2 Is a Restriction Factor in Rabies Virus Pathogenicity.

    Science.gov (United States)

    Davis, Benjamin M; Fensterl, Volker; Lawrence, Tessa M; Hudacek, Andrew W; Sen, Ganes C; Schnell, Matthias J

    2017-09-01

    Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma cells in vitro This effect was replicated in vivo , where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type mice after intranasal inoculation of RABV. This increase in pathogenicity correlated to an increase in RABV mRNA and live viral load in the brain, as well as to an accelerated spread to brain regions normally affected by this RABV model. These results suggest that Ifit2 exerts its antiviral effect mainly at the level of viral replication, as opposed to functioning as a mechanism that restricts viral entry/egress or transports RABV particles through axons. IMPORTANCE Rabies is a fatal zoonotic disease with a nearly 100% case fatality rate. Although there are effective vaccines for rabies, this disease still takes the lives of about 50,000 people each year. Victims tend to be children living in regions without comprehensive medical infrastructure who present to health care workers too late for postexposure prophylaxis. The protein discussed in our report, Ifit2, is found to be an important restriction factor for rabies virus, acting directly or indirectly against viral replication. A more nuanced understanding of this interaction may reveal a step of a pathway or site at which the system could be exploited for the development of a targeted therapy. Copyright © 2017 American Society for Microbiology.

  6. «I Am Legend»: comparison of the fictional virus infection and Rabies virus

    Directory of Open Access Journals (Sweden)

    José Francisco CAMACHO AGUILERA

    2016-04-01

    Full Text Available Using the movie I am legend (2007 by, the rabies virus infection is reviewed in this article, given its strong resemblance to the fictional disease created in this film caused by the virus Krippin. A review of history, virus characteristics, viral transmission, clinical manifestations, diagnostics, mortality, treatment and prevention, are presented and are contrasted with the film.

  7. PROFILAKSIS RABIES

    Directory of Open Access Journals (Sweden)

    Susilawathi NM

    2014-09-01

    Full Text Available Rabies merupakan penyakit ensefalitis akut yang disebabkan oleh virus RNA, famili Rhabdoviridae, genus lyssavirus. Anjing adalah reservoir utama penularan rabies, puluhan ribu kematian per tahun disebabkan oleh gigitan anjing rabies. Bila seseorang menunjukkan gejala rabies, biasanya selalu fatal.  Profilaksis terhadap rabies merupakan tindakan efektif dan aman. Mencuci luka dan vaksinasi segera setelah kontak dengan hewan tersangka rabies dapat mencegah timbulnya rabies hampir 100%. Strategi yang paling efektif untuk mencegah rabies adalah mengurangi penularan rabies pada anjing melalui vaksinasi.[MEDICINA 2009;40:55-9].

  8. Incidence of human rabies and characterization of rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China, 2002-2012.

    Science.gov (United States)

    Zhang, Jian-Ming; Zhang, Zhi-Shan; Deng, Yan-Qin; Wu, Shou-Li; Wang, Wei; Yan, Yan-Sheng

    2017-08-30

    Rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. Recently, there has been an increase in the incidence of rabies in China. The aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from Fujian Province, Southeast China from 2002 to 2012. Data pertaining to human rabies cases in Fujian Province during the period from 2002 through 2012 were collected, and the epidemiological profiles were described. The saliva and brain specimens were collected from dogs in Quanzhou, Longyan and Sanming cities of the province, and the rabies virus antigen was determined in the canine saliva specimens using an ELISA assay. Rabies virus RNA was extracted from canine brain specimens, and rabies virus nucleoprotein gene was amplified using a nested RT-PCR assay, followed by sequencing and genotyping. A total of 226 human rabies cases were reported in Fujian Province from 2002 to 2012, in which 197 cases were detected in three cities of Quanzhou, Longyan and Sanming. ELISA assay revealed positive rabies virus antigen in six of eight rabid dogs and 165 of 3492 seemingly healthy dogs. The full-length gene fragment of the rabies virus nucleoprotein gene was amplified from the brain specimens of seven rabid dogs and 12 seemingly healthy dogs. Sequence alignment and phylogenetic analysis revealed that these 19 rabies virus nucleoprotein genes all belonged to genotype I, and were classified into three genetic groups. Sequencing analysis showed a 99.7% to 100% intra-group and an 86.4% to 89.3% inter-group homology. This study is the first description pertaining to the epidemiological characteristics of human rabies cases and characterization of the rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China. Our findings may provide valuable knowledge for the development of strategies targeting the prevention and control of

  9. Experimental infection of the bat tick Carios fonsecai (Acari: Ixodidae with the rabies virus

    Directory of Open Access Journals (Sweden)

    Silvana Regina Favoretto

    2013-12-01

    Full Text Available Introduction This study assessed the viability of the rabies virus in the argasid tick Carios fonsecai following experimental infection. Methods The mouse inoculation test (MIT, fluorescent antibody test (FAT and polymerase chain reaction (PCR were used. The rabies virus was administered to ticks via the intra-coelomic route, and the ticks were sacrificed at different time points. Results The inoculated ticks were negative for rabies according to the MIT. Ticks macerated with rabies virus were positive according to the MIT and FAT. All of the tick lots tested by PCR were positive. Conclusions The rabies virus became unviable shortly after its inoculation into tick bodies. Ticks are not likely to play an important role in the epidemiology of rabies.

  10. [Biological characteristics of a chimeric rabies virus expressing canine parvovirus VP2 protein].

    Science.gov (United States)

    Niu, Xue-Feng; Liu, Xiao-Hui; Sun, Zhao-Jin; Shi, He-He; Chen, Jing; Jiang, Bido; Sun, Jing-Chen; Guo, Xiao-Feng

    2009-09-01

    To obtain a bivalence vaccine against canine rabies virus and canine parvovirus, a chimeric rabies virus expressing canine parvovirus VP2 protein was generated by the technique of reverse genetics. It was shown that the chimeric virus designated as HEP-Flury (VP2) grew well on BHK-21 cells and the VP2 gene could still be stably expressed after ten passages on BHK-21 cells. Experiments on the mice immunized with the chimeric virus HEP-Flury (VP2) demonstrated that specific antibodies against rabies virus and canine parvovirus were induced in immunized mice after vaccination with the live chimeric virus.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Infection of neuroblastoma cells by rabies virus is modulated by the virus titer.

    Science.gov (United States)

    Fuoco, Natalia Langenfeld; Dos Ramos Silva, Sandriana; Fernandes, Elaine Raniero; Luiz, Fernanda Guedes; Ribeiro, Orlando Garcia; Katz, Iana Suly Santos

    2018-01-01

    Rabies is a lethal viral infection that can affect almost all mammals, including humans. To better understand the replication of Rabies lyssavirus, we investigated if the viral load in brains naturally infected with rabies influences viral internalization and viral growth kinetics in neuroblastoma cells, and if the viral load affects mortality in mice after intradermal infection. We noted that high initial viral loads in brains (group II) were unfavourable for increasing viral titers during serial passages in neuroblastoma cells when compared to low initial viral loads in brains (group I). In addition, group I strains showed higher viral growth and enhanced internalization efficiency in neuroblastoma cells than group II strains. However, we observed that the dominant virus subpopulation in group II promoted efficient viral infection in the central nervous system in the new host, providing a selective advantage to the virus. Our data indicate that rabies infection in animal models depends on not only the virus strain but also the amount of virus. This study may serve as a basis for understanding the biologic proprieties of Rabies lyssavirus strains with respect to the effects on viral replication and the impact on pathogenesis, improving virus yields for use in vaccine development. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 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

  14. Rabies

    Science.gov (United States)

    ... procurement, and usage are expected from rabies biological suppliers in both India and Viet Nam. Once complete, ... as part of a Bill & Melinda Gates Foundation project led by WHO, recently showed that a reduction ...

  15. The serological response of young dogs to the Flury LEP strain of rabies virus vaccine.

    Science.gov (United States)

    Aghomo, H O; Oduye, O O; Rupprecht, C E

    1990-01-01

    The serological response of puppies from Nigeria to live Flury low egg passage (LEP) rabies vaccine was determined. Two sets of puppies were used: one set from rabies-vaccinated bitches and another set from non-vaccinated bitches. Puppies were vaccinated intramuscularly with Flury LEP strain rabies vaccine and serially bled from the 4th week to the 30th week. Serum rabies virus neutralizing antibodies (VNA) were measured by a modified rapid fluorescent focus inhibition test (RFFIT). Puppies from non-vaccinated bitches responded well to vaccination after the 4th week and through to the 10th week of age, showing a progressive increase in VNA. In contrast, puppies from vaccinated bitches responded well to rabies vaccination only at 10 weeks of age, although detectable maternal rabies VNA and rabies anti-ribonucleoprotein (RNP) antibodies had decreased by 6 weeks post partum.

  16. A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice.

    Science.gov (United States)

    Li, Zhili; Wang, Jigui; Yuan, Daoli; Wang, Shuang; Sun, Jiazeng; Yi, Bao; Hou, Qiang; Mao, Yaping; Liu, Weiquan

    2015-06-01

    Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of the dog. CDV, a member of the morbillivirus genus, has shown promise as an expression vector. The glycoprotein from RV is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. In this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression by the recombinant viruses was confirmed. Furthermore, G was proved to be incorporated into the surface of CDV particles. While replication of the recombinant virus was slightly reduced compared with the parental CDV, it stably expressed the RV-G over ten serial passages. Inoculation of mice induced specific neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has the potential as a vaccine that may be used to control rabies virus infection in dogs and other animals.

  17. 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

  18. Rabies

    Science.gov (United States)

    ... news-room/fact-sheets/detail/rabies","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... prevention and control in communities includes education and information on responsible pet ownership, how to prevent dog ...

  19. Rabies (image)

    Science.gov (United States)

    ... messages between the brain and the body. The rabies virus spreads through the nerves, first causing flu- ... to hallucinations, delirium, and insomnia. If left untreated, rabies is nearly always fatal.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. A surface plasmon resonance biosensor for direct detection of the rabies virus

    Directory of Open Access Journals (Sweden)

    Jing Xu

    2012-01-01

    Full Text Available A surface plasmon resonance biosensor chip was constructed for detection of rabies virus. For the construction of the biosensor chip, N protein specific antibody and N protein specific antibody combined with G protein specific antibody of rabies virus were linked on two different flow cells on one CM5 chip, respectively. The chip was tested for the detection of rabies virus antigens using the crude extract of rabies virus from infected BHK cell strain culture. Tenfold serial dilutions of SRV9 strain virus-infected cell cultures were tested by the biosensor chip to establish the detection limit. The limit detection was approximately 70 pg/ml of nucleoprotein and glycoprotein. The biosensor chip developed in this study was employed for the detection of rabies virus in five suspect infectious specimens of brain tissue from guinea pigs; the results were compared by fluorescent antibody test. Surface plasmon resonance biosensor chip could be a useful automatic tool for prompt detection of rabies virus infection.

  3. Enzyme immunoassay for rabies antibody in hybridoma culture fluids and its application to differentiation of street and laboratory strains of rabies virus.

    OpenAIRE

    Smith, J S; Sumner, J W; Roumillat, L F

    1984-01-01

    A rapid and sensitive enzyme immunoassay is described for detecting rabies antibody in hybridoma culture fluids. Glass fiber filter disks were used to immobilize gamma-irradiated mouse neuroblastoma cells infected with street or laboratory strains of rabies virus. Bound rabies-specific antibody was detected by reaction with horseradish peroxidase-labeled goat anti-mouse immunoglobulin G. The assay was performed in a 96-well filtration device developed by Cleveland et al. (J. Clin. Microbiol. ...

  4. Alanine scanning of the rabies virus glycoprotein antigenic site III using recombinant rabies virus: implication for post-exposure treatment.

    Science.gov (United States)

    Papaneri, Amy B; Wirblich, Christoph; Marissen, Wilfred E; Schnell, Matthias J

    2013-12-02

    The safety and availability of the human polyclonal sera that is currently utilized for post-exposure treatment (PET) of rabies virus (RABV) infection remain a concern. Recombinant monoclonal antibodies have been postulated as suitable alternatives by WHO. To this extent, CL184, the RABV human antibody combination comprising monoclonal antibodies (mAbs) CR57 and CR4098, has been developed and has delivered promising clinical data to support its use for RABV PET. For this fully human IgG1 cocktail, mAbs CR57 and CR4098 are produced in the PER.C6 human cell line and combined in equal amounts in the final product. During preclinical evaluation, CR57 was shown to bind to antigenic site I whereas CR4098 neutralization was influenced by a mutation of position 336 (N336) located within antigenic site III. Here, alanine scanning was used to analyze the influence of mutations within the potential binding site for CR4098, antigenic site III, in order to evaluate the possibility of mutated rabies viruses escaping neutralization. For this approach, twenty flanking amino acids (10 upstream and 10 downstream) of the RABV glycoprotein (G) asparagine (N336) were exchanged to alanine (or serine, if already alanine) by site-directed mutagenesis. Analysis of G expression revealed four of the twenty mutant Gs to be non-functional, as shown by their lack of cell surface expression, which is a requirement for the production of infectious RABV. Therefore, these mutants were excluded from further study. The remaining sixteen mutants were introduced in an infectious clone of RABV, and recombinant RABVs (rRABVs) were recovered and utilized for in vitro neutralization assays. All of the viruses were effectively neutralized by CR4098 as well as by CR57, indicating that single amino acid exchanges in this region does not affect the broad neutralizing capability of the CL184 mAb combination. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Rabies Virus Exposure of Brazilian Free-ranging Wildlife from Municipalities without Clinical Cases in Humans or in Terrestrial Wildlife.

    Science.gov (United States)

    Marcelo Azevedo de Paula Antunes, João; de Castro Demoner, Larissa; Morosini de Andrade Cruvinel, Tatiana; Paula Kataoka, Ana; Fátima Alves Martorelli, Luzia; Puglia Machado, Gustavo; Megid, Jane

    2017-07-01

    Rabies is a zoonosis that causes thousands of animal and human deaths worldwide. Serological studies provide information concerning rabies virus circulation among animals and humans. We evaluated the circulation of the rabies virus in wildlife in nine municipalities of São Paulo State, Brazil. We took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. Sera were tested with the use of the rapid fluorescent focus inhibition test (RFFIT) for the detection of rabies virus-neutralizing antibodies (RVNA). The RFFIT was positive in 100% of the samples, with many (81.48%) showing protective titer levels (>0.5 IU/mL) with other samples (18.52%) showing titers representing exposure (rabies virus in municipalities without a history of human rabies cases, which demonstrated a need for research to understand the role of these animals in the circulation and transmission of the disease.

  6. Antigen detection, rabies virus isolation, and Q-PCR in the quantification of viral load in a natural infection of the North American beaver (Castor canadensis).

    Science.gov (United States)

    Morgan, Shannon M D; Pouliott, Craig E; Rudd, Robert J; Davis, April D

    2015-01-01

    All mammals are believed susceptible to rabies virus infection, yet transmission from nonreservoir hosts to humans is uncommon. However, interactions between nonreservoir hosts and humans occur frequently and risk of exposure increases where rabies is enzootic. We describe rabies and apparent pantropism of rabies virus in a beaver (Castor canadensis).

  7. Lyssaviruses: special emphasis on rabies virus and other members of the lyssavirus genus.

    Science.gov (United States)

    Harkess, Graeme; Fooks, Anthony R

    2011-01-01

    Rabies is routinely diagnosed based on the clinical description and history of exposure in a rabies-endemic country. A negative diagnostic test for rabies virus or a related lyssavirus does not exclude the clinical diagnosis. Diagnostic tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. Often, only a sample from a single time point is investigated reducing the overall sensitivity of any diagnosis. With the advent of molecular biology, tests have been developed that are rapid, robust, and sensitive in support of the rapid detection and strain identification of rabies virus from clinical specimens. These molecular tests complement conventional tests in rabies diagnosis, particularly for human cases, for which an early laboratory diagnosis is critical and may decrease the number of unnecessary contacts with the patient, reduce the requirement for invasive and costly interventions, and enable the appropriate medical treatment regimen to be administered for the patient. The barrier to success is in transferring the technology for the latest techniques in rabies diagnosis to rabies-endemic countries. These barriers are not insurmountable and in liaison with international organisations, especially OIE, FAO, and WHO, these diagnostic tests will be validated for rabies diagnosis and surveillance, and implemented in modern and well-equipped diagnostic laboratories throughout the world.

  8. Safety study of the Bio-10-SAD Bern strain of the rabies virus on the rhesus macaque monkey species

    Directory of Open Access Journals (Sweden)

    Vladimír Vrzal

    2013-01-01

    Full Text Available Based on a WHO recommendation, residual pathogenicity of the Bio-10-SAD Bern rabies virus strain (component of the Lysvulpen por. ad us. vet. vaccine was tested on rhesus macaque monkeys. Each of the ten monkeys, females, two years old, was administered orally 2 ml × 109 TCID50 of the Bio-10-SAD Bern rabies strain. The animals were monitored for 90 days. Subsequently, the animals were sacrificed and their brains were examined for presence of the vaccination rabies virus by the immunofluorescence and PCR methods. The occurrence of anti-rabies antibodies prior to and following administration of the vaccination rabies virus was also evaluated. No clinical signs of rabies were observed nor did any of the animals die of rabies following application of the virus. No rabies was detected in the study animals by post mortem examination. All of the 10 animals developed anti-rabies antibodies during the 90 days following administration of the rabies virus. It can be concluded, that Bio-10-SAD Bern virus administered at a dose equal to the tenfold maximum dose specified for field uses is safe to monkeys of the rhesus macaque species. This study is the first of its type performed in rhesus macaque monkey species.

  9. Comparison of G protein sequences of South African street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.

    Science.gov (United States)

    Seo, Wonhyo; Servat, Alexandre; Cliquet, Florence; Akinbowale, Jenkins; Prehaud, Christophe; Lafon, Monique; Sabeta, Claude

    Rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. In South Africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. In this study, pathogenicity differences of South African canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. Comparison of glycoprotein gene sequences revealed amino acid differences that may underpin the observed pathogenicity differences. Cumulatively, our results suggest that the canid rabies virus may be more neurovirulent in mice than the mongoose rabies variant. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Glycoprotein-G-gene-based molecular and phylogenetic analysis of rabies viruses associated with a large outbreak of bovine rabies in southern Brazil.

    Science.gov (United States)

    Cargnelutti, Juliana F; de Quadros, João M; Martins, Mathias; Batista, Helena B C R; Weiblen, Rudi; Flores, Eduardo F

    2017-12-01

    A large outbreak of hematophagous-bat-associated bovine rabies has been occurring in Rio Grande do Sul (RS), the southernmost Brazilian state, since 2011, with official estimates exceeding 50,000 cattle deaths. The present article describes a genetic characterization of rabies virus (RABV) recovered from 59 affected cattle and two sheep, from 56 herds in 16 municipalities (2012-2016). Molecular analysis was performed using the nucleotide (nt) and predicted amino acid (aa) sequences of RABV glycoprotein G (G). A high level of nt and aa sequence identity was observed among the examined G sequences, ranging from 98.4 to 100%, and from 97.3 to 100%, respectively. Likewise, high levels of nt and aa sequence identity were observed with bovine (nt, 99.8%; aa, 99.8%) and hematophagous bat (nt, 99.5%; aa, 99.4%) RABV sequences from GenBank, and lower levels were observed with carnivore RABV sequences (nt, 92.8%; aa, 88.1%). Some random mutations were observed in the analyzed sequences, and a few consistent mutations were observed in some sequences belonging to cluster 2, subcluster 2b. The clustering of the sequences was observed in a phylogenetic tree, where two distinct clusters were evident. Cluster 1 comprised RABV sequences covering the entire study period (2012 to 2016), but subclusters corresponding to different years could be identified, indicating virus evolution and/or introduction of new viruses into the population. In some cases, viruses from the same location obtained within a short period grouped into different subclusters, suggesting co-circulation of viruses of different origins. Subcluster segregation was also observed in sequences obtained in the same region during different periods, indicating the involvement of different viruses in the cases at different times. In summary, our results indicate that the outbreaks occurring in RS (2012 to 2016) probably involved RABV of different origins, in addition to a possible evolution of RABV isolates within this

  11. 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.

  12. 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.

  13. Virus neutralizing antibody response in mice and dogs with a bicistronic DNA vaccine encoding rabies virus glycoprotein and canine parvovirus VP2.

    Science.gov (United States)

    Patial, Sonika; Chaturvedi, V K; Rai, A; Saini, M; Chandra, Rajesh; Saini, Y; Gupta, Praveen K

    2007-05-16

    A bicistronic DNA vaccine against rabies and parvovirus infection of dogs was developed by subcloning rabies glycoprotein and canine parvovirus (CPV) VP2 genes into a bicistronic vector. After characterizing the expression of both the proteins in vitro, the bicistronic DNA vaccine was injected in mice and induced immune response was compared with monocistronic DNA vaccines. There was no significant difference in ELISA and virus neutralizing (VN) antibody responses against rabies and CPV in mice immunized with either bicistronic or monocistronic DNA vaccine. Further, there was significantly similar protection in mice immunized with either bicistronic or monocistronic rabies DNA vaccine on rabies virus challenge. Similarly, dogs immunized with monocistronic and bicistronic DNA vaccines developed comparable VN antibodies against rabies and CPV. This study indicated that bicistronic DNA vaccine can be used in dogs to induce virus neutralizing immune responses against both rabies and CPV.

  14. JST Thesaurus Headwords and Synonyms: rabies virus [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term rabies virus 名詞 一般 * * * * 狂犬病ウイル...ス キョウケンビョウウイルス キョーケンビョーウイルス Thesaurus2015 200906050189230870 C LS07 UNKNOWN_2 rabies virus

  15. 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

  16. Rabies virus glycoprotein as a carrier for anthrax protective antigen

    International Nuclear Information System (INIS)

    Smith, Mary Ellen; Koser, Martin; Xiao Sa; Siler, Catherine; McGettigan, James P.; Calkins, Catherine; Pomerantz, Roger J.; Dietzschold, Bernhard; Schnell, Matthias J.

    2006-01-01

    Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems

  17. 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.

  18. Two potential recombinant rabies vaccines expressing canine parvovirus virion protein 2 induce immunogenicity to canine parvovirus and rabies virus.

    Science.gov (United States)

    Luo, Jun; Shi, Hehe; Tan, Yeping; Niu, Xuefeng; Long, Teng; Zhao, Jing; Tian, Qin; Wang, Yifei; Chen, Hao; Guo, Xiaofeng

    2016-08-17

    Both rabies virus (RABV) and canine parvovirus (CPV) cause lethal diseases in dogs. In this study, both high egg passage Flury (HEP-Flury) strains of RABV and recombinant RABV carrying double RABV glycoprotein (G) gene were used to express the CPV virion protein 2 (VP2) gene, and were designated rHEP-VP2 and, rHEP-dG-VP2 respectively. The two recombinant RABVs maintained optimal virus titration according to their viral growth kinetics assay compared with the parental strain HEP-Flury. Western blotting indicated that G protein and VP2 were expressed in vitro. The expression of VP2 in Crandell feline kidney cells post-infection by rHEP-VP2 and rHEP-dG-VP2 was confirmed by indirect immunofluorescence assay with antibody against VP2. Immunogenicity of recombinant rabies viruses was tested in Kunming mice. Both rHEP-VP2 and rHEP-dG-VP2 induced high levels of rabies antibody compared with HEP-Flury. Mice immunized with rHEP-VP2 and rHEP-dG-VP2 both had a high level of antibodies against VP2, which can protect against CPV infection. A challenge experiment indicated that more than 80% mice immunized with recombinant RABVs survived after infection of challenge virus standard 24 (CVS-24). Together, this study showed that recombinant RABVs expressing VP2 induced protective immune responses to RABV and CPV. Therefore, rHEP-VP2 and rHEP-dG-VP2 might be potential combined vaccines for RABV and CPV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Directory of Open Access Journals (Sweden)

    Pan Kyeom Kim

    Full Text Available Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC. Two kinds of chimeric human antibodies (chimeric #7 and #17 were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  20. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Science.gov (United States)

    Kim, Pan Kyeom; Keum, Sun Ju; Osinubi, Modupe O V; Franka, Richard; Shin, Ji Young; Park, Sang Tae; Kim, Man Su; Park, Mi Jung; Lee, Soo Young; Carson, William; Greenberg, Lauren; Yu, Pengcheng; Tao, Xiaoyan; Lihua, Wang; Tang, Qing; Liang, Guodong; Shampur, Madhusdana; Rupprecht, Charles E; Chang, Shin Jae

    2017-01-01

    Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  1. [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.

  2. Frequency of Virus Coinfection in Raccoons ( Procyon lotor) and Striped Skunks ( Mephitis mephitis) During a Concurrent Rabies and Canine Distemper Outbreak.

    Science.gov (United States)

    Jardine, Claire M; Buchanan, Tore; Ojkic, Davor; Campbell, G Douglas; Bowman, Jeff

    2018-03-08

    Rabies and canine distemper virus infections in wildlife share similar presenting signs. Canine distemper virus was detected using real-time PCR of conjunctival swabs in rabies positive raccoons (22/32) and skunks (7/34) during a concurrent rabies and canine distemper outbreak in Ontario, Canada in 2015-2016. Coinfections with both viruses should be considered, particularly in distemper endemic areas that are at risk of rabies incursion.

  3. 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.

  4. Antibodies against rabies virus in dogs with and without history of vaccination in Santa Maria - RS - Brazil

    Directory of Open Access Journals (Sweden)

    Karina Gonzalez Fernandes

    2017-10-01

    Full Text Available ABSTRACT: The present study investigated the frequency and magnitude of neutralizing antibodies to rabies virus (RABV in dogs with and without historic of vaccination in Santa Maria/RS. Group A included serum samples from 440 dogs with recent historic of vaccination against rabies, obtained during the 2015 rabies vaccination campaign. Group B included 300 serum samples from dogs submitted to the Veterinary Hospital of the Universidade Federal de Santa Maria in 2015, whose historic of rabies vaccination was unknown. Serum samples were submitted to the rapid fluorescent focus inhibition test (RFFIT to detect neutralizing antibodies against RABV. In group A, 70.6% (310/440 of the samples had neutralizing antibody titers ≥0.5 international units per milliliter (IU mL-1, considered an indicative of protection against rabies by the World Health Organization. However, approximately 30% of the dogs did not contain antibodies in adequate levels. In group B, 42.3% (127/300 of the samples contained neutralizing antibody titers ≥0.5IU mL-1 and 57.7% (173/300 were negative or contained titers below of the value considered immunized. These results demonstrate that an important proportion of vaccinated dogs (~30% did not develop adequate antibody levels, mainly those receiving a single vaccine dose. Serologic testing of animals with unknown historic of vaccination revealed relatively low vaccine coverage in the general dog population. Thus, reformulation of immunization strategies - especially the recommendation of a boost vaccination 30 days after the primary dose - and extension of vaccination campaigns are necessary to reach adequate levels and coverage of immunity against RABV in the canine population.

  5. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Comparison of the ribonucleoproteins of different rabies virus serotypes by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Bruns, M; Dietzschold, B; Schneider, L G; Cox, J H [Federal Research Inst. for Animal Virus Diseases, Tuebingen (Germany, F.R.)

    1977-12-01

    Radioimmunoassay (RIA) provides a sensitive serological procedure for detecting rabies virus ribonucleoprotein (RNP) as well as its specific antibodies. RIA was carried out using highly purified RNPs labelled by the chloramine-T method. This paper describes optimal conditions for iodination of RNP with high specific activity. The optimal concentrations of /sup 125/I, RNP, chloramine-T, and reducing agent as well as the effect of pH on the reaction were investigated. RIA proved to be extremely sensitive for detection of homologous antibodies. In competition experiments the part-relationship of the group-specific RNPs of the three rabies virus serotypes (HEP, MOK, and LBV) was confirmed.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Evolutionary History and Phylogeography of Rabies Viruses Associated with Outbreaks in Trinidad

    Science.gov (United States)

    Seetahal, Janine F. R.; Velasco-Villa, Andres; Allicock, Orchid M.; Adesiyun, Abiodun A.; Bissessar, Joseph; Amour, Kirk; Phillip-Hosein, Annmarie; Marston, Denise A.; McElhinney, Lorraine M.; Shi, Mang; Wharwood, Cheryl-Ann; Fooks, Anthony R.; Carrington, Christine V. F.

    2013-01-01

    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. PMID:23991230

  9. Immunological Detection of Rabies Virus in Brain Tissues of Infected Dogs by Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Nyoman Mantik Astawa

    2010-12-01

    Full Text Available In order to establish an immunological detection of rabies virus in tissues of infected dogs, monoclonalantibodies (mAbs against rabies virus (RV were produced. The mAbs were produced by fusion of mielomacells with the lymphocytes of mice immunized with RV. The mAbs produced were then characterized andused for the detection of rabies virus in brain tissues of infected dogs. Six mAbs designated CC6, EG4,DG10, BB12, CA9 dan EB5 were used in this study. In Western blotting test, some mAbs reacted with 66KDa which is the glycoprotein of the virus. In immunoperoxidase, 2 mAbs (CC6 and DG10 detected RVin the brain of infected dogs. By direct immunoflourescence, flourescence isotyocyanate (FITC labelledDG10 mAbs detected RV in fresh and formaldehyde fixed brain tissues. RV was detected in 12 infecteddogs but not in normal uninfected dogs. In this study it was confirmed that rabies virus can be detected inthe brain tissues of infected dogs by monoclonal antibodies.

  10. 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

    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...... of RABV in different arctic fox lineages. These data are invaluable to support future initiatives for arctic fox rabies control and elimination in Greenland....

  11. [Phylogenetic analysis of rabies viruses isolated from animals in Tokyo in the 1950s].

    Science.gov (United States)

    Hatakeyama, Kaoru; Sadamasu, Kenji; Kai, Akemi

    2011-05-01

    Molecular epidemiological analysis of 96 rabies viruses isolated from animals in Tokyo in the 1950s involves Japanese fixed virus, Komatsugawa, Takamen, and Nishigahara strains. Strains isolated in Tokyo were divided into Tokyo 1 and Tokyo 2, and grouped into a worldwide distribution cluster differing from Takamen and Nishigahara. Tokyo 1 was grouped into the same cluster as viruses isolated from United States west coast dogs in the 1930s and 1940s. Tokyo 2 was grouped into the same cluster as the Komatsugawa strain, also known as a cluster of viruses from the Khabarovsk raccoon dog, and the Lake Baikal stepped fox in Russia. These findings suggest that 1950s Tokyo rabies viruses were related to those in Russia and the USA.

  12. Rabies postexposure prophylaxis. Human and domestic animal considerations.

    Science.gov (United States)

    Fearneyhough, M G

    2001-05-01

    The emphasis on rabies control and prevention in the United States seems to be a function of our perception of proximity of the threat. Wildlife rabies epizootics within a state may be of little concern to the uninformed urban dweller. Additionally, many parts of the western United States are free of terrestrial rabies; were it not for the presence of bat rabies, people in those areas would likely interpret rabies control as a minor public health concern. It is essential that federal, state, and local public health programs emphasize the importance of rabies control through activities that include rabies education, sponsorship of legislated requirements for domestic animal vaccination, support for local animal control programs, and the promotion of recommendations that encourage the appropriate use of PEP. We are almost guaranteed that rabies is going to remain a major public health issue well into the next century because of expanding wildlife rabies epizootics, identification of new rabies viral variants with increased public health concern, emotional and legal concerns associated with rabies exposure, and increasing national cost associated with rabies control and prevention. Nevertheless, the development of new laboratory technology that allows an understanding of the epidemiologic nature of the rabies virus based on an evolving genetic history and the interrelationship with wildlife reservoirs should allow access to valuable tools for rabies control. When combined with programs using new developments in oral rabies vaccine that can immunize whole populations of wildlife reservoirs, that technology offers encouragement in our effort to control one of the diseases of antiquity.

  13. New introduction and spread of rabies among dog population in Bangui.

    Science.gov (United States)

    Nakouné, E; Digol, M; Konamna, X; Selekon, B; Le Faou, A

    2012-08-01

    Rabies is endemic in the Central African Republic (CAR) and a neglected enzootic disease which represents a serious public health problem. Before April 2009, rabies was not a notifiable disease in CAR. Vaccination of animals is expensive and not commonly done. In 2005, none rabies case was recorded in Bangui. To understand how rabies was introduced and propagated in the city of Bangui from 2006 to 2008, we analyzed samplings of dog brain as well as reviewed the records of dog owners. A total of 86 out of 101 samples (84.8%) tested positive for rabies virus during this period. Previous phylogenetic analysis of some strains circulating in Bangui between 2006 and 2008 indicated that virus of cosmopolitan and Africa 2 clade are found. Given the time frame and location of these samples, one possible explanation for this alarming result may be that two different strains of rabies virus were introduced at different times in Bangui. Stray dogs are solely responsible for the spread of the epidemic. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. A Novel Expression Cassette of Lyssavirus Shows that the Distantly Related Mokola Virus Can Rescue a Defective Rabies Virus Genome

    Science.gov (United States)

    Le Mercier, Philippe; Jacob, Yves; Tanner, Kyle; Tordo, Noël

    2002-01-01

    By comparing three expression vectors for the rabies virus (Rv) minigenome, we show that the characteristic of the Rv RNA is important for efficient rescue despite its not being crucial for replication. Moreover, we show that the coexpression of the viral proteins from helper Rv and Mokola virus could rescue the Rv minigenome while Rv-related European bat lyssavirus 1 could not, suggesting that the signals controlling transcription and replication are conserved in the distantly related Rv and Mokola virus. PMID:11799201

  15. The phylogeography and spatiotemporal spread of south-central skunk rabies virus.

    Directory of Open Access Journals (Sweden)

    Natalia A Kuzmina

    Full Text Available The south-central skunk rabies virus (SCSK is the most broadly distributed terrestrial viral lineage in North America. Skunk rabies has not been efficiently targeted by oral vaccination campaigns and represents a natural system of pathogen invasion, yielding insights to rabies emergence. In the present study we reconstructed spatiotemporal spread of SCSK in the whole territory of its circulation using a combination of Bayesian methods. The analysis based on 241 glycoprotein gene sequences demonstrated that SCSK is much more divergent phylogenetically than was appreciated previously. According to our analyses the SCSK originated in the territory of Texas ~170 years ago, and spread geographically during the following decades. The wavefront velocity in the northward direction was significantly greater than in the eastward and westward directions. Rivers (except the Mississippi River and Rio Grande River did not constitute significant barriers for epizootic spread, in contrast to deserts and mountains. The mean dispersal rate of skunk rabies was lower than that of the raccoon and fox rabies. Viral lineages circulate in their areas with limited evidence of geographic spread during decades. However, spatiotemporal reconstruction shows that after a long period of stability the dispersal rate and wavefront velocity of SCSK are increasing. Our results indicate that there is a need to develop control measures for SCSK, and suggest how such measure can be implemented most efficiently. Our approach can be extrapolated to other rabies reservoirs and used as a tool for investigation of epizootic patterns and planning interventions towards disease elimination.

  16. 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.

  17. Rabies Virus in Bats, State of Pará, Brazil, 2005-2011.

    Science.gov (United States)

    Pereira, Armando de Souza; Casseb, Livia Medeiros Neves; Barbosa, Taciana Fernandes Souza; Begot, Alberto Lopes; Brito, Roberto Messias Oliveira; Vasconcelos, Pedro Fernando da Costa; Travassos da Rosa, Elizabeth Salbé

    2017-08-01

    Rabies is an acute, progressive zoonotic viral infection that in general produces a fatal outcome. This disease is responsible for deaths in humans and animals worldwide and, because it can affect all mammals, is considered one of the most important viral infections for public health. This study aimed to determine the prevalence of rabies in bats of different species found in municipalities of the state of Pará from 2005 to 2011. The rabies virus was detected in 12 (0.39%) bats in a total of 3100 analyzed, including hematophagous, frugivorous, and insectivorous bats. Of these, eleven were characterized as AgV3, which is characteristic of the hematophagous bat Desmodus rotundus (E. Geoffroy 1810); one insectivorous animal showed a different profile compatible with the Eptesicus pattern and may therefore be a new antigenic variant. This study identified the need for greater intensification of epidemiological surveillance in municipalities lacking rabies surveillance (silent areas); studies of rabies virus in bats with different alimentary habits, studies investigating the prevalence of AgV3, and prophylactic measures in areas where humans may be infected are also needed.

  18. Proteomics analysis of BHK-21 cells infected with a fixed strain of rabies virus.

    Science.gov (United States)

    Zandi, Fatemeh; Eslami, Naser; Soheili, Masoomeh; Fayaz, Ahmad; Gholami, Alireza; Vaziri, Behrouz

    2009-05-01

    Rabies is a neurotropic virus that causes a life threatening acute viral encephalitis. The complex relationship of rabies virus (RV) with the host leads to its replication and spreading toward the neural network, where viral pathogenic effects appeared as neuronal dysfunction. In order to better understand the molecular basis of this relationship, a proteomics study on baby hamster kidney cells infected with challenge virus standard strain of RV was performed. This cell line is an in vitro model for rabies infection and is commonly used for viral seed preparation. The direct effect of the virus on cellular protein machinery was investigated by 2-DE proteome mapping of infected versus control cells followed by LC-MS/MS identification. This analysis revealed significant changes in expression of 14 proteins, seven of these proteins were viral and the remaining were host proteins with different known functions: cytoskeletal (capping protein, vimentin), anti-oxidative stress (superoxide dismutase), regulatory (Stathmin), and protein synthesis (P0). Despite of limited changes appeared upon rabies infection, they present a set of interesting biochemical pathways for further investigation on viral-host interaction.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. In vitro and in vivo inhibition of rabies virus replication by RNA interference.

    Science.gov (United States)

    Durymanova Ono, Ekaterina A; Iamamoto, Keila; Castilho, Juliana G; Carnieli, Pedro; de Novaes Oliveira, Rafael; Achkar, Samira M; Carrieri, Maria L; Kotait, Ivanete; Brandão, Paulo E

    2013-01-01

    Rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (RABV) (Mononegavirales: Rhabdoviridae: Lyssavirus). Currently, human rabies treatment is based on the Milwaukee Protocol which consists on the induction of coma and massive antiviral therapy. The aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering RNAs. To this end, three siRNAs were used with antisense strands complementary to rabies virus nucleoprotein (N) mRNA. BHK-21 cells monolayers were infected with 1000 to 0.1 TCID50 of PV and after 2 hours the cells were transfected with each of tree RNAs in separate using Lipofectamine-2000. All three siRNAs reduced the titer of PV strain in a least 0.72 logTCID50/mL and no cytotoxic effect was observed in the monolayers treated with Lipofectamine-2000. Swiss albino mice infected with 10.000 to 1 LD of PV strain by the intracerebral route were also transfected after two hours of infection with a pool 3 siRNAs with Lipofectamine-2000 by the intracerebral route, resulting in a survival rate of 30% in mice inoculated with 100 LD50, while the same dose led to 100% mortality in untreated animals. Lipofectamine-2000 showed no toxic effect in control mice. These results suggest that intracerebral administration of siRNAs might be an effective antiviral strategy for rabies.

  1. In vitro and in vivo inhibition of rabies virus replication by RNA interference

    Directory of Open Access Journals (Sweden)

    Ekaterina A. Durymanova Ono

    2013-09-01

    Full Text Available Rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (RABV (Mononegavirales: Rhabdoviridae: Lyssavirus. Currently, human rabies treatment is based on the Milwaukee Protocol which consists on the induction of coma and massive antiviral therapy. The aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering RNAs. To this end, three siRNAs were used with antisense strands complementary to rabies virus nucleoprotein (N mRNA. BHK-21 cells monolayers were infected with 1000 to 0.1 TCID50 of PV and after 2 hours the cells were transfected with each of tree RNAs in separate using Lipofectamine-2000. All three siRNAs reduced the titer of PV strain in a least 0.72 logTCID50/mL and no cytotoxic effect was observed in the monolayers treated with Lipofectamine-2000. Swiss albino mice infected with 10.000 to 1 LD of PV strain by the intracerebral route were also transfected after two hours of infection with a pool 3 siRNAs with Lipofectamine-2000 by the intracerebral route, resulting in a survival rate of 30% in mice inoculated with 100 LD50, while the same dose led to 100% mortality in untreated animals. Lipofectamine-2000 showed no toxic effect in control mice. These results suggest that intracerebral administration of siRNAs might be an effective antiviral strategy for rabies.

  2. Survey of rabies virus antibodies in confined, hunting and roaming ...

    African Journals Online (AJOL)

    In view of the recent upsurge in adoption of exotic and local dogs as pets in Nigeria associated with increased contact between the dogs and their owners, and the traditional close relationship between hunters and their dogs, there is a need for studies to determine the level of protection of these dogs against rabies. In this ...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Short interfering RNAs targeting a vampire-bat related rabies virus phosphoprotein mRNA.

    Science.gov (United States)

    Ono, Ekaterina Alexandrovna Durymanova; Taniwaki, Sueli Akemi; Brandão, Paulo

    The aim of this study was to assess the in vitro and in vivo effects of short-interfering RNAs (siRNAs) against rabies virus phosphoprotein (P) mRNA in a post-infection treatment for rabies as an extension of a previous report (Braz J Microbiol. 2013 Nov 15;44(3):879-82). To this end, rabies virus strain RABV-4005 (related to the Desmodus rotundus vampire bat) were used to inoculate BHK-21 cells and mice, and the transfection with each of the siRNAs was made with Lipofectamine-2000™. In vitro results showed that siRNA 360 was able to inhibit the replication of strain RABV-4005 with a 1log decrease in virus titter and 5.16-fold reduction in P mRNA, 24h post-inoculation when compared to non-treated cells. In vivo, siRNA 360 was able to induce partial protection, but with no significant difference when compared to non-treated mice. These results indicate that, despite the need for improvement for in vivo applications, P mRNA might be a target for an RNAi-based treatment for rabies. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  5. A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice

    International Nuclear Information System (INIS)

    Li Jianwei; Faber, Milosz; Papaneri, Amy; Faber, Marie-Luise; McGettigan, James P.; Schnell, Matthias J.; Dietzschold, Bernhard

    2006-01-01

    Rabies vaccines based on live attenuated rabies viruses or recombinant pox viruses expressing the rabies virus (RV) glycoprotein (G) hold the greatest promise of safety and efficacy, particularly for oral immunization of wildlife. However, while these vaccines induce protective immunity in foxes, they are less effective in other animals, and safety concerns have been raised for some of these vaccines. Because canine adenovirus 2 (CAV2) is licensed for use as a live vaccine for dogs and has an excellent efficacy and safety record, we used this virus as an expression vector for the RVG. The recombinant CAV2-RV G produces virus titers similar to those produced by wild-type CAV2, indicating that the RVG gene does not affect virus replication. Comparison of RVG expressed by CAV2-RV G with that of vaccinia-RV G recombinant virus (V-RG) revealed similar amounts of RV G on the cell surface. A single intramuscular or intranasal immunization of mice with CAV2-RVG induced protective immunity in a dose-dependent manner, with no clinical signs or discomfort from the virus infection regardless of the route of administration or the amount of virus

  6. Evidence of two distinct phylogenetic lineages of dog rabies virus circulating in Cambodia.

    Science.gov (United States)

    Mey, Channa; Metlin, Artem; Duong, Veasna; Ong, Sivuth; In, Sotheary; Horwood, Paul F; Reynes, Jean-Marc; Bourhy, Hervé; Tarantola, Arnaud; Buchy, Philippe

    2016-03-01

    This first extensive retrospective study of the molecular epidemiology of dog rabies in Cambodia included 149 rabies virus (RABV) entire nucleoprotein sequences obtained from 1998-2011. The sequences were analyzed in conjunction with RABVs from other Asian countries. Phylogenetic reconstruction confirmed the South-East Asian phylogenetic clade comprising viruses from Cambodia, Vietnam, Thailand, Laos and Myanmar. The present study represents the first attempt to classify the phylogenetic lineages inside this clade, resulting in the confirmation that all the Cambodian viruses belonged to the South-East Asian (SEA) clade. Three distinct phylogenetic lineages in the region were established with the majority of viruses from Cambodia closely related to viruses from Thailand, Laos and Vietnam, forming the geographically widespread phylogenetic lineage SEA1. A South-East Asian lineage SEA2 comprised two viruses from Cambodia was identified, which shared a common ancestor with RABVs originating from Laos. Viruses from Myanmar formed separate phylogenetic lineages within the major SEA clade. Bayesian molecular clock analysis suggested that the time to most recent common ancestor (TMRCA) of all Cambodian RABVs dated to around 1950. The TMRCA of the Cambodian SEA1 lineage was around 1964 and that of the SEA2 lineage was around 1953. The results identified three phylogenetically distinct and geographically separated lineages inside the earlier identified major SEA clade, covering at least five countries in the region. A greater understanding of the molecular epidemiology of rabies in South-East Asia is an important step to monitor progress on the efforts to control canine rabies in the region. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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

  8. Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus.

    Science.gov (United States)

    Lakshmanan, Nallakannu; Gore, Thomas C; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

    2006-01-01

    Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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 (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-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 RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    Wanda Markotter

    2015-05-01

    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.

  12. Rabies virus in a pregnant naturally infected southern yellow bat (Lasiurus ega

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    SD Allendorf

    2011-01-01

    Full Text Available Current knowledge on bat lyssavirus infections in their native hosts is limited and little is known about the virulence, virus dissemination and transmission among free-living insectivorous bats. The present study is a brief description of rabies virus (RABV dissemination in tissues of a naturally infected pregnant southern yellow bat (Lasiurus ega and its fetuses, obtained by reverse-transcriptase polymerase chain reaction (RT-PCR. The RT-PCR was positive in samples from the brain, salivary gland, tongue, lungs, heart, kidneys and liver. On the other hand, the placenta, three fetuses, spleen, intestine and brown fat tissue tested negative. This research demonstrated the absence of rabies virus in the fetuses, thus, in this specific case, the transplacentary transmission was not observed.

  13. Characterization of Sri Lanka rabies virus isolates using nucleotide sequence analysis of nucleoprotein gene.

    Science.gov (United States)

    Arai, Y T; Takahashi, H; Kameoka, Y; Shiino, T; Wimalaratne, O; Lodmell, D L

    2001-01-01

    Thirty-four suspected rabid brain samples from 2 humans, 24 dogs, 4 cats, 2 mongooses, I jackal and I water buffalo were collected in 1995-1996 in Sri Lanka. Total RNA was extracted directly from brain suspensions and examined using a one-step reverse transcription-polymerase chain reaction (RT-PCR) for the rabies virus nucleoprotein (N) gene. Twenty-eight samples were found positive for the virus N gene by RT-PCR and also for the virus antigens by fluorescent antibody (FA) test. Rabies virus isolates obtained from different animal species in different regions of Sri Lanka were genetically homogenous. Sequences of 203 nucleotides (nt)-long RT-PCR products obtained from 16 of 27 samples were found identical. Sequences of 1350 nt of N genes of 14 RT-PCR products were determined. The Sri Lanka isolates under study formed a specific cluster that included also an earlier isolate from India but did not include the known isolates from China, Thailand, Malaysia, Israel, Iran, Oman, Saudi Arabia, Russia, Nepal, Philippines, Japan and from several other countries. These results suggest that one type of rabies virus is circulating among human, dog, cat, mongoose, jackal and water buffalo living near Colombo City and in other five remote regions in Sri Lanka.

  14. Fusion Peptide Improves Stability and Bioactivity of Single Chain Antibody against Rabies Virus.

    Science.gov (United States)

    Xi, Hualong; Zhang, Kaixin; Yin, Yanchun; Gu, Tiejun; Sun, Qing; Shi, Linqing; Zhang, Renxia; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2017-04-28

    The combination of rabies immunoglobulin (RIG) with a vaccine is currently effective against rabies infections, but improvements are needed. Genetic engineering antibody technology is an attractive approach for developing novel antibodies to replace RIG. In our previous study, a single-chain variable fragment, scFv57R, against rabies virus glycoprotein was constructed. However, its inherent weak stability and short half-life compared with the parent RIG may limit its diagnostic and therapeutic application. Therefore, an acidic tail of synuclein (ATS) derived from the C-terminal acidic tail of human alpha-synuclein protein was fused to the C-terminus of scFv57R in order to help it resist adverse stress and improve the stability and halflife. The tail showed no apparent effect on the preparation procedure and affinity of the protein, nor did it change the neutralizing potency in vitro. In the ELISA test of molecular stability, the ATS fusion form of the protein, scFv57R-ATS, showed an increase in thermal stability and longer half-life in serum than scFv57R. The protection against fatal rabies virus challenge improved after fusing the tail to the scFv, which may be attributed to the improved stability. Thus, the ATS fusion approach presented here is easily implemented and can be used as a new strategy to improve the stability and half-life of engineered antibody proteins for practical applications.

  15. Whole genome sequence phylogenetic analysis of four Mexican rabies viruses isolated from cattle.

    Science.gov (United States)

    Bárcenas-Reyes, I; Loza-Rubio, E; Cantó-Alarcón, G J; Luna-Cozar, J; Enríquez-Vázquez, A; Barrón-Rodríguez, R J; Milián-Suazo, F

    2017-08-01

    Phylogenetic analysis of the rabies virus in molecular epidemiology has been traditionally performed on partial sequences of the genome, such as the N, G, and P genes; however, that approach raises concerns about the discriminatory power compared to whole genome sequencing. In this study we characterized four strains of the rabies virus isolated from cattle in Querétaro, Mexico by comparing the whole genome sequence to that of strains from the American, European and Asian continents. Four cattle brain samples positive to rabies and characterized as AgV11, genotype 1, were used in the study. A cDNA sequence was generated by reverse transcription PCR (RT-PCR) using oligo dT. cDNA samples were sequenced in an Illumina NextSeq 500 platform. The phylogenetic analysis was performed with MEGA 6.0. Minimum evolution phylogenetic trees were constructed with the Neighbor-Joining method and bootstrapped with 1000 replicates. Three large and seven small clusters were formed with the 26 sequences used. The largest cluster grouped strains from different species in South America: Brazil, and the French Guyana. The second cluster grouped five strains from Mexico. A Mexican strain reported in a different study was highly related to our four strains, suggesting common source of infection. The phylogenetic analysis shows that the type of host is different for the different regions in the American Continent; rabies is more related to bats. It was concluded that the rabies virus in central Mexico is genetically stable and that it is transmitted by the vampire bat Desmodus rotundus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Molecular characterization and phylogenetic relatedness of dog-derived Rabies Viruses circulating in Cameroon between 2010 and 2016.

    Directory of Open Access Journals (Sweden)

    Serge Alain Sadeuh-Mba

    2017-10-01

    Full Text Available Rabies is enzootic among dog populations in some parts of Cameroon and the risk of human rabies is thought to be steadily high in these regions. However, the molecular epidemiology of circulating Rabies Virus (RABV has been hardly considered in Cameroon as well as in most neighboring central African countries. To address this fundamental gap, 76 nucleoprotein (N gene sequences of dog-derived RABV were obtained from 100 brain specimens sampled in Cameroon from 2010 to 2016. Studied sequences were subjected to molecular and phylogenetic analyses with reference strains retrieved from databases. The 71 studied Africa-1 isolates displayed 93.5-100% nucleotide (nt and 98.3-100% amino-acid (aa identities to each other while, the 5 studied Africa-2 isolates shared 99.4-99.7% sequence similarities at nt and aa levels. Maximum Likelihood based phylogenies inferred from nucleotide sequences confirmed all studied RABV isolates as members of the dog-related species 1 of the Lyssavirus genus. Individual isolates could be unambiguously assigned as either the Africa-1 subclade of the Cosmopolitan clade or the Africa 2 clade. The Africa-1 subclade appeared to be more prevalent and diversified. Indeed, 70 studied isolates segregated into 3 distinct circulating variants within Africa-1a lineage while a unique isolate was strikingly related to the Africa-1b lineage known to be prevalent in the neighboring Central African Republic and eastern Africa. Interestingly, all five Africa-2 isolates fell into the group-E lineage even though they appeared to be loosely related to databases available reference RABV; including those previously documented in Cameroon. This study uncovered the co-circulation of several Africa-1 and Africa-2 lineages in the southern regions of Cameroon. Striking phylogenetic outcasts to the geographic differentiation of RABV variants indicated that importation from close regions or neighboring countries apparently contributes to the sustainment

  17. Molecular characterization and phylogenetic relatedness of dog-derived Rabies Viruses circulating in Cameroon between 2010 and 2016.

    Science.gov (United States)

    Sadeuh-Mba, Serge Alain; Momo, Jean Blaise; Besong, Laura; Loul, Sévérin; Njouom, Richard

    2017-10-01

    Rabies is enzootic among dog populations in some parts of Cameroon and the risk of human rabies is thought to be steadily high in these regions. However, the molecular epidemiology of circulating Rabies Virus (RABV) has been hardly considered in Cameroon as well as in most neighboring central African countries. To address this fundamental gap, 76 nucleoprotein (N) gene sequences of dog-derived RABV were obtained from 100 brain specimens sampled in Cameroon from 2010 to 2016. Studied sequences were subjected to molecular and phylogenetic analyses with reference strains retrieved from databases. The 71 studied Africa-1 isolates displayed 93.5-100% nucleotide (nt) and 98.3-100% amino-acid (aa) identities to each other while, the 5 studied Africa-2 isolates shared 99.4-99.7% sequence similarities at nt and aa levels. Maximum Likelihood based phylogenies inferred from nucleotide sequences confirmed all studied RABV isolates as members of the dog-related species 1 of the Lyssavirus genus. Individual isolates could be unambiguously assigned as either the Africa-1 subclade of the Cosmopolitan clade or the Africa 2 clade. The Africa-1 subclade appeared to be more prevalent and diversified. Indeed, 70 studied isolates segregated into 3 distinct circulating variants within Africa-1a lineage while a unique isolate was strikingly related to the Africa-1b lineage known to be prevalent in the neighboring Central African Republic and eastern Africa. Interestingly, all five Africa-2 isolates fell into the group-E lineage even though they appeared to be loosely related to databases available reference RABV; including those previously documented in Cameroon. This study uncovered the co-circulation of several Africa-1 and Africa-2 lineages in the southern regions of Cameroon. Striking phylogenetic outcasts to the geographic differentiation of RABV variants indicated that importation from close regions or neighboring countries apparently contributes to the sustainment of the enzootic

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

    Directory of Open Access Journals (Sweden)

    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

  19. Phylogenetic analysis of partial RNA-polymerase blocks II and III of Rabies virus isolated from the main rabies reservoirs in Brazil.

    Science.gov (United States)

    Carnieli, Pedro; de Novaes Oliveira, Rafael; de Oliveira Fahl, Willian; de Carvalho Ruthner Batista, Helena Beatriz; Scheffer, Karin Corrêa; Iamamoto, Keila; Castilho, Juliana Galera

    2012-08-01

    This study describes the results of the sequencing and analysis of segments of Blocks II and III of the RNA polymerase L gene of Rabies virus isolates from different reservoir species of Brazil. The phylogenetic relations of the virus were determined and a variety of species-specific nucleotides were found in the analyzed areas, but the majority of these mutations were found to be synonymous. However, an analysis of the putative amino acid sequences were shown to have some characteristic mutations between some reservoir species of Brazil, indicating that there was positive selection in the RNA polymerase L gene of Rabies virus. On comparing the putative viral sequences obtained from the Brazilian isolates and other Lyssavirus, it was determined that amino acid mutations occurred in low-restriction areas. This study of the L gene of Rabies virus is the first to be conducted with samples of virus isolates from Brazil, and the results obtained will help in the determination of the phylogenetic relations of the virus.

  20. Achieving population-level immunity to rabies in free-roaming dogs in Africa and Asia.

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    Michelle K Morters

    Full Text Available Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors. This may reduce the proportion of dogs that seroconvert to the vaccine during vaccination campaigns and the duration of immunity of those dogs that seroconvert. Vaccination coverage may also be limited through insufficient vaccine delivery during vaccination campaigns and the loss of vaccinated individuals from populations through demographic processes. This is the first longitudinal study to evaluate temporal variations in rabies vaccine-induced serological responses, and factors associated with these variations, at the individual level in previously unvaccinated free-roaming dog populations. Individual-level serological and health-based data were collected from three cohorts of dogs in regions where rabies is endemic, one in South Africa and two in Indonesia. We found that the vast majority of dogs seroconverted to the vaccine; however, there was considerable variation in titres, partly attributable to illness and lactation at the time of vaccination. Furthermore, >70% of the dogs were vaccinated through community engagement and door-to-door vaccine delivery, even in Indonesia where the majority of the dogs needed to be caught by net on successive occasions for repeat blood sampling and vaccination. This demonstrates the feasibility of achieving population-level immunity in free-roaming dog populations in rabies-endemic regions. However, attrition of immune individuals through demographic processes and waning immunity necessitates repeat vaccination of populations within at least

  1. The effect of interferon on the receptor sites to rabies virus on mouse neuroblastoma cells

    International Nuclear Information System (INIS)

    Briggs, D.J.

    1989-01-01

    The binding of rabies virus to mouse neuroblastoma cells (MNA) primed with alpha interferon (IFN-α), beta interferon (IFN-β), or alpha bungarotoxin (BTX) was examined. A saturable number of receptor sites to rabies virus was calculated by increasing the amount of 3 H-CVS added to a constant number of untreated MNA cells. MNA cells were then exposed to 20 I.U. of IFN-α, IFN-β, or 1 μg of BTX and assayed to determine if these treatments had an effect on the number of receptor sites to rabies virus. Total amount of 3 H-CVS bound to MNA cells was determined during a three hour incubation period. Cold competition assays using 1,000 fold excess unlabeled CVS were used to determine non-specific binding for each treatment. Specific binding was then calculated by subtracting non-specific binding from the total amount of CVS bound to MNA cells. A similar amount of total viral protein bound to untreated and IFN-β, and BTX treated cells after 180 minutes of incubation. The bound protein varied by only 0.07 μg. However, the amount of specific and non-specific binding varied a great deal between treatments. BTX caused an increase in non-specific and a decrease in specific binding of rabies virus. IFN-β produced variable results in non-specific and specific binding while IFN-α caused mainly specific binding to occur. The most significant change brought about by IFN-α was an increase in the rate of viral attachment. At 30 minutes post-infection, IFN-α treated cells had bound 90% of the total amount of virus bound to untreated cells after 180 minutes. The increased binding rate did not cause a productive infection of rabies virus. No viral production was evident after an incubation period of 48 hours in either IFN-α or IFN-β treated cells

  2. 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.

  3. 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.

  4. Molecular characterization of atypical antigenic variants of canine rabies virus reveals its reintroduction by wildlife vectors in southeastern Mexico.

    Science.gov (United States)

    Garcés-Ayala, Fabiola; Aréchiga-Ceballos, Nidia; Ortiz-Alcántara, Joanna M; González-Durán, Elizabeth; Pérez-Agüeros, Sandra I; Méndez-Tenorio, Alfonso; Torres-Longoria, Belem; López-Martínez, Irma; Hernández-Rivas, Lucía; Díaz-Quiñonez, José Alberto; Ramírez-González, José Ernesto

    2017-12-01

    Rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. In Mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. Here we report on the molecular characterization of six rabies virus strains found in Yucatan and Chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a reduced panel of eight monoclonal antibodies was performed. Phylogenetic analyses on the RNA sequences unveiled that the three atypical strains from Yucatan are associated with skunks. Analysis using the virus entire genome showed that they belong to a different lineage distinct from the variants described for this animal species in Mexico. The Chiapas atypical strain was grouped in a lineage that was considered extinct, while the others are clustered within classic dog variants.

  5. Rabies virus infection in Eptesicus fuscus bats born in captivity (naïve 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.

  6. 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.

  7. Costs analysis of a population level rabies control programme in Tamil Nadu, India.

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    Syed Shahid Abbas

    2014-02-01

    Full Text Available The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu's efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was $0.7 million (Rs 36 million and $2.2 million (Rs 119 million, respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be $ 44 million (Rs 2,350 million, $23 million (Rs 1,230 million and $ 11 million (Rs 590 million, respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme.

  8. Costs analysis of a population level rabies control programme in Tamil Nadu, India.

    Science.gov (United States)

    Abbas, Syed Shahid; Kakkar, Manish; Rogawski, Elizabeth Tacket

    2014-02-01

    The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu's efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was $0.7 million (Rs 36 million) and $2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be $ 44 million (Rs 2,350 million), $23 million (Rs 1,230 million) and $ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme.

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

    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......), the Veterinary Laboratories Agency (VLA; United Kingdom), and the DTU National Veterinary Institute (Lindholm, Denmark), covering the global diversity of rabies virus lineages, it was shown that both the newly developed assay and a previously described one had some detection failures. This was overcome...

  11. Biological and immunogenic properties of rabies virus glycoprotein expressed by canine herpesvirus vector.

    Science.gov (United States)

    Xuan, X; Tuchiya, K; Sato, I; Nishikawa, Y; Onoderaz, Y; Takashima, Y; Yamamoto, A; Katsumata, A; Iwata, A; Ueda, S; Mikami, T; Otsuka, H

    1998-01-01

    In order to evaluate whether canine herpesvirus (CHV) could be used as a live vector for the expression of heterologous immunogenes, we constructed a recombinant canine herpesvirus (CHV) expressing glycoprotein (G protein) of rabies virus (RV). The gene of G protein was inserted within the thymidine kinase gene of CHV YP11mu strain under the control of the human cytomegalovirus immediate early promoter. The G protein expressed by the recombinant CHV was processed and transported to the cell surface as in RV infected cells, and showed the same biological activities such as low pH dependent cell fusion and hemadsorption. The antigenic authenticity of the recombinant G protein was confirmed by a panel of monoclonal antibodies specific for G protein. Dogs inoculated intransally with the recombinant CHV produced higher titres of virus neutralizing antibodies against RV than those inoculated with a commercial, inactivated rabies vaccine. These results suggest that the CHV recombinant expressing G protein can be used as a vaccine to control canine rabies and that CHV may be useful as a vector to develop live recombinant against other infectious diseases in dogs.

  12. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in Arizona during 2001-2009.

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    Ivan V Kuzmin

    Full Text Available In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001-2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T₂₄₂ in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our

  14. Desmodus rotundus and Artibeus spp. bats might present distinct rabies virus lineages

    Directory of Open Access Journals (Sweden)

    Willian Oliveira Fahl

    Full Text Available In Brazil, bats have been assigned an increasing importance in public health as they are important rabies reservoirs. Phylogenetic studies have shown that rabies virus (RABV strains from frugivorous bats Artibeus spp. are closely associated to those from the vampire bat Desmodus rotundus, but little is known about the molecular diversity of RABV in Artibeus spp. The N and G genes of RABV isolated from Artibeus spp. and cattle infected by D. rotundus were sequenced, and phylogenetic trees were constructed. The N gene nucleotides tree showed three clusters: one for D. rotundus and two for Artibeus spp. Regarding putative N amino acid-trees, two clusters were formed, one for D. rotundus and another for Artibeus spp. RABV G gene phylogeny supported the distinction between D. rotundus and Artibeus spp. strains. These results show the intricate host relationship of RABV's evolutionary history, and are invaluable for the determination of RABV infection sources.

  15. Desmodus rotundus and Artibeus spp. bats might present distinct rabies virus lineages

    Directory of Open Access Journals (Sweden)

    Willian Oliveira Fahl

    2012-12-01

    Full Text Available In Brazil, bats have been assigned an increasing importance in public health as they are important rabies reservoirs. Phylogenetic studies have shown that rabies virus (RABV strains from frugivorous bats Artibeus spp. are closely associated to those from the vampire bat Desmodus rotundus, but little is known about the molecular diversity of RABV in Artibeus spp. The N and G genes of RABV isolated from Artibeus spp. and cattle infected by D. rotundus were sequenced, and phylogenetic trees were constructed. The N gene nucleotides tree showed three clusters: one for D. rotundus and two for Artibeus spp. Regarding putative N amino acid-trees, two clusters were formed, one for D. rotundus and another for Artibeus spp. RABV G gene phylogeny supported the distinction between D. rotundus and Artibeus spp. strains. These results show the intricate host relationship of RABV's evolutionary history, and are invaluable for the determination of RABV infection sources.

  16. Desmodus rotundus and Artibeus spp. bats might present distinct rabies virus lineages.

    Science.gov (United States)

    Fahl, Willian Oliveira; Carnieli, Pedro; Castilho, Juliana Galera; Carrieri, Maria Luiza; Kotait, Ivanete; Iamamoto, Keila; Oliveira, Rafael Novaes; Brandão, Paulo Eduardo

    2012-01-01

    In Brazil, bats have been assigned an increasing importance in public health as they are important rabies reservoirs. Phylogenetic studies have shown that rabies virus (RABV) strains from frugivorous bats Artibeus spp. are closely associated to those from the vampire bat Desmodus rotundus, but little is known about the molecular diversity of RABV in Artibeus spp. The N and G genes of RABV isolated from Artibeus spp. and cattle infected by D. rotundus were sequenced, and phylogenetic trees were constructed. The N gene nucleotides tree showed three clusters: one for D. rotundus and two for Artibeus spp. Regarding putative N amino acid-trees, two clusters were formed, one for D. rotundus and another for Artibeus spp. RABV G gene phylogeny supported the distinction between D. rotundus and Artibeus spp. strains. These results show the intricate host relationship of RABV's evolutionary history, and are invaluable for the determination of RABV infection sources. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

  17. 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.

  18. Detection of rabies virus nucleoprotein-RNA in several organs outside the Central Nervous System in naturally-infected vampire bats

    Directory of Open Access Journals (Sweden)

    Luiz F. P Vieira

    2011-10-01

    Full Text Available Rabies is a neurological disease, but the rabies virus spread to several organs outside the central nervous system (CNS. The rabies virus antigen or RNA has been identified from the salivary glands, the lungs, the kidneys, the heart and the liver. This work aimed to identify the presence of the rabies virus in non-neuronal organs from naturally-infected vampire bats and to study the rabies virus in the salivary glands of healthy vampire bats. Out of the five bats that were positive for rabies in the CNS, by fluorescent antibody test (FAT, viral isolation in N2A cells and reverse transcription - polymerase chain reaction (RT-PCR, 100% (5/5 were positive for rabies in samples of the tongue and the heart, 80% (4/5 in the kidneys, 40% (2/5 in samples of the salivary glands and the lungs, and 20% (1/5 in the liver by RT-PCR test. All the nine bats that were negative for rabies in the CNS, by FAT, viral isolation and RT-PCR were negative for rabies in the salivary glands by RT-PCR test. Possible consequences for rabies epidemiology and pathogenesis are discussed in this work.

  19. Assessing the potential impacts of a changing climate on the distribution of a rabies virus vector.

    Directory of Open Access Journals (Sweden)

    Mark A Hayes

    Full Text Available Common vampire bats (Desmodus rotundus occur throughout much of South America to northern México. Vampire bats have not been documented in recent history in the United States, but have been documented within about 50 km of the U.S. state of Texas. Vampire bats feed regularly on the blood of mammals and can transmit rabies virus to native species and livestock, causing impacts on the health of prey. Thus cattle producers, wildlife management agencies, and other stakeholders have expressed concerns about whether vampire bats might spread into the southern United States. On the other hand, concerns about vampire-borne rabies can also result in wanton destruction at bat roosts in areas occupied by vampire bats, but also in areas not known to be occupied by this species. This can in turn negatively affect some bat roosts, populations, and species that are of conservation concern, including vampire bats. To better understand the current and possible future distribution of vampire bats in North America and help mitigate future cattle management problems, we used 7,094 vampire bat occurrence records from North America and species distribution modeling (SDM to map the potential distribution of vampire bats in North America under current and future climate change scenarios. We analysed and mapped the potential distribution of this species using 5 approaches to species distribution modeling: logistic regression, multivariate adaptive regression splines, boosted regression trees, random forest, and maximum entropy. We then projected these models into 17 "worst-case" future climate scenarios for year 2070 to generate hypotheses about how the vampire bat distribution in North America might change in the future. Of the variables used in this analysis, minimum temperature of the coldest month had the highest variable importance using all 5 SDM approaches. These results suggest two potential near-future routes of vampire bat dispersal into the U.S., one via

  20. Generalization of the Rabi population inversion dynamics in the sub-one-cycle pulse limit

    International Nuclear Information System (INIS)

    Doslic, N.

    2006-01-01

    We consider the population inversion in a two-level system generated by a sub-one-cycle pulse excitation. Specifically, we explore the effect that the time derivative of the pulse envelope has on the Rabi dynamics. Our analysis is based on a combination of analytical, perturbative, and nonperturbative treatments and is complemented by numerical simulations. We find a shortening of the Rabi inversion period and show that complete inversion is unobtainable under resonant, ultrashort pulse conditions. The impact of nonresonant and carrier-envelope phase-dependent effects on the dynamics of two-level and multilevel systems is studied numerically, and conditions for complete population inversion are derived

  1. 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...... and arctic-like strains of classical rabies virus due to the primer design and is therefore expected to be universally applicable independent of region of the world where the virus is isolated. Of the samples tested all were found to be positive after incubation for 25 to 30 minutes. The method made use...

  2. MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

    Science.gov (United States)

    Kip, E; Staal, J; Verstrepen, L; Tima, H G; Terryn, S; Romano, M; Lemeire, K; Suin, V; Hamouda, A; Kalai, M; Beyaert, R; Van Gucht, S

    2018-04-15

    MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1 -/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1 -/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1 -/- mice at 10 dpi compared to MALT1 +/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1 +/+ mice. Moreover, MALT1 -/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain. IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular

  3. Defining objective clusters for rabies virus sequences using affinity propagation clustering.

    Directory of Open Access Journals (Sweden)

    Susanne Fischer

    2018-01-01

    Full Text Available Rabies is caused by lyssaviruses, and is one of the oldest known zoonoses. In recent years, more than 21,000 nucleotide sequences of rabies viruses (RABV, from the prototype species rabies lyssavirus, have been deposited in public databases. Subsequent phylogenetic analyses in combination with metadata suggest geographic distributions of RABV. However, these analyses somewhat experience technical difficulties in defining verifiable criteria for cluster allocations in phylogenetic trees inviting for a more rational approach. Therefore, we applied a relatively new mathematical clustering algorythm named 'affinity propagation clustering' (AP to propose a standardized sub-species classification utilizing full-genome RABV sequences. Because AP has the advantage that it is computationally fast and works for any meaningful measure of similarity between data samples, it has previously been applied successfully in bioinformatics, for analysis of microarray and gene expression data, however, cluster analysis of sequences is still in its infancy. Existing (516 and original (46 full genome RABV sequences were used to demonstrate the application of AP for RABV clustering. On a global scale, AP proposed four clusters, i.e. New World cluster, Arctic/Arctic-like, Cosmopolitan, and Asian as previously assigned by phylogenetic studies. By combining AP with established phylogenetic analyses, it is possible to resolve phylogenetic relationships between verifiably determined clusters and sequences. This workflow will be useful in confirming cluster distributions in a uniform transparent manner, not only for RABV, but also for other comparative sequence analyses.

  4. Rabies virus vaccine as an immune adjuvant against cancers and glioblastoma: new studies may resurrect a neglected potential.

    Science.gov (United States)

    Altinoz, M A; Guloksuz, S; Elmaci, I

    2017-07-01

    To review the literature about the use of Rabies Virus-Vaccine (RV-V) as an anticancer immunotherapeutic modality in the light of recent findings. The literature search in relevant databases with the following key words: Rabies virus, cancer, remission. Remissions occured following RV-V injections in patients with cervical cancer and melanoma. Pilot clinical studies showed that RV-V injections enhanced survival in glioblastoma patients, which is supported by findings in GL261 mouse glioma model. If public health studies demonstrate protective role of RV-V against certain types of cancers, it can be benefitted as a novel immune adjuvant in clinic.

  5. Chimeric rabies viruses for trans-species comparison of lyssavirus glycoprotein ectodomain functions in virus replication and pathogenesis.

    Science.gov (United States)

    Genz, Berit; Nolden, Tobias; Negatsch, Alexandra; Teifke, Jens-Peter; Conzelmann, Karl-Klaus; Finke, Stefan

    2012-01-01

    The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV- and EBLV-2). These "envelope-switched" recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The "envelope-switched" RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity.

  6. Vampire Bat Rabies: Ecology, Epidemiology and Control

    Science.gov (United States)

    Johnson, Nicholas; Aréchiga-Ceballos, Nidia; Aguilar-Setien, Alvaro

    2014-01-01

    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. PMID:24784570

  7. Vampire Bat Rabies: Ecology, Epidemiology and Control

    Directory of Open Access Journals (Sweden)

    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.

  8. 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 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.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.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.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 of new terrestrial rabies virus variants.

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

    Science.gov (United States)

    Baby, Julie; Mani, Reeta Subramaniam; Abraham, Swapna Susan; Thankappan, Asha T; Pillai, Prasad Madhavan; Anand, Ashwini Manoor; Madhusudana, Shampur Narayan; Ramachandran, Jayachandran; Sreekumar, Sachin

    2015-01-01

    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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?

    Science.gov (United States)

    Evans, Jennifer S; Horton, Daniel L; Easton, Andrew J; Fooks, Anthony R; Banyard, Ashley C

    2012-12-14

    All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  13. Interferon production and immune response induction in pathogenic rabies virus-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Marcovistz, R; Leal, E C; De Souza Matos, D C [Departamento de Immunologia, Instituto Oswaldo Cruz, Caixa Postal 926, 21045 Rio de Janeiro (Brazil); Tsiang, H [Service Rage, Istitut Pasteur, Paris (France)

    1994-08-01

    Pathogenic parental rabies virus strain CVS (challenge virus standard) and its apathogenic variant RV194-2 were shown to differ in their ability to induce interferon (IFN) and immune response of the host. After intracerebral inoculation. IFN and antibody production was higher in the RV194-2 virus-infected mice than in the CVS infection. The enhancement of 2-5A synthetase activity, an IFN-mediated enzyme marker, showed biochemical evidence that IFN is active in both apathogenic and pathogenic infections. On the other hand, spontaneous proliferation in vitro of thymocytes and splenocytes from CVS virus-infected mice was strongly inhibited in contrast to the RV194-2 infection. In the CVS infection, the thymocyte proliferation However, in the RV194-2 infection, the thymocyte proliferation was higher than of the splenocytes. These results suggest a better performance of T-cell response to the RV194-2 infection. This fact can be critical for an enhancement of antibody production in the apathogenic infection and subsequent virus clearance from the brain of RV194-2 virus-infected mice. (author) 1 fig., 3 tabs., 32 refs.

  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. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Validation of the rapid fluorescent focus inhibition test for rabies virus-neutralizing antibodies in clinical samples

    NARCIS (Netherlands)

    Kostense, Stefan; Moore, Susan; Companjen, Arjen; Bakker, Alexander B. H.; Marissen, Wilfred E.; von Eyben, Rie; Weverling, Gerrit Jan; Hanlon, Cathleen; Goudsmit, Jaap

    2012-01-01

    Monoclonal antibodies are successful biologics in treating a variety of diseases, including the prevention or treatment of viral infections. CL184 is a 1:1 combination of two human monoclonal IgG1 antibodies (CR57 and CR4098) against rabies virus, produced in the PER.C6 human cell line. The two

  16. Comparison of complete genome sequences of dog rabies viruses isolated from China and Mexico reveals key amino acid changes that may be associated with virus replication and virulence.

    Science.gov (United States)

    Yu, Fulai; Zhang, Guoqing; Zhong, Xiangfu; Han, Na; Song, Yunfeng; Zhao, Ling; Cui, Min; Rayner, Simon; Fu, Zhen F

    2014-07-01

    Rabies is a global problem, but its impact and prevalence vary across different regions. In some areas, such as parts of Africa and Asia, the virus is prevalent in the domestic dog population, leading to epidemic waves and large numbers of human fatalities. In other regions, such as the Americas, the virus predominates in wildlife and bat populations, with sporadic spillover into domestic animals. In this work, we attempted to investigate whether these distinct environments led to selective pressures that result in measurable changes within the genome at the amino acid level. To this end, we collected and sequenced the full genome of two isolates from divergent environments. The first isolate (DRV-AH08) was from China, where the virus is present in the dog population and the country is experiencing a serious epidemic. The second isolate (DRV-Mexico) was taken from Mexico, where the virus is present in both wildlife and domestic dog populations, but at low levels as a consequence of an effective vaccination program. We then combined and compared these with other full genome sequences to identify distinct amino acid changes that might be associated with environment. Phylogenetic analysis identified strain DRV-AH08 as belonging to the China-I lineage, which has emerged to become the dominant lineage in the current epidemic. The Mexico strain was placed in the D11 Mexico lineage, associated with the West USA-Mexico border clade. Amino acid sequence analysis identified only 17 amino acid differences in the N, G and L proteins. These differences may be associated with virus replication and virulence-for example, the short incubation period observed in the current epidemic in China.

  17. Induction of antigen-specific antibody response in human pheripheral blood lymphocytes in vitro by a dog kidney cell vaccine against rabies virus (DKCV).

    NARCIS (Netherlands)

    F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert); H.G. Loggen; R.H.J. Bakker (Roland); J.A.A.M. van Asten (Jack); J.G. Kreeftenberg; P. van der Marel; G. van Steenis (Bert)

    1983-01-01

    textabstractIn the present report an in vitro method for obtaining a secondary human antibody response to a dog kidney cell vaccine against rabies virus (DKCV) is described. Cultures of peripheral blood mononuclear cells from normal rabies-immune and nonimmune donors were stimulated in vitro by

  18. An In Vitro RNA Synthesis Assay for Rabies Virus Defines Ribonucleoprotein Interactions Critical for Polymerase Activity.

    Science.gov (United States)

    Morin, Benjamin; Liang, Bo; Gardner, Erica; Ross, Robin A; Whelan, Sean P J

    2017-01-01

    We report an in vitro RNA synthesis assay for the RNA-dependent RNA polymerase (RdRP) of rabies virus (RABV). We expressed RABV large polymerase protein (L) in insect cells from a recombinant baculovirus vector and the phosphoprotein cofactor (P) in Escherichia coli and purified the resulting proteins by affinity and size exclusion chromatography. Using chemically synthesized short RNA corresponding to the first 19 nucleotides (nt) of the rabies virus genome, we demonstrate that L alone initiates synthesis on naked RNA and that P serves to enhance the initiation and processivity of the RdRP. The L-P complex lacks full processivity, which we interpret to reflect the lack of the viral nucleocapsid protein (N) on the template. Using this assay, we define the requirements in P for stimulation of RdRP activity as residues 11 to 50 of P and formally demonstrate that ribavirin triphosphate (RTP) inhibits the RdRP. By comparing the properties of RABV RdRP with those of the related rhabdovirus, vesicular stomatitis virus (VSV), we demonstrate that both polymerases can copy the heterologous promoter sequence. The requirements for engagement of the N-RNA template of VSV by its polymerase are provided by the C-terminal domain (CTD) of P. A chimeric RABV P protein in which the oligomerization domain (OD) and the CTD were replaced by those of VSV P stimulated RABV RdRP activity on naked RNA but was insufficient to permit initiation on the VSV N-RNA template. This result implies that interactions between L and the template N are also required for initiation of RNA synthesis, extending our knowledge of ribonucleoprotein interactions that are critical for gene expression. The current understanding of the structural and functional significance of the components of the rabies virus replication machinery is incomplete. Although structures are available for the nucleocapsid protein in complex with RNA, and also for portions of P, information on both the structure and function of the L

  19. 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.

  20. [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

  1. 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...... sequences from the Arctic and Arctic-like viruses, which were distinct from rabies isolates originating ill the Baltic region of Europe, the Steppes in Russia and from North America. The Arctic-like group consist of isolates from India, Pakistan, southeast Siberia and Japan. The Arctic group...... in northeast Siberia and Alaska. Arctic 2b isolates represent a biotype, which is dispersed throughout the Arctic region. The broad distribution of rabies in the Arctic regions including Greenland, Canada and Alaska provides evidence for the movement of rabies across borders....

  2. Sero-prevalence of virus neutralizing antibodies for rabies in different groups of dogs following vaccination.

    Science.gov (United States)

    Pimburage, R M S; Gunatilake, M; Wimalaratne, O; Balasuriya, A; Perera, K A D N

    2017-05-18

    Mass vaccination of dogs is considered fundamental for national rabies control programmes in Sri Lanka, as dog is the main reservoir and transmitter of the disease. Dogs were followed to determine the sero-prevalence of antibodies to the rabies virus. Altogether 510 previously vaccinated and unvaccinated dogs with owners (domestic dogs) and dogs without owners (stray dogs) of the local guard dog breed in different age groups recruited from Kalutara District, Sri Lanka. The dogs were vaccinated with a monovalent inactivated vaccine intramuscularly and serum antibody titres on days 0, 30, 180 and 360 were determined by the Rapid Fluorescent Focus Inhibition Test (RFFIT). The results indicated, a single dose of anti-rabies vaccination fails to generate a protective level of immunity (0.5 IU/ml) which lasts until 1 year in 40.42% of dogs without owners and 57.14% of previously unvaccinated juvenile (age: 3 months to 1 year) dogs with owners. More than one vaccination would help to maintain antibody titres above the protective level in the majority of dogs. The pattern of antibody titre development in annually vaccinated and irregularly vaccinated (not annual) adult dogs with owners is closely similar irrespective of regularity in vaccination. Previously vaccinated animals have higher (2 IU/ml) antibody titres to begin with and have a higher antibody titre on day 360 too. They show a very good antibody titre by day 180. Unvaccinated animals start with low antibody titre and return to low titres by day 360, but have a satisfactory antibody titre by day 180. A single dose of anti-rabies vaccination is not sufficient for the maintenance of antibody titres for a period of 1 year in puppies, juvenile dogs with owners and in dogs without owners. Maternal antibodies do not provide adequate protection to puppies of previously vaccinated dams and puppies of previously unvaccinated dams. Immunity development after vaccination seems to be closely similar in both the groups

  3. The Role of Dog Population Management in Rabies Elimination—A Review of Current Approaches and Future Opportunities

    Science.gov (United States)

    Taylor, Louise H.; Wallace, Ryan M.; Balaram, Deepashree; Lindenmayer, Joann M.; Eckery, Douglas C.; Mutonono-Watkiss, Beryl; Parravani, Ellie; Nel, Louis H.

    2017-01-01

    Free-roaming dogs and rabies transmission are integrally linked across many low-income countries, and large unmanaged dog populations can be daunting to rabies control program planners. Dog population management (DPM) is a multifaceted concept that aims to improve the health and well-being of free-roaming dogs, reduce problems they may cause, and may also aim to reduce dog population size. In theory, DPM can facilitate more effective rabies control. Community engagement focused on promoting responsible dog ownership and better veterinary care could improve the health of individual animals and dog vaccination coverage, thus reducing rabies transmission. Humane DPM tools, such as sterilization, could theoretically reduce dog population turnover and size, allowing rabies vaccination coverage to be maintained more easily. However, it is important to understand local dog populations and community attitudes toward them in order to determine whether and how DPM might contribute to rabies control and which DPM tools would be most successful. In practice, there is very limited evidence of DPM tools achieving reductions in the size or turnover of dog populations in canine rabies-endemic areas. Different DPM tools are frequently used together and combined with rabies vaccinations, but full impact assessments of DPM programs are not usually available, and therefore, evaluation of tools is difficult. Surgical sterilization is the most frequently documented tool and has successfully reduced dog population size and turnover in a few low-income settings. However, DPM programs are mostly conducted in urban settings and are usually not government funded, raising concerns about their applicability in rural settings and sustainability over time. Technical demands, costs, and the time necessary to achieve population-level impacts are major barriers. Given their potential value, we urgently need more evidence of the effectiveness of DPM tools in the context of canine rabies control

  4. The Role of Dog Population Management in Rabies Elimination—A Review of Current Approaches and Future Opportunities

    Directory of Open Access Journals (Sweden)

    Louise H. Taylor

    2017-07-01

    Full Text Available Free-roaming dogs and rabies transmission are integrally linked across many low-income countries, and large unmanaged dog populations can be daunting to rabies control program planners. Dog population management (DPM is a multifaceted concept that aims to improve the health and well-being of free-roaming dogs, reduce problems they may cause, and may also aim to reduce dog population size. In theory, DPM can facilitate more effective rabies control. Community engagement focused on promoting responsible dog ownership and better veterinary care could improve the health of individual animals and dog vaccination coverage, thus reducing rabies transmission. Humane DPM tools, such as sterilization, could theoretically reduce dog population turnover and size, allowing rabies vaccination coverage to be maintained more easily. However, it is important to understand local dog populations and community attitudes toward them in order to determine whether and how DPM might contribute to rabies control and which DPM tools would be most successful. In practice, there is very limited evidence of DPM tools achieving reductions in the size or turnover of dog populations in canine rabies-endemic areas. Different DPM tools are frequently used together and combined with rabies vaccinations, but full impact assessments of DPM programs are not usually available, and therefore, evaluation of tools is difficult. Surgical sterilization is the most frequently documented tool and has successfully reduced dog population size and turnover in a few low-income settings. However, DPM programs are mostly conducted in urban settings and are usually not government funded, raising concerns about their applicability in rural settings and sustainability over time. Technical demands, costs, and the time necessary to achieve population-level impacts are major barriers. Given their potential value, we urgently need more evidence of the effectiveness of DPM tools in the context of canine

  5. Update on rabies

    Directory of Open Access Journals (Sweden)

    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

  6. Cross-border spread, lineage displacement and evolutionary rate estimation of rabies virus in Yunnan Province, China.

    Science.gov (United States)

    Zhang, Yuzhen; Vrancken, Bram; Feng, Yun; Dellicour, Simon; Yang, Qiqi; Yang, Weihong; Zhang, Yunzhi; Dong, Lu; Pybus, Oliver G; Zhang, Hailin; Tian, Huaiyu

    2017-06-03

    Rabies is an important but underestimated threat to public health, with most cases reported in Asia. Since 2000, a new epidemic wave of rabies has emerged in Yunnan Province, southwestern China, which borders three countries in Southeast Asia. We estimated gene-specific evolutionary rates for rabies virus using available data in GenBank, then used this information to calibrate the timescale of rabies virus (RABV) spread in Asia. We used 452 publicly available geo-referenced complete nucleoprotein (N) gene sequences, including 52 RABV sequences that were recently generated from samples collected in Yunnan between 2008 and 2012. The RABV N gene evolutionary rate was estimated to be 1.88 × 10 -4 (1.37-2.41 × 10 -4 , 95% Bayesian credible interval, BCI) substitutions per site per year. Phylogenetic reconstructions show that the currently circulating RABV lineages in Yunnan result from at least seven independent introductions (95% BCI: 6-9 introductions) and represent each of the three main Asian RABV lineages, SEA-1, -2 and -3. We find that Yunnan is a sink location for the domestic spread of RABV and connects RABV epidemics in North China, South China, and Southeast Asia. Cross-border spread from southeast Asia (SEA) into South China, and intermixing of the North and South China epidemics is also well supported. The influx of RABV into Yunnan from SEA was not well-supported, likely due to the poor sampling of SEA RABV diversity. We found evidence for a lineage displacement of the Yunnan SEA-2 and -3 lineages by Yunnan SEA-1 strains, and considered whether this could be attributed to fitness differences. Overall, our study contributes to a better understanding of the spread of RABV that could facilitate future rabies virus control and prevention efforts.

  7. Immunogenicity of ORFV-based vectors expressing the rabies virus glycoprotein in livestock species.

    Science.gov (United States)

    Martins, Mathias; Joshi, Lok R; Rodrigues, Fernando S; Anziliero, Deniz; Frandoloso, Rafael; Kutish, Gerald F; Rock, Daniel L; Weiblen, Rudi; Flores, Eduardo F; Diel, Diego G

    2017-11-01

    The parapoxvirus Orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. Here we describe the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). The RABV-G gene was inserted in the ORFV024 or ORFV121 gene loci, which encode for IMPs that are unique to parapoxviruses and inhibit activation of the NF-κB signaling pathway. The immunogenicity of the resultant recombinant viruses (ORFV ∆024 RABV-G or ORFV ∆121 RABV-G, respectively) was evaluated in pigs and cattle. Immunization of the target species with ORFV ∆024 RABV-G and ORFV ∆121 RABV-G elicited robust neutralizing antibody responses against RABV. Notably, neutralizing antibody titers induced in ORFV ∆121 RABV-G-immunized pigs and cattle were significantly higher than those detected in ORFV ∆024 RABV-G-immunized animals, indicating a higher immunogenicity of ORFV Δ121 -based vectors in these animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    George, D.B.; Webb, C.T.; Farnsworth, Matthew L.; O'Shea, T.J.; Bowen, R.A.; Smith, D.L.; Stanley, T.R.; Ellison, L.E.; Rupprecht, C.E.

    2011-01-01

    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.

  9. Identification and genetic characterization of rabies virus from Egyptian water buffaloes (Bubalus bubalis) bitten by a fox.

    Science.gov (United States)

    El-Tholoth, Mohamed; El-Beskawy, Mohamed; Hamed, Mohamed F

    2015-09-01

    Rabies is caused by negative strand RNA-virus classified in the genus Lyssavirus, family Rhabdoviridae of the order Mononegavirales. The aim of the present study was to identify and analyze nucleotides sequence of nucleoprotein (N) gene of rabies virus (RABV) from two cases of water buffaloes (Bubalus bubalis) bitten by a fox in Egypt, 2013. The diseased buffaloes showed nervous manifestations with fever. Specimens from brains of the buffaloes with suspected rabies were collected. RABV in collected samples was identified using direct fluorescent antibody (dFA) technique, histopathological examination and reverse transcription-polymerase chain reaction (RT-PCR). Also, nucleotides sequence of partially amplified nucleoprotein (N) gene was compared with the other street strains of RABV available on GenBank. The results revealed that RABV antigen was identified in the brains of diseased buffaloes by dFA technique and the characteristic intracytoplasmic inclusions (Negri bodies) and RABV nucleic acid were detected by histopathology and RT-PCR, respectively. The identified virus showed close genetic relationship with street strains identified previously from dogs in different Governorates in Egypt and with strains identified in Israel and Jordan indicating transmission of the virus between Egyptian Governorates with a potential transmission from and/or to our neighboring countries.

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

    International Nuclear Information System (INIS)

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Development and evaluation of an anti-rabies virus phosphoprotein-specific monoclonal antibody for detection of rabies neutralizing antibodies using RFFIT.

    Science.gov (United States)

    Um, Jihye; Chun, Byung Chul; Lee, Yeong Seon; Hwang, Kyu Jam; Yang, Dong-Kun; Park, Jun-Sun; Kim, Su Yeon

    2017-12-01

    Rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. The rapid fluorescent focus inhibition test (RFFIT) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. Here, we report the development of a new monoclonal antibody (mAb) designed to react specifically with Rabies virus (RABV) phosphoprotein (P protein), and the evaluation of its applicability to the RFFIT and its effectiveness as a diagnostic reagent for human rabies. The mAb KGH P 16B8 was produced to target the P protein of the Korean KGH RABV strain. An indirect immunofluorescence assay (IFA) was conducted to detect various strains of RABV in various cell lines. Alexa-conjugated KGH P 16B8 (16B8-Alexa) was developed for the RFFIT. The IFA test could detect RABV up to a 1:2,500 dilution, with a detection limit comparable to that of a commercial diagnostic reagent. The sensitivity, specificity, positive predictive value, and negative predictive value of the RFFIT using 16B8-Alexa in 414 clinical specimens were 98.67%, 99.47%, 99.55%, and 98.42%, respectively. The results of the RFFIT with 16B8-Alexa were strongly correlated with those obtained using an existing commercial diagnostic reagent (r = 0.995, prabies neutralizing antibody titer and establish a diagnosis in human. Thus, 16B8-Alexa is expected to serve as an alternative diagnostic reagent that is widely accessible, with potentially broad applications beyond those of the RFFIT in Korea. Further studies with 16B8-Alexa should provide insight into the immunological mechanism of the P protein of Korean RABV.

  13. [Complete genome sequencing and analyses of rabies viruses isolated from wild animals (Chinese Ferret-Badger) in Zhejiang province].

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    Lei, Yong-Liang; Wang, Xiao-Guang; Liu, Fu-Ming; Chen, Xiu-Ying; Ye, Bi-Feng; Mei, Jian-Hua; Lan, Jin-Quan; Tang, Qing

    2009-08-01

    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 strains isolated from Chinese wildlife. Overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses of the N genes from Chinese Ferret-Badger, sika deer, vole, dog. Vaccine strains were then determined. The two full-length genomes were completely sequenced to find out that they had the same genetic structure with 11 923 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 two 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 two full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so that the nucleotide mutations happened in these two genomes were most probably as synonymous mutations. Compared to the referenced rabies viruses, the lengths of the five protein coding regions did not show any changes or recombination, but only with a few-point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the two ferret badgers genomes were similar to the referenced vaccine or street strains. The two strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessing the distinct geographyphic characteristics of China. All the evidence suggested a cue that these two ferret badgers

  14. Rabies in southeast Brazil: a change in the epidemiological pattern.

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    Queiroz, Luzia Helena; Favoretto, Silvana Regina; Cunha, Elenice Maria S; Campos, Angélica Cristine A; Lopes, Marissol Cardoso; de Carvalho, Cristiano; Iamamoto, Keila; Araújo, Danielle Bastos; Venditti, Leandro Lima R; Ribeiro, Erica S; Pedro, Wagner André; Durigon, Edison Luiz

    2012-01-01

    This epidemiological study was conducted using antigenic and genetic characterisation of rabies virus isolates obtained from different animal species in the southeast of Brazil from 1993 to 2007. An alteration in the epidemiological profile was observed. One hundred two samples were tested using a panel of eight monoclonal antibodies, and 94 were genetically characterised by sequencing the nucleoprotein gene. From 1993 to 1997, antigenic variant 2 (AgV-2), related to a rabies virus maintained in dog populations, was responsible for rabies cases in dogs, cats, cattle and horses. Antigenic variant 3 (AgV-3), associated with Desmodus rotundus, was detected in a few cattle samples from rural areas. From 1998 to 2007, rabies virus was detected in bats and urban pets, and four distinct variants were identified. A nucleotide similarity analysis resulted in two primary groups comprising the dog and bat antigenic variants and showing the distinct endemic cycles maintained in the different animal species in this region.

  15. [Hematophagous bats as reservoirs of rabies].

    Science.gov (United States)

    Scheffer, Karin Corrêa; Iamamoto, Keila; Asano, Karen Miyuki; Mori, Enio; Estevez Garcia, Andrea Isabel; Achkar, Samira M; Fahl, Williande Oliveira

    2014-04-01

    Rabies continues to be a challenge for public health authorities and a constraint to the livestock industry in Latin America. Wild and domestic canines and vampire bats are the main transmitter species and reservoirs of the disease. Currently, variations observed in the epidemiological profile of rabies, where the species of hematophagous bat Desmodus rotundus constitutes the main transmitting species. Over the years, knowledge has accumulated about the ecology, biology and behavior of this species and the natural history of rabies, which should lead to continuous development of methods of population control of d. Rotundus as well as prevention and diagnostic tools for rabies. Ecological relationships of this species with other hematophagous and non-hematophagous bats is unknown, and there is much room for improvement in reporting systems and surveillance, as well as creating greater awareness among the farming community. Understanding the impact of human-induced environmental changes on the rabies virus in bats should be cause for further investigation. This will require a combination of field studies with mathematical models and new diagnostic tools. This review aims to present the most relevant issues on the role of hematophagous bats as reservoirs and transmitters of the rabies virus.

  16. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    Science.gov (United States)

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

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

  17. Chimeric rabies glycoprotein with a transmembrane domain and cytoplasmic tail from Newcastle disease virus fusion protein incorporates into the Newcastle disease virion at reduced levels.

    Science.gov (United States)

    Yu, Gui Mei; Zu, Shu Long; Zhou, Wei Wei; Wang, Xi Jun; Shuai, Lei; Wang, Xue Lian; Ge, Jin Ying; Bu, Zhi Gao

    2017-08-31

    Rabies remains an important worldwide health problem. Newcastle disease virus (NDV) was developed as a vaccine vector in animals by using a reverse genetics approach. Previously, our group generated a recombinant NDV (LaSota strain) expressing the complete rabies virus G protein (RVG), named rL-RVG. In this study, we constructed the variant rL-RVGTM, which expresses a chimeric rabies virus G protein (RVGTM) containing the ectodomain of RVG and the transmembrane domain (TM) and a cytoplasmic tail (CT) from the NDV fusion glycoprotein to study the function of RVG's TM and CT. The RVGTM did not detectably incorporate into NDV virions, though it was abundantly expressed at the surface of infected BHK-21 cells. Both rL-RVG and rL-RVGTM induced similar levels of NDV virus-neutralizing antibody (VNA) after initial and secondary vaccination in mice, whereas rabies VNA induction by rL-RVGTM was markedly lower than that induced by rL-RVG. Though rL-RVG could spread from cell to cell like that in rabies virus, rL-RVGTM lost this ability and spread in a manner similar to the parental NDV. Our data suggest that the TM and CT of RVG are essential for its incorporation into NDV virions and for spreading of the recombinant virus from the initially infected cells to surrounding cells.

  18. In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184 Against Diverse North American Bat Rabies Virus Variants

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    Richard Franka

    2017-09-01

    Full Text Available Following rabies virus (RABV exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG are essential components of modern post-exposure prophylaxis (PEP. Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098, against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV; western canyon bat (Ph RABV; big brown bat (Ef-w1 RABV and Mexican free-tailed bat RABV (Tb RABV. 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic

  19. Contribution to rabies prevention.

    Science.gov (United States)

    Sureau, P

    1992-01-01

    After the end of the Second World War, an outbreak of fox rabies invaded Europe. For the immunization of human populations and domestic animals against the risk of rabies transmitted by infected wild animals, it appeared necessary to replace the first generation of rabies vaccines (nerve tissue vaccines) by more potent and safer vaccines. The European vaccine manufacturers, in close collaboration with the research institutes engaged in rabies research, soon and quickly developed a second generation of rabies vaccines, produced in cell cultures including continuous cell lines grown in bioreactors of industrial scale. The third generation of rabies vaccines is already available: the vaccinia-rabies glycoprotein recombinant vaccine is presently applied on a large scale in some European countries for immunization of wildlife. The canarypox recombinant vaccine has already been considered and successfully tested for human immunization.

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

    Science.gov (United States)

    Blaney, Joseph E; Marzi, Andrea; Willet, Mallory; Papaneri, Amy B; Wirblich, Christoph; Feldmann, Friederike; Holbrook, Michael; Jahrling, Peter; Feldmann, Heinz; Schnell, Matthias J

    2013-01-01

    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.

  1. 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.

  2. Development of in vitro and in vivo rabies virus neutralization assays based on a high-titer pseudovirus system

    Science.gov (United States)

    Nie, Jianhui; Wu, Xiaohong; Ma, Jian; Cao, Shouchun; Huang, Weijin; Liu, Qiang; Li, Xuguang; Li, Yuhua; Wang, Youchun

    2017-01-01

    Pseudoviruses are useful virological tools because of their safety and versatility; however the low titer of these viruses substantially limits their wider applications. We developed a highly efficient pseudovirus production system capable of yielding 100 times more rabies pseudovirus than the traditional method. Employing the high-titer pseudoviruses, we have developed robust in vitro and in vivo neutralization assays for the evaluation of rabies vaccine, which traditionally relies on live-virus based assays. Compared with current rapid fluorescent focus inhibition test (RFFIT), our in vitro pseudovirus-based neutralization assay (PBNA) is much less labor-intensive while demonstrating better reproducibility. Moreover, the in vivo PBNA assay was also found to be superior to the live virus based assay. Following intravenous administration, the pseudovirus effectively infected the mice, with dynamic viral distributions being sequentially observed in spleen, liver and brain. Furthermore, data from in vivo PBNA showed great agreement with those generated from the live virus model but with the experimental time significantly reduced from 2 weeks to 3 days. Taken together, the effective pseudovirus production system facilitated the development of novel PBNA assays which could replace live virus-based traditional assays due to its safety, rapidity, reproducibility and high throughput capacity. PMID:28218278

  3. Development and validation of sensitive real-time RT-PCR assay for broad detection of rabies virus.

    Science.gov (United States)

    Faye, Martin; Dacheux, Laurent; Weidmann, Manfred; Diop, Sylvie Audrey; Loucoubar, Cheikh; Bourhy, Hervé; Sall, Amadou Alpha; Faye, Ousmane

    2017-05-01

    Rabies virus (RABV) remains one of the most important global zoonotic pathogens. RABV causes rabies, an acute encephalomyelitis associated with a high rate of mortality in humans and animals and affecting different parts of the world, particularly in Asia and Africa. Confirmation of rabies diagnosis relies on laboratory diagnosis, in which molecular techniques such as detection of viral RNA by reverse transcription polymerase chain reaction (RT-PCR) are increasingly being used. In this study, two real-time quantitative RT-PCR assays were developed for large-spectrum detection of RABV, with a focus on African isolates. The primer and probe sets were targeted highly conserved regions of the nucleoprotein (N) and polymerase (L) genes. The results indicated the absence of non-specific amplification and cross-reaction with a range of other viruses belonging to the same taxonomic family, i.e. Rhabdoviridae, as well as negative brain tissues from various host species. Analytical sensitivity ranged between 100 to 10 standard RNA copies detected per reaction for N-gene and L-gene assays, respectively. Effective detection and high sensitivity of these assays on African isolates showed that they can be successfully applied in general research and used in diagnostic process and epizootic surveillance in Africa using a double-check strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Vaccine-induced rabies in a red fox (Vulpes vulpes): isolation of vaccine virus in brain tissue and salivary glands.

    Science.gov (United States)

    Hostnik, Peter; Picard-Meyer, Evelyne; Rihtarič, Danijela; Toplak, Ivan; Cliquet, Florence

    2014-04-01

    Oral vaccination campaigns to eliminate fox rabies were initiated in Slovenia in 1995. In May 2012, a young fox (Vulpes vulpes) with typical rabies signs was captured. Its brain and salivary gland tissues were found to contain vaccine strain SAD B19. The Basic Logical Alignment Search Tool alignment of 589 nucleotides determined from the N gene of the virus isolated from the brain and salivary glands of the affected fox was 100% identical to the GenBank reference SAD B19 strain. Sequence analysis of the N and M genes (4,351 nucleotides) showed two nucleotide modifications at position 1335 (N gene) and 3114 (M gene) in the KC522613 isolate identified in the fox compared to SAD B19.

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

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    Minako Ogino

    2016-05-01

    Full Text Available 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.

  6. 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.

  7. 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

    2014-01-01

    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. PMID:25648208

  8. 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

  9. Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories.

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    Jovan Nikolic

    2016-10-01

    Full Text Available Stress granules (SGs are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1, T-cell intracellular antigen 1 (TIA-1 and poly(A-binding protein (PABP in the RNA granules formed during viral infection. As shown by live cell imaging, RABV-induced SGs are highly dynamic structures that increase in number, grow in size by fusion events, and undergo assembly/disassembly cycles. Some SGs localize in close proximity to cytoplasmic viral factories, known as Negri bodies (NBs. Three dimensional reconstructions reveal that both structures remain distinct even when they are in close contact. In addition, viral mRNAs synthesized in NBs accumulate in the SGs during viral infection, revealing material exchange between both compartments. Although RABV-induced SG formation is not affected in MEFs lacking TIA-1, TIA-1 depletion promotes viral translation which results in an increase of viral replication indicating that TIA-1 has an antiviral effect. Inhibition of PKR expression significantly prevents RABV-SG formation and favors viral replication by increasing viral translation. This is correlated with a drastic inhibition of IFN-B gene expression indicating that SGs likely mediate an antiviral response which is however not sufficient to fully counteract RABV infection.

  10. 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.

  11. 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.

  12. A Study of the Fruit Bat (Rousettus sp Brain Anatomy as Natural Reservoir Wild Animal for the Rabies Virus

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    Karina Mayang Sari

    2015-06-01

    Full Text Available Rousettus sp. (Fruit bat is one type of fruit bats in Indonesia and act as a natural reservoir of rabies. Rabies is caused by a virus from genus Lyssavirus, family Rhabdoviridae, which attack central nervous system (CNS.The brain is an organ that is sensitive to rabies infection. The purpose of this study was to determine the anatomical structure of the fruit bat brain macroscopically. Five fruit bat were used in this study, they were anaesthetized using ketamine and xylazin. Animals were perfused using physiological saline and 10% buffered formalin. Brains were taken using tweezers after all the bones of the skull were separated. Analysis of macroscopic brain was done descriptively. The results showed that the fruit bat brain were generally divided into cerebrum, cerebellum and brain stem. Gyrus, sulcus and the paraflokulus lobes of the fruit bat brain were less developed than that of the dogs brain.

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

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    Velasco-Villa, Andrés; Orciari, Lillian A.; Juárez-Islas, Víctor; Gómez-Sierra, Mauricio; Padilla-Medina, Irma; Flisser, Ana; Souza, Valeria; Castillo, Amanda; Franka, Richard; Escalante-Mañe, Maribel; Sauri-González, Isaias; Rupprecht, Charles E.

    2006-01-01

    Bat rabies and its transmission to humans and other species in Mexico were investigated. Eighty-nine samples obtained from rabid livestock, cats, dogs, and humans in Mexico were studied by antigenic typing and partial sequence analysis. Samples were further compared with enzootic rabies associated with different species of bats in the Americas. Patterns of nucleotide variation allowed the definition of at least 20 monophyletic clusters associated with 9 or more different bat species. Several ...

  14. 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.

  15. Prevention and control of rabies in an age of global travel: a review of travel- and trade-associated rabies events--United States, 1986-2012.

    Science.gov (United States)

    Lankau, E W; Cohen, N J; Jentes, E S; Adams, L E; Bell, T R; Blanton, J D; Buttke, D; Galland, G G; Maxted, A M; Tack, D M; Waterman, S H; Rupprecht, C E; Marano, N

    2014-08-01

    Rabies prevention and control efforts have been successful in reducing or eliminating virus circulation regionally through vaccination of specific reservoir populations. A notable example of this success is the elimination of canine rabies virus variant from the United States and many other countries. However, increased international travel and trade can pose risks for rapid, long-distance movements of ill or infected persons or animals. Such travel and trade can result in human exposures to rabies virus during travel or transit and could contribute to the re-introduction of canine rabies variant or transmission of other viral variants among animal host populations. We present a review of travel- and trade-associated rabies events that highlight international public health obligations and collaborative opportunities for rabies prevention and control in an age of global travel. Rabies is a fatal disease that warrants proactive coordination among international public health and travel industry partners (such as travel agents, tour companies and airlines) to protect human lives and to prevent the movement of viral variants among host populations. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  16. Antibody response to an anti-rabies vaccine in a dog population under field conditions in Bolivia.

    Science.gov (United States)

    Suzuki, K; González, E T; Ascarrunz, G; Loza, A; Pérez, M; Ruiz, G; Rojas, L; Mancilla, K; Pereira, J A C; Guzman, J A; Pecoraro, M R

    2008-10-01

    Rabies remains an important public health issue in Bolivia, South America. Public concern and fears are most focussed on dogs as the source of rabies. The objective of the present study was to assess immunity of an inactivated suckling mouse brain vaccine against canine rabies used for the official vaccination campaigns under field conditions in an endemic area of rabies in Bolivia. A total of 236 vaccinated and 44 unvaccinated dogs in Santa Cruz de la Sierra, selected using stratified random sampling, were investigated in order to obtain owned dog characteristics and antibody titres against rabies in April 2007. The proportion of vaccinated dogs with an antibody titre exceeded the protection threshold value of 0.5 EU/ml was 58% [95% confidence intervals (CI): 52-65], indicating that vaccination is likely to elicit an antibody response (odds ratio 6.3, 95% CI: 1.2-11.5). The range of geometric mean of antibody titre for vaccinated dogs (0.89 EU/ml; 95% CI: 0.75-1.04) was considered to meet the minimal acceptable level indicating an adequate immune response to the vaccine. However, the titre level was not satisfactory in comparison with the results from other field investigations with inactivated tissue culture vaccines. It is recommended for public health authorities to (1) consider modernizing their vaccine manufacturing method because the level of immunity induced by the current vaccine is comparably low, (2) conduct frequent vaccination campaigns to maintain high levels of vaccination coverage, and (3) actively manage the domestic dog population in the study area, which is largely responsible for rabies maintenance.

  17. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

    Science.gov (United States)

    Kimitsuki, Kazunori; Yamada, Kentaro; Shiwa, Nozomi; Inoue, Satoshi; Nishizono, Akira; Park, Chun-Ho

    2017-06-10

    Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10 6 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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

  1. Incidence and economic impact of rabies in the cattle population of Ethiopia

    NARCIS (Netherlands)

    Jibat, Tariku; Mourits, Monique C.M.; Hogeveen, Henk

    2016-01-01

    Rabies is a viral disease that can cause fatal encephalomyelitis both in animals and humans. Although incidences of the disease in cattle have been reported, insight in the economic impact of the disease in livestock remains limited. By affecting cattle in subsistence systems, rabies may have

  2. Processes Underlying Rabies Virus Incursions across US-Canada Border as Revealed by Whole-Genome Phylogeography.

    Science.gov (United States)

    Trewby, Hannah; Nadin-Davis, Susan A; Real, Leslie A; Biek, Roman

    2017-09-01

    Disease control programs aim to constrain and reduce the spread of infection. Human disease interventions such as wildlife vaccination play a major role in determining the limits of a pathogen's spatial distribution. Over the past few decades, a raccoon-specific variant of rabies virus (RRV) has invaded large areas of eastern North America. Although expansion into Canada has been largely prevented through vaccination along the US border, several outbreaks have occurred in Canada. Applying phylogeographic approaches to 289 RRV whole-genome sequences derived from isolates collected in Canada and adjacent US states, we examined the processes underlying these outbreaks. RRV incursions were attributable predominantly to systematic virus leakage of local strains across areas along the border where vaccination has been conducted but also to single stochastic events such as long-distance translocations. These results demonstrate the utility of phylogeographic analysis of pathogen genomes for understanding transboundary outbreaks.

  3. First Complete Genomic Sequence of a Rabies Virus from the Republic of Tajikistan Obtained Directly from a Flinders Technology Associates Card

    OpenAIRE

    Goharriz, H.; Marston, D. A.; Sharifzoda, F.; Ellis, R. J.; Horton, D. L.; Khakimov, T.; Whatmore, A.; Khamroev, K.; Makhmadshoev, A. N.; Bazarov, M.; Fooks, A. R.; Banyard, A. C.

    2017-01-01

    ABSTRACT A brain homogenate derived from a rabid dog in the district of Tojikobod, Republic of Tajikistan, was applied to a Flinders Technology Associates (FTA) card. A full-genome sequence of rabies virus (RABV) was generated from the FTA card directly without extraction, demonstrating the utility of these cards for readily obtaining genetic data.

  4. Glycoprotein from street rabies virus BD06 induces early and robust immune responses when expressed from a non-replicative adenovirus recombinant.

    Science.gov (United States)

    Wang, Shuchao; Sun, Chenglong; Zhang, Shoufeng; Zhang, Xiaozhuo; Liu, Ye; Wang, Ying; Zhang, Fei; Wu, Xianfu; Hu, Rongliang

    2015-09-01

    The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines.

  5. Rabies virus-specific human T cell clones provide help for an in vitro antibody response against neutralizing antibody-inducing determinants of the viral glycoprotein.

    NARCIS (Netherlands)

    H. Bunschoten; R.J. Klapmuts; I.J.Th.M. Claassen (Ivo); S.D. Reijneveld; A.D.M.E. Osterhaus (Albert); F.G.C.M. Uytdehaag (Fons)

    1989-01-01

    textabstractHuman T cell clones were prepared from peripheral blood mononuclear cells from a vaccinated human donor and kept in culture in the presence of rabies virus antigen and growth factors. Phenotypic analysis of the T cell clones revealed expression of the CD3 and CD4 cell surface markers,

  6. Prevalence of neutralizing antibodies to rabies virus in serum of seven species of insectivorous bats from Colorado and New Mexico, United States

    Science.gov (United States)

    Bowen, Richard A.; O'Shea, Thomas J.; Shankar, Vidya; Neubaum, Melissa A.; Neubaum, Daniel J.; Rupprecht, Charles E.

    2013-01-01

    We determined the presence of rabies-virus-neutralizing antibodies (RVNA) in serum of 721 insectivorous bats of seven species captured, sampled, and released in Colorado and New Mexico, United States in 2003-2005. A subsample of 160 bats was tested for rabies-virus RNA in saliva. We sampled little brown bats (Myotis lucifugus) at two maternity roosts in Larimer County, Colorado; big brown bats (Eptesicus fuscus) at three maternity roosts in Morgan County, Colorado; and big brown bats at five maternity roosts in Larimer County. We also sampled hoary bats (Lasiurus cinereus) and silver-haired bats (Lasionycteris noctivagans) captured while drinking or foraging over water in Bernalillo County, New Mexico and at various locations in Larimer County. Big brown bats, little brown bats, long-legged myotis (Myotis volans), long-eared myotis (Myotis evotis), and fringed myotis (Myotis thysanodes) were also sampled over water in Larimer County. All species except long-eared myotis included individuals with RVNA, with prevalences ranging from 7% in adult female silver-haired bats to 32% in adult female hoary bats. None of the bats had detectable rabies-virus RNA in oropharyngeal swabs, including 51 bats of 5 species that had RVNA in serum. Antibody-positive bats were present in nine of the 10 maternity colonies sampled. These data suggest that wild bats are commonly exposed to rabies virus and develop a humoral immune response suggesting some degree of viral replication, but many infections fail to progress to clinical disease.

  7. First Complete Genomic Sequence of a Rabies Virus from the Republic of Tajikistan Obtained Directly from a Flinders Technology Associates Card.

    Science.gov (United States)

    Goharriz, H; Marston, D A; Sharifzoda, F; Ellis, R J; Horton, D L; Khakimov, T; Whatmore, A; Khamroev, K; Makhmadshoev, A N; Bazarov, M; Fooks, A R; Banyard, A C

    2017-07-06

    A brain homogenate derived from a rabid dog in the district of Tojikobod, Republic of Tajikistan, was applied to a Flinders Technology Associates (FTA) card. A full-genome sequence of rabies virus (RABV) was generated from the FTA card directly without extraction, demonstrating the utility of these cards for readily obtaining genetic data. © Crown copyright 2017.

  8. 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.

  9. Rabies: An overview

    Directory of Open Access Journals (Sweden)

    Tarun Kumar Dutta

    2014-01-01

    Full Text Available Rabies is a fatal disease caused by rabies virus, a neurotropic virus and a prototype of Lyssavirus of Rhabdoviridae family. It is transmitted to human beings through infected saliva of dogs and cats during bite. Dog is the cause of more than 90% of human rabies in India. The incubation period is 4-8 weeks (but it may vary from 5 days to 7 years. There are two clinical types of rabies - encephalitic (furious and paralytic (dumb types. In the encephalitic (furious form, the principal malfunction is in the brain stem and limbic system. Patient has hydrophobia in the full-blown form, but the mind remains clear till the end. Death occurs within a week after the onset of symptoms. Paralytic rabies resembles Guillain-Barre syndrome. Diagnosis is mostly clinical. However, direct fluorescent antibody test is used to identify the antigen in skin biopsy from the nape of neck. In the postmortem specimen, demonstration of Negri bodies in the brain confirms the diagnosis. Anti-rabies vaccine is used for pre- and post-exposure prophylaxis. The commonly used intramuscular (IM regimen is being superseded by intradermal (ID vaccine because it makes the treatment economical. Whereas touching of animal or lick on intact skin does not require vaccination, any transdermal bite with bleeding requires immediate administration of rabies immunoglobulin (RIG and simultaneous vaccination with a tissue culture vaccine (TCV. Minor abrasion without bleeding may require only vaccination and no RIG. Rabies human monoclonal antibody (RMAb is the newest entry in the prophylaxis of rabies which may ultimately replace RIG. Prognosis is grave since there are just six reports of survivors. Treatment is mainly palliative with heavy sedation and/or therapeutic coma (Milwaukee protocol.

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

    Directory of Open Access Journals (Sweden)

    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

  11. A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.

    Science.gov (United States)

    Mesquita, Leonardo Pereira; Gamon, Thais Helena Martins; Cuevas, Silvia Elena Campusano; Asano, Karen Miyuki; Fahl, Willian de Oliveira; Iamamoto, Keila; Scheffer, Karin Correa; Achkar, Samira Maria; Zanatto, Dennis Albert; Mori, Cláudia Madalena Cabrera; Maiorka, Paulo César; Mori, Enio

    2017-12-01

    Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD 50 ) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

  12. Population genetic structure of serotine bats (Eptesicus serotinus) across Europe and implications for the potential spread of bat rabies (European bat lyssavirus EBLV-1).

    Science.gov (United States)

    Moussy, C; Atterby, H; Griffiths, A G F; Allnutt, T R; Mathews, F; Smith, G C; Aegerter, J N; Bearhop, S; Hosken, D J

    2015-07-01

    Understanding of the movements of species at multiple scales is essential to appreciate patterns of population connectivity and in some cases, the potential for pathogen transmission. The serotine bat (Eptesicus serotinus) is a common and widely distributed species in Europe where it frequently harbours European bat lyssavirus type 1 (EBLV-1), a virus causing rabies and transmissible to humans. In the United Kingdom, it is rare, with a distribution restricted to south of the country and so far the virus has never been found there. We investigated the genetic structure and gene flow of E. serotinus across the England and continental Europe. Greater genetic structuring was found in England compared with continental Europe. Nuclear data suggest a single population on the continent, although further work with more intensive sampling is required to confirm this, while mitochondrial sequences indicate an east-west substructure. In contrast, three distinct populations were found in England using microsatellite markers, and mitochondrial diversity was very low. Evidence of nuclear admixture indicated strong male-mediated gene flow among populations. Differences in connectivity could contribute to the high viral prevalence on the continent in contrast with the United Kingdom. Although the English Channel was previously thought to restrict gene flow, our data indicate relatively frequent movement from the continent to England highlighting the potential for movement of EBLV-1 into the United Kingdom.

  13. 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.

  14. 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.

  15. Exposure to Rabies in Small Indian Mongooses (Herpestes auropunctatus) from Two Regions in Puerto Rico.

    Science.gov (United States)

    Berentsen, Are R; Johnson, Shylo R; Gilbert, Amy T; VerCauteren, Kurt C

    2015-10-01

    The small Indian mongoose (Herpestes auropunctatus) was introduced to several Caribbean Islands to control rat (Rattus spp.) damage to sugarcane plantations. Mongooses failed at suppressing rat populations and are now considered pests throughout most of their introduced range. Importantly, mongooses are rabies reservoirs on several Caribbean Islands. In Puerto Rico, mongooses have been implicated in up to 70% of reported animal rabies cases. There is no rabies vaccination program for wildlife in Puerto Rico, and data on rabies in mongooses are limited. We conducted a serosurvey of mongooses in two different ecologic environments in Puerto Rico: El Yunque National Forest and Cabo Rojo National Wildlife Refuge. We collected 119 serum samples from 112 mongooses, 44 (39.3%) of which were positive for rabies virus-neutralizing antibodies. We also collected oral swabs from 147 mongooses, including 88 from which we also collected serum. No oral swabs were positive for rabies virus RNA. Our data support previous research suggesting rabies virus is circulating within the mongoose population on Puerto Rico.

  16. Owned and Unowned Dog Population Estimation, Dog Management and Dog Bites to Inform Rabies Prevention and Response on Lombok Island, Indonesia

    Science.gov (United States)

    Mustiana, Ana; Toribio, Jenny-Ann; Abdurrahman, Muktasam; Suadnya, I. Wayan; Hernandez-Jover, Marta; Putra, Anak Agung Gde; Ward, Michael P.

    2015-01-01

    Although Indonesia has been rabies-infected since at least the 1880s, some islands remain rabies-free, such as Lombok. However, due to its adjacency to rabies-infected islands such as Bali and Flores, there is considerable risk of a rabies incursion. As part of a rabies risk assessment project, surveys were conducted to estimate the size of the dog population and to describe dog management practices of households belonging to different ethnic groups. A photographic-recapture method was employed and the number of unowned dogs was estimated. A total of 400 dog owning households were interviewed, 300 at an urban site and 100 at a rural site. The majority of the interviewed households belonged to the Balinese ethnic group. Owned dogs were more likely male, and non-pedigree or local breed. These households kept their dogs either fully restricted, semi-free roaming or free-roaming but full restriction was reported only at the urban site. Dog bite cases were reported to be higher at the urban site, and commonly affected children/young adults to 20 years old and males. A higher number of unowned dogs was observed at the urban site than at the rural site. Data generated within these surveys can inform rabies risk assessment models to quantify the probability of rabies being released into Lombok and resulting in the infection of the local dog population. The information gained is critical for efforts to educate dog owners about rabies, as a component of preparedness to prevent the establishment of rabies should an incursion occur. PMID:25932916

  17. 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...... putative new lyssavirus species Bokeloh Bat Lyssavirus (BBLV) and the West Caucasian Bat Virus (WCBV). Unlike in the new world, bat rabies cases in Europe are comparatively less frequent, possibly as a result of varying intensity of surveillance. Thus, the objective was to provide an assessment of the bat...... rabies surveillance data in Europe, taking both reported data to the WHO Rabies Bulletin Europe and published results into account. In Europe, 959 bat rabies cases were reported to the RBE in the time period 1977–2010 with the vast majority characterized as EBLV-1, frequently isolated in the Netherlands...

  18. 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

    Directory of Open Access Journals (Sweden)

    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.

  19. A Systematic Review of Human Bat Rabies Virus Variant Cases: Evaluating Unprotected Physical Contact with Claws and Teeth in Support of Accurate Risk Assessments.

    Science.gov (United States)

    Dato, Virginia M; Campagnolo, Enzo R; Long, Jonah; Rupprecht, Charles E

    2016-01-01

    In the United States and Canada, the most recent documented cases of rabies have been attributed to bat rabies viruses (RABV). We undertook this systematic review in an effort to summarize and enhance understanding of the risk of infection for individuals who have been potentially exposed to a suspect or confirmed rabid bat. United States rabies surveillance summaries documented a total of 41 human bat-rabies virus variant verified non-transplant cases between 1990 and 2015. All cases were fatal. Seven (17.1%) of 41 cases reported a bite from a bat. Ten (24.3%) cases had unprotected physical contact (UPC); these included seven cases that had a bat land or crawl on them (contact with claws) and one case that touched a bat's teeth. Seven (17.1%) cases had probable UPC. Insectivorous bat teeth are extremely sharp and highly efficient for predation upon arthropod prey. Bats also have sharp claws on the end of their thumbs and feet. One of the most common bat RABV variants has an ability to replicate in non-neural cells. Questioning individuals about unprotected contact with bat teeth and claws (including a bat landing or crawling on a person) may help identify additional exposures.

  20. Impact of Rabies Vaccination History on Attainment of an Adequate Antibody Titre Among Dogs Tested for International Travel Certification, Israel - 2010-2014.

    Science.gov (United States)

    Yakobson, B; Taylor, N; Dveres, N; Rotblat, S; Spero, Ż; Lankau, E W; Maki, J

    2017-06-01

    Rabies is endemic in wildlife or domestic carnivore populations globally. Infection of domestic dogs is of particular concern in many areas. In regions where domestic animals are at risk of exposure to rabies virus, dogs should be routinely vaccinated against rabies to protect both pet and human populations. Many countries require demonstration of an adequate level of serum rabies neutralizing antibodies to permit entry of dogs during international travel. We analysed rabies titres of dogs seeking travel certification in Israel to assess demographic and vaccine history factors associated with antibody titres below the acceptable threshold for travel certification. Having received only one previous rabies vaccination and a longer duration since the most recent vaccination was received were primary risk factors for not achieving an adequate rabies virus neutralizing antibody titre for travel certification. These risk factors had stronger effects in younger animals, but were consistent for dogs of all ages. In particular, these findings reiterate the importance of administering at least two rabies vaccinations (the primo vaccination and subsequent booster) to ensure population-level protection against rabies in dogs globally. © 2016 Blackwell Verlag GmbH.

  1. High level of Bcl-2 counteracts apoptosis mediated by a live rabies virus vaccine strain and induces long-term infection

    International Nuclear Information System (INIS)

    Thoulouze, Maria-Isabel; Lafage, Mireille; Yuste, Victor J.; Baloul, Leiela; Edelman, Lena; Kroemer, Guido; Israel, Nicole; Susin, Santos A.; Lafon, Monique

    2003-01-01

    We report here that rabies virus strains, currently used to immunize wildlife against rabies, induce not only caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway involving the apoptosis-inducing factor (AIF). In contrast, a strain of neurotropic RV that does not induce apoptosis did not activate caspases or induce AIF translocation. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both pathways. ERA infection and production were similar in Jurkat-vect and Jurkat-Bcl-2 cells, indicating Bcl-2 has no direct antiviral effects. Bcl-2 production is naturally upregulated by day 3 in ERA-infected Jurkat-vect cultures. The increase in Bcl-2 levels seems to be controlled by the virus infection itself and results in the establishment of long-term, persistently infected cultures that continue to produce virus. Thus, in infections with live RV vaccine strains, infected cells may be productive reservoirs of virus in the long term. This may account for the high efficacy of live rabies vaccines

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

    Directory of Open Access Journals (Sweden)

    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.

  3. A comparative rabies laboratory diagnosis: Peculiar features of ...

    African Journals Online (AJOL)

    Many diagnostic methods have been used to detect rabies virus antigen. The preferred method for routine rabies diagnosis in fresh brain tissue is fluorescent antibody test (FAT). In this study, FAT was used to evaluate the presence of rabies virus antigen in the brain (hippocampus) of fifty apparently healthy dogs. Mouse ...

  4. Retrospective: animal attacks and rabies exposures in Thai children.

    Science.gov (United States)

    Sriaroon, Chakrapol; Sriaroon, Panida; Daviratanasilpa, Svastijaya; Khawplod, Pakamatz; Wilde, Henry

    2006-09-01

    Over 50% of animal bites and potential rabies exposures in Thailand are in children and they also have the more severe injuries due to inexperience, smaller size and less ability to fend off attacks. Potential rabies exposures and animal bites are common in Thailand. Majority of these are in children where the extent of the injuries is also much more severe. The bitten areas correlate to the age of the children and level of the bitten animal head. These are areas noted for a higher risk of infection with rabies virus and shorter incubation periods. The vast majority of bites are due to dogs (86%) of which 74.6% are stray or community-owned animals. The prevalence of dog bites shows no seasonal variation in adults but there are two peaks during school vacation period for children. Extensive educational efforts directed at the Thai public are responsible for the rapid presentation of victims for post-exposure treatment. The dramatic reduction of human rabies deaths in Thailand during the last decades was achieved largely by the provision of expensive WHO standard post-exposure treatment, utilizing modern tissue culture vaccines and immunoglobulins. Canine and feline rabies is nevertheless still endemic and not likely to be controlled or eliminated till sustainable humane methods of dog population control and comprehensive countrywide canine rabies vaccination become possible through government policy.

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

    Science.gov (United States)

    Wadhwa, Ashutosh; Wilkins, Kimberly; Gao, Jinxin; Condori Condori, Rene Edgar; Gigante, Crystal M; Zhao, Hui; Ma, Xiaoyue; Ellison, James A; Greenberg, Lauren; Velasco-Villa, Andres; Orciari, Lillian; Li, Yu

    2017-01-01

    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, its high

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

    Directory of Open Access Journals (Sweden)

    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

  7. Bat Rabies in Guatemala

    Science.gov (United States)

    Ellison, James A.; Gilbert, Amy T.; Recuenco, Sergio; Moran, David; Alvarez, Danilo A.; Kuzmina, Natalia; Garcia, Daniel L.; Peruski, Leonard F.; Mendonça, Mary T.; Lindblade, Kim A.; Rupprecht, Charles E.

    2014-01-01

    Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. As part of a larger pathogen detection program, enhanced bat rabies surveillance was conducted in Guatemala, between 2009 and 2011. A total of 672 bats of 31 species were sampled and tested for rabies. The prevalence of rabies virus (RABV) detection among all collected bats was low (0.3%). Viral antigens were detected and infectious virus was isolated from the brains of two common vampire bats (Desmodus rotundus). RABV was also isolated from oral swabs, lungs and kidneys of both bats, whereas viral RNA was detected in all of the tissues examined by hemi-nested RT-PCR except for the liver of one bat. Sequencing of the nucleoprotein gene showed that both viruses were 100% identical, whereas sequencing of the glycoprotein gene revealed one non-synonymous substitution (302T,S). The two vampire bat RABV isolates in this study were phylogenetically related to viruses associated with vampire bats in the eastern states of Mexico and El Salvador. Additionally, 7% of sera collected from 398 bats demonstrated RABV neutralizing antibody. The proportion of seropositive bats varied significantly across trophic guilds, suggestive of complex intraspecific compartmentalization of RABV perpetuation. PMID:25080103

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Dog Ecology and Barriers to Canine Rabies Control in the Republic of Haiti, 2014-2015.

    Science.gov (United States)

    Schildecker, S; Millien, M; Blanton, J D; Boone, J; Emery, A; Ludder, F; Fenelon, N; Crowdis, K; Destine, A; Etheart, M; Wallace, R M

    2017-10-01

    An estimated 59 000 persons die annually of infection with the rabies virus worldwide, and dog bites are responsible for 95% of these deaths. Haiti has the highest rate of animal and human rabies in the Western Hemisphere. This study describes the status of animal welfare, animal vaccination, human bite treatment, and canine morbidity and mortality in Haiti in order to identify barriers to rabies prevention and control. An epidemiologic survey was used for data collection among dog owners during government-sponsored vaccination clinics at fourteen randomly selected sites from July 2014 to April 2015. A total of 2005 surveys were collected and data were analysed using parametric methods. Over 50% of owned dogs were allowed to roam freely, a factor associated with rabies transmission. More than 80% of dog owners reported experiencing barriers to accessing rabies vaccination for their dogs. Nearly one-third of the dog population evaluated in this study died in the year preceding the survey (32%) and 18% of these deaths were clinically consistent with rabies. Dog bites were commonly reported, with more than 3% of the study population bitten within the year preceding the survey. The incidence of canine rabies in Haiti is high and is exacerbated by low access to veterinary care, free-roaming dog populations and substandard animal welfare practices. Programmes to better understand the dog ecology and development of methods to improve access to vaccines are needed. Rabies deaths are at historical lows in the Western Hemisphere, but Haiti and the remaining canine rabies endemic countries still present a significant challenge to the goal of rabies elimination in the region. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

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

    Directory of Open Access Journals (Sweden)

    Camila Appolinário

    2015-09-01

    Full Text Available 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.

  11. Rabies Epidemiology and Control in Ecuador

    Science.gov (United States)

    Ortiz-Prado, Esteban; Ponce-Zea, Jorge; Ramirez, Dario; Stewart-Ibarra, Anna M.; Armijos, Luciana; Yockteng, Jaime; Cárdenas, Washington B.

    2016-01-01

    Objective: Describe the epidemiology and the control effort for rabies in Ecuador. Methods: This observational study included data from the Ecuadorian National Institute of Census and Statistics (INEC), and mortality and morbidity data reported by the Ministry of Public Health and the National Institute for Social Security. We conducted a phylogeny analyses to compare the N gene from the Challenge Virus Standard (CVS) vaccine strain used in Ecuador with published Cosmopolitan, Asian and Sylvatic strains. Descriptive and inferential statistics were used to determine the significance of the data. Results: In 1996 Ecuador suffered the highest rate of rabies per capita in the Americas, with an incidence rate of 0.56 cases per 100 000 people per year. Human and canine rabies showed a sharp decline until 2012. Between 1994 and 2014, we found a correlation of 0.925 (pEcuador. The incidence of human and canine rabies, also known as urban rabies, has clearly decreased due to massive canine vaccination campaigns. Phylogenetic analysis of the prevailing vaccine used in the country showed a clear separation from bat-derived rabies, the source of recent rabies outbreaks. Efforts are ongoing to develop rabies vaccines that are highly specific to the rabies virus genotype circulating in the region, including sylvatic rabies. These efforts include the implementation of reverse genetics to generate recombinant virus coding for the prevailing glycoprotein gene. PMID:26493436

  12. Rabies Epidemiology and Control in Ecuador.

    Science.gov (United States)

    Ortiz-Prado, Esteban; Ponce-Zea, Jorge; Ramirez, Dario; Stewart-Ibarra, Anna M; Armijos, Luciana; Yockteng, Jaime; Cardenas, Washington Bolivar

    2015-07-12

    Describe the epidemiology and the control effort for rabies in Ecuador. This observational study included data from the Ecuadorian National Institute of Census and Statistics (INEC), and mortality and morbidity data reported by the Ministry of Public Health and the National Institute for Social Security. We conducted a phylogeny analyses to compare the N gene from the Challenge Virus Standard (CVS) vaccine strain used in Ecuador with published Cosmopolitan, Asian and Sylvatic strains. Descriptive and inferential statistics were used to determine the significance of the data. In 1996 Ecuador suffered the highest rate of rabies per capita in the Americas, with an incidence rate of 0.56 cases per 100 000 people per year. Human and canine rabies showed a sharp decline until 2012. Between 1994 and 2014, we found a correlation of 0.925 (pEcuador. The incidence of human and canine rabies, also known as urban rabies, has clearly decreased due to massive canine vaccination campaigns. Phylogenetic analysis of the prevailing vaccine used in the country showed a clear separation from bat-derived rabies, the source of recent rabies outbreaks. Efforts are ongoing to develop rabies vaccines that are highly specific to the rabies virus genotype circulating in the region, including sylvatic rabies. These efforts include the implementation of reverse genetics to generate recombinant virus coding for the prevailing glycoprotein gene.

  13. Hormesis of specific IgG antibody to rabies virus in serum of mice irradiated with low dose γ-rays

    International Nuclear Information System (INIS)

    Liu Qingjie; Chen Deqing

    1998-01-01

    Objective: To explore the effect of low dose ionizing radiation on specific antibody in mouse serum. Methods: Kunming strain male mice, weighing 18-22 g, aged 6-8 weeks, were immunized intraperitoneally with rabies vaccine after exposure to cobalt-60 γ-rays. The specific IgG antibody against rabies virus in mouse serum was measured. Results: (1) The serum levels of specific IgG in mice irradiated with 5-30 cGy γ-rays were significantly elevated in comparison with those in control mice (P<0.01), the optimum stimulating dose being 10 cGy. (2) Exposure to 10 cGy caused significant enhancement and earlier emergence of the peak level of specific IgG in serum. (3) The hormesis of specific IgG to rabies virus induced by 10 cGy γ-rays could last one week at least. Conclusion: Low dose ionizing radiation can enhance the level of specific antibody in mouse serum, and this effect can last for one week at least

  14. Eliminating Rabies in Estonia

    Science.gov (United States)

    Cliquet, Florence; Robardet, Emmanuelle; Must, Kylli; Laine, Marjana; Peik, Katrin; Picard-Meyer, Evelyne; Guiot, Anne-Laure; Niin, Enel

    2012-01-01

    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. PMID:22393461

  15. First administration to humans of a monoclonal antibody cocktail against rabies virus: safety, tolerability, and neutralizing activity

    NARCIS (Netherlands)

    Bakker, A. B. H.; Python, C.; Kissling, C. J.; Pandya, P.; Marissen, W. E.; Brink, M. F.; Lagerwerf, F.; Worst, S.; van Corven, E.; Kostense, S.; Hartmann, K.; Weverling, G. J.; Uytdehaag, F.; Herzog, C.; Briggs, D. J.; Rupprecht, C. E.; Grimaldi, R.; Goudsmit, J.

    2008-01-01

    Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Free-Roaming Dog Population Estimation and Status of the Dog Population Management and Rabies Control Program in Dhaka City, Bangladesh

    Science.gov (United States)

    Tenzin, Tenzin; Ahmed, Rubaiya; Debnath, Nitish C.; Ahmed, Garba; Yamage, Mat

    2015-01-01

    Beginning January 2012, a humane method of dog population management using a Catch-Neuter-Vaccinate-Release (CNVR) program was implemented in Dhaka City, Bangladesh as part of the national rabies control program. To enable this program, the size and distribution of the free-roaming dog population needed to be estimated. We present the results of a dog population survey and a pilot assessment of the CNVR program coverage in Dhaka City. Free-roaming dog population surveys were undertaken in 18 wards of Dhaka City on consecutive days using mark-resight methods. Data was analyzed using Lincoln-Petersen index-Chapman correction methods. The CNVR program was assessed over the two years (2012–2013) whilst the coverage of the CNVR program was assessed by estimating the proportion of dogs that were ear-notched (processed dogs) via dog population surveys. The free-roaming dog population was estimated to be 1,242 (95 % CI: 1205–1278) in the 18 sampled wards and 18,585 dogs in Dhaka City (52 dogs/km2) with an estimated human-to-free-roaming dog ratio of 828:1. During the two year CNVR program, a total of 6,665 dogs (3,357 male and 3,308 female) were neutered and vaccinated against rabies in 29 of the 92 city wards. A pilot population survey indicated a mean CNVR coverage of 60.6% (range 19.2–79.3%) with only eight wards achieving > 70% coverage. Given that the coverage in many neighborhoods was below the WHO-recommended threshold level of 70% for rabies eradications and since the CNVR program takes considerable time to implement throughout the entire Dhaka City area, a mass dog vaccination program in the non-CNVR coverage area is recommended to create herd immunity. The findings from this study are expected to guide dog population management and the rabies control program in Dhaka City and elsewhere in Bangladesh. PMID:25978406

  19. Effects of gamma radiation immunogenicity of ribonucleoprotein (RNPs) of rabies virus and purification of anti-RNPs antibodies for diagnosis

    International Nuclear Information System (INIS)

    Costa, Ana Elena Boamorte da

    2010-01-01

    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)

  20. Investigating the effect of carbon source on rabies virus glycoprotein production in Pichia pastoris by a transcriptomic approach.

    Science.gov (United States)

    Ben Azoun, Safa; Kallel, Héla

    2017-08-01

    Several factors affect protein expression in Pichia pastoris, one among them is the carbon source. In this work, we studied the effect of this factor on the expression level of rabies virus glycoprotein (RABV-G) in two recombinant clones harboring seven copies of the gene of interest. The expression was driven either by the constitutive glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter or the inducible alcohol oxidase1 (AOX1) promoter. Clones were compared in terms of cell physiology and carbon source metabolism. The transcription levels of 16 key genes involved in the central metabolic pathway, the methanol catabolism, and the oxidative stress were investigated in both clones. Cell size, as a parameter reflecting cell physiological changes, was also monitored. Our results showed that when glucose was used as the sole carbon source, large cells were obtained. Transcript levels of the genes of the central metabolic pathway were also upregulated, whereas antioxidative gene transcript levels were low. By contrast, the use of methanol as a carbon source generated small cells and a shift in carbon metabolism toward the dissimilatory pathway by the upregulation of formaldehyde dehydrogenase gene and the downregulation of those of the central metabolic. These observations are in favor of the use of glucose to enhance the expression of RABV-G in P. pastoris. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  1. Arctic Rabies – A Review

    Directory of Open Access Journals (Sweden)

    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.

  2. Comparison of the protective efficacy between single and combination of recombinant adenoviruses expressing complete and truncated glycoprotein, and nucleoprotein of the pathogenic street rabies virus in mice.

    Science.gov (United States)

    Kim, Ha-Hyun; Yang, Dong-Kun; Nah, Jin-Ju; Song, Jae-Young; Cho, In-Soo

    2017-06-24

    Rabies is an important viral zoonosis that causes acute encephalitis and death in mammals. To date, several recombinant vaccines have been developed based on G protein, which is considered to be the main antigen, and these vaccines are used for rabies control in many countries. Most recombinant viruses expressing RABV G protein retain the G gene from attenuated RABV. Not enough is currently known about the protective effect against RABV of a combination of recombinant adenoviruses expressing the G and N proteins of pathogenic street RABV. We constructed a recombinant adenovirus (Ad-0910Gsped) expressing the signal peptide and ectodomain (sped) of G protein of the Korean street strain, and evaluated the immunological protection conferred by a single and combination of three kinds of recombinant adenoviruses (Ad-0910Gsped and Ad-0910G with or without Ad-0910 N) in mice. A combination of Ad-0910G and Ad-0910 N conferred improved immunity against intracranial challenge compared to single administration of Ad-0910G. The Ad-0910G virus, expressing the complete G protein, was more immunogenic than Ad-0910Gsped, which expressed a truncated G protein with the transmembrane and cytoplasmic domains removed. Additionally, oral vaccination using a combination of viruses led to complete protection. Our results suggest that this combination of viruses is a viable new intramuscular and oral vaccine candidate.

  3. The epidemiology of rabies in Zimbabwe. 1. Rabies in dogs (Canis familiaris).

    Science.gov (United States)

    Bingham, J; Foggin, C M; Wandeler, A I; Hill, F W

    1999-03-01

    The epidemiology of rabies in dogs in Zimbabwe is described using data from 1950, when rabies was re-introduced after a 37-year absence, to 1996. Dogs constituted 45.7% of all laboratory-confirmed rabies cases and were the species most frequently diagnosed with the disease. Slightly more cases were diagnosed from June to November than in other months. From 1950 to the early 1980s, most dog cases were recorded from commercial farming areas, but since the early 1980s most have been recorded from communal (subsistence farming) areas. This change appears to be due to improved surveillance in communal areas and not to any change in the prevalence of rabies. Dog rabies therefore appears to be maintained mainly in communal area dog populations, particularly the large communal area blocks. Urban rabies was not important except in the city of Mutare. Where dog rabies prevalence was high, the disease was cyclic with periods between peak prevalence ranging from 4-7 years. Dog rabies cases were, on the whole, independent of jackal rabies and rabies in other carnivores. There was a significant negative relationship between the annual number of rabies vaccine doses administered nationally to dogs and the annual number of dog rabies cases lagged by one year, indicating that the past levels of immunisation coverage have had a significant effect on the number of rabies cases. However, dog vaccination coverage has clearly not been adequate to prevent the regular occurrence of rabies in dogs.

  4. Spontaneous pneumomediastinum due to paralytic rabies

    Directory of Open Access Journals (Sweden)

    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.

  5. Spontaneous pneumomediastinum due to paralytic rabies

    Directory of Open Access Journals (Sweden)

    Wuping Wang

    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.

  6. Engineering of a novel zipFv using leucine zipper motif against rabies virus glycoprotein G with improved protection potency in vivo.

    Science.gov (United States)

    Xi, Hualong; Zhang, Kaixin; Yin, Yanchun; Gu, Tiejun; Sun, Qing; Li, Zhuang; Cheng, Yue; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2017-06-01

    Rabies is an acute zoonotic infectious disease with a high fatality rate but is preventable with vaccination and rabies immunoglobulin (RIG). The single-chain Fv fragment (scFv), a small engineered antigen-binding protein derived from antibody variable heavy (V H ) and light (V L ) chains connected by a peptide linker, can potentially be used to replace RIG. Here, we produced two peptides V H -JUN-HIS and V L -FOS-HA separately in Escherichia coli and assembled them to form zipFv successfully in vitro. The new zipFv utilizes FOS and JUN leucine zippers to form an antibody structure similar to the IgG counterpart with two free N-terminal ends of V H and V L . The zipFv protein showed notable improvement in binding ability and affinity over its corresponding scFv. The zipFv also demonstrated greater stability in serum and the same protective rate as RIG against challenge with a standard rabies virus (CVS-24) in mice. Our results indicated zipFv as a novel and efficient antibody form with enhanced neutralizing potency. Copyright © 2017. Published by Elsevier B.V.

  7. Detection of Rabies Antigen in the Brain Tissues of Apparetly ...

    African Journals Online (AJOL)

    Rabies is a serious public health hazard and recently outbreaks of the disease have been reported in three local government areas in Cross River State. Detection of rabies antigen in the brain tissues of apparently healthy dogs indicates the presence of rabies virus and this is a significant factor in the transmission and ...

  8. Protective role of interferon against cytotoxcicity induced by rabies ...

    African Journals Online (AJOL)

    Rabies remains an important public health problem in the world due to uncontrolled enzootic rabies, lack of safe efficient vaccines and poor information on the risk of contracting rabies post animal exposure. The lethality and mutagenic potential of challenge virus standard (CVS) was evaluated in mice. Mice were ...

  9. Outbreak of human rabies in the Peruvian jungle.

    Science.gov (United States)

    Lopez, A; Miranda, P; Tejada, E; Fishbein, D B

    1992-02-15

    Transmission of rabies to man by vampire bats has been known for 60 years but there have been few reports of the features of rabies transmitted in this way. These aspects of the disease were investigated during an outbreak in Peru in early 1990. Between Jan 1 and April 30, 1990, 29 (5%) of 636 residents of the two rural communities in the Amazon Jungle in Peru acquired an illness characterised by hydrophobia, fever, and headache and died shortly thereafter. A census in one of the two towns revealed that the proportion affected was significantly higher for 5-14 year olds (17%) than for other age-groups (p less than 10(-5). Interviews conducted with 23 of the patients or their families revealed that 22 (96%) had a history of bat bite, compared with 66 (22%) of 301 community members who remained healthy (p less than 10(-6). A rabies virus strain identical to those isolated from vampire bats (Desmodus rotundus) was isolated from the brain of the only person on whom necropsy could be done. Because of the extreme isolation of this and other communities affected by bat-transmitted rabies, preventive measures should be directed at decreasing the risk of nocturnal exposure to bats by bat proofing dwellings or use of mosquito nets and at prompt wound care. Rabies pre-exposure or postexposure vaccination is clearly indicated, but may not be feasible in these isolated populations.

  10. Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus.

    Science.gov (United States)

    Suu-Ire, Richard; Begeman, Lineke; Banyard, Ashley C; Breed, Andrew C; Drosten, Christian; Eggerbauer, Elisa; Freuling, Conrad M; Gibson, Louise; Goharriz, Hooman; Horton, Daniel L; Jennings, Daisy; Kuzmin, Ivan V; Marston, Denise; Ntiamoa-Baidu, Yaa; Riesle Sbarbaro, Silke; Selden, David; Wise, Emma L; Kuiken, Thijs; Fooks, Anthony R; Müller, Thomas; Wood, James L N; Cunningham, Andrew A

    2018-03-01

    Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation. To allow comparison between strains, we ensured the same titer of virus was inoculated in the same location of the brain of each bat. All bats (n = 3 per strain) were infected, and developed neurological signs, and fatal meningoencephalitis with lyssavirus antigen expression in neurons. There were three main differences among the groups. First, time to death was substantially shorter in the Senegal and Ghana groups (4 to 6 days) than in the Nigeria group (8 days). Second, each virus strain produced a distinct clinical syndrome. Third, the spread of virus to peripheral tissues, tested by hemi-nested reverse transcriptase PCR, was frequent (3 of 3 bats) and widespread (8 to 10 tissues positive of 11 tissues examined) in the Ghana group, was frequent and less widespread in the Senegal group (3/3 bats, 3 to 6 tissues positive), and was rare and restricted in the Nigeria group (1/3 bats, 2 tissues positive). Centrifugal spread of virus from brain to tissue of excretion in the oral cavity is required to enable lyssavirus transmission. Therefore, the Senegal and Ghana strains seem most suitable for further pathogenesis, and for transmission, studies in the straw-colored fruit bat.

  11. A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

    Science.gov (United States)

    Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

    2012-01-01

    Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958

  12. 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

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

    Science.gov (United States)

    Xiang, Z.Q.; Greenberg, L.; Ertl, H. C.; Rupprecht, C.E.

    2014-01-01

    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. PMID:24503087

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

    Directory of Open Access Journals (Sweden)

    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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Müller, Thomas F.; Schröder, Ronald; Wysocki, Patrick; Mettenleiter, Thomas C.; Freuling, Conrad M.

    2015-01-01

    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. PMID:26280895

  20. 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. Copyright © 2015. Published by Elsevier Ltd.

  1. Novel vaccines to human rabies.

    Directory of Open Access Journals (Sweden)

    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.

  2. [The growth of attenuated strains of canine parvovirus, mink enteritis virus, feline panleukopenia virus, and rabies virus on various types of cell cultures].

    Science.gov (United States)

    Zuffa, T

    1987-10-01

    The growth characteristics were studied in the attenuated strains of canine parvovirus CPVA-BN 80/82, mink enteritis virus MEVA-BN 63/82 and feline panleucopenia virus FPVA-BN 110/83 on the stable feline kidney cell line FE, and in the attenuated canine distemper virus CDV-F-BN 10/83 on chicken embryo cell cultures (KEB) and cultures of the stable cell line VERO. When the FE cultures were infected with different parvoviruses in cell suspension at MOI 2-4 TKID50 per cell, the first multiplication of the intracellular virus was recorded 20 hours p. i. In the canine parvovirus, the content of intracellular and extracellular virus continued increasing parallelly until the fourth day; then, from the fourth to the sixth day, the content of extracellular virus still increased whereas that of intracellular virus fell rapidly. In the case of the mink enteritis virus the release of the virus into the culture medium continued parallelly with the production of the cellular virus until the sixth day. In the case of the feline panleucopenia virus the values concerning free virus and virus bound to cells were lower, starting from the second day p. i. When KEB or VERO cultures were infected in cell suspension with the canine distemper virus at MOI about 0.004 per 1 cell, the replicated intracellular virus was first recorded in the KEB cultures five hours after infection but in the VERO cultures only 20 hours after infection, with a timely release of the virus into the culture medium in both kinds of tissue. In the KEB and VERO cultures the highest values of infection titres were recorded on the fourth day p. i., the course of virus multiplication on the cells being parallel with its release into the culture medium.

  3. Learning about Bats and Rabies

    Science.gov (United States)

    ... Rabies and Kids! Rabies Learning about bats and rabies Recommend on Facebook Tweet Share Compartir Most bats ... might contact people and pets. Bats and human rabies in the United States Rabies in humans is ...

  4. Why has canine rabies remained endemic in the Kilosa district of Tanzania? Lessons learnt and the way forward.

    Science.gov (United States)

    Kipanyula, M J

    2015-11-30

    Domestic dogs are the main targets for rabies control as they are the principal reservoir for transmission of the rabies virus to humans and other domestic animals. The purpose of this study was to identify the factors that contribute to the rabies virus infecting the human population in a rural community of Eastern Tanzania. Using a cross-sectional study design, field visits were conducted to gather information on villagers' knowledge on and practices associated with canine rabies control and dog vaccination campaigns. A total of 248 individuals were interviewed in the Kilosa district, Tanzania. Almost two-thirds (61.3 %) had a primary school education. The majority (91.1 %) of the respondents were aware that rabies is acquired through dog bites and 66.9 % knew about the clinical signs of rabies in an animal. Very few (17.7 %), however, were aware of the clinical signs of rabies in humans. Only 20.4 % of the respondents knew how rabies is controlled in dogs and 71 % were not aware of dog vaccination campaigns. The average number of dogs kept per household was 4 ± 3.3; 70.0 % of the respondents had one to five dogs, 28.3 % had six to dog dogs, and 1.6 % had 16-20 dogs. The dogs were primarily used to guard livestock and property, and to hunt. About 59.7 % of the respondents indicated that rabies was a public health problem. Low vaccination coverage was observed in the study area, with previous mass vaccination campaigns covering only 24.4 % of the dog population. Dogs appeared to have limited value in the studied community. Furthermore, there were no proper waste disposal facilities and oftentimes wild canids and felids visited the villages to scavenge on kitchen leftovers. Although communities in the Kilosa district had knowledge on rabies in dogs, they were not aware of the public health implication of the disease, which thus led a poor response during mass dog vaccination campaigns. Establishment of a well-coordinated rabies control program, strategic public

  5. 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. 2015 FRAME.

  6. Burden of Rabies

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    ... this? Submit Button Past Emails The Burden of Rabies Recommend on Facebook Tweet Share Compartir Learn how ... bitten by an animal that has the disease. Rabies in the U.S. Rabies continues to be a ...

  7. Travelers' Health: Rabies

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    ... Fever Chapter 3 - Perspectives: Intradermal Rabies Preexposure Immunization Rabies Brett W. Petersen, Ryan M. Wallace, David R. ... animal. Box 3-04. World Health Organization, human rabies case definition Clinical case definition: a person presenting ...

  8. A thermostable messenger RNA based vaccine against rabies.

    Science.gov (United States)

    Stitz, Lothar; Vogel, Annette; Schnee, Margit; Voss, Daniel; Rauch, Susanne; Mutzke, Thorsten; Ketterer, Thomas; Kramps, Thomas; Petsch, Benjamin

    2017-12-01

    Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.

  9. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

    2016-01-01

    Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

  10. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

    Directory of Open Access Journals (Sweden)

    Sanne Terryn

    2016-08-01

    Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

  11. Immunization against Rabies with Plant-Derived Antigen

    Science.gov (United States)

    Modelska, Anna; Dietzschold, Bernard; Sleysh, N.; Fu, Zhen Fang; Steplewski, Klaudia; Hooper, D. Craig; Koprowski, Hilary; Yusibov, Vidadi

    1998-03-01

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

  12. Rabies (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Rabies KidsHealth / For Parents / Rabies What's in this article? ... Treatment Prevention Print en español La rabia About Rabies Rabies infections in people are rare in the ...

  13. A single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults.

    Science.gov (United States)

    Recuenco, Sergio; Warnock, Eli; Osinubi, Modupe O V; Rupprecht, Charles E

    2017-08-03

    In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naïve and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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

  15. Re-emerging of rabies in Shaanxi province, China, from 2009 to 2015.

    Science.gov (United States)

    Ma, Chaofeng; Hao, Xiaoyun; Deng, Huiling; Wu, Rui; Liu, Jifeng; Yang, Yang; Li, Shen; Han, Yifei; Wei, Mingmin; Zhang, Junjun; Wang, Jingjun; Li, Hengxin; Tian, Huaiyu; Xu, Bing; Yu, Pengbo; Wu, Xiaokang

    2017-09-01

    To explore the epidemiological, phylogeographic, and migration characteristics of human rabies in Shaanxi province, China from 2009 to 2015. The collected data were described and the sequenced glycoprotein (G) and nucleoprotein (N) genes were implemented to estimate the evolutionary rates and phylogeographic patterns using BEAST v.1.8.2. A total of 269 rabies cases were reported and 70.26% of the cases were male and 61.71% were between the ages of 19-59. The majority of the cases were farmers (83.27%). The estimated evolutionary rate of the N genes was 2.4 × 10 -4 substitutions/site/year and the G genes was 3.4 × 10 -4 . The time of the most recent common ancestor (TMRCA) was estimated around 1990. We detected viral migration paths from Sichuan, Guizhou, and Hunan to Hanzhong prefecture of Shaanxi and then spreaded to Xi'an and other prefectures. The main population affected by rabies virus was male adult farmers. The evolution rate of rabies viruses in Shaanxi was similar with the prior results reported by others and the ancestor virus should be circulating in neighboring province Sichuan around 1990 and then transmitted to Shaanxi. Promptly standard wound treatment and timely post-exposure prophylaxis should be compulsory for the dog-bitten victims. © 2017 Wiley Periodicals, Inc.

  16. Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway

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    Bin Tian

    2018-01-01

    Full Text Available Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV, evades the host immune response and infects the host central nervous system (CNS has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt, RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I or melanoma differentiation-associated protein 5 (MDA5. Activation of mitochondrial antiviral-signaling protein (MAVS, the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.

  17. Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine.

    Science.gov (United States)

    Stading, Ben; Ellison, James A; Carson, William C; Satheshkumar, Panayampalli Subbian; Rocke, Tonie E; Osorio, Jorge E

    2017-10-01

    Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). Mice vaccinated and boosted intradermally with 1 x 107 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x107 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x108 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN-luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of

  18. A human monoclonal antibody cocktail as a novel component of rabies postexposure prophylaxis

    NARCIS (Netherlands)

    de Kruif, John; Bakker, Alexander B. H.; Marissen, Wilfred E.; Kramer, R. Arjen; Throsby, Mark; Rupprecht, Charles E.; Goudsmit, Jaap

    2007-01-01

    The currently recommended treatment for individuals exposed to rabies virus is the combined administration of rabies vaccine and rabies immune globulin (RIG). This review sets out the criteria used to guide development of a cocktail of human monoclonal antibodies as a replacement for RIG. Using this

  19. 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.

  20. 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

  1. Rabies in Iraq: trends in human cases 2001-2010 and characterisation of animal rabies strains from Baghdad.

    Directory of Open Access Journals (Sweden)

    Daniel L Horton

    Full Text Available Control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. These are challenging in any circumstances, but particularly during conflict. Here we describe available human rabies surveillance data from Iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from Iraq. Human rabies is notifiable, with reported cases increasing since 2003, and a marked increase in Baghdad between 2009 and 2010. These changes coincide with increasing numbers of reported dog bites. There is no laboratory confirmation of disease or virus characterisation and no systematic surveillance for rabies in animals. To address these issues, brain samples were collected from domestic animals in the greater Baghdad region and tested for rabies. Three of 40 brain samples were positive using the fluorescent antibody test and hemi-nested RT-PCR for rabies virus (RABV. Bayesian phylogenetic analysis using partial nucleoprotein gene sequences derived from the samples demonstrated the viruses belong to a single virus variant and share a common ancestor with viruses from neighbouring countries, 22 (95% HPD 14-32 years ago. These include countries lying to the west, north and east of Iraq, some of which also have other virus variants circulating concurrently. These results suggest possible multiple introductions of rabies into the Middle East, and regular trans-boundary movement of disease. Although 4000 years have passed since the original description of disease consistent with rabies, animals and humans are still dying of this preventable and neglected zoonosis.

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

    International Nuclear Information System (INIS)

    Xiang, Z.Q.; Greenberg, L.; Ertl, H.C.; Rupprecht, C.E.

    2014-01-01

    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

  3. Investigation of an Imported Case of Rabies in a Juvenile Dog with Atypical Presentation

    Directory of Open Access Journals (Sweden)

    Trudy Goddard

    2011-11-01

    Full Text Available Movement of dogs between rabies-endemic and rabies-free countries carries the inherent risk of introducing the disease. In April of 2008, a juvenile dog was imported to the UK from Sri Lanka. It died shortly after transfer to a quarantine facility in the south-east of England following a short history of diarrhoea and convulsions but no overt signs of aggression. Subsequent investigation confirmed that rabies was the cause of death. Rabies virus was isolated from brain samples taken from the dog and the subsequent phylogenetic investigation confirmed that the genomic sequence from this virus shared over 99% homology with endemic rabies viruses from Sri Lanka. Histological examination of the brain demonstrated clear signs of encephalitis and rabies antigenic labeling in numerous neurons. In this particular case, Negri bodies were absent. As this case was diagnosed in a quarantine facility, the ‘rabies-free’ status of the UK was un-affected.

  4. 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.

  5. Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

    Science.gov (United States)

    Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael

    2018-02-09

    Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

  6. Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus

    NARCIS (Netherlands)

    Suu-Ire, R. (Richard); L. Begeman (Lineke); A. Banyard (Ashley); A.C. Breed; C. Drosten (Christian); Eggerbauer, E. (Elisa); Freuling, C.M. (Conrad M.); Gibson, L. (Louise); Goharriz, H. (Hooman); D.L. Horton; Jennings, D. (Daisy); I.V. Kuzmin (Ivan); D.A. Marston (Denise); Ntiamoa-Baidu, Y. (Yaa); Riesle Sbarbaro, S. (Silke); Selden, D. (David); Wise, E.L. (Emma L.); Kuiken, T. (Thijs); A.R. Fooks (Anthony); T. Müller (Thomas); Wood, J.L.N. (James L. N.); A.A. Cunningham

    2018-01-01

    textabstractRabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no

  7. Vaccination of Ferrets for Rabies and Distemper.

    Science.gov (United States)

    Wade, Laura L

    2018-01-01

    Companion ferrets need to be vaccinated against 2 viral diseases that cause neurologic illness: canine distemper and rabies. Although not common in ferrets, both viruses are fatal in ferrets and rabies virus is also fatal in humans. In this article, we provide a basic review of the 2 diseases, highlighting key neurologic concerns. We also review and update current vaccine concerns from a practitioner's perspective, including available vaccines, vaccine schedule recommendations, vaccine reactions, and risk assessment. Last, we mention the ferret and its use in cutting-edge vaccine development. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Photoluminescence of double core/shell infrared (CdSeTe)/ZnS quantum dots conjugated to Pseudo rabies virus antibodies

    Science.gov (United States)

    Torchynska, T. V.; Casas Espinola, J. L.; Jaramillo Gómez, J. A.; Douda, J.; Gazarian, K.

    2013-06-01

    Double core CdSeTe/ZnS quantum dots (QDs) with emission at 800 nm (1.60 eV) have been studied by photoluminescence (PL) and Raman scattering methods in the non-conjugated state and after the conjugation to the Pseudo rabies virus (PRV) antibodies. The transformation of PL spectra, stimulated by the electric charge of antibodies, has been detected for the bioconjugated QDs. Raman scattering spectra are investigated with the aim to reveal the CdSeTe core compositions. The double core QD energy diagrams were designed that help to analyze the PL spectra and their transformation at the bioconjugation. It is revealed that the interface in double core QDs has the type II quantum well character that permits to explain the near IR optical transition (1.60 eV) in the double core QDs. It is shown that the essential transformation of PL spectra is useful for the study of QD bioconjugation with specific antibodies and can be a powerful technique in early medical diagnostics.

  9. Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

    Science.gov (United States)

    Zhu, Shimao; Guo, Caiping

    2016-01-01

    Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies. PMID:27801824

  10. Rabies virus co-localizes with early (Rab5) and late (Rab7) endosomal proteins in neuronal and SH-SY5Y cells.

    Science.gov (United States)

    Ahmad, Waqas; Li, Yingying; Guo, Yidi; Wang, Xinyu; Duan, Ming; Guan, Zhenhong; Liu, Zengshan; Zhang, Maolin

    2017-06-01

    Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated. Immunofluorescence, TCID 50 titers, electron microscopy and western blotting were carried out to determine the molecular interaction of the nucleoprotein (N) of RABV with early or late endosomal proteins in these cell lines. The expression of N was also determined by down-regulating Rab5 and Rab7 in both cell lines through RNA interference. The results were indicative that N proficiently colocalized with Rab5/EEA1 and Rab7/LAMP1 in both cell lines at 24 and 48 h post-infection, while N titers significantly decreased in early infection of RABV. Down-regulation of Rab5 and Rab7 did not inhibit N expression, but it prevented productive infection via blocking the normal trafficking of RABV in a low pH environment. Ultrathin sections of cells studied by electron microscope also verified the close association of RABV with Rab5 and Rab7 in neurons. From the data it was concluded that primary entry of RABV strongly correlates with the kinetics of Rab-proteins present on early and late vesicles, which provides helpful clues to explain the early events of RABV in nerve cells.

  11. Rabies in the Americas

    Science.gov (United States)

    Rabies in the Americas Search this site Welcome Previous Meetings Steering Committee Contact Sitemap Welcome The Rabies in the Americas (RITA) meeting is an annual event that has been held since 1990 managers of rabies programs, wildlife biologists, laboratory personnel and other people interested in

  12. Ecology and Geography of Transmission of Two Bat-Borne Rabies Lineages in Chile

    OpenAIRE

    Escobar, Luis E.; Peterson, A. Townsend; Favi, Myriam; Yung, Ver?nica; Pons, Daniel J.; Medina-Vogel, Gonzalo

    2013-01-01

    Rabies was known to humans as a disease thousands of years ago. In America, insectivorous bats are natural reservoirs of rabies virus. The bat species Tadarida brasiliensis and Lasiurus cinereus, with their respective, host-specific rabies virus variants AgV4 and AgV6, are the principal rabies reservoirs in Chile. However, little is known about the roles of bat species in the ecology and geographic distribution of the virus. This contribution aims to address a series of questions regarding th...

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

    International Nuclear Information System (INIS)

    Zhang, Yi; Zhang, Shoufeng; Li, Wei; Hu, Yuchi; Zhao, Jinyan; Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu; Hu, Rongliang; Shao, Hui; Li, Lietao

    2016-01-01

    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

  14. 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

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

    Science.gov (United States)

    Yao, Hong-Wu; Yang, Yang; Liu, Kun; Li, Xin-Lou; Zuo, Shu-Qing; Sun, Ruo-Xi; Fang, Li-Qun; Cao, Wu-Chun

    2015-02-01

    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.

  16. 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

  17. [Calbindin and parvalbumin distribution in spinal cord of normal and rabies-infected mice].

    Science.gov (United States)

    Monroy-Gómez, Jeison; Torres-Fernández, Orlando

    2013-01-01

    Rabies is a fatal infectious disease of the nervous system; however, the knowledge about the pathogenic neural mechanisms in rabies is scarce. In addition, there are few studies of rabies pathology of the spinal cord. To study the distribution of calcium binding proteins calbindin and parvalbumin and assessing the effect of rabies virus infection on their expression in the spinal cord of mice. MATERIALES Y METHODS: Mice were inoculated with rabies virus, by intracerebral or intramuscular route. The spinal cord was extracted to perform some crosscuts which were treated by immunohistochemistry with monoclonal antibodies to reveal the presence of the two proteins in normal and rabies infected mice. We did qualitative and quantitative analyses of the immunoreactivity of the two proteins. Calbindin and parvalbumin showed differential distribution in Rexed laminae. Rabies infection produced a decrease in the expression of calbindin. On the contrary, the infection caused an increased expression of parvalbumin. The effect of rabies infection on the two proteins expression was similar when comparing both routes of inoculation. The differential effect of rabies virus infection on the expression of calbindin and parvalbumin in the spinal cord of mice was similar to that previously reported for brain areas. This result suggests uniformity in the response to rabies infection throughout the central nervous system. This is an important contribution to the understanding of the pathogenesis of rabies.

  18. Bat Rabies and Other Lyssavirus Infections

    Science.gov (United States)

    Constantine, Denny G.; Blehert, David S.

    2009-01-01

    Bat Rabies and Other Lyssavirus Infections offers readers an overview of the virus variants that cause bat rabies, and geographical patterns in occurrence of this disease. The section Species Susceptibility describes infection rates and trends among bats, humans, and other animals. Disease Ecology considers the biological and environmental dynamics of the disease in various species of bats. Points to Ponder: Interspecies Interactions in Potential Bat Rabies Transmission Settings discusses the narrowing interface of bat colonies and human society and how humans and domestic animals play a role in transmission of bat rabies. Disease Prevention and Control outlines how to limit exposure to rabid bats and other animals. Appendixes include extensive tables of reported infections in bat species and in humans, and a glossary of technical terms is included. The author, Denny G. Constantine, helped define rabies infection in insect-eating bats and has investigated bat rabies ecology for more than half a century. He has authored more than 90 papers during the course of his career and is widely considered to be the world's foremost authority on the disease. Currently, Dr. Constantine is a public health officer emeritus and veterinary epidemiologist for the California Department of Health Services Viral and Rickettsial Disease Laboratory. Milt Friend, first director of the USGS National Wildlife Health Center, wrote the foreword. David Blehert, a USGS microbiologist who is investigating the emergence and causes of bat white-nose syndrome, edited the volume. Bat Rabies is intended for scholars and the general public. Dr. Constantine presents the material in a simple, straightforward manner that serves both audiences. The goal of the author is to increase people's understanding of both bat and disease ecology and also provide a balanced perspective on human risks pertaining to bat rabies.

  19. Geographical Clusters and Predictors of Rabies in Three Southeastern States.

    Science.gov (United States)

    Reilly, Sara; Sanderson, Wayne T; Christian, W Jay; Browning, Steven R

    2017-06-01

    The rabies virus causes progressive encephalomyelitis that is fatal in nearly 100% of untreated cases. In the United States, wildlife act as the primary reservoir for rabies; prevention, surveillance, and control costs remain high. The purpose of this study is to understand the current distribution of wildlife rabies in three southeastern states, with particular focus on raccoons as the primary eastern reservoir, as well as identify demographic and geographic factors which may affect the risk of human exposure. This ecologic study obtained county-level rabies surveillance data from state health departments and the United States Department of Agriculture Wildlife services for North Carolina, Virginia, and West Virginia from 2010 to 2013. A spatial statistical analysis was performed to identify county clusters with high or low rates of raccoon rabies in the three states. Potential demographic and geographic factors associated with these varying rates of rabies were assessed using a multivariable negative binomial regression model. In North Carolina, raccoons constituted 50% of positive tests, in Virginia, 49%, and in West Virginia, 50%. Compared to persons residing in West Virginia counties, persons in North Carolina counties had 1.67 times the risk of exposure (p rabies exposure. Further research is needed to better understand the effect of the oral rabies vaccine program in controlling the risk of human exposure to raccoon rabies.

  20. Application and Comparative Evaluation of Fluorescent Antibody, Immunohistochemistry and Reverse Transcription Polymerase Chain Reaction Tests for the Detection of Rabies Virus Antigen or Nucleic Acid in Brain Samples of Animals Suspected of Rabies in India

    Directory of Open Access Journals (Sweden)

    K. Nithin Prabhu

    2018-02-01

    Full Text Available Accurate and early diagnosis of animal rabies is critical for undertaking public health measures. Whereas the direct fluorescent antibody (DFA technique is the recommended test, the more convenient, direct rapid immunochemistry test (dRIT, as well as the more sensitive, reverse transcription polymerase chain reaction (RT-PCR, have recently been employed for the laboratory diagnosis of rabies. We compared the three methods on brain samples from domestic (dog, cat, cattle, buffalo, horse, pig and goat and wild (leopard, wolf and jackal animals from various parts of India. Of the 257 samples tested, 167 were positive by all the three tests; in addition, 35 of the 36 decomposed samples were positive by RT-PCR. This is the first study in which such large number of animal samples have been subjected to the three tests simultaneously. The results confirm 100% corroboration between DFA and dRIT, buttress the applicability of dRIT in the simple and rapid diagnosis of rabies in animals, and reaffirm the suitability of RT-PCR for samples unfit for testing either by DFA or dRIT.

  1. Application and Comparative Evaluation of Fluorescent Antibody, Immunohistochemistry and Reverse Transcription Polymerase Chain Reaction Tests for the Detection of Rabies Virus Antigen or Nucleic Acid in Brain Samples of Animals Suspected of Rabies in India.

    Science.gov (United States)

    Prabhu, K Nithin; Isloor, Shrikrishna; Veeresh, B Hanchinal; Rathnamma, Doddamane; Sharada, R; Das, Lekshmi J; Satyanarayana, M L; Hegde, Nagendra R; Rahman, Sira Abdul

    2018-02-28

    Accurate and early diagnosis of animal rabies is critical for undertaking public health measures. Whereas the direct fluorescent antibody (DFA) technique is the recommended test, the more convenient, direct rapid immunochemistry test (dRIT), as well as the more sensitive, reverse transcription polymerase chain reaction (RT-PCR), have recently been employed for the laboratory diagnosis of rabies. We compared the three methods on brain samples from domestic (dog, cat, cattle, buffalo, horse, pig and goat) and wild (leopard, wolf and jackal) animals from various parts of India. Of the 257 samples tested, 167 were positive by all the three tests; in addition, 35 of the 36 decomposed samples were positive by RT-PCR. This is the first study in which such large number of animal samples have been subjected to the three tests simultaneously. The results confirm 100% corroboration between DFA and dRIT, buttress the applicability of dRIT in the simple and rapid diagnosis of rabies in animals, and reaffirm the suitability of RT-PCR for samples unfit for testing either by DFA or dRIT.

  2. Serological Surveillance for Non-Rabies Lyssaviruses among ...

    African Journals Online (AJOL)

    Out of the seven recognized and four putative genotypes of lyssaviruses, genotypes 1-3 comprising namely the classical rabies virus (RABV), Lagos bat virus (LBV) and Mokola virus (MOKV) respectively have been reported in Nigeria. The domestic dog, Canis familiaris, is recognized as the reservoir for genotype 1, and the ...

  3. Human rabies due to lyssavirus infection of bat origin.

    Science.gov (United States)

    Johnson, N; Vos, A; Freuling, C; Tordo, N; Fooks, A R; Müller, T

    2010-05-19

    Rabies is a fatal viral encephalitis and results from infection with viruses belonging to the genus Lyssavirus. Infection usually results from a bite from a dog infected with classical rabies virus. However, a small number of cases result from contact with bats. It is within bats that most lyssavirus variants, referred to as genotypes, are found. The lyssaviruses found in bats have a distinct geographical distribution and are often restricted to specific bat species. Most have been associated with rabies in humans and in some cases spill-over to domestic animals. Many diagnostic techniques are unable to differentiate rabies virus from other genotypes so it is possible that some human and animal cases go unreported. Furthermore, current vaccines have limited efficacy against some genotypes. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  4. [Diagnosis of rabies infection in animals using monoclonal antibodies].

    Science.gov (United States)

    Akacem, O; Taril, A; Benelmouffok, A; Bemansour, A; Couillin, P; Brahimi, M; Benhassine, M

    1989-01-01

    Two monoclonal antibodies (M.A.), specific for viral nucleocapsid, the M.A. D-20 and the M.A. D-43 raised against a fixed strain of rabies virus (C.V.S. 11), have been tested in parallel with a standard antirabies serum (S.A.R.) in diagnosis of animal rabies virus infection. 44 brain imprints from animals which died from rabies were tested by indirect immunofluorescent technique with monoclonal antibodies. Constant correlation has been found between the M.A. D-43 and the S.A.R. in the diagnosis of animal rabies virus infection in all cases studied. For M.A. D-20, concordance of results with S.A.R. was found only in limited number of cases.

  5. The evolution of RNA viruses: A population genetics view

    Science.gov (United States)

    Moya, Andrés; Elena, Santiago F.; Bracho, Alma; Miralles, Rosario; Barrio, Eladio

    2000-01-01

    RNA viruses are excellent experimental models for studying evolution under the theoretical framework of population genetics. For a proper justification of this thesis we have introduced some properties of RNA viruses that are relevant for studying evolution. On the other hand, population genetics is a reductionistic theory of evolution. It does not consider or make simplistic assumptions on the transformation laws within and between genotypic and phenotypic spaces. However, such laws are minimized in the case of RNA viruses because the phenotypic space maps onto the genotypic space in a much more linear way than on higher DNA-based organisms. Under experimental conditions, we have tested the role of deleterious and beneficial mutations in the degree of adaptation of vesicular stomatitis virus (VSV), a nonsegmented virus of negative strand. We also have studied how effective population size, initial genetic variability in populations, and environmental heterogeneity shapes the impact of mutations in the evolution of vesicular stomatitis virus. Finally, in an integrative attempt, we discuss pros and cons of the quasispecies theory compared with classic population genetics models for haploid organisms to explain the evolution of RNA viruses. PMID:10860958

  6. Rabies surveillance in bats in Northwestern State of São Paulo

    Directory of Open Access Journals (Sweden)

    Daiene Karina Azevedo Casagrande

    2014-12-01

    Full Text Available Introduction Rabies is an important zoonosis that occurs in mammals, with bats acting as Lyssavirus reservoirs in urban, rural and natural areas. Rabies cases in bats have been recorded primarily in urban areas in Northwestern State of São Paulo since 1998. This study investigated the circulation of rabies virus by seeking to identify the virus in the brain in several species of bats in this region and by measuring rabies-virus neutralizing antibody levels in the hematophagous bat Desmodus rotundus. Methods From 2008 to 2012, 1,490 bat brain samples were sent to the Universidade Estadual Paulista (UNESP Rabies Laboratory in Araçatuba, and 125 serum samples from vampire bats that were captured in this geographical region were analyzed. Results Rabies virus was detected in the brains of 26 (2% of 1,314 non-hematophagous bats using the fluorescent antibody test (FAT and the mouse inoculation test (MIT. None of the 176 hematophagous bat samples were positive for rabies virus when a virus detection test was utilized. Out of 125 vampire bat serum samples, 9 (7% had levels of rabies virus neutralization antibodies (RVNAs that were higher than 0.5IU/mL; 65% (81/125 had titers between 0.10IU/mL and 0.5IU/mL; and 28% (35/125 were negative for RVNAs using the simplified fluorescent inhibition microtest (SFIMT in BHK21 cells. The observed positivity rate (1.7% was higher than the average positivity rate of 1.3% that was previously found in this region. Conclusions The high percentage of vampire bats with neutralizing antibodies suggests that recent rabies virus exposure has occurred, indicating the necessity of surveillance measures in nearby regions that are at risk to avoid diffusion of the rabies virus and possible rabies occurrences.

  7. Changes in Population Dynamics in Mutualistic versus Pathogenic Viruses

    Directory of Open Access Journals (Sweden)

    Marilyn J. Roossinck

    2011-01-01

    Full Text Available Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics.

  8. 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.

  9. Canine Rabies: A Looming Threat to Public Health

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    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.

  10. Rabies in Kazakhstan

    OpenAIRE

    Sultanov, Akmetzhan A.; Abdrakhmanov, Sarsenbay K.; Abdybekova, Aida M.; Karatayev, Bolat S.; Torgerson, Paul R.

    2016-01-01

    Background 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. Methodology/Principal Findings We used detailed public health and veterina...

  11. Rabies in Kazakhstan.

    Science.gov (United States)

    Sultanov, Akmetzhan A; Abdrakhmanov, Sarsenbay K; Abdybekova, Aida M; Karatayev, Bolat S; Torgerson, Paul R

    2016-08-01

    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 Kazakhstan.

  12. 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.

  13. Rabies surveillance in the United States during 2010

    Science.gov (United States)

    Blanton, Jesse D.; Palmer, Dustyn; Dyer, Jessie; Rupprecht, Charles E.

    2016-01-01

    Summary During 2010, 48 states and Puerto Rico reported 6,154 rabid animals and 2 human rabies cases to the CDC, representing an 8% decrease from the 6,690 rabid animals and 4 human cases reported in 2009. Hawaii and Mississippi did not report any laboratory-confirmed rabid animals during 2010. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,246 raccoons (36.5%), 1,448 skunks (23.5%), 1,430 bats (23.2%), 429 foxes (6.9%), 303 cats (4.9%), 71 cattle (1.1%), and 69 dogs (1.1%). Compared with 2009, number of reported rabid animals decreased across all animal types with the exception of a 1% increase in the number of reported rabid cats. Two cases of rabies involving humans were reported from Louisiana and Wisconsin in 2010. Louisiana reported an imported human rabies case involving a 19-year-old male migrant farm worker who had a history of a vampire bat (Desmodus rotundus) bite received while in Mexico. This represents the first human rabies case reported in the United States confirmed to have been caused by a vampire bat rabies virus variant. Wisconsin reported a human rabies case involving a 70-year-old male that was confirmed to have been caused by a rabies virus variant associated with tri-colored bats (Perimyotis subflavus). PMID:21916759

  14. Influenza D Virus Infection in Feral Swine Populations, United States.

    Science.gov (United States)

    Ferguson, Lucas; Luo, Kaijian; Olivier, Alicia K; Cunningham, Fred L; Blackmon, Sherry; Hanson-Dorr, Katie; Sun, Hailiang; Baroch, John; Lutman, Mark W; Quade, Bianca; Epperson, William; Webby, Richard; DeLiberto, Thomas J; Wan, Xiu-Feng

    2018-06-01

    Influenza D virus (IDV) has been identified in domestic cattle, swine, camelid, and small ruminant populations across North America, Europe, Asia, South America, and Africa. Our study investigated seroprevalence and transmissibility of IDV in feral swine. During 2012-2013, we evaluated feral swine populations in 4 US states; of 256 swine tested, 57 (19.1%) were IDV seropositive. Among 96 archived influenza A virus-seropositive feral swine samples collected from 16 US states during 2010-2013, 41 (42.7%) were IDV seropositive. Infection studies demonstrated that IDV-inoculated feral swine shed virus 3-5 days postinoculation and seroconverted at 21 days postinoculation; 50% of in-contact naive feral swine shed virus, seroconverted, or both. Immunohistochemical staining showed viral antigen within epithelial cells of the respiratory tract, including trachea, soft palate, and lungs. Our findings suggest that feral swine might serve an important role in the ecology of IDV.

  15. 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.

  16. Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies.

    Science.gov (United States)

    Vora, N M; Orciari, L A; Niezgoda, M; Selvaggi, G; Stosor, V; Lyon, G M; Wallace, R M; Gabel, J; Stanek, D R; Jenkins, P; Shiferaw, M; Yager, P; Jackson, F; Hanlon, C A; Damon, I; Blanton, J D; Recuenco, S; Franka, R

    2015-06-01

    The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies

    Science.gov (United States)

    Vora, N.M.; Orciari, L.A.; Niezgoda, M.; Selvaggi, G.; Stosor, V.; Lyon, G.M.; Wallace, R.M.; Gabel, J.; Stanek, D.R.; Jenkins, P.; Shiferaw, M.; Yager, P.; Jackson, F.; Hanlon, C.A.; Damon, I.; Blanton, J.D.; Recuenco, S.; Franka, R.

    2015-01-01

    Background The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. Methods As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. Results All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. Conclusions The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies. PMID:25851103

  18. 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.

  19. Challenges and needs for China to eliminate rabies.

    Science.gov (United States)

    Yin, Wenwu; Dong, Jie; Tu, Changchun; Edwards, John; Guo, Fusheng; Zhou, Hang; Yu, Hongjie; Vong, Sirenda

    2013-10-02

    In China, rabies is a significant public health concern where dogs remain the main reservoir of disease transmission to humans; rabies-related mortality ranks second in the world.We compiled all published articles and official documents on rabies in mainland China to examine challenges and needs to eliminate rabies in the country. The Chinese authorities have identified rabies as a priority, recognized rabies control in dogs as key to control rabies in humans and required intersectoral collaborations. Efforts have been made to respond effectively to the latest re-emergence of rabies, which peaked in 2007 with >3,300 cases. Despite these outcomes and the increasing volume of publications and regulations in the recent years, our review points to some major information gaps to improve rabies control activities and envisage elimination program. An emphasis on laboratory or pathogen-associated and basic epidemiology research in the literature has contrasted with the absence of information to monitor various systems in humans and animals (e.g. quality of surveillance, response and post-exposure prophylaxis). Information is also lacking to appropriately inform policymakers (e.g. economic disease burden, impact of policies) and assist program managers (e.g. comprehensive and strategic guidance for cost-effective prevention and control activities, public education and dog population management).In conclusion, strategic planning is needed to provide a sense of direction, demonstrate feasibility of elimination in China, and develop a research agenda, addressing country's operational needs and constraints. The planning should be a multisectoral effort.

  20. Nuclear Trafficking of the Rabies Virus Interferon Antagonist P-Protein Is Regulated by an Importin-Binding Nuclear Localization Sequence in the C-Terminal Domain.

    Directory of Open Access Journals (Sweden)

    Caitlin L Rowe

    Full Text Available Rabies virus P-protein is expressed as five isoforms (P1-P5 which undergo nucleocytoplasmic trafficking important to roles in immune evasion. Although nuclear import of P3 is known to be mediated by an importin (IMP-recognised nuclear localization sequence in the N-terminal region (N-NLS, the mechanisms underlying nuclear import of other P isoforms in which the N-NLS is inactive or has been deleted have remained unresolved. Based on the previous observation that mutation of basic residues K214/R260 of the P-protein C-terminal domain (P-CTD can result in nuclear exclusion of P3, we used live cell imaging, protein interaction analysis and in vitro nuclear transport assays to examine in detail the nuclear trafficking properties of this domain. We find that the effect of mutation of K214/R260 on P3 is largely dependent on nuclear export, suggesting that nuclear exclusion of mutated P3 involves the P-CTD-localized nuclear export sequence (C-NES. However, assays using cells in which nuclear export is pharmacologically inhibited indicate that these mutations significantly inhibit P3 nuclear accumulation and, importantly, prevent nuclear accumulation of P1, suggestive of effects on NLS-mediated import activity in these isoforms. Consistent with this, molecular binding and transport assays indicate that the P-CTD mediates IMPα2/IMPβ1-dependent nuclear import by conferring direct binding to the IMPα2/IMPβ1 heterodimer, as well as to a truncated form of IMPα2 lacking the IMPβ-binding autoinhibitory domain (ΔIBB-IMPα2, and IMPβ1 alone. These properties are all dependent on K214 and R260. This provides the first evidence that P-CTD contains a genuine IMP-binding NLS, and establishes the mechanism by which P-protein isoforms other than P3 can be imported to the nucleus. These data underpin a refined model for P-protein trafficking that involves the concerted action of multiple NESs and IMP-binding NLSs, and highlight the intricate regulation of P

  1. The Formation of the Eastern Africa Rabies Network: A Sub-Regional Approach to Rabies Elimination.

    Science.gov (United States)

    Pieracci, Emily G; Scott, Terence P; Coetzer, Andre; Athman, Mwatondo; Mutembei, Arithi; Kidane, Abraham Haile; Bekele, Meseret; Ayalew, Girma; Ntegeyibizaza, Samson; Assenga, Justine; Markalio, Godson; Munyua, Peninah; Nel, Louis H; Blanton, Jesse

    2017-01-01

    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.

  2. Surveillance and control of rabies in La Reunion, Mayotte, and Madagascar

    Science.gov (United States)

    2013-01-01

    Mayotte and La Reunion islands are currently free of animal rabies and surveillance is performed by the French Human and Veterinary Public Health Services. However, dog rabies is still enzootic in Madagascar with 4 to 10 confirmed human cases each year. The number of antirabies medical centres in Madagascar is still scarce to provide easy access to the local population for post-exposure rabies prophylaxis. Furthermore, stray dog populations are considerable and attempts to control rabies by mass campaigns of dog vaccination have not received sufficient attention from the national health authorities. To address these challenges, an expanded program to control rabies needs to be initiated by the Malagasy authorities. PMID:24016204

  3. Geographical Analysis for Detecting High-Risk Areas for Bovine/Human Rabies Transmitted by the Common Hematophagous Bat in the Amazon Region, Brazil.

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    Fernanda A G de Andrade

    Full Text Available 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.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.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.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 measures and controls.

  4. Rabies Vaccine and Rabies Immunoglobulin in Cambodia: Use and Obstacles to Use.

    Science.gov (United States)

    Tarantola, Arnaud; Ly, Sowath; In, Sotheary; Ong, Sivuth; Peng, Yiksing; Heng, Nayyim; Buchy, Philippe

    2015-01-01

    Authorities have pledged to eliminate canine rabies by 2020 in Cambodia, a country with a very high rabies burden. Logistic and financial access to timely and adequate postexposure prophylaxis (PEP) is essential for preventing rabies in humans. We undertook a survey of the few identified sites where PEP rabies vaccination and rabies immunoglobulin (RIG) are available in Cambodia. We examined the Rabies Prevention Center at Institut Pasteur du Cambodge (rpc@ipc) database and rpc@ipc order forms for 2012 to assess vaccine and RIG use. We conducted a rapid internet survey of centers that provide rabies vaccine and RIG in Cambodia, other than rpc@ipc. The cost of a full course of intramuscular or intradermal PEP in Cambodia, with and without RIG, was also estimated. Rabies vaccination is free of charge in one foundation hospital and is accessible for a fee at Institut Pasteur du Cambodge (IPC), some institutions, and some Cambodian private clinics. In 2012, 27,500 rabies vaccine doses (0.5 mL) and 591 equine RIG doses were used to provide intradermal PEP to 20,610 persons at rpc@ipc following animal bites. Outside of rpc@ipc, an estimated total of 53,400 vaccine doses and 200 RIG doses were used in Cambodia in 2012. The wholesale cost of full rabies PEP was estimated at 50% to 100% of a Cambodian farmer's monthly wage. Local populations and travelers cannot be sure to locally access adequate and timely PEP due to high costs and low access to RIG. Travelers to high-endemic areas such as Cambodia are strongly encouraged to undergo pre-exposure vaccination or seek expert advice, as per World Health Organization (WHO) recommendations. State-subsidized, pre-positioned stocks of human vaccine and RIG in bite management centers would extend the rabies prevention centers network. Support from Institut Pasteur du Cambodge for staff training, cold chain, and quality control would contribute to reducing the risk of rabies deaths in Cambodia. © 2015 International Society of

  5. Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and laboratory findings

    Directory of Open Access Journals (Sweden)

    Sunil Karande

    2015-07-01

    Full Text Available A 6-year-old boy from India developed an atypical form of rabies following a stray dog bite and as a consequence of not receiving the standard World Health Organization recommended post-exposure prophylaxis for category III wounds. Serial rising rabies virus neutralizing antibody titres in serum and cerebrospinal fluid by rapid fluorescent focus inhibition test helped confirm the diagnosis of rabies. The child has survived for 4 months since the onset of illness, albeit with neurological sequelae.

  6. Homogeneity of Powassan virus populations in naturally infected Ixodes scapularis

    International Nuclear Information System (INIS)

    Brackney, Doug E.; Brown, Ivy K.; Nofchissey, Robert A.; Fitzpatrick, Kelly A.; Ebel, Gregory D.

    2010-01-01

    Powassan virus (POWV, Flaviviridae: Flavivirus) is the sole North American member of the tick-borne encephalitis complex and consists of two distinct lineages that are maintained in ecologically discrete enzootic transmission cycles. The underlying genetic mechanisms that lead to niche partitioning in arboviruses are poorly understood. Therefore, intra- and interhost genetic diversity was analyzed to determine if POWV exists as a quasispecies in nature and quantify selective pressures within and between hosts. In contrast to previous reports for West Nile virus (WNV), significant intrahost genetic diversity was not observed. However, pN (0.238) and d N /d S ratios (0.092) for interhost diversity were similar to those of WNV. Combined, these data suggest that purifying selection and/or population bottlenecks constrain quasispecies diversity within ticks. These same selective and stochastic mechanisms appear to drive minor sequence changes between ticks. Moreover, Powassan virus populations seem not to be structured as quasispecies in naturally infected adult deer ticks.

  7. Continuous Influx of Genetic Material from Host to Virus Populations.

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    Clément Gilbert

    2016-02-01

    Full Text Available Many genes of large double-stranded DNA viruses have a cellular origin, suggesting that host-to-virus horizontal transfer (HT of DNA is recurrent. Yet, the frequency of these transfers has never been assessed in viral populations. Here we used ultra-deep DNA sequencing of 21 baculovirus populations extracted from two moth species to show that a large diversity of moth DNA sequences (n = 86 can integrate into viral genomes during the course of a viral infection. The majority of the 86 different moth DNA sequences are transposable elements (TEs, n = 69 belonging to 10 superfamilies of DNA transposons and three superfamilies of retrotransposons. The remaining 17 sequences are moth sequences of unknown nature. In addition to bona fide DNA transposition, we uncover microhomology-mediated recombination as a mechanism explaining integration of moth sequences into viral genomes. Many sequences integrated multiple times at multiple positions along the viral genome. We detected a total of 27,504 insertions of moth sequences in the 21 viral populations and we calculate that on average, 4.8% of viruses harbor at least one moth sequence in these populations. Despite this substantial proportion, no insertion of moth DNA was maintained in any viral population after 10 successive infection cycles. Hence, there is a constant turnover of host DNA inserted into viral genomes each time the virus infects a moth. Finally, we found that at least 21 of the moth TEs integrated into viral genomes underwent repeated horizontal transfers between various insect species, including some lepidopterans susceptible to baculoviruses. Our results identify host DNA influx as a potent source of genetic diversity in viral populations. They also support a role for baculoviruses as vectors of DNA HT between insects, and call for an evaluation of possible gene or TE spread when using viruses as biopesticides or gene delivery vectors.

  8. The 'Milwaukee protocol' (MP hope does not succeeds for rabies victim

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    Anil Kumar Agarwal

    2017-01-01

    Full Text Available Rabies is caused by the rabies virus, an RNA-based virus in the genus Lyssavirus. Transmission typically occurs when virus-laden saliva from a rabid animal enters a wound or mucous membrane. The Milwaukee protocol, a novel procedure in which the patient was placed in a drug-induced coma and given an antiviral cocktail composed of ketamine, ribavirin, and amantadine. Considering the theory that rabies pathology stems from central nervous system neurotransmitter dysfunction, doctors hypothesized suppressed brain activity would minimize damage while the patient's immune system developed an adequate response.

  9. Potency of veterinary rabies vaccines in The Netherlands: A case for continued vigilance.

    NARCIS (Netherlands)

    E.J.M. Rooijakkers; J.H.M. Nieuwenhuijs; A.A. Vermeulen; A.D.M.E. Osterhaus (Albert); G. van Steenis (Bert)

    1996-01-01

    textabstractCommercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and

  10. Rabies elimination research: juxtaposing optimism, pragmatism and realism.

    Science.gov (United States)

    Cleaveland, Sarah; Hampson, Katie

    2017-12-20

    More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a 'One Health' approach. © 2017 The Authors.

  11. 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.

  12. 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.

  13. 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.

  14. VIRUS FAMILIES – contd

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. VIRUS FAMILIES – contd. Minus strand RNA viruses. Rhabdovirus e.g. rabies. Paramyxovirus e.g. measles, mumps. Orthomyxovirus e.g. influenza. Retroviruses. RSV, HTLV, MMTV, HIV. Notes:

  15. Rabies in the Eastern Cape Province of South Africa - where are we going wrong?

    Directory of Open Access Journals (Sweden)

    S.J. Van Sittert

    2010-05-01

    Full Text Available Rabies is a growing problem in the Eastern Cape Province of South Africa. This study investigated dog ecology, vaccination coverage and rabies neutralising antibody levels in 203 randomly selected dogs within a local municipality in the former Transkei area. Responses to vaccination were also evaluated in 80 of these dogs. The population was remarkably uniform in size, breed and condition. Slightly over 1/5th of the population was between 6 weeks and 1 year of age, while very few dogs reached 10 years or older. According to owner responses, the Animal Health Technicians achieved a total vaccination coverage of 65 % of owned dogs over several years, but only 56 % within the previous 12 months. Only 32%of dogs had adequate circulating rabies virus neutralisation antibodies (≥0.5IU/ℓ. After vaccination, 83 % had seroconverted to this level. The magnitude of seroconversion was independent of body condition or age. This study proposes a different approach to vaccination strategies than those currently employed in certain areas of the province.

  16. Poxvirus-vectored vaccines for rabies--a review.

    Science.gov (United States)

    Weyer, Jacqueline; Rupprecht, Charles E; Nel, Louis H

    2009-11-27

    Oral rabies vaccination of target reservoir species has proved to be one of the pillars of successful rabies elimination programs. The use of live attenuated rabies virus vaccines has been extensive but several limitations hamper its future use. A recombinant vaccinia-rabies vaccine has also been successfully used for the oral vaccination of several species. Nevertheless, its lack of efficacy in certain important rabies reservoirs and concerns on the use of this potent live virus as vaccine carrier (vector) impair the expansion of its use for new target species and new areas. Several attenuated and host-restricted poxvirus alternatives, which supposedly offer enhanced safety, have been investigated. Once again, efficacy in certain target species and innocuity through the oral route remain major limitations of these vaccines. Alternative recombinant vaccines using adenovirus as an antigen delivery vector have been extensively investigated and may provide an important addition to the currently available oral rabies vaccine repertoire, but are not the primary subject of this review.

  17. 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

  18. Anisotropic Rabi model

    OpenAIRE

    Xie, Qiong-Tao; Cui, Shuai; Cao, Jun-Peng; Amico, Luigi; Fan, Heng

    2014-01-01

    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 th...

  19. 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

  20. 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

  1. Protective role of interferon against cytotoxcicity induced by rabies ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-02-15

    Feb 15, 2010 ... lack of safe efficient vaccines and poor information on the risk of contracting rabies post animal exposure. .... cell was considered centromerically attenuated when it contains at least ..... population by adenovirus. In: Genetic ...

  2. Spatial and temporal trends of bat-borne rabies in Chile.

    Science.gov (United States)

    Escobar, L E; Restif, O; Yung, V; Favi, M; Pons, D J; Medina-Vogel, G

    2015-05-01

    In Chile, while dog rabies has decreased markedly over the last 30 years, bat rabies is still reported frequently. In order to shed new light on the spatiotemporal trends of these reports, we analysed active and passive data from years 1985 and 2012, which included 61 076 samples from 289 counties of Chile. We found that from 1994 to 2012, more than 15 000 bat samples were submitted for diagnostics through passive surveillance, 9·5% of which tested positive for rabies. By contrast, the prevalence of infection was only ~0·4% among the nearly 12 000 bat samples submitted through active surveillance. We found that the prevalence of dog rabies dropped steadily over the same period, with just a single confirmed case since 1998. None of the 928 samples from wild animals, other than bats, were positive for rabies. Although there has been only one confirmed case of human rabies in Chile since 1985, and a single confirmed case in a dog since 1998, bats remain a reservoir for rabies viruses. While active surveillance indicates that rabies prevalence is low in bat colonies, the high proportion of positive bats submitted through passive surveillance is a concern. To prevent human rabies, local public health agencies should increase research on the basic ecology of bats and the role of stray dogs and cats as potential rabies amplifiers.

  3. Animal and Rabies Control in Joint Operations Areas (Working Paper)

    Science.gov (United States)

    2012-08-13

    appear lethargic with hypersalivation and anorexia . Two rabies syndromes are recognized in animals—the paralytic or “dumb” and hyperactive or “furious... nutritional needs, making populated areas a preferred habitat and increasing the reproductive capacity of animals which is attributed to improved... nutrition . Without appropriate vaccination and population control, feral animals contribute to the maintenance of sylvatic rabies cycles in local wildlife

  4. Ecology and geography of transmission of two bat-borne rabies lineages in Chile.

    Science.gov (United States)

    Escobar, Luis E; Peterson, A Townsend; Favi, Myriam; Yung, Verónica; Pons, Daniel J; Medina-Vogel, Gonzalo

    2013-01-01

    Rabies was known to humans as a disease thousands of years ago. In America, insectivorous bats are natural reservoirs of rabies virus. The bat species Tadarida brasiliensis and Lasiurus cinereus, with their respective, host-specific rabies virus variants AgV4 and AgV6, are the principal rabies reservoirs in Chile. However, little is known about the roles of bat species in the ecology and geographic distribution of the virus. This contribution aims to address a series of questions regarding the ecology of rabies transmission in Chile. Analyzing records from 1985-2011 at the Instituto de Salud Pública de Chile (ISP) and using ecological niche modeling, we address these questions to help in understanding rabies-bat ecological dynamics in South America. We found ecological niche identity between both hosts and both viral variants, indicating that niches of all actors in the system are undifferentiated, although the viruses do not necessarily occupy the full geographic distributions of their hosts. Bat species and rabies viruses share similar niches, and our models had significant predictive power even across unsampled regions; results thus suggest that outbreaks may occur under consistent, stable, and predictable circumstances.

  5. Ecology and Geography of Transmission of Two Bat-Borne Rabies Lineages in Chile

    Science.gov (United States)

    Escobar, Luis E.; Peterson, A. Townsend; Favi, Myriam; Yung, Verónica; Pons, Daniel J.; Medina-Vogel, Gonzalo

    2013-01-01

    Rabies was known to humans as a disease thousands of years ago. In America, insectivorous bats are natural reservoirs of rabies virus. The bat species Tadarida brasiliensis and Lasiurus cinereus, with their respective, host-specific rabies virus variants AgV4 and AgV6, are the principal rabies reservoirs in Chile. However, little is known about the roles of bat species in the ecology and geographic distribution of the virus. This contribution aims to address a series of questions regarding the ecology of rabies transmission in Chile. Analyzing records from 1985–2011 at the Instituto de Salud Pública de Chile (ISP) and using ecological niche modeling, we address these questions to help in understanding rabies-bat ecological dynamics in South America. We found ecological niche identity between both hosts and both viral variants, indicating that niches of all actors in the system are undifferentiated, although the viruses do not necessarily occupy the full geographic distributions of their hosts. Bat species and rabies viruses share similar niches, and our models had significant predictive power even across unsampled regions; results thus suggest that outbreaks may occur under consistent, stable, and predictable circumstances. PMID:24349592

  6. Factors Influencing Virulence and Plaque Properties of Attenuated Venezuelan Equine Encephalomyelitis Virus Populations

    Science.gov (United States)

    Hearn, Henry J.; Seliokas, Zenonas V.; Andersen, Arthur A.

    1969-01-01

    A minority of stable large-plaque virus increased proportionally in stored unstable attenuated (9t) Venezuelan equine encephalomyelitis virus populations. L-cell-grown progeny (9t2) of stored 9t showed large amounts of large-plaque virus and increased virulence. Small-plaque virus inhibited large-plaque virus but not the reverse. Serial passage of small-plaque virus from 9t2 yielded a strain (20t) that was more attenuated than 9t. PMID:5823235

  7. Rabies and Risk to Travelers

    Centers for Disease Control (CDC) Podcasts

    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.

  8. [Epidemiologic investigation into characteristics of canine and feline population in a district close to a rural area in Cuiabá-MT, with a view to control of animal rabies].

    Science.gov (United States)

    Caramori Junior, João Garcia; Lubas, Marco Antônio da Silva; Kawatake, Make Silva; Sales, Katia Gouvea; Guedes, Julio Capilé; Schmitt, Aline Conceição

    2003-01-01

    Questionnaires answered by 476 students (age 15-20 yrs) attending a local school in the neighborhood of Pedra 90 in Cuiabá -MT were analyzed in order to study the characteristics of feline and canine populations in the region. The results showed that 371 (78%) of the 476 families kept 513 dogs and 307 cats. Of 573 dogs, 289 (56.3%) were male and 224 (43.7%) were female. Of 307 cats, 182 (59.28%) were male and 125 (40.72%) were female. The owners of 474 (92.4%) dogs and 267 (86.9%) cats reported that their pets had been vaccinated against rabies.

  9. 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.

  10. Rabi oscillations in extreme ultraviolet ionization of atomic argon

    Science.gov (United States)

    Flögel, Martin; Durá, Judith; Schütte, Bernd; Ivanov, Misha; Rouzée, Arnaud; Vrakking, Marc J. J.

    2017-02-01

    We demonstrate Rabi oscillations in nonlinear ionization of argon by an intense femtosecond extreme ultraviolet (XUV) laser field produced by high-harmonic generation. We monitor the formation of A r2 + as a function of the time delay between the XUV pulse and an additional near-infrared (NIR) femtosecond laser pulse, and show that the population of an A r+* intermediate resonance exhibits strong modulations both due to an NIR laser-induced Stark shift and XUV-induced Rabi cycling between the ground state of A r+ and the A r+* excited state. Our experiment represents a direct experimental observation of a Rabi-cycling process in the XUV regime.

  11. Vaccine-induced rabies case in a cow (Bos taurus): Molecular characterisation of vaccine strain in brain tissue.

    Science.gov (United States)

    Vuta, Vlad; Picard-Meyer, Evelyne; Robardet, Emmanuelle; Barboi, Gheorghe; Motiu, Razvan; Barbuceanu, Florica; Vlagioiu, Constantin; Cliquet, Florence

    2016-09-22

    Rabies is a fatal neuropathogenic zoonosis caused by the rabies virus of the Lyssavirus genus, Rhabdoviridae family. The oral vaccination of foxes - the main reservoir of rabies in Europe - using a live attenuated rabies virus vaccine was successfully conducted in many Western European countries. In July 2015, a rabies vaccine strain was isolated from the brain tissues of a clinically suspect cow (Bos taurus) in Romania. The nucleotide analysis of both N and G gene sequences showed 100% identity between the rabid animal, the GenBank reference SAD B19 strain and five rabies vaccine batches used for the national oral vaccination campaign targeting foxes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Knowledge, attitudes and practices regarding rabies risk in community members and healthcare professionals: Pétionville, Haiti, 2013.

    Science.gov (United States)

    Fenelon, N; Dely, P; Katz, M A; Schaad, N D; Dismer, A; Moran, D; Laraque, F; Wallace, R M

    2017-06-01

    Haiti has the highest human rabies burden in the Western Hemisphere. There is no published literature describing the public's perceptions of rabies in Haiti, information that is critical to developing effective interventions and government policies. We conducted a knowledge, attitudes and practices survey of 550 community members and 116 health professionals in Pétionville, Haiti in 2013 to understand the perception of rabies in these populations. The majority of respondents (85%) knew that dogs were the primary reservoir for rabies, yet only 1% were aware that bats and mongooses could transmit rabies. Animal bites were recognized as a mechanism of rabies transmission by 77% of the population and 76% were aware that the disease could be prevented by vaccination. Of 172 persons reporting a bite, only 37% sought medical treatment. The annual bite incidence rate in respondents was 0·9%. Only 31% of bite victims reported that they started the rabies vaccination series. Only 38% of respondents reported that their dog had been vaccinated against rabies. The majority of medical professionals recognized that dogs were the main reservoir for rabies (98%), but only 28% reported bats and 14% reported mongooses as posing a risk for rabies infection. Bites were reported as a mechanism of rabies transmission by 73% of respondents; exposure to saliva was reported by 20%. Thirty-four percent of medical professionals reported they would wash a bite wound with soap and water and 2·8% specifically mentioned rabies vaccination as a component of post-bite treatment. The majority of healthcare professionals recommended some form of rabies assessment for biting animals; 68·9% recommended a 14-day observation period, 60·4% recommended a veterinary consultation, and 13·2% recommended checking the vaccination status of the animal. Fewer than 15% of healthcare professionals had ever received training on rabies prevention and 77% did not know where to go to procure rabies vaccine for

  13. Fighting rabies in Eastern Europe, the Middle East and Central Asia--experts call for a regional initiative for rabies elimination.

    Science.gov (United States)

    Aikimbayev, A; Briggs, D; Coltan, G; Dodet, B; Farahtaj, F; Imnadze, P; Korejwo, J; Moiseieva, A; Tordo, N; Usluer, G; Vodopija, R; Vranješ, N

    2014-05-01

    MEEREB is an informal network of rabies experts from the Middle East, Eastern Europe and Central Asia, seeking to eliminate rabies from the region. They met for the second time to review the current rabies situation, both globally and in their respective countries, highlighting current rabies control problems and potential solutions. Success stories in Latin America, in Western Europe, in some Asian countries, as well as in Croatia and Serbia prove that elimination of human rabies is achievable in the MEEREB region. It requires political willingness and cooperation of all stakeholders, including Ministries of Health and of Agriculture; adequate management of animal bites through post-exposure prophylaxis; pre-exposure prophylaxis for populations at high risk of rabies exposure, animal vaccination and humane control of stray dog populations. MEEREB members called for a regional initiative for rabies elimination in Eastern Europe and the Middle East. They are confident that the elimination of human rabies of canine origin can be achieved in the region through adopting a One Health approach, and that campaigns for rabies elimination will have significant benefit for public health, including strengthening the structure for control of other zoonoses. © 2013 Blackwell Verlag GmbH.

  14. Advances in Diagnosis of Rabies

    Directory of Open Access Journals (Sweden)

    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

  15. Oral vaccination of wildlife against rabies: Differences among host species in vaccine uptake efficiency.

    Science.gov (United States)

    Vos, Ad; Freuling, Conrad M; Hundt, Boris; Kaiser, Christiane; Nemitz, Sabine; Neubert, Andreas; Nolden, Tobias; Teifke, Jens P; Te Kamp, Verena; Ulrich, Reiner; Finke, Stefan; Müller, Thomas

    2017-07-13

    Oral vaccination using attenuated and recombinant rabies vaccines has been proven a powerful tool to combat rabies in wildlife. However, clear differences have been observed in vaccine titers needed to induce a protective immune response against rabies after oral vaccination in different reservoir species. The mechanisms contributing to the observed resistance against oral rabies vaccination in some species are not completely understood. Hence, the immunogenicity of the vaccine virus strain, SPBN GASGAS, was investigated in a species considered to be susceptible to oral rabies vaccination (red fox) and a species refractory to this route of administration (striped skunk). Additionally, the dissemination of the vaccine virus in the oral cavity was analyzed for these two species. It was shown that the palatine tonsils play a critical role in vaccine virus uptake. Main differences could be observed in palatine tonsil infection between both species, revealing a locally restricted dissemination of infected cells in foxes. The absence of virus infected cells in palatine tonsils of skunks suggests a less efficient uptake of or infection by vaccine virus which may lead to a reduced response to oral vaccination. Understanding the mechanisms of oral resistance to rabies virus vaccine absorption and primary replication may lead to the development of novel strategies to enhance vaccine efficacy in problematic species like the striped skunk. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Comparative pathogenesis of rabies in bats and carnivores, and implications for spillover to humans.

    Science.gov (United States)

    Begeman, Lineke; GeurtsvanKessel, Corine; Finke, Stefan; Freuling, Conrad M; Koopmans, Marion; Müller, Thomas; Ruigrok, Tom J H; Kuiken, Thijs

    2018-04-01

    Bat-acquired rabies is becoming increasingly common, and its diagnosis could be missed partly because its clinical presentation differs from that of dog-acquired rabies. We reviewed the scientific literature to compare the pathogenesis of rabies in bats and carnivores-including dogs-and related this pathogenesis to differences in the clinical presentation of bat-acquired and dog-acquired rabies in human beings. For bat-acquired rabies, we found that the histological site of exposure is usually limited to the skin, the anatomical site of exposure is more commonly the face, and the virus might be more adapted for entry via the skin than for dog-acquired rabies. These factors could help to explain several differences in clinical presentation between individuals with bat-acquired and those with dog-acquired rabies. A better understanding of these differences should improve the recording of a patient's history, enable drawing up of a more sophisticated list of clinical characteristics, and therefore obtain an earlier diagnosis of rabies after contact with a bat or carnivore that has rabies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Spatial and temporal distribution of rabies in northern Tanzania in the period of 1993-2002.

    Science.gov (United States)

    Swai, E S; Moshy, W E; Kaaya, J E; Mtui, P F

    2010-01-01

    A retrospective study was carried out to investigate the occurrence and distribution patterns of rabies cases in northern Tanzania. Data on laboratory confirmed brain samples and associated case reports submitted to the Arusha Veterinary Investigation Centre, for a period of ten years (1993-2002) was retrieved and reviewed. A total of 98 suspected rabies brain specimens from different animal species and geographical areas were submitted and processed during the period under review. Rabies was confirmed using Fluorescent Antibody Technique test. Of the 98 brain specimens processed, 65 (66.3%) were confirmed to be rabies cases. Canine rabies accounted for 73.8% of the cases and was diagnosed in dogs (43), jackals (4) and hyenas (1). Rabies in wildlife accounted for 5 out of 48 canine confirmed cases. Most of the cases were from Arusha Municipality (20) followed by Arumeru (19), Ngorongoro (9) and Moshi (8) districts. Rabies positive cases in other animal species were in the following order of frequencies: bovine (9 out of 11); feline (5 out of 10); equine (1 out of 2); caprine (2 out of 2). One porcine brain specimen was rabies negative. The high proportion of rabies positive cases confirmed suggests the level of their endemicity in the northern regions of Tanzania. Moreover, the findings highlights the need for sustained surveillance and institution of control measures among dog population and awareness creation particularly among general public and children whom are at high risk of contracting rabies because of their close contact with dogs.

  18. Rabies Across Borders

    Centers for Disease Control (CDC) Podcasts

    2017-12-04

    Dr. Roman Biek, with the Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, discusses rabies outbreaks in Canada from the U.S.  Created: 12/4/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 12/4/2017.

  19. 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.

  20. Rabies: Diagnosis in Animals and Humans

    Science.gov (United States)

    ... R S T U V W X Y Z # Rabies Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rabies Homepage Exposure What materials can spread rabies? What ...

  1. A case study of rabies diagnosis from formalin-fixed brain material : short communication

    Directory of Open Access Journals (Sweden)

    J. Coertse

    2011-05-01

    Full Text Available Rabies is caused by several Lyssavirus species, a group of negative sense RNA viruses. Although rabies is preventable, it is often neglected particularly in developing countries in the face of many competing public and veterinary health priorities. Epidemiological information based on laboratory-based surveillance data is critical to adequately strategise control and prevention plans. In this regard the fluorescent antibody test for rabies virus antigen in brain tissues is still considered the basic requirement for laboratory confirmation of animal cases. Occasionally brain tissues from suspected rabid animals are still submitted in formalin, although this has been discouraged for a number of years. Immunohistochemical testing or a modified fluorescent antibody technique can be performed on such samples. However, this method is cumbersome and cannot distinguish between different Lyssavirus species. Owing to RNA degradation in formalin-fixed tissues, conventional RT-PCR methodologies have also been proven to be unreliable. This report is concerned with a rabies case in a domestic dog from an area in South Africa where rabies is not common. Typing of the virus involved was therefore important, but the only available sample was submitted as a formalin-fixed specimen. A real-time RT-PCR method was therefore applied and it was possible to confirmrabies and obtain phylogenetic information that indicated a close relationship between this virus and the canid rabies virus variants from another province (KwaZulu-Natal in South Africa.

  2. Surveillance of Human Rabies by National Authorities--A Global Survey.

    Science.gov (United States)

    Taylor, L H; Knopf, L

    2015-11-01

    Effective prevention of deaths due to human rabies is currently hampered by a lack of understanding of the scale of the problem, and the distribution of both animal and human cases across countries, regions and continents. Unfortunately, despite the severity of the disease, accurate data on which to assess these questions and to prioritize and direct public health interventions are not available for many parts of the world. This survey sought to understand the current global situation regarding the surveillance of human rabies. Data were collected from 91 countries across all continents and all categories of human rabies risk, generating the most complete and representative global data set currently available. Respondents were asked key questions about whether human rabies was a notifiable disease, how the surveillance system for human rabies operated and whether the respondent considered that the surveillance system was working effectively. Across the 91 countries from which data were collated, human rabies was a notifiable disease in all but eight. Despite international guidance, surveillance systems were very varied. Even where rabies is a notifiable disease, many countries had surveillance system judged to be ineffective, almost all of these being high and moderate rabies risk countries in Africa and Asia. Overall, 41% of the population covered by this survey (around 2.5 billion people) live in countries where there is no or ineffective rabies surveillance. The lack of robust surveillance is hindering rabies control efforts. However, whilst worldwide rabies surveillance would be improved if rabies were notifiable in all countries, many other challenges to the implementation of effective global human rabies surveillance systems remain. © 2015 Blackwell Verlag GmbH.

  3. Towards canine rabies elimination: Economic comparisons of three project sites.

    Science.gov (United States)

    Elser, J L; Hatch, B G; Taylor, L H; Nel, L H; Shwiff, S A

    2018-02-01

    An appreciation of the costs of implementing canine rabies control in different settings is important for those planning new or expanded interventions. Here we compare the costs of three canine rabies control projects in South Africa, the Philippines and Tanzania to identify factors that influence the overall costs of rabies control efforts. There was considerable variation in the cost of vaccinating each dog, but across the sites these were lower where population density was higher, and later in the projects when dog vaccination coverage was increased. Transportation costs comprised a much higher proportion of total costs in rural areas and where house-to-house vaccination campaigns were necessary. The association between the cost of providing PEP and human population density was less clear. The presence of a pre-existing national rabies management programme had a marked effect on keeping infrastructure and equipment costs for the project low. Finally, the proportion of the total costs of the project provided by the external donor was found to be low for the projects in the Philippines and South Africa, but likely covered close to the complete costs of the project in Tanzania. The detailed economic evaluation of three recent large-scale rabies control pilot projects provides the opportunity to examine economic costs across these different settings and to identify factors influencing rabies control costs that could be applied to future projects. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  4. 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.

  5. A One Health Message about Bats Increases Intentions to Follow Public Health Guidance on Bat Rabies.

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    Hang Lu

    Full Text Available Since 1960, bat rabies variants have become the greatest source of human rabies deaths in the United States. Improving rabies awareness and preventing human exposure to rabid bats remains a national public health priority today. Concurrently, conservation of bats and the ecosystem benefits they provide is of increasing importance due to declining populations of many bat species. This study used a visitor-intercept experiment (N = 521 in two U.S. national parks where human and bat interactions occur on an occasional basis to examine the relative persuasiveness of four messages differing in the provision of benefit and uncertainty information on intentions to adopt a rabies exposure prevention behavior. We found that acknowledging benefits of bats in a risk message led to greater intentions to adopt the recommended rabies exposure prevention behavior without unnecessarily stigmatizing bats. These results signify the importance of communicating benefits of bats in bat rabies prevention messages to benefit both human and wildlife health.

  6. Transmission dynamics and prospects for the elimination of canine rabies.

    Directory of Open Access Journals (Sweden)

    Katie Hampson

    2009-03-01

    Full Text Available Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R0, is very low in our study area in rural Africa (approximately 1.2 and throughout its historic global range (<2. This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.

  7. Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV)

    DEFF Research Database (Denmark)

    Snow, M.; Bain, N.; Black, J.

    2004-01-01

    The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the m......The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders...... this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups...... of isolates associated with rainbow trout aquaculture (Genotype la) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also...

  8. Community perception regarding rabies prevention and stray dog control in urban slums in India.

    Science.gov (United States)

    Herbert, Mrudu; Riyaz Basha, S; Thangaraj, Selvi

    2012-12-01

    The lack of community awareness about rabies control is a major issue that thwarts efforts to prevent human deaths caused by rabies. The objectives of this study were (1) to assess community knowledge and attitudes about rabies, rabies prevention and stray dog control in an urban slum community and (2) to determine the factors that influence rabies awareness in urban slums. Using a systematic random sampling strategy, 185 participants were selected from 8 urban slums. The data were collected by direct interview using a pre-tested, structured questionnaire. In the study population, 74.1% of the participants had heard about rabies, and 54.1% knew that rabies is a fatal disease. Only 33.5% of the interviewees felt that people in the community had a role to play in controlling the stray dog population. Gender, age and educational status were significantly associated with rabies awareness. Our study indicates that there are gaps in the knowledge and attitudes of individuals living in urban slums regarding rabies prevention and control. Efforts to promote awareness should be targeted at men, older people and uneducated individuals. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  9. Two-electron Rabi oscillations in real-time time-dependent density-functional theory

    International Nuclear Information System (INIS)

    Habenicht, Bradley F.; Tani, Noriyuki P.; Provorse, Makenzie R.; Isborn, Christine M.

    2014-01-01

    We investigate the Rabi oscillations of electrons excited by an applied electric field in several simple molecular systems using time-dependent configuration interaction (TDCI) and real-time time-dependent density-functional theory (RT-TDDFT) dynamics. While the TDCI simulations exhibit the expected single-electron Rabi oscillations at a single resonant electric field frequency, Rabi oscillations in the RT-TDDFT simulations are a two-electron process. The existence of two-electron Rabi oscillations is determined both by full population inversion between field-free molecular orbitals and the behavior of the instantaneous dipole moment during the simulations. Furthermore, the Rabi oscillations in RT-TDDFT are subject to an intensity threshold of the electric field, below which Rabi oscillations do not occur and above which the two-electron Rabi oscillations occur at a broad range of frequencies. It is also shown that at field intensities near the threshold intensity, the field frequency predicted to induce Rabi oscillations by linear response TDDFT only produces detuned Rabi oscillations. Instead, the field frequency that yields the full two-electron population inversion and Rabi oscillation behavior is shown to be the average of single-electron transition frequencies from the ground S 0 state and the doubly-excited S 2 state. The behavior of the two-electron Rabi oscillations is rationalized via two possible models. The first model is a multi-photon process that results from the electric field interacting with the three level system such that three level Rabi oscillations may occur. The second model suggests that the mean-field nature of RT-TDDFT induces paired electron propagation

  10. The Health Impact of Rabies in Haiti and Recent Developments on the Path Toward Elimination, 2010-2015.

    Science.gov (United States)

    Wallace, Ryan; Etheart, Melissa; Ludder, Fleurinord; Augustin, Pierre; Fenelon, Natael; Franka, Richard; Crowdis, Kelly; Dely, Patrick; Adrien, Paul; Pierre-Louis, J; Osinubi, Modupe; Orciari, Lillian; Vigilato, Marco; Blanton, Jesse; Patel, Roopal; Lowrance, David; Liverdieu, Andrecy; Coetzer, Andre; Boone, John; Lindenmayer, Joanne; Millien, M

    2017-10-01

    Haiti, a Caribbean country of 10.5 million people, is estimated to have the highest burden of canine-mediated human rabies deaths in the Western Hemisphere, and one of the highest rates of human rabies deaths in the world. Haiti is also the poorest country in the Western Hemisphere and has numerous economic and health priorities that compete for rabies-control resources. As a result, primary rabies-control actions, including canine vaccination programs, surveillance systems for human and animal rabies, and appropriate postbite treatment, have not been fully implemented at a national scale. After the 2010 earthquake that further hindered the development of public health program infrastructure and services, the U.S. Centers for Disease Control and Prevention worked with the Ministry of Public Health and Population and key health development partners (including the Pan-American Health Organization) to provide technical expertise and funding for general disease surveillance systems, laboratory capacity, and selected disease control programs; including rabies. In 2011, a cross-ministerial rabies consortium was convened with participation from multiple international rabies experts to develop a strategy for successful rabies control in Haiti. The consortium focused on seven pillars: 1) enhancement of laboratory diagnostic capacity, 2) development of comprehensive animal surveillance system, 3) development of comprehensive human rabies surveillance system, 4) educational outreach, 5) sustainable human rabies biologics supply, 6) achievement of sustained canine vaccination rates of ≥ 70%, and 7) finalization of a national rabies control strategy. From 2010 until 2015, Haiti has seen improvements in the program infrastructure for canine rabies control. The greatest improvements were seen in the area of animal rabies surveillance, in support of which an internationally recognized rabies laboratory was developed thereby leading to an 18-fold increase in the detection of

  11. Korelasi dan Penyebaran Kejadian Rabies pada Anjing dan Manusia di Kabupaten Klungkung Bali Tahun 2010-2014

    Directory of Open Access Journals (Sweden)

    Rendi Tegar Pratama

    2016-06-01

    Full Text Available Rabies atau penyakit anjing gila merupakan penyakit virus yang disebabkan oleh genus Lyssavirus dari famili Rhabdoviridae bersifat akut serta sangat berbahaya dan mengakibatkan kematian karena mampu menginfeksi sistem saraf pusat yakni otak dan sumsum tulang belakang. Penelitian ini bertujuan untuk mengetahui kawasan rabies, penyebaran rabies dan korelasi antara kejadian rabies pada anjing dan manusia di Kabupaten Klungkung tahun 2010-2014. Metode yang digunakan dalam penelitian ini adalah analisis deskriptif. Untuk mengetahui hubungan kejadian rabies pada anjing dan manusia dilakukan uji korelasi Rank Spearman. Berdasarkan uji korelasi Spearman diperoleh hasil bahwa terdapat hubungan yang searah antara kejadian rabies pada anjing dan manusia. Dari uji Spearman yang dilakukan nilai koefisiensi yang diperoleh adalah 0,468 dengan nilai signifikansi 0,037.

  12. Implementation of an Intersectoral Program to Eliminate Human and Canine Rabies: The Bohol Rabies Prevention and Elimination Project

    Science.gov (United States)

    Lapiz, Stella Marie D.; Miranda, Mary Elizabeth G.; Garcia, Romulo G.; Daguro, Leonida I.; Paman, Meydalyn D.; Madrinan, Frederick P.; Rances, Polizena A.; Briggs, Deborah J.

    2012-01-01

    Background The province of Bohol, located in the Visayas islands region in the Philippines has a human population of 1.13 million and was the 4th highest region for human rabies deaths in the country, averaging 10 per year, prior to the initiation of the Bohol Rabies Prevention and Elimination Project (BRPEP). Aims The BRPEP was initiated in 2007 with the goal of building a sustainable program that would prevent human rabies by eliminating rabies at its source, in dogs, by 2010. This goal was in line with the Philippine National Rabies Program whose objective is to eliminate rabies by 2020. Methods The intersectoral BRPEP was launched in 2007 and integrated the expertise and resources from the sectors of agriculture, public health and safety, education, environment, legal affairs, interior and local government. The program included: increasing local community involvement; implementing dog population control; conducting mass dog vaccination; improving dog bite management; instituting veterinary quarantine; and improving diagnostic capability, surveillance and monitoring. Funding was secured from the national government, provincial, municipal and village units, dog owners, NGOs, the regional office of the WHO, the UBS Optimus Foundation, and the Global Alliance for Rabies Control. The BRPEP was managed by the Bohol Rabies Prevention and Eradication Council (BRPEC) under the jurisdiction of the Governor of Bohol. Parallel organizations were created at the municipal level and village level. Community volunteers facilitated the institution of the program. Dog population surveys were conducted to plan for sufficient resources to vaccinate the required 70% of the dogs living in the province. Two island-wide mass vaccination campaigns were conducted followed by “catch up” vaccination campaigns. Registration of dogs was implemented including a small fee that was rolled back into the program to maintain sustainability. Children were educated by introducing rabies

  13. Reemergence of rabies in the southern Han river region, Korea.

    Science.gov (United States)

    Oem, Jae-Ku; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Myoung-Heon; Lee, Kyoung-Ki

    2014-07-01

    Recently, 11 cases of animal rabies were reported in the southern region (Suwon and Hwaseong cities) of Gyeonggi Province, South Korea. The cases were temporally separated into two cases in dogs (Canis lupus familiaris) in spring 2012 and nine cases in domestic animals and wildlife in winter 2012-13. All carcasses were submitted for histopathologic examination and viral antigen identification. Sequences of the glycoprotein, nucleoprotein, and glycoprotein-large polymerase protein intergenic noncoding loci of the 11 strains were determined and compared with published reference sequences. All rabies strains were closely related to the Gangwon strains isolated in 2008-09, suggesting that the rabies virus strains isolated in Gyeonggi were introduced from Gangwon Province.

  14. Rabies surveillance in the United States during 2011

    Science.gov (United States)

    Blanton, Jesse D.; Dyer, Jessie; McBrayer, Jesse; Rupprecht, Charles E.

    2016-01-01

    Summary During 2011, 49 states and Puerto Rico reported 6,031 rabid animals and 6 human rabies cases to the CDC, representing a 1.9% decrease from the 6,153 rabid animals and 2 human cases reported in 2010. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 1,981 raccoons (32.8%), 1,627 skunks (270%), 1,380 bats (22.9%), 427 foxes (71%), 303 cats (5.0%), 65 cattle (1.1%), and 70 dogs (1.2%). Compared with 2010, there was a substantial increase in the number of rabid skunks reported. Six cases of rabies involving humans were reported from California, Massachusetts, New Jersey, New York, and South Carolina. Three cases reported from Massachusetts, New Jersey, and New York were determined to be a result of canine rabies virus variants acquired outside the United States. PMID:22947154

  15. Anisotropic Rabi model

    Science.gov (United States)

    Xie, Qiong-Tao; Cui, Shuai; Cao, Jun-Peng; Amico, Luigi; Fan, Heng

    2014-04-01

    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.

  16. Anisotropic Rabi model

    Directory of Open Access Journals (Sweden)

    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.

  17. Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review

    Science.gov (United States)

    Devleesschauwer, Brecht; Aryal, Arjun; Sharma, Barun Kumar; Ale, Anita; Declercq, Anne; Depraz, Stephanie; Gaire, Tara Nath; Gongal, Gyanendra; Karki, Surendra; Pandey, Basu Dev; Pun, Sher Bahadur; Duchateau, Luc; Dorny, Pierre; Speybroeck, Niko

    2016-01-01

    dog populations and the true contribution of the sylvatic cycle. Interpretation Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal. PMID:26871689

  18. Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Brecht Devleesschauwer

    2016-02-01

    populations and the true contribution of the sylvatic cycle.Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal.

  19. A generic rabies risk assessment tool to support surveillance.

    Science.gov (United States)

    Ward, Michael P; Hernández-Jover, Marta

    2015-06-01

    The continued spread of rabies in Indonesia poses a risk to human and animal populations in the remaining free islands, as well as the neighbouring rabies-free countries of Timor Leste, Papua New Guinea and Australia. Here we describe the development of a generic risk assessment tool which can be used to rapidly determine the vulnerability of rabies-free islands, so that scarce resources can be targeted to surveillance activities and the sensitivity of surveillance systems increased. The tool was developed by integrating information on the historical spread of rabies, anthropological studies, and the opinions of local animal health experts. The resulting tool is based on eight critical parameters that can be estimated from the literature, expert opinion, observational studies and information generated from routine surveillance. In the case study presented, results generated by this tool were most sensitive to the probability that dogs are present on private and fishing boats and it was predicted that rabies-infection (one infected case) might occur in a rabies-free island (upper 95% prediction interval) with a volume of 1000 boats movements. With 25,000 boat movements, the median of the probability distribution would be equal to one infected case, with an upper 95% prediction interval of six infected cases. This tool could also be used at the national-level to guide control and eradication plans. An initial recommendation from this study is to develop a surveillance programme to determine the likelihood that boats transport dogs, for example by port surveillance or regularly conducted surveys of fisherman and passenger ferries. However, the illegal nature of dog transportation from rabies-infected to rabies-free islands is a challenge for developing such surveillance. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Estimating the Global Burden of Endemic Canine Rabies

    Science.gov (United States)

    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

    Background Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. Methodology/Principal Findings We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). Conclusions/Significance This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to

  1. Estimating the global burden of endemic canine rabies.

    Directory of Open Access Journals (Sweden)

    Katie Hampson

    2015-04-01

    Full Text Available Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment 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. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000 human deaths, over 3.7 million (95% CIs: 1.6-10.4 million disability-adjusted life years (DALYs and 8.6 billion USD (95% CIs: 2.9-21.5 billion economic losses annually. The largest component of the economic burden is due to premature death (55%, followed by direct costs of post-exposure prophylaxis (PEP, 20% and lost income whilst seeking PEP (15.5%, with only limited costs to the veterinary sector due to dog vaccination (1.5%, and additional costs to communities from livestock losses (6%.This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.

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

    Directory of Open Access Journals (Sweden)

    Ye Liu

    2016-09-01

    Full Text Available 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. Systems Biomedicine of Rabies Delineates the Affected Signaling pathways

    Directory of Open Access Journals (Sweden)

    Sayed Hamid Reza Mozhgani

    2016-11-01

    Full Text Available The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. The psychological symptoms and the underlying etiology, as well as the rare survival rate from rabies encephalitis, has still remained a mystery. We, therefore, undertook a systems biomedicine approach to identify the network of gene products implicated in rabies. This was done by meta-analyzing whole-transcriptome microarray datasets of the CNS infected by strain CVS-11, and integrating them with interactome data using computational and statistical methods. We first determined the differentially expressed genes (DEGs in each study and horizontally integrated the results at the mRNA and microRNA levels separately. A total of 61 seed genes involved in signal propagation system were obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then reconstructed a refined protein-protein interaction network (PPIN of infected cells to elucidate the rabies-implicated signal transduction network (RISN. To validate our findings, we confirmed differential expression of randomly selected genes in the network using Real-time PCR. In conclusion, the identification of seed genes and their network neighborhood within the refined PPIN can be useful for demonstrating signaling pathways including interferon circumvent, toward proliferation and survival, and neuropathological clue, explaining the intricate underlying molecular neuropathology of rabies infection and thus rendered a molecular framework for predicting potential drug targets.

  4. Systems Biomedicine of Rabies Delineates the Affected Signaling Pathways

    Science.gov (United States)

    Azimzadeh Jamalkandi, Sadegh; Mozhgani, Sayed-Hamidreza; Gholami Pourbadie, Hamid; Mirzaie, Mehdi; Noorbakhsh, Farshid; Vaziri, Behrouz; Gholami, Alireza; Ansari-Pour, Naser; Jafari, Mohieddin

    2016-01-01

    The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. The psychological symptoms and the underlying etiology, as well as the rare survival rate from rabies encephalitis, has still remained a mystery. We, therefore, undertook a systems biomedicine approach to identify the network of gene products implicated in rabies. This was done by meta-analyzing whole-transcriptome microarray datasets of the CNS infected by strain CVS-11, and integrating them with interactome data using computational and statistical methods. We first determined the differentially expressed genes (DEGs) in each study and horizontally integrated the results at the mRNA and microRNA levels separately. A total of 61 seed genes involved in signal propagation system were obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then reconstructed a refined protein–protein interaction network (PPIN) of infected cells to elucidate the rabies-implicated signal transduction network (RISN). To validate our findings, we confirmed differential expression of randomly selected genes in the network using Real-time PCR. In conclusion, the identification of seed genes and their network neighborhood within the refined PPIN can be useful for demonstrating signaling pathways including interferon circumvent, toward proliferation and survival, and neuropathological clue, explaining the intricate underlying molecular neuropathology of rabies infection and thus rendered a molecular framework for predicting potential drug targets. PMID:27872612

  5. Systems Biomedicine of Rabies Delineates the Affected Signaling Pathways.

    Science.gov (United States)

    Azimzadeh Jamalkandi, Sadegh; Mozhgani, Sayed-Hamidreza; Gholami Pourbadie, Hamid; Mirzaie, Mehdi; Noorbakhsh, Farshid; Vaziri, Behrouz; Gholami, Alireza; Ansari-Pour, Naser; Jafari, Mohieddin

    2016-01-01

    The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. The psychological symptoms and the underlying etiology, as well as the rare survival rate from rabies encephalitis, has still remained a mystery. We, therefore, undertook a systems biomedicine approach to identify the network of gene products implicated in rabies. This was done by meta-analyzing whole-transcriptome microarray datasets of the CNS infected by strain CVS-11, and integrating them with interactome data using computational and statistical methods. We first determined the differentially expressed genes (DEGs) in each study and horizontally integrated the results at the mRNA and microRNA levels separately. A total of 61 seed genes involved in signal propagation system were obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then reconstructed a refined protein-protein interaction network (PPIN) of infected cells to elucidate the rabies-implicated signal transduction network (RISN). To validate our findings, we confirmed differential expression of randomly selected genes in the network using Real-time PCR. In conclusion, the identification of seed genes and their network neighborhood within the refined PPIN can be useful for demonstrating signaling pathways including interferon circumvent, toward proliferation and survival, and neuropathological clue, explaining the intricate underlying molecular neuropathology of rabies infection and thus rendered a molecular framework for predicting potential drug targets.

  6. Standardization and assessment of cell culture media quantities in roller poly ethylene terephthalate bottles employed in the industrial rabies viral vaccine production.

    Science.gov (United States)

    Jagannathan, S; Chaansha, S; Rajesh, K; Santhiya, T; Charles, C; Venkataramana, K N

    2009-09-15

    Vero cells are utilized for production of rabies vaccine. This study deals with the optimize quantity media require for the rabies vaccine production in the smooth roller surface. The rabies virus (Pasteur vaccine strain) is infected to monolayer of the various experimented bottles. To analyze the optimal quantity of media for the production of rabies viral harvest during the process of Vero cell derived rabies vaccine. The trials are started from 200 to 400 mL (PTARV-1, PTARV-2, PTARV-3, PTARV-4 and PTARV-5). The samples are taken in an appropriate time intervals for analysis of In Process Quality Control (IPQC) tests. The collected viral harvests are further processed to rabies vaccine in a pilot level and in addition to scale up an industrial level. Based on the evaluation the PTARV-2 (250 mL) show highly encouraging results for the Vero cell derived rabies vaccine production.

  7. Enzootic and Epizootic Rabies Associated with Vampire Bats, Peru

    Science.gov (United States)

    Streicker, Daniel G.; Cabezas-Sanchez, Cesar; Velasco-Villa, Andres

    2013-01-01

    During the past decade, incidence of human infection with rabies virus (RABV) spread by the common vampire bat (Desmodus rotundus) increased considerably in South America, especially in remote areas of the Amazon rainforest, where these bats commonly feed on humans. To better understand the epizootiology of rabies associated with vampire bats, we used complete sequences of the nucleoprotein gene to infer phylogenetic relationships among 157 RABV isolates collected from humans, domestic animals, and wildlife, including bats, in Peru during 2002–2007. This analysis revealed distinct geographic structuring that indicates that RABVs spread gradually and involve different vampire bat subpopulations with different transmission cycles. Three putative new RABV lineages were found in 3 non–vampire bat species that may represent new virus reservoirs. Detection of novel RABV variants and accurate identification of reservoir hosts are critically important for the prevention and control of potential virus transmission, especially to humans.

  8. 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.

  9. Importation of canid rabies in a horse relocated from Zimbabwe to South Africa : research communication

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    C.T. Sabeta

    2005-09-01

    Full Text Available In July 2003 a 2-year-old Thoroughbred colt was imported from Harare, Zimbabwe to the Ashburton Training Centre, Pietermaritzburg, South Africa. Five months after importation, the colt presented with clinical signs suggestive of rabies: it was uncoordinated, showed muscle tremors and was biting at itself. Brain tissue was submitted for analysis and the clinical diagnosis was confirmed by the fluorescent antibody test and reverse-transcription polymerase chain reaction (RT-PCR. Phylogenetic analysis of the nucleotide sequence of the cytoplasmic domain of the glycoprotein and the G-L intergenic region of the rabies virus confirmed it to be an infection with a canid rabies virus, originating from an area in Zimbabwe endemic for the domestic dog (Canis familiaris and side-striped jackal (Canis adustus rabies.

  10. Designing programs for eliminating canine rabies from islands: Bali, Indonesia as a case study.

    Science.gov (United States)

    Townsend, Sunny E; Sumantra, I Putu; Pudjiatmoko; Bagus, Gusti Ngurah; Brum, Eric; Cleaveland, Sarah; Crafter, Sally; Dewi, Ayu P M; Dharma, Dewa Made Ngurah; Dushoff, Jonathan; Girardi, Janice; Gunata, I Ketut; Hiby, Elly F; Kalalo, Corlevin; Knobel, Darryn L; Mardiana, I Wayan; Putra, Anak Agung Gde; Schoonman, Luuk; Scott-Orr, Helen; Shand, Mike; Sukanadi, I Wayan; Suseno, Pebi Purwo; Haydon, Daniel T; Hampson, Katie

    2013-01-01

    Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies. Using data from Bali, we estimated the basic reproductive number, R(0), of rabies in dogs, to be ~1 · 2, almost identical to that obtained in ten-fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance.

  11. Evidence of recombination in intrapatient populations of hepatitis C virus.

    Science.gov (United States)

    Sentandreu, Vicente; Jiménez-Hernández, Nuria; Torres-Puente, Manuela; Bracho, María Alma; Valero, Ana; Gosalbes, María José; Ortega, Enrique; Moya, Andrés; González-Candelas, Fernando

    2008-09-18

    Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. HCV is characterized by a high level of genetic heterogeneity. Although homologous recombination has been demonstrated in many members of the family Flaviviridae, to which HCV belongs, there are only a few studies reporting recombination on natural populations of HCV, suggesting that these events are rare in vivo. Furthermore, these few studies have focused on recombination between different HCV genotypes/subtypes but there are no reports on the extent of intra-genotype or intra-subtype recombination between viral strains infecting the same patient. Given the important implications of recombination for RNA virus evolution, our aim in this study has been to assess the existence and eventually the frequency of intragenic recombination on HCV. For this, we retrospectively have analyzed two regions of the HCV genome (NS5A and E1-E2) in samples from two different groups: (i) patients infected only with HCV (either treated with interferon plus ribavirin or treatment naïve), and (ii) HCV-HIV co-infected patients (with and without treatment against HIV). The complete data set comprised 17712 sequences from 136 serum samples derived from 111 patients. Recombination analyses were performed using 6 different methods implemented in the program RDP3. Recombination events were considered when detected by at least 3 of the 6 methods used and were identified in 10.7% of the amplified samples, distributed throughout all the groups described and the two genomic regions studied. The resulting recombination events were further verified by detailed phylogenetic analyses. The complete experimental procedure was applied to an artificial mixture of relatively closely viral populations and the ensuing analyses failed to reveal artifactual recombination. From these results we conclude that recombination should be considered as a potentially

  12. Bat Rabies Surveillance in Europe

    NARCIS (Netherlands)

    Schatz, J.; Fooks, A.R.; McElhinney, L.M.; Horton, D.; Echevarria, J.; Vázquez-Morón, S.; Kooi, E.A.; Rasmussen, T.B.; Müller, T.; Freuling, C.

    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

  13. The Mad Fox Disease: Rabies.

    Science.gov (United States)

    Keller, Rosanne

    One of a series of instructional materials produced by the Literacy Council of Alaska, this booklet provides information about the control of rabies. Using both simplified sentence structure and vocabulary, it describes how rabies may be spread, its symptoms, its treatment, and ways it can be prevented. (FL)

  14. Risco de transmissão do vírus da raiva oriundo de sagui (Callithrix jacchus, domiciliado e semidomiciliado, para o homem na região metropolitana de Fortaleza, estado do Ceará Risks of transmitting rabies virus from captive domiciliary common marmoset (Callithrix jacchus to human beings, in the metropolitan region of Fortaleza, state of Ceará, Brazil

    Directory of Open Access Journals (Sweden)

    Tereza D'ávila de Freitas Aguiar

    2011-06-01

    Full Text Available INTRODUÇÃO: Uma variante do vírus da raivafoi identificadaem associação a casos de raiva humanos, no Estado do Ceará, transmitidos por saguis (Callithrix jacchus, primatas frequentemente criados como animais de estimação. Essa variante não apresenta proximidade antigênica ou relação genética com as variantes do vírus encontradas em morcegos e mamíferos terrestres das Américas. O objetivo do estudo foi avaliar os fatores de risco de transmissão do vírus da raiva oriundo de sagui (C. jacchus, criado como animal de estimação, para o homem na região metropolitana de Fortaleza, Ceará. MÉTODOS: Foi aplicado um questionário estruturado aos criadores de saguis, residentes nos municípios de Aquiraz e Maranguape, Ceará, enfocando o manejo e a interação desses primatas com humanos. Para avaliação da ocorrência de antígenos rábicos, através do teste de imunofluorescência direta (IFD, foram coletadas amostras de saliva dos saguis domiciliados e semidomiciliados. Com base nos resultados obtidos desses espécimes, foram analisadas amostras de sistema nervoso central (SNC. RESULTADOS: Na análise dos questionários, observou-se a proximidade dos criadores de saguis durante o manejo desses animais nos domicílios, bem como, seus conhecimentos limitados sobre a raiva, demonstrando haver risco quanto à transmissão do vírus. De 29 amostras de saliva de saguis reavaliadas, uma (3,4% apresentou reação de IFD positiva. De 11 amostras de SNC, três (27,3% apresentaram positividade. CONCLUSÕES: Os dados laboratoriais estão de acordo com os achados dos questionários, confirmando haver risco da transmissão do vírus da raiva devido à convivência de humanos com saguis (C. jacchus.INTRODUCTION: In the State of Ceará, a new variant of the rabies virus was identified associated with cases of human rabies transmitted by common marmosets (Callithrix jacchus, which are frequently kept as pets. This new variant does not present

  15. Active surveillance of bat rabies in France: a 5-year study (2004-2009)

    OpenAIRE

    Picard-Meyer , Evelyne; Dubourg-Savage , Marie-Jo; Arthur , Laurent; Barataud , Michel; Bécu , David; Bracco , Sandrine; Borel , Christophe; Larcher , Gérald; Meme-Lafond , Benjamin; Moinet , Marie; Robardet , Emmanuelle; Wasniewski , Marine; Cliquet , Florence

    2011-01-01

    Abstract Active surveillance of bats in France started in 2004 with an analysis of 18 of the 45 bat species reported in Europe. Rabies antibodies were detected in six indigenous species, mainly in Eptesicus serotinus and Myotis myotis, suggesting previous contact with the EBLV-1 rabies virus. Nineteen of the 177 tested bats were shown serologically positive in seven sites, particularly in central and south-western France. Neither infectious viral particles nor viral genomes were de...

  16. Isolation of rabies virus from the parotid salivary glands of foxes (Pseudalopex vetulus from Paraíba State, Northeastern Brazil Isolamento de vírus rábico de glândulas salivares parótidas de raposas (Pseudalopex vetulus do Estado da Paraíba, Nordeste do Brasil

    Directory of Open Access Journals (Sweden)

    Maria Luana Cristiny Rodrigues Silva

    2009-09-01

    Full Text Available To determine the presence of rabies virus in the parotid salivary glands, 12 road-killed rabies-positive hoary foxes (Pseudoalopex vetulus were tested by using the fluorescent antibody test (FAT and mouse inoculation test (MIT. All 12 parotid salivary glands were positive for both tests, although in some cases several passages were required. The findings of this study support the importance of the hoary fox as rabies reservoir in the semi-arid region of Paraíba State, Northeastern Brazil.Para determinar a presença de vírus rábico em glândulas salivares parótidas, 12 raposas (Pseudalopex vetulus atropeladas em rodovias e positivas para raiva foram testadas pelo teste de imunofluorescência direta (IFD e teste de inoculação em camundongos (IC. Todas as 12 glândulas salivares parótidas foram positivas em ambos os testes, embora, em alguns casos, várias passagens terem sido necessárias. Os achados do presente trabalho reforçam a importância das raposas como reservatórios de raiva no semi-árido do Estado da Paraíba, Nordeste do Brasil.

  17. The rise and fall of rabies in Japan: A quantitative history of rabies epidemics in Osaka Prefecture, 1914-1933.

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    Aiko Kurosawa

    2017-03-01

    Full Text Available Japan has been free from rabies since the 1950s. However, during the early 1900s several large-scale epidemics spread throughout the country. Here we investigate the dynamics of these epidemics between 1914 and 1933 in Osaka Prefecture, using archival data including newspapers. The association between dog rabies cases and human population density was investigated using Mixed-effects models and epidemiological parameters such as the basic reproduction number (R0, the incubation and infectious period and the serial interval were estimated. A total of 4,632 animal rabies cases were reported, mainly in dogs (99.0%, 4,584 cases during two epidemics from 1914 to 1921, and 1922 to 1933 respectively. The second epidemic was larger (3,705 cases than the first (879 cases, but had a lower R0 (1.50 versus 2.42. The first epidemic was controlled through capture of stray dogs and tethering of pet dogs. Dog mass vaccination began in 1923, with campaigns to capture stray dogs. Rabies in Osaka Prefecture was finally eliminated in 1933. A total of 3,805 rabid dog-bite injuries, and 75 human deaths were reported. The relatively low incidence of human rabies, high ratio of post-exposure vaccines (PEP and bite injuries by rabid dogs (minimum 6.2 to maximum 73.6, between 1924 and 1928, and a decline in the proportion of bite victims that developed hydrophobia over time (slope = -0.29, se = 3, p < 0.001, indicated that increased awareness and use of PEP might have prevented disease. Although significantly more dog rabies cases were detected at higher human population densities (slope = 0.66, se = 0.03, p < 0.01, there were fewer dog rabies cases detected per capita (slope = -0.34, se = 0.03, p < 0.01. We suggest that the combination of mass vaccination and restriction of dog movement enabled by strong legislation was key to eliminate rabies. Moreover, the prominent role of the media in both reporting rabies cases and efforts to control the disease likely contributed

  18. Evolutionary history of rabies in Ghana.

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    David T S Hayman

    2011-04-01

    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

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

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    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

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

    Science.gov (United States)

    2012-01-01

    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 regarding

  1. Awareness of rabies prevention and control measures among public health workers in Northern Vietnam.

    Science.gov (United States)

    Nguyen, A K T; Nguyen, H T T; Pham, T N; Hoang, T V; Olowokure, B

    2015-12-01

    To assess and compare rabies related knowledge and awareness of public health workers at provincial and district levels in the seven provinces with the highest number of deaths from human rabies in northern Vietnam. A cross-sectional study. A survey was administered to a convenience sample of public health workers attending four workshops on rabies disease, control and prevention between 16 October and 21 November, 2012. Total knowledge scores (maximum 38 points) were categorized into: 'high' (>30 points) 'moderate' (21-30) and 'low' (workers attending the workshops: 57% were male; 76% worked at the district level compared with 24% who worked at provincial level; and 45% had worked in rabies control for control for >5 years. Overall knowledge was patchy and ranked as 'moderate'. Important gaps in knowledge were identified particularly in relation to indications for rabies vaccine and rabies immunoglobulin, and routes of exposure to rabies virus. One in ten respondents did not know that rabies virus could be transmitted by the bite of an infected animal. When examining the overall mean knowledge scores, marginally significant differences were identified. The average scores for district level health workers (DLHW) and provincial level health workers (PLHW) were 28 ± 3 and 29 ± 3 points respectively (p = 0.098), which fell within the study definition of 'moderate' knowledge. In contrast, when 'high' knowledge scores were compared, a significantly greater proportion of PLHW achieved >30 points compared to DLHW (44.0% vs 22.5%, p = 0.044). Important gaps in knowledge and awareness of public health workers were identified particularly in relation to routes of exposure to rabies virus and indications for rabies vaccine and rabies immunoglobulin. Overall, comparison of knowledge scores revealed significant differences between district and provincial public health workers. The results obtained suggest that in order for rabies control programmes to succeed public health

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

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    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

  3. Rabies, encephalomyelitis: MRI findings

    International Nuclear Information System (INIS)

    Peloso, Raul; Gonzalez, Roberto

    2002-01-01

    The authors present a 14 year old patient who started with walking and swallowing difficulty; followed by fever, abdominal and lower back pain. Mechanical breathing difficulties required a respiratory mechanic assistance. The diagnosis of Guillain-Barre syndrome was thought at first. Since the patient have had previous contact with a bat two months before the symptoms began, this suggested rabies as the main diagnosis, which was later confirmed by hair-bulb, cornea, oral mucosa and salival immunofluorescence. The brain and spinal cord MRI showed focal lesions in T2 and FLAIR sequences, compatible with encephalomyelitis. (author)

  4. Rabies vaccination in dogs using a dissolving microneedle patch.

    Science.gov (United States)

    Arya, Jaya M; Dewitt, Kristopher; Scott-Garrard, Maya; Chiang, Yu-Wei; Prausnitz, Mark R

    2016-10-10

    Because humans get rabies primarily through dog bites, stray dog population control and mass or mandatory vaccination of domestic dogs and other animals has virtually eliminated human rabies in industrialized countries. However, thousands of people in developing countries die of rabies each year due to the inability to control dog populations and implement mass vaccination because of financial, logistical and other challenges. The availability of an easier-to-administer and more cost-effective vaccine may help to address some of these issues. Here, we propose the use of dissolving microneedle patches for simple and potentially cost-effective rabies vaccination, and assess the safety and immunogenicity of microneedle patch vaccination using a rabies DNA vaccine in dogs. The vaccine was stable upon formulation and storage for at least 3weeks at 4°C in a microneedle patch. For vaccination, the patches were applied to the inner ear by hand without an applicator. Microneedle patches were well tolerated in the skin, with mild erythema, minimal wheal formation and complete resolution of skin reactions within 7days, and generated no systemic adverse events. Microneedle patches were at least as immunogenic as intramuscular injection at the same dose, as demonstrated by similar serum neutralizing antibody titers. A ten-fold lower vaccine dose administered by microneedle patch generated a weaker immune response compared to full-dose intramuscular vaccination. We conclude that dissolving microneedle patches may provide an innovative approach to mass vaccination of dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    OpenAIRE

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

    2017-01-01

    Background 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...

  6. Integrability of the Rabi Model

    International Nuclear Information System (INIS)

    Braak, D.

    2011-01-01

    The Rabi model is a paradigm for interacting quantum systems. It couples a bosonic mode to the smallest possible quantum model, a two-level system. I present the analytical solution which allows us to consider the question of integrability for quantum systems that do not possess a classical limit. A criterion for quantum integrability is proposed which shows that the Rabi model is integrable due to the presence of a discrete symmetry. Moreover, I introduce a generalization with no symmetries; the generalized Rabi model is the first example of a nonintegrable but exactly solvable system.

  7. 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.

  8. Epidemiology of Hepatitis C Virus in Bangladeshi General Population

    Directory of Open Access Journals (Sweden)

    Mamun Al-Mahtab

    2009-11-01

    Full Text Available Background: Hepatitis C virus is encountered sporadically in Bangladesh. It results in a wide range liver diseases, with asymptomatic acute hepatitis rarely at one end to HCC at the other end of the spectrum. Methods: 1018 individuals of different age groups and sex with varied religious, educational and social backgrounds were tested for anti-HCV by ELISA. Before testing, blood samples were preserved at -20°C. The study was conducted in a semi-urban location on the outskirts of Dhaka. Results: 0.88% tested positive for anti HCV. None of them tested positive for HBsAg. There was a male predominance and those who tested positive were mostly between 17 and 50 years of age. Major risk factors for exposure to HBV appeared to be injudicious use of injectable medications, treatment by unqualified, traditional practitioners, mass-vaccination against cholera and smallpox, barbers and body piercing. Conclusion: HCV remains an important cause of morbidity and mortality in Bangladesh. Key words: HCV; prevalence; general population; Bangladesh.DOI: 10.3329/bsmmuj.v2i1.3705 BSMMU J 2009; 2(1: 14-17

  9. Seroprevalence of hepatitis E virus in the UK farming population.

    Science.gov (United States)

    Meader, E; Thomas, D; Salmon, R; Sillis, M

    2010-12-01

    Hepatitis E is a zoonosis that can be acquired by the consumption of contaminated food or water, or via person-to-person spread. However, little is known about the transmission of hepatitis E virus (HEV) in the UK. We investigated the epidemiology of indigenous hepatitis E infection using the PHLS Farm Cohort, a sentinel group with a history of close contact with a range of domestic animals. Ten of the 413 subjects tested were positive for hepatitis E IgG antibodies (2.4%). Seroprevalence peaked in those aged 51 to 60 years (relative risk 3.3, 95% CI: 1.0-10.5). Male participants (relative risk 3.6, 95% CI: 0.6-21.2) and those from farms in the Hereford area of the United Kingdom (relative risk 2.7, 95% CI: 0.8-8.4), an area of mixed livestock farming, were more likely to have serological evidence of previous HEVs exposure, although these findings were not statistically significant. Exposure to pigs, or water from a private supply, was not identified as a significant risk factor. The results of this study suggest that UK farming populations are exposed to HEV, but the predominant route of transmission remains elusive. © 2009 The Authors. Journal compilation © 2009 Blackwell Verlag GmbH.

  10. Human papilloma virus prevalence in a multiethnic screening population.

    Science.gov (United States)

    Chen, Kang Mei; Stephen, Josena K; Ghanem, Tamer; Stachler, Robert; Gardner, Glendon; Jones, Lamont; Schweitzer, Vanessa P; Hall, Francis; Divine, George; Worsham, Maria J

    2013-03-01

    The goal was to determine the prevalence of high-risk HPV16 using saliva in a screening population in Detroit, Michigan. Real-time quantitative polymerase chain reaction was applied to detect HPV16 in saliva DNA from 349 screening subjects without head and neck cancer (HNC), 156 with HNC, and 19 controls. Cut points for human papilloma virus (HPV) positivity were >0 and >0.001 copy/cell. Proportions were compared between groups using exact χ(2) or Fisher exact tests (P 0, each group had an overall HPV prevalence of more than 5%, with a higher prevalence of 30.8% in the HNC patient group. At a cut point >0.001, the prevalence was lower: 0% in the control, 1.2% in the screening, and 16.7% in the HNC group. In the latter, for both cut points, HPV prevalence was different across sites (0, women in the screening group had a higher prevalence of HPV than did men (P = .010), and at >0.001, the prevalence was higher for men in the HNC group than for women (P = .035). In the screening group, at >0, only African Americans had a higher prevalence than Caucasian Americans (P = .025). In the screening group, a 6.9% and 1.2% screening rate was noted at cut points >0 and >0.001, respectively. The results provide data to inform public health considerations of the feasibility of saliva as a screening tool in at-risk populations with the long-term goal of prophylactic vaccination against oral HPV.

  11. Rabies in humans and non-human in the state of Pará, Brazilian Amazon

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    Marcus Emanuel Barroncas Fernandes

    2013-04-01

    Full Text Available We evaluate the relationship of positive cases of rabies with the continuing expansion of livestock production, and analyse the trends of this zoonosis in human population in the state of Pará, Brazilian Amazon. The distribution of rabies cases was recorded between 1999 and 2004. Of 148 cases of rabies, 21% were in humans and 79% in non-human mammals. The rapid growth in livestock numbers seems to be associated with the increase of positive cases in bovine livestock transmitted by vampire bats. This idea is supported by positive and significant relationship of both events in time (p < 0.01, but failed when spatial distribution among regions of the state was considered. However, rabies cases tend to occur toward the northeastern of the state of Pará, where rabies cases are proportionally five times greater than other mesoregions, suggesting that increased livestock production may influence the increase of this zoonosis.

  12. Rabies in humans and non-human in the state of Pará, Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Marcus Emanuel Barroncas Fernandes

    Full Text Available We evaluate the relationship of positive cases of rabies with the continuing expansion of livestock production, and analyse the trends of this zoonosis in human population in the state of Pará, Brazilian Amazon. The distribution of rabies cases was recorded between 1999 and 2004. Of 148 cases of rabies, 21% were in humans and 79% in non-human mammals. The rapid growth in livestock numbers seems to be associated with the increase of positive cases in bovine livestock transmitted by vampire bats. This idea is supported by positive and significant relationship of both events in time (p < 0.01, but failed when spatial distribution among regions of the state was considered. However, rabies cases tend to occur toward the northeastern of the state of Pará, where rabies cases are proportionally five times greater than other mesoregions, suggesting that increased livestock production may influence the increase of this zoonosis.

  13. A review of current strategy for rabies prevention and control in the developing world

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    Suneela Garg

    2017-03-01

    Full Text Available The control of Rabies, a zoonotic viral disease is a major public challenge in several developing countries. Current approaches for rabies control are overwhelmingly directed towards provision of effective post exposure prophylaxis (PEP to animal bite victims. The enormous costs involved in rabies prophylaxis is an important factor precluding its universal application in all animal bite victims especially in those residing in resource constrained settings. The intradermal route of administration has been shown to be cost effective except in peripheral regions with fewer animal bite cases. Nevertheless, rabies control program with their expected emphasis on human rabies prophylaxis have neglected canine vaccination. The feasibility of canine rabies vaccination depends primarily upon allocation of resources through political commitment and effective public private partnerships. However, in large parts of the world including India formal dog ownership constitutes a small minority of the overall canine population while state funded canine vaccination drives often fail to impress policy makers who struggle to maintain budgets for adequate coverage of rabies PEP for animal bite victims. The key to rabies control may therefore rest upon a one health approach with development of newer vaccine technology which is cost effective for vaccination in both, man and animal.

  14. Designing Programs for Eliminating Canine Rabies from Islands: Bali, Indonesia as a Case Study

    Science.gov (United States)

    Townsend, Sunny E.; Sumantra, I Putu; Pudjiatmoko; Bagus, Gusti Ngurah; Brum, Eric; Cleaveland, Sarah; Crafter, Sally; Dewi, Ayu P. M.; Dharma, Dewa Made Ngurah; Dushoff, Jonathan; Girardi, Janice; Gunata, I Ketut; Hiby, Elly F.; Kalalo, Corlevin; Knobel, Darryn L.; Mardiana, I Wayan; Putra, Anak Agung Gde; Schoonman, Luuk; Scott–Orr, Helen; Shand, Mike; Sukanadi, I Wayan; Suseno, Pebi Purwo; Haydon, Daniel T.; Hampson, Katie

    2013-01-01

    Background Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies. Methodology/Principal Findings Using data from Bali, we estimated the basic reproductive number, R 0, of rabies in dogs, to be ∼1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (<0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ∼550 human lives and ∼$15 million in prophylaxis costs over the next ten years. Conclusions/Significance The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance. PMID:23991233

  15. Advancements in web-database applications for rabies surveillance

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    Bélanger Denise

    2011-08-01

    Full Text Available Abstract Background Protection of public health from rabies is informed by the analysis of surveillance data from human and animal populations. In Canada, public health, agricultural and wildlife agencies at the provincial and federal level are responsible for rabies disease control, and this has led to multiple agency-specific data repositories. Aggregation of agency-specific data into one database application would enable more comprehensive data analyses and effective communication among participating agencies. In Québec, RageDB was developed to house surveillance data for the raccoon rabies variant, representing the next generation in web-based database applications that provide a key resource for the protection of public health. Results RageDB incorporates data from, and grants access to, all agencies responsible for the surveillance of raccoon rabies in Québec. Technological advancements of RageDB to rabies surveillance databases include 1 automatic integration of multi-agency data and diagnostic results on a daily basis; 2 a web-based data editing interface that enables authorized users to add, edit and extract data; and 3 an interactive dashboard to help visualize data simply and efficiently, in table, chart, and cartographic formats. Furthermore, RageDB stores data from citizens who voluntarily report sightings of rabies suspect animals. We also discuss how sightings data can indicate public perception to the risk of racoon rabies and thus aid in directing the allocation of disease control resources for protecting public health. Conclusions RageDB provides an example in the evolution of spatio-temporal database applications for the storage, analysis and communication of disease surveillance data. The database was fast and inexpensive to develop by using open-source technologies, simple and efficient design strategies, and shared web hosting. The database increases communication among agencies collaborating to protect human health from

  16. A DNA Logic Gate Automaton for Detection of Rabies and Other Lyssaviruses.

    Science.gov (United States)

    Vijayakumar, Pavithra; Macdonald, Joanne

    2017-07-05

    Immediate activation of biosensors is not always desirable, particularly if activation is due to non-specific interactions. Here we demonstrate the use of deoxyribozyme-based logic gate networks arranged into visual displays to precisely control activation of biosensors, and demonstrate a prototype molecular automaton able to discriminate between seven different genotypes of Lyssaviruses, including Rabies virus. The device uses novel mixed-base logic gates to enable detection of the large diversity of Lyssavirus sequence populations, while an ANDNOT logic gate prevents non-specific activation across genotypes. The resultant device provides a user-friendly digital-like, but molecule-powered, dot-matrix text output for unequivocal results read-out that is highly relevant for point of care applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Dog bite histories and response to incidents in canine rabies-enzootic KwaZulu-Natal, South Africa.

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    Melinda Hergert

    Full Text Available The objective of this paper is to report evaluated observations from survey records captured through a cross-sectional observational study regarding canine populations and dog owners in rabies enzootic KwaZulu-Natal province, South Africa. Our aim was to evaluate respondent knowledge of canine rabies and response to dog bite incidents towards improved rabies control. Six communities consisting of three land use types were randomly sampled from September 2009 to January 2011, using a cluster design. A total of 1992 household records were analyzed using descriptive statistics and regression modeling to evaluate source of rabies knowledge, experiences with dog bites, and factors affecting treatment received within respective households that occurred within the 365 day period prior to the surveys. 86% of the population surveyed had heard of rabies. Non-dog owners were 1.6 times more likely to have heard of rabies than dog owners; however, fear of rabies was not a reason for not owning a dog. Government veterinary services were reported most frequently as respondent source of rabies knowledge. Nearly 13% of households had a member bitten by a dog within the year prior to the surveys with 82% of the victims visiting a clinic as a response to the bite. 35% of these clinic visitors received at least one rabies vaccination. Regression modeling determined that the only response variable that significantly reflected the likelihood of a patient receiving rabies vaccination or not was the term for the area surveyed. Overall the survey showed that most respondents have heard of dog associated rabies and seek medical assistance at a clinic in response to a dog bite regardless of offending dog identification. An in-depth study involving factors associated within area clinics may highlight the area dependency for patients receiving rabies post exposure prophylaxis shown by this model.

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

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    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.

  19. Role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells

    International Nuclear Information System (INIS)

    Miller, A.; Morse, H.C. III; Winkelstein, J.; Nathanson, N.

    1978-01-01

    The avirulent high egg passage (HEP) strain of rabies virus produces an inapparent infection limited to the central nervous system (CNS) in intracerebrally inoculated adult mice. Heavy chain isotype (anti-μ antiserum) immunosuppression potentiates the infection, with a mortality of about 60% and with elevated virus titers in the brain. Anti-μ-treated mice fail to raise antibody responses to rabies virus although their T cell function is normal when measured by the concanavalin A response of splenic lymphocytes. This indicates that the B cell response plays an important role in clearance of rabies virus from the neuroparenchyma. Treatment with cyclophosphamide or by adult thymectomy, x-irradiation, and bone marrow reconstitution potentiates HEP infection to a greater extent than does isotype supression. Since these suppressive techniques impair both T and B lymphocyte responses, the data suggest that cellular immune mechanisms may also contribute to host defenses against this central nervous system (CNS) virus infection

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

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    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

  1. Emergency rabies control in a community of two high-density hosts

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    Singer Alexander

    2012-06-01

    Full Text Available Abstract Background Rabies is a fatal viral disease that potentially can affect all mammals. Terrestrial rabies is not present in the United Kingdom and has been eliminated from Western Europe. Nevertheless the possibility remains that rabies could be introduced to England, where it would find two potentially suitable hosts, red foxes and badgers. With the aim to analyse the spread and emergency control of rabies in this two species host community, a simulation model was constructed. Different control strategies involving anti-rabies vaccination and population culling were developed, considering control application rates, spatial extent and timing. These strategies were evaluated for efficacy and feasibility to control rabies in hypothetical rural areas in the South of England immediately after a disease outbreak. Results The model confirmed that both fox and badger populations, separately, were competent hosts for the spread of rabies. Realistic vaccination levels were not sufficient to control rabies in high-density badger populations. The combined species community was a very strong rabies host. However, disease spread within species appeared to be more important than cross-species infection. Thus, the drivers of epidemiology depend on the potential of separate host species to sustain the disease. To control a rabies outbreak in the two species, both species had to be targeted. Realistic and robust control strategies involved vaccination of foxes and badgers, but also required badger culling. Although fox and badger populations in the UK are exceptionally dense, an outbreak of rabies can be controlled with a higher than 90% chance, if control response is quick and follows a strict regime. This requires surveillance and forceful and repeated control campaigns. In contrast, an uncontrolled rabies outbreak in the South of England would quickly develop into a strong epizootic involving tens of thousands of rabid foxes and badgers. Conclusions If

  2. Cost-effectiveness of dog rabies vaccination programs in East Africa

    Science.gov (United States)

    Borse, Rebekah H.; Atkins, Charisma Y.; Gambhir, Manoj; Undurraga, Eduardo A.; Blanton, Jesse D.; Kahn, Emily B.; Dyer, Jessie L.; Rupprecht, Charles E.

    2018-01-01

    Background Dog rabies annually causes 24,000–70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. Methods RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). Results Without dog vaccination, over 10 years there would a total of be approximately 44,000–65,000 rabid dogs and 2,100–2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000–1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000–1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). Conclusions Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies

  3. Rabies: What Care Will I Receive?

    Science.gov (United States)

    ... closure should be decided together with your doctor. Rabies Postexposure Vaccinations For people who have never been ... you through the process. Also see: Preexposure Vaccinations Rabies Biologics Currently Available—United States, 2018 1 Human ...

  4. Rabies vaccine is associated with decreased all-cause mortality in dogs.

    Science.gov (United States)

    Knobel, Darryn L; Arega, Sintayehu; Reininghaus, Bjorn; Simpson, Gregory J G; Gessner, Bradford D; Stryhn, Henrik; Conan, Anne

    2017-07-05

    Evidence suggests that rabies vaccine may have non-specific protective effects in animals and children. We analyzed four years of data (2012-2015) from an observational study of the health and demographics of a population of owned, free-roaming dogs in a low-income community in South Africa. The objective of this analysis was to assess the association between rabies vaccine and all-cause mortality in dogs, stratified by age group (0-3months, 4-11months, and 12months and older), and controlling for the effects of sex and number of dogs in the residence. Rabies vaccination reduced the risk of death from any cause by 56% (95% CI=16-77%) in dogs aged 0-3months, by 44% (95% CI=21-60%) in dogs aged 4-11months and by 16% (95% CI=0-29%) in dogs aged 12months and older. We hypothesize that the protective association between rabies vaccination status and all-cause mortality is due to a protective effect of rabies vaccine against diseases other than rabies. Existence of a strong non-specific protective effect of rabies vaccine on mortality in dogs would have implications for the design of dog rabies control programs that aim to eliminate dog-mediated human rabies cases. Further, we propose that owned domestic dogs in high mortality settings provide a useful animal model to better understand any non-specific protective effect of rabies vaccine in children, due to dogs' high numbers, high morbidity and mortality rates, relatively short lifespan, exposure to a variety of infectious and parasitic diseases, and shared environment with people. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. HCMV spread and cell tropism are determined by distinct virus populations.

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    Laura Scrivano

    Full Text Available Human cytomegalovirus (HCMV can infect many different cell types in vivo. Two gH/gL complexes are used for entry into cells. gH/gL/pUL(128,130,131A shows no selectivity for its host cell, whereas formation of a gH/gL/gO complex only restricts the tropism mainly to fibroblasts. Here, we describe that depending on the cell type in which virus replication takes place, virus carrying the gH/gL/pUL(128,130,131A complex is either released or retained cell-associated. We observed that virus spread in fibroblast cultures was predominantly supernatant-driven, whereas spread in endothelial cell (EC cultures was predominantly focal. This was due to properties of virus released from fibroblasts and EC. Fibroblasts released virus which could infect both fibroblasts and EC. In contrast, EC released virus which readily infected fibroblasts, but was barely able to infect EC. The EC infection capacities of virus released from fibroblasts or EC correlated with respectively high or low amounts of gH/gL/pUL(128,130,131A in virus particles. Moreover, we found that focal spread in EC cultures could be attributed to EC-tropic virus tightly associated with EC and not released into the supernatant. Preincubation of fibroblast-derived virus progeny with EC or beads coated with pUL131A-specific antibodies depleted the fraction that could infect EC, and left a fraction that could predominantly infect fibroblasts. These data strongly suggest that HCMV progeny is composed of distinct virus populations. EC specifically retain the EC-tropic population, whereas fibroblasts release EC-tropic and non EC-tropic virus. Our findings offer completely new views on how HCMV spread may be controlled by its host cells.

  6. Antemortem diagnosis of human rabies in a veterinarian infected when handling a herbivore in Minas Gerais, Brazil

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    Mariana Gontijo de Brito

    2011-02-01

    Full Text Available The Ministry of Health's National Human Rabies Control Program advocates pre-exposure prophylaxis (PEP for professionals involved with animals that are at risk of contracting rabies. We report an antemortem and postmortem diagnosis of rabies in a veterinarian who became infected when handling herbivores with rabies. The antemortem diagnosis was carried out with a saliva sample and a biopsy of hair follicles using molecular biology techniques, while the postmortem diagnosis used a brain sample and conventional techniques. The veterinarian had collected samples to diagnose rabies in suspect herbivores (bovines and caprines that were subsequently confirmed to be positive in laboratory tests. After onset of classic rabies symptoms, saliva and hair follicles were collected and used for antemortem diagnostic tests and found to be positive by RT-PCR. Genetic sequencing showed that the infection was caused by variant 3 (Desmodus rotundus, a finding confirmed by tests on the brain sample. It is essential that professionals who are at risk of infection by the rabies virus undergo pre-exposure prophylaxis. This study also confirms that molecular biology techniques were used successfully for antemortem diagnosis and therefore not only allow therapeutic methods to be developed, but also enable the source of infection in human rabies cases to be identified accurately and quickly.

  7. Rabies prevention and management of cats in the context of trap-neuter-vaccinate-release programmes.

    Science.gov (United States)

    Roebling, A D; Johnson, D; Blanton, J D; Levin, M; Slate, D; Fenwick, G; Rupprecht, C E

    2014-06-01

    Domestic cats are an important part of many Americans' lives, but effective control of the 60-100 million feral cats living throughout the country remains problematic. Although trap-neuter-vaccinate-return (TNVR) programmes are growing in popularity as alternatives to euthanizing feral cats, their ability to adequately address disease threats and population growth within managed cat colonies is dubious. Rabies transmission via feral cats is a particular concern as demonstrated by the significant proportion of rabies post-exposure prophylaxis associated with exposures involving cats. Moreover, TNVR has not been shown to reliably reduce feral cat colony populations because of low implementation rates, inconsistent maintenance and immigration of unsterilized cats into colonies. For these reasons, TNVR programmes are not effective methods for reducing public health concerns or for controlling feral cat populations. Instead, responsible pet ownership, universal rabies vaccination of pets and removal of strays remain integral components to control rabies and other diseases. © 2013 Blackwell Verlag GmbH.

  8. Rabies Prevention and Management of Cats in the Context of Trap, Neuter, Vaccinate, Release Programs

    Science.gov (United States)

    Roebling, Allison D.; Johnson, Dana; Blanton, Jesse D.; Levin, Michael; Slate, Dennis; Fenwick, George; Rupprecht, Charles E.

    2016-01-01

    Summary Domestic cats are an important part of many Americans’ lives, but effective control of the 60–100 million feral cats living throughout the country remains problematic. Although Trap-Neuter-Vaccinate-Return (TNVR) programs are growing in popularity as alternatives to euthanizing feral cats, their ability to adequately address disease threats and population growth within managed cat colonies is dubious. Rabies transmission via feral cats is a particular concern as demonstrated by the significant proportion of rabies postexposure prophylaxis associated with exposures involving cats. Moreover, TNVR has not been shown to reliably reduce feral cat colony populations because of low implementation rates, inconsistent maintenance, and immigration of unsterilized cats into colonies. For these reasons, TNVR programs are not effective methods for reducing public health concerns or for controlling feral cat populations. Instead, responsible pet ownership, universal rabies vaccination of pets, and removal of strays remain integral components to control rabies and other diseases. PMID:23859607

  9. Determinants of Vaccination Coverage and Consequences for Rabies Control in Bali, Indonesia.

    Science.gov (United States)

    Arief, Riana A; Hampson, Katie; Jatikusumah, Andri; Widyastuti, Maria D W; Sunandar; Basri, Chaerul; Putra, Anak A G; Willyanto, Iwan; Estoepangestie, Agnes T S; Mardiana, I W; Kesuma, I K G N; Sumantra, I P; Doherty, Paul F; Salman, M D; Gilbert, Jeff; Unger, Fred

    2016-01-01

    Maintaining high vaccination coverage is key to successful rabies control, but mass dog vaccination can be challenging and population turnover erodes coverage. Declines in rabies incidence following successive island-wide vaccination campaigns in Bali suggest that prospects for controlling and ultimately eliminating rabies are good. Rabies, however, has continued to circulate at low levels. In the push to eliminate rabies from Bali, high coverage needs to be maintained across all areas of the island. We carried out door-to-door (DTD) questionnaire surveys ( n  = 10,352 dog-owning households) and photographic mark-recapture surveys (536 line transects, 2,597 observations of free-roaming dogs) in 2011-2012 to estimate dog population sizes and assess rabies vaccination coverage and dog demographic characteristics in Bali, Indonesia. The median number of dogs per subvillage unit ( banjar ) was 43 (range 0-307) for owned dogs estimated from the DTD survey and 17 (range 0-83) for unconfined dogs (including both owned and unowned) from transects. Vaccination coverage of owned dogs was significantly higher in adults (91.4%) compared to juveniles (Bali to have the highest chance of eliminating rabies, concerted effort should be made to vaccinate free-roaming dogs particularly in suburban and rural areas, with advertising to ensure that owners vaccinate pups. Long-lasting, cheap, and quick methods are needed to mark vaccinated animals and reassure communities of the reach of vaccination campaigns.

  10. Bat rabies surveillance in France: first report of unusual mortality among serotine bats.

    Science.gov (United States)

    Picard-Meyer, Evelyne; Servat, Alexandre; Wasniewski, Marine; Gaillard, Matthieu; Borel, Christophe; Cliquet, Florence

    2017-12-13

    Rabies is a fatal viral encephalitic disease that is caused by lyssaviruses which can affect all mammals, including human and bats. In Europe, bat rabies cases are attributed to five different lyssavirus species, the majority of rabid bats being attributed to European bat 1 lyssavirus (EBLV-1), circulating mainly in serotine bats (Eptesicus serotinus). In France, rabies in bats is under surveillance since 1989, with 77 positive cases reported between 1989 and 2016. In the frame of the bat rabies surveillance, an unusual mortality of serotine bats was reported in 2009 in a village in North-East France. Six juvenile bats from an E. serotinus maternity colony counting ~200 individuals were found to be infected with EBLV-1. The active surveillance of the colony by capture sessions of bats from July to September 2009 showed a high detection rate of neutralising EBLV-1 antibodies (≈ 50%) in the colony. Moreover, one out of 111 animals tested was found to shed viable virus in saliva, while lyssavirus RNA was detected by RT-PCR for five individuals. This study demonstrated that the lyssavirus infection in the serotine maternity colony was followed by a high rate of bat rabies immunity after circulation of the virus in the colony. The ratio of seropositive bats is probably indicative of an efficient virus transmission coupled to a rapid circulation of EBLV-1 in the colony.

  11. Pre-exposure rabies prophylaxis: a systematic review

    Science.gov (United States)

    Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

    2017-01-01

    Abstract Objective To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings. Methods We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Findings Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Conclusion Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities. PMID:28250534

  12. 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

  13. Bat rabies in France: a 24-year retrospective epidemiological study.

    Directory of Open Access Journals (Sweden)

    Evelyne Picard-Meyer

    Full Text Available 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.

  14. Rabies surveillance in the United States during 2013

    Science.gov (United States)

    Dyer, Jessie L.; Yager, Pamela; Orciari, Lillian; Greenberg, Lauren; Wallace, Ryan; Hanlon, Cathleen A.; Blanton, Jesse D.

    2016-01-01

    Summary During 2013, 53 reporting jurisdictions reported 5,865 rabid animals and 3 human rabies cases to the CDC, representing a 4.8% decrease from the 6,162 rabid animals and 1 human case reported in 2012. Ninety-two percent of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 1,898 raccoons (32.4%), 1,598 bats (27.2%), 1,447 skunks (24.7%), 344 foxes (5.9%), 247 cats (4.2%), 86 cattle (1.5%), and 89 dogs (1.5%). One human case was reported from Maryland. The infection was determined to have been transmitted via organ transplantation. Infection in the organ donor, a North Carolina resident, was retrospectively diagnosed. Both the organ donor and the organ recipient were infected with the raccoon rabies virus variant. The third human case, reported by Texas, involved a Guatemalan resident who was detained while crossing the US border. The infection was determined to be caused by a canine rabies virus variant that circulates in Central America. PMID:25356711

  15. Error baseline rates of five sample preparation methods used to characterize RNA virus populations.

    Directory of Open Access Journals (Sweden)

    Jeffrey R Kugelman

    Full Text Available Individual RNA viruses typically occur as populations of genomes that differ slightly from each other due to mutations introduced by the error-prone viral polymerase. Understanding the variability of RNA virus genome populations is critical for understanding virus evolution because individual mutant genomes may gain evolutionary selective advantages and give rise to dominant subpopulations, possibly even leading to the emergence of viruses resistant to medical countermeasures. Reverse transcription of virus genome populations followed by next-generation sequencing is the only available method to characterize variation for RNA viruses. However, both steps may lead to the introduction of artificial mutations, thereby skewing the data. To better understand how such errors are introduced during sample preparation, we determined and compared error baseline rates of five different sample preparation methods by analyzing in vitro transcribed Ebola virus RNA from an artificial plasmid-based system. These methods included: shotgun sequencing from plasmid DNA or in vitro transcribed RNA as a basic "no amplification" method, amplicon sequencing from the plasmid DNA or in vitro transcribed RNA as a "targeted" amplification method, sequence-independent single-primer amplification (SISPA as a "random" amplification method, rolling circle reverse transcription sequencing (CirSeq as an advanced "no amplification" method, and Illumina TruSeq RNA Access as a "targeted" enrichment method. The measured error frequencies indicate that RNA Access offers the best tradeoff between sensitivity and sample preparation error (1.4-5 of all compared methods.

  16. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers.

    Science.gov (United States)

    Scarlatti, G; Leitner, T; Halapi, E; Wahlberg, J; Marchisio, P; Clerici-Schoeller, M A; Wigzell, H; Fenyö, E M; Albert, J; Uhlén, M

    1993-01-01

    We have compared the variable region 3 sequences from 10 human immunodeficiency virus type 1 (HIV-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA of cultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission. PMID:8446584

  17. 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)

  18. Rabies: Need for active and passive immunisation

    Directory of Open Access Journals (Sweden)

    G N S Sangeetha Lakshmi

    2014-01-01

    Full Text Available Rabies is an acute highly fatal viral disease of the CNS caused by Lyssavirus Type-I. It has a long and variable incubation period. It is a communicable disease of man that is always fatal. The combined administration of a single dose of anti rabies serum with a course of vaccine, together with local treatment of the wound is the best specific prophylactic treatment after exposure of man to rabies. Here, we report a case of rabies, who developed the disease in spite of having taken three doses of anti rabies vaccine (Post exposure.

  19. Population dynamics of swine influenza virus in finishing pigs

    NARCIS (Netherlands)

    Loeffen, W.L.A.

    2008-01-01

    Influenza virus infections in swine were first noticed in the US in 1918, during the human pandemic of the Spanish flu. In Europe, seroprevalences for the three most common swine influenza strains at the moment, H1N1, H3N2 and H1N2, range from 20-80% in finishing pigs at the end of the finishing

  20. Optimal frequency of rabies vaccination campaigns in Sub-Saharan Africa.

    Science.gov (United States)

    Bilinski, Alyssa M; Fitzpatrick, Meagan C; Rupprecht, Charles E; Paltiel, A David; Galvani, Alison P

    2016-11-16

    Rabies causes more than 24 000 human deaths annually in Sub-Saharan Africa. The World Health Organization recommends annual canine vaccination campaigns with at least 70% coverage to control the disease. While previous studies have considered optimal coverage of animal rabies vaccination, variation in the frequency of vaccination campaigns has not been explored. To evaluate the cost-effectiveness of rabies canine vaccination campaigns at varying coverage and frequency, we parametrized a rabies virus transmission model to two districts of northwest Tanzania, Ngorongoro (pastoral) and Serengeti (agro-pastoral). We found that optimal vaccination strategies were every 2 years, at 80% coverage in Ngorongoro and annually at 70% coverage in Serengeti. We further found that the optimality of these strategies was sensitive to the rate of rabies reintroduction from outside the district. Specifically, if a geographically coordinated campaign could reduce reintroduction, vaccination campaigns every 2 years could effectively manage rabies in both districts. Thus, coordinated campaigns may provide monetary savings in addition to public health benefits. Our results indicate that frequency and coverage of canine vaccination campaigns should be evaluated simultaneously and tailored to local canine ecology as well as to the risk of disease reintroduction from surrounding regions. © 2016 The Author(s).

  1. Rabies in a Vaccinated 9-Month-Old German Shepherd Dog, Akure, 2010: A Case Report

    Directory of Open Access Journals (Sweden)

    A. M. Qasim

    2013-01-01

    Full Text Available After the onset of symptoms, the clinical course of rabies is almost invariably fatal. Rabies has traditionally been associated with dogs more than any other animal, and in parts of the world where domestic animal control and vaccination programs are limited, dogs remain the most important reservoir of the disease. We report a case of canine rabies in a vaccinated 9-month-old German shepherd female dog. The presenting clinical sign was jaw muscle paralysis with a hanging bronze color like tongue without salivation. Following encephalectomy, a rabies positive diagnosis was confirmed by fluorescent antibody technique at the Rabies Laboratory, National Veterinary Research Institute, Vom. The epidemiology of the rabies case is not understood. This case is of public health significance because of the at-risk population including animal health care service provider and animals. The following were recommended, (a a reinvigorated control measure that includes the awareness program on prevention, responsible dog ownership with dog registration at veterinary hospitals, and registered veterinary clinics by the government and (b a yearly rabies vaccination campaign that must be improved through the veterinary public health and other health departments collaborating.

  2. Bat Rabies in Massachusetts, USA, 1985–2009

    OpenAIRE

    Wang, Xingtai; DeMaria, Alfred; Smole, Sandra; Brown, Catherine M.; Han, Linda

    2010-01-01

    To investigate rabies in Massachusetts, we analyzed bat rabies test results before and after introduction of raccoon variant rabies and after release of revised 1999 US Advisory Committee on Immunization Practices recommendations for rabies postexposure prophylaxis. Bat submissions were associated with level of rabies awareness and specific postexposure recommendations.

  3. Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

    Science.gov (United States)

    Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

    2017-10-01

    Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

  4. Observations of Rabi oscillations in a non-polar InGaN quantum dot

    International Nuclear Information System (INIS)

    Reid, Benjamin P. L.; Chan, Christopher C. S.; Taylor, Robert A.; Kocher, Claudius; Zhu, Tongtong; Oehler, Fabrice; Emery, Robert; Oliver, Rachel A.

    2014-01-01

    Experimental observation of Rabi rotations between an exciton excited state and the crystal ground state in a single non-polar InGaN quantum dot is presented. The exciton excited state energy is determined by photoluminescence excitation spectroscopy using two-photon excitation from a pulsed laser. The population of the exciton excited state is seen to undergo power dependent damped Rabi oscillations.

  5. Observations of Rabi oscillations in a non-polar InGaN quantum dot

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Benjamin P. L., E-mail: benjamin.reid@physics.ox.ac.uk; Chan, Christopher C. S.; Taylor, Robert A. [Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Kocher, Claudius [Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Konstanz University, Konstanz (Germany); Zhu, Tongtong; Oehler, Fabrice; Emery, Robert; Oliver, Rachel A. [Department of Materials Science and Metallurgy, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom)

    2014-06-30

    Experimental observation of Rabi rotations between an exciton excited state and the crystal ground state in a single non-polar InGaN quantum dot is presented. The exciton excited state energy is determined by photoluminescence excitation spectroscopy using two-photon excitation from a pulsed laser. The population of the exciton excited state is seen to undergo power dependent damped Rabi oscillations.

  6. [The immune status of the population of the Crimea to the tick-borne encephalitis virus].

    Science.gov (United States)

    Markeshin, S Ia; Karavanov, A S; Kovin, V V; Zakharova, T F; Evstratov, Iu V; Bychkova, M V; Evstaf'ev, I L

    1991-10-01

    The immune status of the Crimean population with respect to tick-borne encephalitis (TBE) virus has been studied. The results of the study confirm the existence of natural foci of TBE in the Crimea. The most active and potentially dangerous foci are located in forests of the mountain area of the peninsula. The study has revealed that humans are mainly exposed to the risk of contacting TBE virus infection during their work and rest in the forest.

  7. A Diverse Range of Novel RNA Viruses in Geographically Distinct Honey Bee Populations.

    Science.gov (United States)

    Remnant, Emily J; Shi, Mang; Buchmann, Gabriele; Blacquière, Tjeerd; Holmes, Edward C; Beekman, Madeleine; Ashe, Alyson

    2017-08-15

    Understanding the diversity and consequences of viruses present in honey bees is critical for maintaining pollinator health and managing the spread of disease. The viral landscape of honey bees ( Apis mellifera ) has changed dramatically since the emergence of the parasitic mite Varroa destructor , which increased the spread of virulent variants of viruses such as deformed wing virus. Previous genomic studies have focused on colonies suffering from infections by Varroa and virulent viruses, which could mask other viral species present in honey bees, resulting in a distorted view of viral diversity. To capture the viral diversity within colonies that are exposed to mites but do not suffer the ultimate consequences of the infestation, we examined populations of honey bees that have evolved naturally or have been selected for resistance to Varroa This analysis revealed seven novel viruses isolated from honey bees sampled globally, including the first identification of negative-sense RNA viruses in honey bees. Notably, two rhabdoviruses were present in three geographically diverse locations and were also present in Varroa mites parasitizing the bees. To characterize the antiviral response, we performed deep sequencing of small RNA populations in honey bees and mites. This provided evidence of a Dicer-mediated immune response in honey bees, while the viral small RNA profile in Varroa mites was novel and distinct from the response observed in bees. Overall, we show that viral diversity in honey bee colonies is greater than previously thought, which encourages additional studies of the bee virome on a global scale and which may ultimately improve disease management. IMPORTANCE Honey bee populations have become increasingly susceptible to colony losses due to pathogenic viruses spread by parasitic Varroa mites. To date, 24 viruses have been described in honey bees, with most belonging to the order Picornavirales Collapsing Varroa -infected colonies are often overwhelmed

  8. A Diverse Range of Novel RNA Viruses in Geographically Distinct Honey Bee Populations

    Science.gov (United States)

    Shi, Mang; Buchmann, Gabriele; Blacquière, Tjeerd; Beekman, Madeleine; Ashe, Alyson

    2017-01-01

    ABSTRACT Understanding the diversity and consequences of viruses present in honey bees is critical for maintaining pollinator health and managing the spread of disease. The viral landscape of honey bees (Apis mellifera) has changed dramatically since the emergence of the parasitic mite Varroa destructor, which increased the spread of virulent variants of viruses such as deformed wing virus. Previous genomic studies have focused on colonies suffering from infections by Varroa and virulent viruses, which could mask other viral species present in honey bees, resulting in a distorted view of viral diversity. To capture the viral diversity within colonies that are exposed to mites but do not suffer the ultimate consequences of the infestation, we examined populations of honey bees that have evolved naturally or have been selected for resistance to Varroa. This analysis revealed seven novel viruses isolated from honey bees sampled globally, including the first identification of negative-sense RNA viruses in honey bees. Notably, two rhabdoviruses were present in three geographically diverse locations and were also present in Varroa mites parasitizing the bees. To characterize the antiviral response, we performed deep sequencing of small RNA populations in honey bees and mites. This provided evidence of a Dicer-mediated immune response in honey bees, while the viral small RNA profile in Varroa mites was novel and distinct from the response observed in bees. Overall, we show that viral diversity in honey bee colonies is greater than previously thought, which encourages additional studies of the bee virome on a global scale and which may ultimately improve disease management. IMPORTANCE Honey bee populations have become increasingly susceptible to colony losses due to pathogenic viruses spread by parasitic Varroa mites. To date, 24 viruses have been described in honey bees, with most belonging to the order Picornavirales. Collapsing Varroa-infected colonies are often

  9. A population screening test for antibody to measles virus

    International Nuclear Information System (INIS)

    Friedman, M.G.

    1981-01-01

    In areas where sporadic cases of measles continue to occur in spite of vaccination programs, the availability of a simple screening test for determination of seropositivity to measles virus is desirable. A sensitive radioimmunoassay (RIA) screening test (ST) for the detection of IgG antibody to measles virus, based on a solid phase RIA, is described. The assays were performed on polyvinyl microtiter plates for which the RIAST requires only 5 μl of serum per subject. Antigen consisted of a sonicated extract of measles virus-infected Vero cells. Rabbit antihuman IgG specific for the Fc-segment of human IgG, labelled with 125 I, was used to detect human IgG bound to viral antigen. The basic RIA method was characterized by carrying out full titrations of sera of 53 healthy adults, 10 children, and 13 patients with measles-associated illness. These sera were also tested by the hemagglutination inhibition (HI) technique; most of the measles sera were also tested by complement fixation (CF). RIAST results (expressed as binding ratios) obtained for 52 healthy adults are compared with their RIA serum titers. Of the 200 sera of patients of various ages tested by the RIAST, 63 borderline sera were also tested by HI. The RIAST, which does not require serum treatment other than inactivation, proved to be more sensitive as an indicator of seropositivity than HI. Implications of the results and practical applications of the screening test are discussed. (author)

  10. Screening of peste des petits ruminants virus in a population of district Khairpur, Pakistan.

    Science.gov (United States)

    Maitlo, A K; Ujan, J A; Ujjan, S A; Ruk, M; Memon, B A; Mahar, A A; Ujjan, A A

    2017-09-28

    Goats are the Pakistan's fastest growing ruminants, and Pakistan is the third largest goat producer in the world after India and China. Goat meat preference is the main reason for its increased demand. In the country, there are 25 goat breeds and two wild relatives such as Mark and Goats. At present, Pakistan has 53.8 million goats, according to the 2006 GOP report, and their population growth rate was more than 3% per year (37, 23, 22, and 18% of the goat population in Punjab, Sindh, Balochistan, and NWFP, respectively). Peste des petits ruminants virus (PPRV) belongs to the family Paramyxoviridae and is considered to be one of the major constraints on increasing the productivity of goats and sheep in the areas where they exist and become local. It is closely related to cattle and buffalo rinderpest virus, dogs and other wild predator distemper virus, human measles virus, and marine mammalian measles virus. The present study aimed to determine the screening of the PPRV, Capra Hircus Lin. population, in the Khairpur Mirs District, Sindh, Pakistan. We selected 290 goats for serum sample collection and analysis using competitive ELISA kits according to the manufacturer's instructions. Our results showed that 59 (64%) of the 92 clinical cases were positive and 33 (36%) were seronegative. The study concluded that PPR might be more prevalent in the Khairpur District. Furthermore, it is highly recommended to use homologous PPR-attenuated vaccines to prevent lethal virus attacks that control PPR in the country.

  11. Border Disease Virus: an exceptional driver of chamois populations among other threats

    Directory of Open Access Journals (Sweden)

    Emmanuel eSerrano

    2015-12-01

    Full Text Available Though it is accepted that emerging infectious diseases are a threat to planet biodiversity, little information exists about their role as drivers of species extinction. Populations are also affected by natural catastrophes and other pathogens, making it difficult to estimate the particular impact of emerging diseases. Border disease virus genogroup 4 (BDV-4 caused a previously unreported decrease in populations of Pyrenean chamois (Rupicapra p. pyrenaica in Spain. Using a population viability analysis, we compared probabilities of extinction of a virtual chamois population affected by winter conditions, density dependence, keratoconjunctivitis, sarcoptic mange and BDV outbreaks. BDV-affected populations showed double risk of becoming extinct in 50 years, confirming the exceptional ability of this virus to drive chamois populations.

  12. Applications of pox virus vectors to vaccination: an update.

    OpenAIRE

    Paoletti, E

    1996-01-01

    Recombinant pox viruses have been generated for vaccination against heterologous pathogens. Amongst these, the following are notable examples. (i) The engineering of the Copenhagen strain of vaccinia virus to express the rabies virus glycoprotein. When applied in baits, this recombinant has been shown to vaccinate the red fox in Europe and raccoons in the United States, stemming the spread of rabies virus infection in the wild. (ii) A fowlpox-based recombinant expressing the Newcastle disease...

  13. 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. © 2016 Blackwell

  14. A Century Spent Combating Rabies in Morocco (1911–2015): How Much Longer?

    Science.gov (United States)

    Darkaoui, Sami; Cliquet, Florence; Wasniewski, Marine; Robardet, Emmanuelle; Aboulfidaa, Nadia; Bouslikhane, Mohammed; Fassi-Fihri, Ouafaa

    2017-01-01

    Rabies has no known beginning in Morocco and to date, government control efforts and plans fail to eradicate the disease. A review and analysis of available epidemiological data are crucial to learn lessons from the past and to propose effective actions. Legally, animal rabies is a notifiable disease since 1913 and legislation has been updated periodically since. Dogs have always been considered as both the disease’s vector and reservoir, while cattle, other herbivores, and humans are victims. Animal rabies cases evolution from 1942 to 2015 is characterized by ascending phase then decreasing one following structured rabies control plan implementation in 1980s. Indeed, from 1986 to 2010, three rabies control plans have been conducted based on free of charge rabies vaccination of owned dogs through mass campaigns. The geographical distribution of rabies is stable over the years with highest cases number in rich rural areas and around cities. Human rabies cases are decreasing over the time (1976–2015) thanks to the opening of new antirabic treatment centers in the last decade which permit the administration of more PEPs. After a century of rabies control, Morocco registered an average of 301 animal cases and 21 human cases annually for the last decade (2005–2015). Few reasons led to those limited results. The lack in law enforcement and, moreover, the fact that the law do not take into account responsible dog ownership aspect are of importance. Lack of dog population knowledge and management and intersectoral coordination deficiency are additional failure reasons. The gathered data will help to build a new strategy with a focus on a “One Health” approach. Dog population ecology parameters’ study is of primary importance. We estimated dog population to be 2.8 million dogs based on human:dog ratio. Enhancing vaccination coverage of dog population is feasible by combining parenteral vaccination and complementary oral vaccination. Updating legislation by

  15. A Century Spent Combating Rabies in Morocco (1911–2015: How Much Longer?

    Directory of Open Access Journals (Sweden)

    Sami Darkaoui

    2017-06-01

    Full Text Available Rabies has no known beginning in Morocco and to date, government control efforts and plans fail to eradicate the disease. A review and analysis of available epidemiological data are crucial to learn lessons from the past and to propose effective actions. Legally, animal rabies is a notifiable disease since 1913 and legislation has been updated periodically since. Dogs have always been considered as both the disease’s vector and reservoir, while cattle, other herbivores, and humans are victims. Animal rabies cases evolution from 1942 to 2015 is characterized by ascending phase then decreasing one following structured rabies control plan implementation in 1980s. Indeed, from 1986 to 2010, three rabies control plans have been conducted based on free of charge rabies vaccination of owned dogs through mass campaigns. The geographical distribution of rabies is stable over the years with highest cases number in rich rural areas and around cities. Human rabies cases are decreasing over the time (1976–2015 thanks to the opening of new antirabic treatment centers in the last decade which permit the administration of more PEPs. After a century of rabies control, Morocco registered an average of 301 animal cases and 21 human cases annually for the last decade (2005–2015. Few reasons led to those limited results. The lack in law enforcement and, moreover, the fact that the law do not take into account responsible dog ownership aspect are of importance. Lack of dog population knowledge and management and intersectoral coordination deficiency are additional failure reasons. The gathered data will help to build a new strategy with a focus on a “One Health” approach. Dog population ecology parameters’ study is of primary importance. We estimated dog population to be 2.8 million dogs based on human:dog ratio. Enhancing vaccination coverage of dog population is feasible by combining parenteral vaccination and complementary oral vaccination. Updating

  16. Rabies - epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review.

    Science.gov (United States)

    Singh, Rajendra; Singh, Karam Pal; Cherian, Susan; Saminathan, Mani; Kapoor, Sanjay; Manjunatha Reddy, G B; Panda, Shibani; Dhama, Kuldeep

    2017-12-01

    Rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus Lyssavirus and family Rhabdoviridae. It affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. Over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Bite of rabid animals and saliva of infected host are mainly responsible for transmission and wildlife like raccoons, skunks, bats and foxes are main reservoirs for rabies. The incubation period is highly variable from 2 weeks to 6 years (avg. 2-3 months). Though severe neurologic signs and fatal outcome, neuropathological lesions are relatively mild. Rabies virus exploits various mechanisms to evade the host immune responses. Being a major zoonosis, precise and rapid diagnosis is important for early treatment and effective prevention and control measures. Traditional rapid Seller's staining and histopathological methods are still in use for diagnosis of rabies. Direct immunofluoroscent test (dFAT) is gold standard test and most commonly recommended for diagnosis of rabies in fresh brain tissues of dogs by both OIE and WHO. Mouse inoculation test (MIT) and polymerase chain reaction (PCR) are superior and used for routine diagnosis. Vaccination with live attenuated or inactivated viruses, DNA and recombinant vaccines can be done in endemic areas. This review describes in detail about epidemiology, transmission, pathogenesis, advances in diagnosis, vaccination and therapeutic approaches along with appropriate prevention and control strategies.

  17. Sokoto Journal of Veterinary Sciences Dog population and ecology ...

    African Journals Online (AJOL)

    ADEYEYE

    of dog movements constitute a great public health risk to human populations in terms of dog bites and rabies outbreaks. Keywords: Dog, Ecology, Nigeria, Rabies, Vaccination. Introduction. Dog population dynamics have major impacts on the effectiveness of rabies control strategies. An understanding of the domestic dog ...

  18. [Epidemiology of rabies in Algeria].

    Science.gov (United States)

    Benelmouffok, A; Belkaid, M; Benhassine, M

    An epidemiological study on rabies in Algeria has been carried out on data provided by the "Institut national de Santé publique" and the "Institut Pasteur d'Algérie". It showed that no region is unhurt. The animal reservoir is of the domestic type, essentially the dog. In 40% of cases, bites are due to stray dogs.

  19. Evolution of natural populations in the Drosophila melanogaster sigma virus system I. Languedoc (southern France).

    Science.gov (United States)

    Fleuriet, A; Periquet, G; Anxolabéhère, D

    1990-01-01

    In natural populations of Drosophila melanogaster, sigma virus is usually present in a minority of individuals. The virus is transmitted transovarially but is not contagious from fly to fly. Two viral Types (I and II) are found in populations. One of them (Type II) is better adapted to an allele for resistance to the virus, present as a polymorphism in fly populations. Previous observations have led to the hypothesis that a viral Type II originating in central France might be invading populations. The study of Languedoc populations was undertaken to examine this hypothesis. Two striking phenomena were observed. The strong increase in Type II clones frequency (from 0.53 to 0.91) confirmed that there was invasion in this region. The frequency of infected flies also increased dramatically, at levels never observed elsewhere yet, which indicates that Languedoc should present some unusual characteristics. The epidemiological consequences of such a burst, in the case of a pathogenic virus would have to be taken into consideration. Significant changes in other viral characteristics, from 1983 to 1987, in Languedoc populations have also been documented.

  20. Rabies: What If I Receive Treatment Outside the United States?

    Science.gov (United States)

    ... R S T U V W X Y Z # Rabies Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rabies Homepage Exposure What materials can spread rabies? What ...

  1. Impact of community-delivered SMS alerts on dog-owner participation during a mass rabies vaccination campaign, Haiti 2017.

    Science.gov (United States)

    Cleaton, Julie M; Wallace, Ryan M; Crowdis, Kelly; Gibson, Andy; Monroe, Benjamin; Ludder, Fleurinord; Etheart, Melissa D; Natal Vigilato, Marco Antonio; King, Alasdair

    2018-04-19

    Haiti has historically vaccinated between 100,000 and 300,000 dogs annually against rabies, however national authorities have not been able to reach and maintain the 70% coverage required to eliminate the canine rabies virus variant. Haiti conducts massive dog vaccination campaigns on an annual basis and utilizes both central point and door-to-door methods. These methods require that dog owners are aware of the dates and locations of the campaign. To improve this awareness among dog owners, 600,000 text messages were sent to phones in two Haitian communes (Gonaives and Saint-Marc) to remind dog owners to attend the campaign. Text messages were delivered on the second day and at the mid-point of the campaign. A post-campaign household survey was conducted to assess dog owner's perception of the text messages and the impact on their participation in the vaccination campaign. Overall, 147 of 160 (91.9%) text-receiving dog owners indicated the text was helpful, and 162 of 187 (86.6%) responding dog owners said they would like to receive text reminders during future rabies vaccination campaigns. In areas hosting one-day central point campaigns, dog owners who received the text were 2.0 (95% CI 1.1, 3.6) times more likely to have participated in the campaign (73.1% attendance among those who received the text vs 36.4% among those who did not). In areas incorporating door-to-door vaccination over multiple days there was no significant difference in participation between dog owners who did and did not receive a text. Text message reminders were well-received and significantly improved campaign attendance, indicating that short message service (SMS) alerts may be a successful strategy in low resource areas with large free roaming dog populations. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.