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

PubMed

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.

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

PubMed Central

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

Vaccination of Ferrets for Rabies and Distemper.

PubMed

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.

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.

PubMed

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.

Tools for rabies serology to monitor the effectiveness of rabies vaccination in domestic and wild carnivores.

PubMed

Servat, A; Wasniewski, M; Cliquet, F

2006-01-01

Serology remains the only way to monitor the effectiveness of vaccination of humans and animals against rabies. Many techniques for determining the level of rabies antibodies have been described, including seroneutralisation techniques such as tests for fluorescent antibody virus neutralisation (FAVN) and rapid fluorescent focus inhibition (RFFIT), enzyme-linked immunosorbent assay (ELISA), and in-vivo tests (the mouse neutralisation test, MNT). The need to verify the effectiveness of rabies vaccination has become widespread, particularly in the context of international trading of domestic carnivores from infected to rabies-free territories. The standardisation of serological techniques, approval of laboratories and proficiency tests are key concepts to ensure the practicability of such systems. Serological tests for rabies are also often used by laboratories in infected territories to assess the efficacy of campaigns aimed at the eradication of the disease via oral vaccination of wildlife. The adaptation of these methods should provide the means to titrate specific antibodies in dogs during mass parenteral vaccination in countries infected by canine rabies. However, in most cases these serological tests are carried without any standardised procedure. On the basis of our experience in rabies serology and its harmonisation throughout laboratories worldwide, we propose here an adapted standard technique for the serological monitoring for rabies in wildlife at the European level. Such harmonisation would allow the monitoring of vaccination campaigns to be enhanced by increasing the exchange of epidemiological data, with the ultimate goal being the eradication of rabies in Europe.

Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain.

PubMed

Garg, Rajni; Kaur, Manpreet; Saxena, Ankur; Prasad, Rajendra; Bhatnagar, Rakesh

2017-05-01

Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD 50 rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2IU/ml and total RVNA titer was observed to be 4IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD 50 of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rabies Vaccination Targets for Stray Dog Populations

PubMed Central

Leung, Tiffany; Davis, Stephen A.

2017-01-01

The role of stray dogs in the persistence of domestic dog rabies, and whether removal of such dogs is beneficial, remains contentious issues for control programs seeking to eliminate rabies. While a community might reach the WHO vaccination target of 70% for dogs that can be handled, the stray or neighborhood dogs that are too wary of humans to be held are a more problematic population to vaccinate. Here, we present a method to estimate vaccination targets for stray dogs when the dog population is made up of stray, free-roaming, and confined dogs, where the latter two types are considered to have an identifiable owner. The control effort required for stray dogs is determined by the type-reproduction number, T1, the number of stray dogs infected by one rabid stray dog either directly or via any chain of infection involving owned dogs. Like the basic reproduction number R0 for single host populations, T1 determines the vaccination effort required to control the spread of disease when control is targeted at one host type, and there is a mix of host types. The application of T1 to rabies in mixed populations of stray and owned dogs is novel. We show that the outcome is sensitive to the vaccination coverage in the owned dog population, such that if vaccination rates of owned dogs were too low then no control effort targeting stray dogs is able to control or eliminate rabies. The required vaccination level also depends on the composition of the dog population, where a high proportion of either stray or free-roaming dogs implies unrealistically high vaccination levels are required to prevent rabies. We find that the required control effort is less sensitive to continuous culling that increases the death rate of stray dogs than to changes in the carrying capacity of the stray dog population. PMID:28451589

Community rabies knowledge and pet vaccination practices after a skunk rabies outbreak in Eddy County, New Mexico.

PubMed

McNeil, Carrie S; Nagy, Samantha; Moonan, Catherine; Wallace, Ryan M; Vora, Neil M; Dyer, Jessie L; Blanton, Jesse D; Dorado, Tina; Heinrich, Mark L; Sankey, Robin; Uhrig, Samantha; Cary, Angela; Houghton, Woods; Ettestad, Paul

2015-06-01

To determine percentages of domestic cats and dogs vaccinated against rabies, identify barriers to vaccination, and assess knowledge about rabies in a semirural New Mexico community after a skunk rabies outbreak. Cross-sectional, door-to-door, bilingual, community-based participatory survey. 366 residential properties in Eddy County, NM. The New Mexico Department of Health and CDC administered surveys and analyzed data. Individuals at 247 of the 366 residential properties participated in the survey. One hundred eighty of the 247 (73%) households owned a dog (n = 292) or cat (163). Cats were more likely than dogs to not have an up-to-date rabies vaccination status (prevalence ratio, 3.2; 95% confidence interval, 2.3 to 4.4). Cost and time or scheduling were the most frequently identified barriers to vaccination. One hundred sixty (65%) respondents did not know livestock can transmit rabies, 78 (32%) did not know rabies is fatal, and 89 (36%) did not know a bat scratching a person can be an exposure. Only 187 (76%) respondents indicated they would contact animal control if they saw a sick skunk, and only 166 (67%) indicated they would contact animal control if bitten by a dog they did not own. Findings indicated that rabies vaccination prevalence among pet dogs and cats was low, despite the fact that the region had experienced a skunk rabies outbreak during the previous 2 years. In addition, substantial percentages of respondents did not have correct knowledge of rabies or rabies exposure.

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

PubMed

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.

Duration of serum antibody response to rabies vaccination in horses.

PubMed

Harvey, Alison M; Watson, Johanna L; Brault, Stephanie A; Edman, Judy M; Moore, Susan M; Kass, Philip H; Wilson, W David

2016-08-15

OBJECTIVE To investigate the impact of age and inferred prior vaccination history on the persistence of vaccine-induced antibody against rabies in horses. DESIGN Serologic response evaluation. ANIMALS 48 horses with an undocumented vaccination history. PROCEDURES Horses were vaccinated against rabies once. Blood samples were collected prior to vaccination, 3 to 7 weeks after vaccination, and at 6-month intervals for 2 to 3 years. Serum rabies virus-neutralizing antibody (RVNA) values were measured. An RVNA value of ≥ 0.5 U/mL was used to define a predicted protective immune response on the basis of World Health Organization recommendations for humans. Values were compared between horses < 20 and ≥ 20 years of age and between horses inferred to have been previously vaccinated and those inferred to be immunologically naïve. RESULTS A protective RVNA value (≥ 0.5 U/mL) was maintained for 2 to 3 years in horses inferred to have been previously vaccinated on the basis of prevaccination RVNA values. No significant difference was evident in response to rabies vaccination or duration of protective RVNA values between horses < 20 and ≥ 20 years of age. Seven horses were poor responders to vaccination. Significant differences were identified between horses inferred to have been previously vaccinated and horses inferred to be naïve prior to the study. CONCLUSIONS AND CLINICAL RELEVANCE A rabies vaccination interval > 1 year may be appropriate for previously vaccinated horses but not for horses vaccinated only once. Additional research is required to confirm this finding and characterize the optimal primary dose series for rabies vaccination.

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

PubMed

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.

Serum antibody titers following routine rabies vaccination in African elephants.

PubMed

Miller, Michele A; Olea-Popelka, Francisco

2009-10-15

To evaluate serum antibody titers in captive African elephants (Loxodonta africana) following routine vaccination with a commercially available, inactivated rabies vaccine. Seroepidemiologic study. 14 captive African elephants from a single herd. Elephants were vaccinated as part of a routine preventive health program. Initially, elephants were vaccinated annually (2 mL, IM), and blood was collected every 4 or 6 months for measurement of rabies virus-neutralizing antibody titer by means of the rapid fluorescent focus inhibition test. Individual elephants were later switched to an intermittent vaccination schedule to allow duration of the antibody response to be determined. All elephants had detectable antibody responses following rabies vaccination, although there was great variability among individual animals in regard to antibody titers, and antibody titers could be detected as long as 24 months after vaccine administration. Young animals were found to develop an antibody titer following administration of a single dose of the rabies vaccine. Age and time since vaccination had significant effects on measured antibody titers. Results indicated that African elephants developed detectable antibody titers in response to inoculation with a standard large animal dose of a commercially available, inactivated rabies vaccine. The persistence of detectable antibody titers in some animals suggested that vaccination could be performed less frequently than once a year if antibody titers were routinely monitored.

Rabies in vaccinated dogs and cats in the United States, 1997-2001.

PubMed

Murray, Kristy O; Holmes, Kelly C; Hanlon, Cathleen A

2009-09-15

To identify cases of rabies involving vaccinated dogs and cats in the United States. Retrospective data review. 41 states that reported >or= 1 rabid dog or cat between 1997 and 2001. States were contacted to request information on numbers of dogs and cats tested for rabies between 1997 and 2001. For animals with a history of rabies vaccination, respondents were asked to provide details of the vaccination history, age, history of exposure to rabid animals, time between exposure and onset of clinical signs, clinical signs, duration of clinical signs, and whether the animal had died or was euthanatized. 21 of the 41 (51%) states agreed to participate in the study. A total of 264 rabid dogs and 840 rabid cats were identified during the study period. Thirteen (4.9%) rabid dogs and 22 (2.6%) rabid cats had a history of rabies vaccination. Of these, 2 dogs and 3 cats were classified as currently vaccinated. Overall, 6 animals (1 dog and 5 cats) had a history of receiving 2 doses of rabies vaccine in their lifetime, including 2 cats that were classified as currently vaccinated. Results suggested that rabies is uncommon in vaccinated dogs and cats but can occur. Veterinarians should include rabies in the differential diagnosis for any dog or cat with clinical signs compatible with rabies regardless of vaccination history. Continued surveillance is imperative to document vaccination failure and identify trends related to vaccination failure.

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

PubMed

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

2017-03-01

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

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

PubMed Central

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

2017-01-01

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

Incidence of adverse events in ferrets vaccinated with distemper or rabies vaccine: 143 cases (1995-2001).

PubMed

Greenacre, Cheryl B

2003-09-01

To determine the incidence of adverse events in ferrets vaccinated with a modified-live avian cell culture canine distemper virus vaccine licensed for use in ferrets, an inactivated rabies vaccine licensed for use in ferrets, or both. Retrospective study. 143 ferrets. Medical records were reviewed to identify ferrets that had an adverse event after vaccination. Adverse events developed within 25 minutes after vaccination in 13 ferrets. One ferret developed an adverse event after receiving a distemper and a rabies vaccine simultaneously and developed a second adverse event the following year after receiving the rabies vaccine alone. Therefore, a total of 14 adverse events were identified. All adverse events were an anaphylactic reaction characterized by generalized hyperemia, hypersalivation, and vomiting. Ten of the 14 anaphylactic reactions occurred after ferrets received both vaccines, 3 occurred after ferrets received the distemper vaccine alone, and 1 occurred after a ferret received the rabies vaccine alone. Incidences of adverse events after administration of both vaccines, the distemper vaccine alone, and the rabies vaccine alone were 5.6, 5.9, and 5.6%, respectively. Ferrets that had an anaphylactic reaction were significantly older at the time of vaccination than were ferrets that did not. Results suggest that there may be a high incidence of anaphylactic reactions after vaccination of domestic ferrets. Ferrets should be observed for at least 25 minutes after vaccination, and veterinarians who vaccinate ferrets should be prepared to treat anaphylactic reactions.

77 FR 40322 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment AGENCY: Animal and Plant Health... assessment relative to an oral rabies vaccination field trial in New Hampshire, New York, Ohio, Vermont, and West Virginia. The environmental assessment analyzes the use of an experimental rabies vaccine in field...

Rabies vaccines: where do we stand, where are we heading?

PubMed

Kaur, Manpreet; Garg, Rajni; Singh, Samer; Bhatnagar, Rakesh

2015-03-01

Rabies being the most lethal zoonotic, vaccine-preventable viral disease with worldwide distribution of reservoir wild animals presents unique challenges for its diagnosis, management and control. Although vaccines available are highly effective, which had played the key role in controlling rabies in North America, western Europe and in a number of Asian and Latin American countries, the requirement of multiple doses along with boosters, associated cost to reduce the incidence in wild animals and prophylactic human vaccination has remained a major impediment towards achieving the same goals in poorer parts of the world such as sub-Saharan Africa and southeast Asia. Current efforts to contain rabies worldwide are directed towards the development of more safe, cheaper and efficacious vaccines along with anti-rabies antibodies for post-exposure prophylaxis. The work presented here provides an overview of the advances made towards controlling the human rabies, particularly in last 10 years, and future perspective.

EDQM biological reference preparation for rabies vaccine (inactivated) for veterinary use.

PubMed

Daas, A; Bruckner, L; Milne, C

2015-01-01

Rabies is a deadly zoonotic disease. Control of rabies in animals by vaccination is an important strategy to protect humans from infection and control the spread of the disease. Requirements for the quality control of rabies vaccines (inactivated) for veterinary use include an in vivo quantitative potency determination as outlined in the Ph. Eur. monograph 0451. Performance of this assay requires a reference preparation calibrated in International Units (IU). A European Pharmacopeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccines (inactivated) for veterinary use, calibrated in IU, has been established for this purpose. Due to the dwindling stocks of the current batch (batch 4) of Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use, a collaborative study was run as part of the EDQM Biological Standardisation Programme to establish BRP batch 5. Ten laboratories, including Official Medicines Control Laboratories and manufacturers, participated. The candidate BRP5 was assayed against the 6(th) International Standard for rabies vaccine using the in vivo vaccination-challenge assay (monograph 0451) to assign a potency value. The candidate was also compared to BRP batch 4 to establish continuity. Taking into account the results from the comparisons a potency of 10 IU/vial was assigned and in March 2015 the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use batch 5. In addition to the in vivo assay 3 laboratories tested the candidate material using their in-house in vitro assays for information.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiang, Z.Q.; Greenberg, L.; Ertl, H.C., E-mail: ertl@wistar.upenn.edu

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 protectsmore » 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.« less

Rabies in a Dog Imported from Egypt with a Falsified Rabies Vaccination Certificate--Virginia, 2015.

PubMed

Sinclair, Julie R; Wallace, Ryan M; Gruszynski, Karen; Freeman, Marilyn Bibbs; Campbell, Colin; Semple, Shereen; Innes, Kristin; Slavinski, Sally; Palumbo, Gabriel; Bair-Brake, Heather; Orciari, Lillian; Condori, Rene E; Langer, Adam; Carroll, Darin S; Murphy, Julia

2015-12-18

Canine rabies virus variant has been eliminated in the United States and multiple other countries. Globally, however, dogs remain the principal source for human rabies infections. The World Health Organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been subjected to a serologic test for rabies before shipment. On June 8, 2015, an adult female dog that had recently been picked up from the streets of Cairo, Egypt, and shipped by a U.S. animal rescue organization to the United States was confirmed to have rabies by the Virginia Department of General Services Division of Consolidated Laboratory Services (DCLS). This dog was part of a large shipment of dogs and cats from Egypt that rescue organizations had distributed to multiple states for adoption. During the investigation, public health officials learned that the rabies vaccination certificate used for entry of the rabid dog into the United States had intentionally been falsified to avoid exclusion of the dog from entry under CDC's current dog importation regulations. This report underscores the ongoing risk posed by U.S. importation of domestic animals that have not been adequately vaccinated against rabies.

Three-year duration of immunity in cats vaccinated with a canarypox-vectored recombinant rabies virus vaccine.

PubMed

Jas, D; Coupier, C; Toulemonde, C Edlund; Guigal, P-M; Poulet, H

2012-11-19

Despite the availability of efficacious vaccines for animals and humans, rabies is still a major zoonosis. Prevention of rabies in dogs and cats is key for reducing the risk of transmission of this deadly disease to humans. Most veterinary vaccines are adjuvanted inactivated vaccines and have been shown to provide one to four-year duration of immunity. In response to debates about the safety of adjuvanted vaccines in cats, a non-adjuvanted feline rabies vaccine with one-year duration of immunity claim was specifically developed using the canarypoxvirus vector technology. The objective of this study was to validate a vaccination program based on primary vaccination, revaccination one year later and boosters every three years. Seronegative cats were vaccinated at 12 weeks of age and received a booster vaccination one year later. This vaccination regimen induced a strong and sustained antibody response, and all vaccinated animals were protected against virulent rabies challenge carried out 3 years after vaccination. These results validated 3-year duration of immunity after a complete basic vaccination program consisting in primary vaccination from 12 weeks of age followed by revaccination one year later with a non-adjuvanted canarypox-vectored vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

Inferior rabies vaccine quality and low immunization coverage in dogs (Canis familiaris) in China

PubMed Central

HU, R. L.; FOOKS, A. R.; ZHANG, S. F.; LIU, Y.; ZHANG, F.

2008-01-01

SUMMARY Human rabies in China continues to increase exponentially, largely due to an inadequate veterinary infrastructure and poor vaccine coverage of naive dogs. We performed an epidemiological survey of rabies both in humans and animals, examined vaccine quality for animal use, evaluated the vaccination coverage in dogs, and checked the dog samples for the presence of rabies virus. The lack of surveillance in dog rabies, together with the low immunization coverage (up to 2·8% in rural areas) and the high percentage of rabies virus prevalence (up to 6·4%) in dogs, suggests that the dog population is a continual threat for rabies transmission from dogs to humans in China. Results also indicated that the quality of rabies vaccines for animal use did not satisfy all of the requirements for an efficacious vaccine capable of fully eliminating rabies. These data suggest that the factors noted above are highly correlated with the high incidence of human rabies in China. PMID:18177524

Examining dog owners' beliefs regarding rabies vaccination during government-funded vaccine clinics in Grenada to improve vaccine coverage rates.

PubMed

Thomas, D; Delgado, A; Louison, B; Lefrancois, T; Shaw, J

2013-07-01

Vaccination of domestic pets is an important component of rabies control and prevention in countries where the disease is maintained in a wildlife reservoir. In Grenada, vaccine coverage rates were low, despite extensive public education and advertising of government-sponsored vaccine clinics where rabies vaccine is administered to animals at no cost to animal owners. Information was needed on reasons for decreased dog owner participation in government-funded rabies vaccination clinics. A total of 120 dog owners from 6 different parishes were asked to complete a questionnaire assessing their currently held beliefs about rabies vaccination and perception of the risk posed by rabies. Over 70% of respondents believed that problems in the organization and management of clinic sites could allow for fighting between dogs or disease spread among dogs, while 35% of owners did not believe that they had the ability or adequate help to bring their dogs to the clinic sites. Recommendations for improving vaccine coverage rates included: improved scheduling of clinic sites and dates; increased biosecurity at clinic locations; focused advertising on the availability of home visits, particularly for aggressive dogs or dogs with visible skin-related diseases such as mange; and the recruitment of community volunteers to assist with bringing dogs to the clinic sites. Copyright © 2013. Published by Elsevier B.V.

[Adverse reaction caused by rabies vaccine in China: a Meta-analysis].

PubMed

Zhang, X R; Wu, Z G; Zhang, W S

2017-06-10

Objective: To conduct a Meta-analysis on the rate of adverse reaction related to rabies vaccine, so as to provide reference for rabies vaccine immunization in China. Methods: We electronically searched databases including CNKI, VIP information resource integration service platform, WanFang Data, CBM, PubMed and The Cochrane Library, to collect studies on Chinese people who had received full rabies vaccination and recording all the adverse reactions, from January 2000 to July 2016. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the adverse reaction rate was performed using the R software. Results: A total of 29 related papers had met the inclusion criteria, with no publication bias noticed. A total number of 11 020 cases had adverse reactions, among all the 94 222 respondents, with an incidence of adverse reactions as 1.04 % -47.78 % . The overall incidence rate of adverse reaction was 9.82 % (95 %CI : 7.58 % -12.72 % ). A combined local adverse reaction rate appeared as 12.05 % (95 % CI : 9.26 % -15.69 % ). The systemic adverse reaction rate was 9.06 % (95 %CI : 7.07 % -11.61 % ). The overall adverse reaction rate on aqueous vaccine was 32.39 % (95 %CI : 21.88 % -47.94 % ). Combined adverse reaction rate of freeze dried vaccine appeared as 8.65 % (95 %CI : 4.54 % -16.51 % ). Significant differences were seen between both groups ( P <0.05). Conclusions: The local adverse reaction rate caused by rabies vaccination was higher than the systemic adverse reaction rate. The adverse reaction rate of aqueous rabies vaccine was higher than that of freeze dried rabies vaccine. Our results suggested that the aqueous vaccine should gradually be eliminated.

[Types of rabies vaccines which were locally injected to the subjects bitten by animals abroad].

PubMed

Takayama, N

1997-08-01

In recent years there have been a number of subjects who were bitten by supposed rabid animals in foreign rabies-epizootic countries and visited our hospital to received post-exposure therapy after their return to Japan. WHO recommends immediate washing of the wound with soap and water, application of human anti-rabies immunoglobulin and administration of tissue-culture rabies vaccine at 0, 3, 7, 14, 30, and 90 days after exposure. However, tissue-culture vaccines, are expensive and they are not always used in all parts of the world. The author checked whether the victims of animal bite were injected with rabies vaccines abroad or not and investigated the type of rabies vaccine when they were vaccinated. About a half of the consulted victims were locally injected with rabies vaccine. By mean of certificates of inoculation or empty boxes of vaccine, types of rabies vaccines were proved in 40 subjects of which 38 received tissue-culture vaccines. Sample-type vaccine was administered to one subject and suckling mouse vaccine was done to another one. When post-exposure prophylaxis was continued after return to Japan, it is important to know the sort of rabies vaccine injected abroad, because brain-tissue vaccines are less effective in inducing antibody than tissue-culture vaccines. Consequently both physicians and travelers should keep in mind that even now brain-tissue vaccines are used in some areas of the world.

Cost-effectiveness of canine vaccination to prevent human rabies in rural Tanzania.

PubMed

Fitzpatrick, Meagan C; Hampson, Katie; Cleaveland, Sarah; Mzimbiri, Imam; Lankester, Felix; Lembo, Tiziana; Meyers, Lauren A; Paltiel, A David; Galvani, Alison P

2014-01-21

The annual mortality rate of human rabies in rural Africa is 3.6 deaths per 100 000 persons. Rabies can be prevented with prompt postexposure prophylaxis, but this is costly and often inaccessible in rural Africa. Because 99% of human exposures occur through rabid dogs, canine vaccination also prevents transmission of rabies to humans. To evaluate the cost-effectiveness of rabies control through annual canine vaccination campaigns in rural sub-Saharan Africa. We model transmission dynamics in dogs and wildlife and assess empirical uncertainty in the biological variables to make probability-based evaluations of cost-effectiveness. Epidemiologic variables from a contact-tracing study and literature and cost data from ongoing vaccination campaigns. Two districts of rural Tanzania: Ngorongoro and Serengeti. 10 years. Health policymaker. Vaccination coverage ranging from 0% to 95% in increments of 5%. Life-years for health outcomes and 2010 U.S. dollars for economic outcomes. Annual canine vaccination campaigns were very cost-effective in both districts compared with no canine vaccination. In Serengeti, annual campaigns with as much as 70% coverage were cost-saving. Across a wide range of variable assumptions and levels of societal willingness to pay for life-years, the optimal vaccination coverage for Serengeti was 70%. In Ngorongoro, although optimal coverage depended on willingness to pay, vaccination campaigns were always cost-effective and lifesaving and therefore preferred. Canine vaccination was very cost-effective in both districts, but there was greater uncertainty about the optimal coverage in Ngorongoro. Annual canine rabies vaccination campaigns conferred extraordinary value and dramatically reduced the health burden of rabies. National Institutes of Health.

Comparison of anamnestic responses to rabies vaccination in dogs and cats with current and out-of-date vaccination status.

PubMed

Moore, Michael C; Davis, Rolan D; Kang, Qing; Vahl, Christopher I; Wallace, Ryan M; Hanlon, Cathleen A; Mosier, Derek A

2015-01-15

To compare anamnestic antibody responses of dogs and cats with current versus out-of-date vaccination status. Cross-sectional study. 74 dogs and 33 cats. Serum samples were obtained from dogs and cats that had been exposed to rabies and brought to a veterinarian for proactive serologic monitoring or that had been brought to a veterinarian for booster rabies vaccination. Blood samples were collected on the day of initial evaluation (day 0) and then again 5 to 15 days later. On day 0, a rabies vaccine was administered according to label recommendations. Paired serum samples were analyzed for antirabies antibodies by means of a rapid fluorescent focus inhibition test. All animals had an antirabies antibody titer ≥ 0.5 IU/mL 5 to 15 days after booster vaccination. Dogs with an out-of-date vaccination status had a higher median increase in titer, higher median fold increase in titer, and higher median titer following booster vaccination, compared with dogs with current vaccination status. Most (26/33) cats, regardless of rabies vaccination status, had a titer ≥ 12 IU/mL 5 to 15 days after booster vaccination. Results indicated that dogs with out-of-date vaccination status were not inferior in their antibody response following booster rabies vaccination, compared with dogs with current vaccination status. Findings supported immediate booster vaccination followed by observation for 45 days of dogs and cats with an out-of-date vaccination status that are exposed to rabies, as is the current practice for dogs and cats with current vaccination status.

Dogs that develop rabies post-vaccination usually manifest the paralytic subtype.

PubMed

Tepsumethanon, Veera; Likitsuntonwong, Wanlop; Thorner, Paul Scott; Shuangshoti, Shanop

2016-09-01

Rabies infection can manifest as either encephalitic (furious) or paralytic (dumb) types, with a ratio of approximately 2:1 in dogs. The clinical type of rabies that develops post-vaccination has only been reported in studies from one country, all with similar findings. We report a study of 36 rabid dogs with obtainable vaccination history, presenting to The Queen Saovabha Memorial Institute, Bangkok, Thailand during 2002-2008. Dogs were classified into encephalitic or paralytic types. Of 22 non-vaccinated dogs, 16 (73%) had the encephalitic type. In contrast, of the 14 vaccinated dogs, 10 (71%) had the paralytic type, a difference that was significant (p=0.016). Recent studies on canine brains have shown that lymphocyte response is more pronounced in paralytic rabies at the brainstem level, whereas viral burden is greater in the encephalitic form. We postulate partial immune response in the vaccinated dogs might influence rabies to manifest as the paralytic type. These results can serve as a natural experiment that can help explain the basis for the differences between the paralytic and encephalitic forms of canine rabies. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of intradermal vaccination at the anti rabies vaccination OPD.

PubMed

Mankeshwar, R; Silvanus, V; Akarte, S

2014-09-01

Rabies is a virtually 100% fatal acute viral encephalitis caused by an RNA virus belonging to family Rhabdoviridae and genus Lyssavirus. The virus can infect all warm blooded animals. The disease is transmitted to humans by the bite, lick or scratch of an infected animal. More than 99% of all human rabies deaths occur in the developing world. It is preventable with timely and proper usage of modern immunobiologicals (vaccines and immunoglobulins). Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. The annual medicinal (vaccines and other drugs) cost for animal bite treatment is Rs. 2 billion approximately (2004). The objective of the present study is to evaluate the performance of the Intradermal (i.d.) route visa vis the Intramuscular (i.m.) route in our clinical setting the Antirabies Vaccination (ARV) OPD, Sir J.J. Hospital, Mumbai. A total of 1460 patients were administered the Antirabies vaccine by the Intradermal route over the 1 year period as compared to 1075 patients who were administered the Antirabies vaccine by the Intramuscular route in the previous year. 1230 (84.2) of the patients who were administered the vaccine by the i.d. route completed the schedule and 230 (15.8%) partially completed the schedule. Four hundred thirty two (40%) of the patients who were administered the vaccine by the Intramuscular route completed the schedule and 643 (59.8%) partially completed the schedule. The vaccine cost for i.d. was Rs. 2,80,600. The vaccine cost for the intramuscular (i.m.) assuming 84% compliance was estimated as Rs. 15, 64, 000. Assuming 40% compliance the cost was estimated as Rs. 7, 82, 230. Thus a saving of Rs. 5, 01, 630 to Rs. 12, 83, 400 was effected. In our setting, the Intradermal regime was cost effective and increased patient adherence and enrolment. It has now been routinely adopted at the clinic.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

... Inspection Service [Docket No. APHIS-2013-0046] Oral Rabies Vaccine Trial; Availability of a Supplemental... Inspection Service has prepared a supplemental environmental assessment (EA) relative to an oral rabies... analyzes expanding the field trial for an experimental oral rabies vaccine for wildlife to additional areas...

[Pasteur's rabies vaccination: 130 years ago successfully started in Vienna, however officially rejected].

PubMed

Flamm, Heinz

2015-08-01

The Viennese surgeon Emerich Ullmann who was trained in rabies vaccination by Pasteur personally started his activity in Vienna on 28.6.1886 vaccinating persons of Austria-Hungary been bitten by rabid animals. Whereas Prof. v.Frisch of the other surgical clinic who also had visited Pasteur carried out animal experiments which urged him to disapprove Pasteur's human rabies vaccination. Ullmann vaccinated with great success but soon there appeared obstructions in Viennese medical journals and hateful discussions in the Austrian Parliament against Pasteur and Ullmann. These facts blocked the necessary financial subvention of Ullmann's self financed vaccinations and resulted in their interruption. After a mass infection of rabies in the Bukowina in 1891 the Supreme Sanitary Board formed an Epidemiologic Committee which recommended the establishment of a vaccination unit in an Austrian hospital. In July 1894 the Vaccination Unit was opened in the Viennese hospital Rudolfstiftung, where Emerich Ullmann carried out the rabies vaccinations.

Rabies Vaccination: Higher Failure Rates in Imported Dogs than in those Vaccinated in Italy.

PubMed

Rota Nodari, E; Alonso, S; Mancin, M; De Nardi, M; Hudson-Cooke, S; Veggiato, C; Cattoli, G; De Benedictis, P

2017-03-01

The current European Union (EU) legislation decrees that pets entering the EU from a rabies-infected third country have to obtain a satisfactory virus-neutralizing antibody level, while those moving within the EU require only rabies vaccination as the risk of moving a rabid pet within the EU is considered negligible. A number of factors driving individual variations in dog vaccine response have been previously reported, including a high rate of vaccine failure in puppies, especially those subject to commercial transport. A total of 21 001 observations collected from dogs (2006-2012) vaccinated in compliance with the current EU regulations were statistically analysed to assess the effect of different risk factors related to rabies vaccine efficacy. Within this framework, we were able to compare the vaccination failure rate in a group of dogs entering the Italian border from EU and non-EU countries to those vaccinated in Italy prior to international travel. Our analysis identified that cross-breeds and two breed categories showed high vaccine success rates, while Beagles and Boxers were the least likely to show a successful response to vaccination (88.82% and 90.32%, respectively). Our analysis revealed diverse performances among the commercially available vaccines, in terms of serological peak windows, and marked differences according to geographical area. Of note, we found a higher vaccine failure rate in imported dogs (13.15%) than in those vaccinated in Italy (5.89%). Our findings suggest that the choice of vaccine may influence the likelihood of an animal achieving a protective serological level and that time from vaccination to sampling should be considered when interpreting serological results. A higher vaccine failure in imported compared to Italian dogs highlights the key role that border controls still have in assessing the full compliance of pet movements with EU legislation to minimize the risk of rabies being reintroduced into a disease-free area. �

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

PubMed

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 (<1 year, 43.9%), likely due to insufficient targeting of pups and from puppies born subsequent to vaccination campaigns. Juveniles had a 10-70 times greater risk of not being vaccinated in urban, suburban, and rural areas [combined odds ratios (ORs): 9.9-71.1, 95% CI: 8.6-96.0]. Free-roaming owned dogs were also 2-3 times more likely to be not vaccinated compared to those confined (combined Ors: 1.9-3.6, 95% CI: 1.4-5.4), with more dogs being confined in urban (71.2%) than in suburban (16.1%) and rural areas (8.0%). Vaccination coverage estimates from transects were also much lower (30.9%) than household surveys (83.6%), possibly due to loss of collars used to identify the vaccination status of free-roaming dogs, but these unconfined dogs may also include dogs that were unowned or more difficult to vaccinate. Overall

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

PubMed Central

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

2017-01-01

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 (<1 year, 43.9%), likely due to insufficient targeting of pups and from puppies born subsequent to vaccination campaigns. Juveniles had a 10–70 times greater risk of not being vaccinated in urban, suburban, and rural areas [combined odds ratios (ORs): 9.9–71.1, 95% CI: 8.6–96.0]. Free-roaming owned dogs were also 2–3 times more likely to be not vaccinated compared to those confined (combined Ors: 1.9–3.6, 95% CI: 1.4–5.4), with more dogs being confined in urban (71.2%) than in suburban (16.1%) and rural areas (8.0%). Vaccination coverage estimates from transects were also much lower (30.9%) than household surveys (83.6%), possibly due to loss of collars used to identify the vaccination status of free-roaming dogs, but these unconfined dogs may also include dogs that were unowned or more difficult to vaccinate

76 FR 48119 - Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

...] Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment AGENCY... environmental assessment relative to an oral rabies vaccination field trial in West Virginia. The environmental... rabies vaccine, analyzes the use of that vaccine in field safety and efficacy trials in West Virginia...

Prevention of the spread of rabies to wildlife by oral vaccination of raccoons in Massachusetts.

PubMed

Robbins, A H; Borden, M D; Windmiller, B S; Niezgoda, M; Marcus, L C; O'Brien, S M; Kreindel, S M; McGuill, M W; DeMaria, A; Rupprecht, C E; Rowell, S

1998-11-15

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

Neutralizing Antibody Response in Dogs and Cats Inoculated with Commercial Inactivated Rabies Vaccines

PubMed Central

SHIRAISHI, Rikiya; NISHIMURA, Masaaki; NAKASHIMA, Ryuji; ENTA, Chiho; HIRAYAMA, Norio

2013-01-01

ABSTRACT In Japan, the import quarantine regulation against rabies has required from 2005 that dogs and cats should be inoculated with the rabies vaccine and that the neutralizing antibody titer should be confirmed to be at least 0.5 international units (IU)/ml. The fluorescent antibody virus neutralization (FAVN) test is used as an international standard method for serological testing for rabies. To achieve proper immunization of dogs and cats at the time of import and export, changes in the neutralizing antibody titer after inoculation of the rabies vaccine should be understood in detail. However, few reports have provided this information. In this study, we aimed to determine evaluated, such changes by using sera from experimental dogs and cats inoculated with the rabies vaccine, and we tested samples using the routine FAVN test. In both dogs and cats, proper, regular vaccination enabled the necessary titer of neutralizing antibodies to be maintained in the long term. However, inappropriate timing of blood sampling after vaccination could result in insufficient detected levels of neutralizing antibodies. PMID:24389741

Neutralizing antibody response in dogs and cats inoculated with commercial inactivated rabies vaccines.

PubMed

Shiraishi, Rikiya; Nishimura, Masaaki; Nakashima, Ryuji; Enta, Chiho; Hirayama, Norio

2014-04-01

In Japan, the import quarantine regulation against rabies has required from 2005 that dogs and cats should be inoculated with the rabies vaccine and that the neutralizing antibody titer should be confirmed to be at least 0.5 international units (IU)/ml. The fluorescent antibody virus neutralization (FAVN) test is used as an international standard method for serological testing for rabies. To achieve proper immunization of dogs and cats at the time of import and export, changes in the neutralizing antibody titer after inoculation of the rabies vaccine should be understood in detail. However, few reports have provided this information. In this study, we aimed to determine evaluated, such changes by using sera from experimental dogs and cats inoculated with the rabies vaccine, and we tested samples using the routine FAVN test. In both dogs and cats, proper, regular vaccination enabled the necessary titer of neutralizing antibodies to be maintained in the long term. However, inappropriate timing of blood sampling after vaccination could result in insufficient detected levels of neutralizing antibodies.

Barriers of attendance to dog rabies static point vaccination clinics in Blantyre, Malawi.

PubMed

Mazeri, Stella; Gibson, Andrew D; Meunier, Natascha; Bronsvoort, Barend M deC; Handel, Ian G; Mellanby, Richard J; Gamble, Luke

2018-01-01

Rabies is a devastating yet preventable disease that causes around 59,000 human deaths annually. Almost all human rabies cases are caused by bites from rabies-infected dogs. A large proportion of these cases occur in Sub Saharan Africa (SSA). Annual vaccination of at least 70% of the dog population is recommended by the World Health Organisation in order to eliminate rabies. However, achieving such high vaccination coverage has proven challenging, especially in low resource settings. Despite being logistically and economically more feasible than door-to-door approaches, static point (SP) vaccination campaigns often suffer from low attendance and therefore result in low vaccination coverage. Here, we investigated the barriers to attendance at SP offering free rabies vaccinations for dogs in Blantyre, Malawi. We analysed data for 22,924 dogs from a city-wide vaccination campaign in combination with GIS and household questionnaire data using multivariable logistic regression and distance estimation techniques. We found that distance plays a crucial role in SP attendance (i.e. for every km closer the odds of attending a SP point are 3.3 times higher) and that very few people are willing to travel more than 1.5 km to bring their dog for vaccination. Additionally, we found that dogs from areas with higher proportions of people living in poverty are more likely to be presented for vaccination (ORs 1.58-2.22). Furthermore, puppies (OR 0.26), pregnant or lactating female dogs (OR 0.60) are less likely to be presented for vaccination. Owners also reported that they did not attend an SP because they were not aware of the campaign (27%) or they could not handle their dog (19%). Our findings will inform the design of future rabies vaccination programmes in SSA which may lead to improved vaccination coverage achieved by SP alone.

Barriers of attendance to dog rabies static point vaccination clinics in Blantyre, Malawi

PubMed Central

Gibson, Andrew D.; Meunier, Natascha; Bronsvoort, Barend M.deC; Handel, Ian G.; Mellanby, Richard J.; Gamble, Luke

2018-01-01

Rabies is a devastating yet preventable disease that causes around 59,000 human deaths annually. Almost all human rabies cases are caused by bites from rabies-infected dogs. A large proportion of these cases occur in Sub Saharan Africa (SSA). Annual vaccination of at least 70% of the dog population is recommended by the World Health Organisation in order to eliminate rabies. However, achieving such high vaccination coverage has proven challenging, especially in low resource settings. Despite being logistically and economically more feasible than door-to-door approaches, static point (SP) vaccination campaigns often suffer from low attendance and therefore result in low vaccination coverage. Here, we investigated the barriers to attendance at SP offering free rabies vaccinations for dogs in Blantyre, Malawi. We analysed data for 22,924 dogs from a city-wide vaccination campaign in combination with GIS and household questionnaire data using multivariable logistic regression and distance estimation techniques. We found that distance plays a crucial role in SP attendance (i.e. for every km closer the odds of attending a SP point are 3.3 times higher) and that very few people are willing to travel more than 1.5 km to bring their dog for vaccination. Additionally, we found that dogs from areas with higher proportions of people living in poverty are more likely to be presented for vaccination (ORs 1.58-2.22). Furthermore, puppies (OR 0.26), pregnant or lactating female dogs (OR 0.60) are less likely to be presented for vaccination. Owners also reported that they did not attend an SP because they were not aware of the campaign (27%) or they could not handle their dog (19%). Our findings will inform the design of future rabies vaccination programmes in SSA which may lead to improved vaccination coverage achieved by SP alone. PMID:29324737

G-protein based ELISA as a potency test for rabies vaccines.

PubMed

Chabaud-Riou, Martine; Moreno, Nadège; Guinchard, Fabien; Nicolai, Marie Claire; Niogret-Siohan, Elisabeth; Sève, Nicolas; Manin, Catherine; Guinet-Morlot, Françoise; Riou, Patrice

2017-03-01

The NIH test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. This test is based on mice immunization followed by intracerebral viral challenge. As part of global efforts to reduce animal experimentation and in the framework of the development of Sanofi Pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an ELISA as an alternative to the NIH test. This ELISA is based on monoclonal antibodies recognizing specifically the native form of the viral G-protein, the major antigen that induces neutralizing antibody response to rabies virus. We show here that our ELISA is able to distinguish between potent and different types of sub-potent vaccine lots. Satisfactory agreement was observed between the ELISA and the NIH test in the determination of the vaccine titer and their capacity to discern conform from non-conform batches. Our ELISA meets the criteria for a stability-indicating assay and has been successfully used to develop the new generation of rabies vaccine candidates. After an EPAA international pre-collaborative study, this ELISA was selected as the assay of choice for the EDQM collaborative study aimed at replacing the rabies vaccine NIH in vivo potency test. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Review on dog rabies vaccination coverage in Africa: a question of dog accessibility or cost recovery?

PubMed

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

2015-02-01

Rabies still poses a significant human health problem throughout most of Africa, where the majority of the human cases results from dog bites. Mass dog vaccination is considered to be the most effective method to prevent rabies in humans. Our objective was to systematically review research articles on dog rabies parenteral vaccination coverage in Africa in relation to dog accessibility and vaccination cost recovery arrangement (i.e.free of charge or owner charged). A systematic literature search was made in the databases of CAB abstracts (EBSCOhost and OvidSP), Scopus, Web of Science, PubMed, Medline (EBSCOhost and OvidSP) and AJOL (African Journal Online) for peer reviewed articles on 1) rabies control, 2) dog rabies vaccination coverage and 3) dog demography in Africa. Identified articles were subsequently screened and selected using predefined selection criteria like year of publication (viz. ≥ 1990), type of study (cross sectional), objective(s) of the study (i.e. vaccination coverage rates, dog demographics and financial arrangements of vaccination costs), language of publication (English) and geographical focus (Africa). The selection process resulted in sixteen peer reviewed articles which were used to review dog demography and dog ownership status, and dog rabies vaccination coverage throughout Africa. The main review findings indicate that 1) the majority (up to 98.1%) of dogs in African countries are owned (and as such accessible), 2) puppies younger than 3 months of age constitute a considerable proportion (up to 30%) of the dog population and 3) male dogs are dominating in numbers (up to 3.6 times the female dog population). Dog rabies parenteral vaccination coverage was compared between "free of charge" and "owner charged" vaccination schemes by the technique of Meta-analysis. Results indicate that the rabies vaccination coverage following a free of charge vaccination scheme (68%) is closer to the World Health Organization recommended coverage rate

Pre-Exposure Rabies Vaccination among US International Travelers: Findings from the Global TravEpiNet Consortium

PubMed Central

Dolan, Samantha B.; Sotir, Mark J.; Han, Pauline; Blanton, Jesse D.; Rao, Sowmya R.; LaRocque, Regina C.; Ryan, Edward T.

2014-01-01

Abstract Background: People who travel to areas with high rabies endemicity and have animal contact are at increased risk for rabies exposure. We examined characteristics of international travelers queried regarding rabies vaccination during pretravel consultations at Global TravEpiNet (GTEN) practices during 2009–2010. Material and Methods: We performed bivariate and multivariable analyses of data collected from 18 GTEN clinics. Travel destinations were classified by strength level of rabies vaccination recommendation. Results: Of 13,235 travelers, 226 (2%) reported previous rabies vaccination, and 406 (3%) received rabies vaccine at the consultation. Common travel purposes for these 406 travelers were leisure (26%), research/education (17%), and nonmedical service work (14%). Excluding the 226 who were previously vaccinated, 8070 (62%) of 13,009 travelers intended to visit one or more countries with a strong recommendation for rabies vaccination; 1675 (21%) of these 8070 intended to travel for 1 month or more. Among these 1675 travelers, 145 (9%) were vaccinated, 498 (30%) declined vaccination, 832 (50%) had itineraries that clinicians determined did not indicate vaccination, and 200 (12%) remained unvaccinated for other reasons. In both bivariate and multivariate analyses, travelers with trip durations >6 months versus 1–3 months (adjusted odds ratio [OR]=4.9 [95% confidence interval [CI] 2.1, 11.4]) and those traveling for “research/education” or to “provide medical care” (adjusted OR=5.1 [95% CI 1.9, 13.7] and 9.5 [95% CI 2.2, 40.8], respectively), compared with leisure travelers, were more likely to receive rabies vaccination. Conclusions: Few travelers at GTEN clinics received rabies vaccine, although many planned trips 1 month long or more to a strong-recommendation country. Clinicians often determined that vaccine was not indicated, and travelers often declined vaccine when it was offered. The decision to vaccinate should take into account the

Pre-exposure rabies vaccination among US international travelers: findings from the global TravEpiNet consortium.

PubMed

Dolan, Samantha B; Jentes, Emily S; Sotir, Mark J; Han, Pauline; Blanton, Jesse D; Rao, Sowmya R; LaRocque, Regina C; Ryan, Edward T; Abraham, George M; Alvarez, Salvador; Ansdell, Vernon; Yates, Johnnie A; Atkins, Elisha H; Cahill, John; Birich, Holly K; Vitek, Dagmar; Connor, Bradley A; Dismukes, Roberta; Kozarsky, Phyllis; Dosunmu, Rone; Goad, Jeffrey A; Hagmann, Stefan; Hale, DeVon; Hynes, Noreen A; Jacquerioz, Frederique; McLellan, Susan; Knouse, Mark; Lee, Jennifer; LaRocque, Regina C; Ryan, Edward T; Oladele, Alawode; Demeke, Hanna; Pasinski, Roger; Wheeler, Amy E; Rao, Sowmya R; Rosen, Jessica; Schwartz, Brian S; Stauffer, William; Walker, Patricia; Vinetz, Joseph

2014-02-01

People who travel to areas with high rabies endemicity and have animal contact are at increased risk for rabies exposure. We examined characteristics of international travelers queried regarding rabies vaccination during pretravel consultations at Global TravEpiNet (GTEN) practices during 2009-2010. We performed bivariate and multivariable analyses of data collected from 18 GTEN clinics. Travel destinations were classified by strength level of rabies vaccination recommendation. Of 13,235 travelers, 226 (2%) reported previous rabies vaccination, and 406 (3%) received rabies vaccine at the consultation. Common travel purposes for these 406 travelers were leisure (26%), research/education (17%), and nonmedical service work (14%). Excluding the 226 who were previously vaccinated, 8070 (62%) of 13,009 travelers intended to visit one or more countries with a strong recommendation for rabies vaccination; 1675 (21%) of these 8070 intended to travel for 1 month or more. Among these 1675 travelers, 145 (9%) were vaccinated, 498 (30%) declined vaccination, 832 (50%) had itineraries that clinicians determined did not indicate vaccination, and 200 (12%) remained unvaccinated for other reasons. In both bivariate and multivariate analyses, travelers with trip durations >6 months versus 1-3 months (adjusted odds ratio [OR]=4.9 [95% confidence interval [CI] 2.1, 11.4]) and those traveling for "research/education" or to "provide medical care" (adjusted OR=5.1 [95% CI 1.9, 13.7] and 9.5 [95% CI 2.2, 40.8], respectively), compared with leisure travelers, were more likely to receive rabies vaccination. Few travelers at GTEN clinics received rabies vaccine, although many planned trips 1 month long or more to a strong-recommendation country. Clinicians often determined that vaccine was not indicated, and travelers often declined vaccine when it was offered. The decision to vaccinate should take into account the strength of the vaccine recommendation at the destination country, duration

Evaluation of Oral Rabies Vaccination: Protection Against Rabies in Wild Caught Raccoons ( Procyon lotor).

PubMed

Blanton, Jesse D; Niezgoda, Michael; Hanlon, Cathleen A; Swope, Craig B; Suckow, Jason; Saidy, Brandi; Nelson, Kathleen; Chipman, Richard B; Slate, Dennis

2018-03-29

Oral rabies vaccination (ORV) is an effective tactic for wildlife rabies control, particularly for containment of disease spread along epizootic fronts. As part of the continuing evaluation of the ORV program in free-ranging raccoons in the US, 37 raccoons from ORV-baited areas in Pennsylvania were live-trapped and transferred to captivity to evaluate protection against rabies in animals with varying levels of existing neutralizing antibodies, expressed in international units per milliliter (IU/mL). Among the 37 raccoons at the date of capture, 24% (9/37) of raccoons were seronegative (<0.05 IU/mL), 22% (8/37) were low positive (≥0.05-0.11 IU/mL), 27% (10/37) were medium positive (>0.11-<0.5 IU/mL), and 27% (10/37) were high positive (≥0.5 IU/mL). Raccoons were held for 86-199 d between the date of capture and rabies virus challenge. At challenge, 68% (25/37) raccoons were seronegative. The overall survival rate among challenged animals was 46% (17/37). Based on the antibody titers at the time of challenge, survivorship was 24% (6/25) among seronegative animals, 100% (4/4) among low positive animals, 83% (5/6) among medium positive animals, and 100% (2/2) among high positive animals. Evidence of high-titer seroconversion after vaccination is a good surrogate indicator of rabies survival; however, survival rates of approximately 45% (15/35) were found among raccoons with detectable titers below 0.5 IU/mL. In contrast, any detectable titer at the time of challenge (>3 mo after vaccination) appeared to be a surrogate indicator of survival. Overall, we illustrated significant differences in the value of specific titers as surrogates for survival based on the timing of measurement relative to vaccination. However, survivorship was generally greater than 45% among animals with any detectable titer regardless of the timing of measurement. These findings suggest that lower titer cutoffs may represent a valid approach to measuring immunization coverage within ORV

Potential for Rabies Control through Dog Vaccination in Wildlife-Abundant Communities of Tanzania

PubMed Central

Fitzpatrick, Meagan C.; Hampson, Katie; Cleaveland, Sarah; Meyers, Lauren Ancel; Townsend, Jeffrey P.; Galvani, Alison P.

2012-01-01

Canine vaccination has been successful in controlling rabies in diverse settings worldwide. However, concerns remain that coverage levels which have previously been sufficient might be insufficient in systems where transmission occurs both between and within populations of domestic dogs and other carnivores. To evaluate the effectiveness of vaccination targeted at domestic dogs when wildlife also contributes to transmission, we applied a next-generation matrix model based on contract tracing data from the Ngorongoro and Serengeti Districts in northwest Tanzania. We calculated corresponding values of R 0, and determined, for policy purposes, the probabilities that various annual vaccination targets would control the disease, taking into account the empirical uncertainty in our field data. We found that transition rate estimates and corresponding probabilities of vaccination-based control indicate that rabies transmission in this region is driven by transmission within domestic dogs. Different patterns of rabies transmission between the two districts exist, with wildlife playing a more important part in Ngorongoro and leading to higher recommended coverage levels in that district. Nonetheless, our findings indicate that an annual dog vaccination campaign achieving the WHO-recommended target of 70% will control rabies in both districts with a high level of certainty. Our results support the feasibility of controlling rabies in Tanzania through dog vaccination. PMID:22928056

Pre-exposure rabies prophylaxis: a systematic review.

PubMed

Kessels, Jocelyn A; Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

2017-03-01

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. 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. 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. 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.

Pre-exposure rabies prophylaxis: a systematic review

PubMed Central

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

Review on Dog Rabies Vaccination Coverage in Africa: A Question of Dog Accessibility or Cost Recovery?

PubMed Central

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

2015-01-01

Background Rabies still poses a significant human health problem throughout most of Africa, where the majority of the human cases results from dog bites. Mass dog vaccination is considered to be the most effective method to prevent rabies in humans. Our objective was to systematically review research articles on dog rabies parenteral vaccination coverage in Africa in relation to dog accessibility and vaccination cost recovery arrangement (i.e.free of charge or owner charged). Methodology/Principal Findings A systematic literature search was made in the databases of CAB abstracts (EBSCOhost and OvidSP), Scopus, Web of Science, PubMed, Medline (EBSCOhost and OvidSP) and AJOL (African Journal Online) for peer reviewed articles on 1) rabies control, 2) dog rabies vaccination coverage and 3) dog demography in Africa. Identified articles were subsequently screened and selected using predefined selection criteria like year of publication (viz. ≥ 1990), type of study (cross sectional), objective(s) of the study (i.e. vaccination coverage rates, dog demographics and financial arrangements of vaccination costs), language of publication (English) and geographical focus (Africa). The selection process resulted in sixteen peer reviewed articles which were used to review dog demography and dog ownership status, and dog rabies vaccination coverage throughout Africa. The main review findings indicate that 1) the majority (up to 98.1%) of dogs in African countries are owned (and as such accessible), 2) puppies younger than 3 months of age constitute a considerable proportion (up to 30%) of the dog population and 3) male dogs are dominating in numbers (up to 3.6 times the female dog population). Dog rabies parenteral vaccination coverage was compared between “free of charge” and “owner charged” vaccination schemes by the technique of Meta-analysis. Results indicate that the rabies vaccination coverage following a free of charge vaccination scheme (68%) is closer to the

Zagreb Regimen, an Abbreviated Intramuscular Schedule for Rabies Vaccination

PubMed Central

Ren, Jiangping; Yao, Linong; Sun, Jimin

2014-01-01

The Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination, was developed by I. Vodopija and colleagues of the Zagreb Institute of Public Health in Croatia in the 1980s. It was recommended by WHO as one of the intramuscular (IM) schedules for rabies vaccination in 2010. We reviewed the literature on the immunogenicity, safety, economic burden, and compliance of the Zagreb 2-1-1 regimen. Compared to Essen, another IM schedule recommended by WHO, Zagreb has higher compliance, lower medical cost, and better immunogenicity at an early stage. PMID:25392012

Oral vaccination of captive small Indian mongoose (Herpestes auropunctatus) against rabies.

PubMed

Vos, Ad; Kretzschmar, Antje; Ortmann, Steffen; Lojkic, Ivana; Habla, Christiane; Müller, Thomas; Kaiser, Christian; Hundt, Boris; Schuster, Peter

2013-10-01

The small Indian mongoose (Herpestes auropunctatus), a rabies reservoir species on several Islands in the Caribbean, was successfully immunized against rabies for the first time by offering animals a vaccine bait specifically designed for this small carnivore. The bait contained on average 0.6 mL of the genetically modified replication-competent rabies virus construct SPBN GASGAS (10(8.5) focus-forming units/mL). Three of four mongooses offered a bait developed an immune response above 0.5 IU/mL, but the response was less pronounced than in two animals offered the vaccine by direct oral instillation.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yi; Zhang, Shoufeng; Li, Wei

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 groupmore » (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

Oral vaccination of wildlife against rabies: opportunities and challenges in prevention and control.

PubMed

Rupprecht, C E; Hanlon, C A; Slate, D

2004-01-01

Rabies is an acute, progressive, fatal encephalitis caused by viruses in the Family Rhabdoviridae, Genus Lyssavirus. Rabies virus is the representative member of the group. Warm-blooded vertebrates are susceptible to experimental infection, but major primary hosts for disease perpetuation encompass bats and mammalian carnivores. The dog is the global reservoir, and important wild carnivores include foxes, raccoons, skunks, and mongoose, among others. Traditionally, reliance upon long-term, widespread, government-supported programmes aimed at population reduction of animals at risk has been unsuccessful as the sole means of rabies control, based in part upon economical, ecological and ethical grounds. In contrast, immunization of domestic dogs with traditional veterinary vaccines by the parenteral route led to the virtual extinction of canine-transmitted rabies in developed countries. Taken from this basic concept of applied herd immunity, the idea of wildlife vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of carnivores by the 1970s. The development of safe and effective rabies virus vaccines applied in attractive baits resulted in the first field trials in Switzerland in 1978. Thereafter, technical improvements occurred in vaccine quality and production, including the design of recombinant viruses, as well as in the ease of mass distribution of millions of edible baits over large geographical areas. Over the past few decades, extensive oral vaccination programmes focusing upon the red fox, using hand and aerial distribution of vaccine-laden baits, have resulted in the virtual disappearance of rabies in Western Europe. The same dramatic observation held true for southern Ontario. During the 1990s in the United States, oral vaccination programmes concentrated upon raccoons, grey foxes, and coyotes, with similar success. For example, raccoon rabies has not spread west of the current focus in

Immunogenicity and efficacy of Rabivac vaccine for animal rabies control in Morocco

PubMed Central

2016-01-01

Purpose To fight animal rabies, Moroccan veterinary authorities organize annual dog mass vaccination campaigns using Rabivac vaccine, an inactivated adjuvanted cell culture veterinary rabies vaccine. Two experiments were undertaken to assess the efficacy and immunogenicity of Rabivac. Materials and Methods The first experiment involved 13 caged dogs (8 vaccinated and 5 negative controls). Dogs were bled at day 0 (D0) and at days D7, D14, D21, D28, D35, D49, D56, D64, D70, D77, D84, D91, D98, D105, D112, and D119 post-vaccination. At D121, a virulent challenge was performed. After 70 days monitoring period, seven out of eight vaccinated dogs survived the challenge (one dog succumbed to a mesenteric torsion accident) and four out of five controls succumbed. All vaccinated dogs seroconverted and the control dogs remained negative. The second experiment consisted in a field study involving 919 owned dogs randomly selected in eight Moroccan districts located in different parts of the country. The dogs were identified and vaccinated by the parenteral route and bled on the vaccination day (D0) and on D30. Results Ninety-two percent of dogs developed a positive rabies virus neutralizing antibody response to vaccination and 24% were positive at D0, suggesting that dogs were previously vaccinated. The increase in rabies antibody titers was highly significant in all districts. No significant difference seemed occurring between the geographical status (rural, semiurban, or urban) of the districts on the results obtained. Conclusion Rabivac is efficacious both in experimental and field conditions. This supports its use in dog mass vaccination campaigns. PMID:26866025

Issues of human rabies immunoglobulin and vaccine: policy versus practice.

PubMed

Folb, Jonathan E; Cooke, Richard P D

2007-03-01

A retrospective audit was conducted of all issues of rabies vaccine or human rabies immunoglobulin (HRIG) from the Clinical Microbiology Department at University Hospital Aintree for post-exposure prophylaxis. The appropriateness of management was reviewed by a blinded panel, which used guidelines issued by the Health Protection Agency (HPA) as a standard. Thirty-six enquiries, on average 9 days following exposure, led to issues of HRIG, rabies vaccine or both. Dog bites accounted for the majority of incidents. In no cases was the biting animal recorded as having been observed for signs of rabies. Management was judged to have been inappropriate in 9 cases, and documentation was judged to have been unsatisfactory in 13 cases. This study has highlighted several areas of ambiguity in the current guidelines, and a number of deficiencies in the information prompted by the standardized proformas used to deal with post-exposure queries.

Determinants of dog owner-charged rabies vaccination in Kinshasa, Democratic Republic of Congo

PubMed Central

Tshilenge, Georges Mbuyi; Mbao, Victor; Njoumemi, Zakariaou; Masumu, Justin

2017-01-01

Rabies is a preventable fatal disease that causes about 61,000 human deaths annually around the world, mostly in developing countries. In Africa, several studies have shown that vaccination of pets is effective in controlling the disease. An annual vaccination coverage of 70% is recommended by the World Health Organization as a control threshold. The effective control of rabies requires vaccination coverage of owned dogs. Identification of the factors determining dog owners’ choice to vaccinate is necessary for evidence-based policy-making. However, for the Democratic Republic of Congo (DRC), the limited data on rabies vaccination coverage makes it difficult for its control and formulation of appropriate policies. A cross-sectional study was conducted in Kinshasa (Lemba commune) with dog-owning households and owned dogs as study populations. The association between dog vaccination and independent factors (household socio-demographics characteristics, dog characteristics, knowledge of rabies and location of veterinary offices/clinics) was performed with Epi-info 7. The Odds Ratio (OR) and p-value < 0.05 were used to determine levels of significance. A total of 166 households owning dogs and 218 owned dogs were investigated. 47% of the dogs had been vaccinated within one year preceding the survey which is higher than the critical coverage (25 to 40%) necessary to interrupt rabies transmission but below the 70% threshold recommended by WHO for control. The determinants of vaccination included socio-economic level of the household (OR = 2.9, p<0.05), formal education level of the dog owner (OR = 4, p<0.05), type of residence (OR = 4.6, p<0.05), knowledge of rabies disease (OR = 8.0, p<0.05), knowledge of location of veterinary offices/clinics (OR = 3.4, p<0.05), dog gender (OR = 1.6, p<0.05) and dog breed (OR = 2.1, p<0.05). This study shows that the vaccination coverage in this area can easily reach the WHO threshold if supplemented by mass vaccination campaigns

Determinants of dog owner-charged rabies vaccination in Kinshasa, Democratic Republic of Congo.

PubMed

Kazadi, Eric Kawaya; Tshilenge, Georges Mbuyi; Mbao, Victor; Njoumemi, Zakariaou; Masumu, Justin

2017-01-01

Rabies is a preventable fatal disease that causes about 61,000 human deaths annually around the world, mostly in developing countries. In Africa, several studies have shown that vaccination of pets is effective in controlling the disease. An annual vaccination coverage of 70% is recommended by the World Health Organization as a control threshold. The effective control of rabies requires vaccination coverage of owned dogs. Identification of the factors determining dog owners' choice to vaccinate is necessary for evidence-based policy-making. However, for the Democratic Republic of Congo (DRC), the limited data on rabies vaccination coverage makes it difficult for its control and formulation of appropriate policies. A cross-sectional study was conducted in Kinshasa (Lemba commune) with dog-owning households and owned dogs as study populations. The association between dog vaccination and independent factors (household socio-demographics characteristics, dog characteristics, knowledge of rabies and location of veterinary offices/clinics) was performed with Epi-info 7. The Odds Ratio (OR) and p-value < 0.05 were used to determine levels of significance. A total of 166 households owning dogs and 218 owned dogs were investigated. 47% of the dogs had been vaccinated within one year preceding the survey which is higher than the critical coverage (25 to 40%) necessary to interrupt rabies transmission but below the 70% threshold recommended by WHO for control. The determinants of vaccination included socio-economic level of the household (OR = 2.9, p<0.05), formal education level of the dog owner (OR = 4, p<0.05), type of residence (OR = 4.6, p<0.05), knowledge of rabies disease (OR = 8.0, p<0.05), knowledge of location of veterinary offices/clinics (OR = 3.4, p<0.05), dog gender (OR = 1.6, p<0.05) and dog breed (OR = 2.1, p<0.05). This study shows that the vaccination coverage in this area can easily reach the WHO threshold if supplemented by mass vaccination campaigns.

Oral Rabies Vaccination in North America: Opportunities, Complexities, and Challenges

PubMed Central

Slate, Dennis; Algeo, Timothy P.; Nelson, Kathleen M.; Chipman, Richard B.; Donovan, Dennis; Blanton, Jesse D.; Niezgoda, Michael; Rupprecht, Charles E.

2009-01-01

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. Progress continues

Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies.

PubMed

Hu, R L; Liu, Y; Zhang, S F; Zhang, F; Fooks, A R

2007-07-20

During the past decade, human rabies caused by cats has ranked the second highest in China. Several recombinant rabies vaccines have been developed for dogs. However, seldom have these vaccines been assessed or used in cats. In this trial, we report the experimental immunization of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Delta-RGP, in cats. Thirty cats were inoculated with the recombinant vaccine intramuscularly, orally and intranasally, respectively. Safety and efficacy studies were undertaken using the fluorescent antibody virus neutralization (FAVN) test and evaluated. Results showed that this recombinant vaccine is safe for cats as demonstrated by the three different routes of administration. The vaccine stimulated an efficient humoral response in the vaccinated cats when 10(8.5)PFU/ml of the recombinant vaccine was injected intramuscularly in a single dose. The neutralizing antibody level increased above 0.5IU/ml at 4 weeks after the vaccination. The mean antibody level ranged from 0.96+/-0.26 to 4.47+/-1.57IU/ml among individuals, and the antibody levels were elicited for at least 12 months. After this period, the immunized cats survived the challenge of CVS-24 and an obvious anemnestic and protective immune response was stimulated after the challenge. The immune response occurred later than the inactivated vaccine and the overall antibody level in the vaccinated cats was lower, but it was sufficient to confer protection of cats against infection. This demonstrated that a single, intramuscular dose of CAV-2-E3Delta-RGP stimulated a long-lasting protective immune response in cats and suggested that CAV-2-E3Delta-RGP could be considered as a potential rabies vaccine candidate for cats.

SINGLE- VERSUS DOUBLE-DOSE RABIES VACCINATION IN CAPTIVE AFRICAN WILD DOGS (LYCAON PICTUS).

PubMed

Connolly, Maren; Thomas, Patrick; Woodroffe, Rosie; Raphael, Bonnie L

2015-12-01

The immune responses of 35 captive African wild dogs (Lycaon pictus) to an inactivated rabies virus vaccine were evaluated. Seventeen animals received one 1-ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. Sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. Rabies neutralizing serum antibody titers were measured by rapid fluorescent focus inhibition testing. Within 3 mo postvaccination, all 28 animals that were tested within that time period had seroconverted. Overall, titers were significantly higher among animals given two doses of vaccine than among those given a single dose, although this difference was no longer significant by 15 mo postvaccination. Regardless of initial dose, a single administration of inactivated rabies virus vaccine resulted in long-term elevation of titers in the African wild dogs in this study. In the two individuals followed for greater than 36 mo, both (one from each group) maintained detectable titers.

Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination.

PubMed

Ren, Jiangping; Yao, Linong; Sun, Jimin; Gong, Zhenyu

2015-01-01

The Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination, was developed by I. Vodopija and colleagues of the Zagreb Institute of Public Health in Croatia in the 1980s. It was recommended by WHO as one of the intramuscular (IM) schedules for rabies vaccination in 2010. We reviewed the literature on the immunogenicity, safety, economic burden, and compliance of the Zagreb 2-1-1 regimen. Compared to Essen, another IM schedule recommended by WHO, Zagreb has higher compliance, lower medical cost, and better immunogenicity at an early stage. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

77 FR 49409 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No Significant... assessment and finding of no significant impact relative to an oral rabies vaccination field trial in New... be prepared. FOR FURTHER INFORMATION CONTACT: Mr. Richard Chipman, Rabies Program Coordinator...

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

PubMed

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.

Rabies in Estonia: situation before and after the first campaigns of oral vaccination of wildlife with SAG2 vaccine bait.

PubMed

Niin, Enel; Laine, M; Guiot, A L; Demerson, J M; Cliquet, F

2008-07-04

Despite the extermination of stray animals and the compulsory vaccination of companion animals, rabies has been widely distributed over Estonia for more than 30 years. The red fox and the raccoon dog are the rabies virus reservoirs. Through a PHARE project, successive oral vaccination campaigns, using Rabidog SAG2 baits, were implemented in the autumn of 2005 in North Estonia, and in the spring and autumn 2006 throughout the whole territory. After the autumn 2005 campaign, 73.5% of the raccoon dogs and foxes were positive for the tetracycline biomarker. After the campaigns of 2006, the seroconversion rate for rabies virus was 64% in both species. After the vaccination campaigns of 2005 and 2006, the incidence of rabies cases dramatically decreased. Of the 97 cases diagnosed in the whole of Estonia until the end of May 2006, 16 cases (16.5%) occurred within the vaccinated area. Only 17 cases were diagnosed between 1 June and 31 December 2006. In 2007, by the end of May, only two rabies cases have been registered.

Factors associated with dog rabies vaccination in Bhol, Philippines: results of a cross-sectional cluster survey conducted following the island-wide rabies elimination campaign.

PubMed

Davlin, S; Lapiz, S M; Miranda, M E; Murray, K

2013-11-01

The Philippines has a long history of rabies control efforts in their dog populations; however, long-term success of such programmes and the goal of rabies elimination have not yet been realized. The Bohol Rabies Prevention and Elimination Program was developed as an innovative approach to canine rabies control in 2007. The objective of this study was to assess canine rabies vaccination coverage in the owned-dog population in Bohol and to describe factors associated with rabies vaccination 2 years after implementation of the programme. We utilized a cross-sectional cluster survey based on the World Health Organization's Expanded Programme on Immunization coverage survey technique. We sampled 460 households and collected data on 539 dogs residing within these households. Seventy-seven per cent of surveyed households reported owning at least one dog. The human-to-dog ratio was approximately 4 : 1, and the mean number of dogs owned per household was 1.6. Based on this ratio, we calculated an owned-dog population of almost 300 000. Overall, 71% of dogs were reported as having been vaccinated for rabies at some time in their lives; however, only 64% of dogs were reported as having been recently vaccinated. Dogs in our study were young (median age = 24 months). The odds of vaccination increased with increasing age. Dogs aged 12-23 months had 4.6 times the odds of vaccination compared to dogs aged 3-11 months (95% CI 1.8-12.0; P = 0.002). Confinement of the dog both day and night was also associated with increased odds of vaccination (OR = 2.1; 95% CI 0.9-4.9; P = 0.07), and this result approached statistical significance. While the programme is on track to meet its goal of 80% vaccination coverage, educational efforts should focus on the need to confine dogs and vaccinate young dogs. © 2012 Blackwell Verlag GmbH.

76 FR 56731 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No Significant... the Animal and Plant Health Inspection Service relative to an oral rabies vaccination field trial in... INFORMATION CONTACT: Dr. Dennis Slate, Rabies Program Coordinator, Wildlife Services, APHIS, 59 Chennell Drive...

Safety studies with the oral rabies virus vaccine strain SPBN GASGAS in the small Indian mongoose (Herpestes auropunctatus).

PubMed

Ortmann, Steffen; Vos, Ad; Kretzschmar, Antje; Walther, Nomusa; Kaiser, Christiane; Freuling, Conrad; Lojkic, Ivana; Müller, Thomas

2018-03-13

Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose.

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

PubMed

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

2017-01-01

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

[Attenuated rabies virus, ERA strain, in cattle and dogs vaccinated with multiple doses].

PubMed

Titoli, F; Pestalozza, S; Irsara, A; Palliola, E; Frescura, T; Civardi, A

1982-01-01

Investigation on the vaccination of 18 cattle and 5 dogs against rabies is reported. Each animal received multiple doses of ERA strain vaccine intramuscularly in the gluteal or masseter region. The saliva, the brain and salivary glands of the vaccinated animals were examined to detect the presence of ERA virus using immunofluorescent test and mouse inoculation. The virus was never found in the saliva and organs of treated animals. Circulating antibodies against ERA rabies virus were detected in all vaccinated cattle and dogs.

Use of geographic information systems in rabies vaccination campaigns.

PubMed

Grisi-Filho, José Henrique de Hildebrand e; Amaku, Marcos; Dias, Ricardo Augusto; Montenegro Netto, Hildebrando; Paranhos, Noemia Tucunduva; Mendes, Maria Cristina Novo Campos; Ferreira Neto, José Soares; Ferreira, Fernando

2008-12-01

To develop a method to assist in the design and assessment of animal rabies control campaigns. A methodology was developed based on geographic information systems to estimate the animal (canine and feline) population and density per census tract and per subregion (known as "Subprefeituras") in the city of São Paulo (Southeastern Brazil) in 2002. The number of vaccination units in a given region was estimated to achieve a certain proportion of vaccination coverage. Census database was used for the human population, as well as estimates ratios of dog:inhabitant and cat:inhabitant. Estimated figures were 1,490,500 dogs and 226,954 cats in the city, i.e. an animal population density of 1138.14 owned animals per km(2). In the 2002 campaign, 926,462 were vaccinated, resulting in a vaccination coverage of 54%. The estimated number of vaccination units to be able to reach a 70%-vaccination coverage, by vaccinating 700 animals per unit on average, was 1,729. These estimates are presented as maps of animal density according to census tracts and "Subprefeituras". The methodology used in the study may be applied in a systematic way to the design and evaluation of rabies vaccination campaigns, enabling the identification of areas of critical vaccination coverage.

Determinants of pre-exposure rabies vaccination among foreign backpackers in Bangkok, Thailand.

PubMed

Gautret, Philippe; Tantawichien, Terapong; Vu Hai, Vinh; Piyaphanee, Watcharapong

2011-05-23

Important variations were observed regarding the proportion of backpackers seeking information about travel-associated diseases before departing for Thailand. The main determinants were nationality, reason for travel and age. Sources of information used by travelers varied substantially according to nationality. Moreover, significant differences were recorded regarding pre-exposure vaccination rates against rabies. Having British or Irish citizenship and seeking advice from travel clinic specialists or friends were the strongest and most significant determinants of rabies vaccination history. A significant relationship between vaccine cost and vaccination coverage was also evidenced. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

Cost-Effectiveness of Mass Dog Vaccination Campaigns against Rabies in Flores Island, Indonesia.

PubMed

Wera, E; Mourits, M C M; Siko, M M; Hogeveen, H

2017-12-01

A dynamic deterministic simulation model was developed to determine the cost-effectiveness of different mass dog vaccination strategies against rabies in a dog population representative of a typical village on Flores Island. Cost-effectiveness was measured as public cost per averted dog-rabies case. Simulations started with the introduction of one infectious dog into a susceptible dog population of 399 dogs and subsequently ran for a period of 10 years. The base scenario represented a situation without any control intervention. Evaluated vaccination strategies were as follows: annual vaccination campaigns with short-acting vaccine (immunity duration of 52 weeks) (AV_52), annual campaigns with long-acting vaccine (immunity duration of 156 weeks) (AV_156), biannual campaigns with short-acting vaccine (BV_52) and once-in-2-years campaigns with long-acting vaccine (O2V_156). The effectiveness of the vaccination strategies was simulated for vaccination coverages of 50% and 70%. Cumulative results were reported for the 10-year simulation period. The base scenario resulted in three epidemic waves, with a total of 1274 dog-rabies cases. The public cost of applying AV_52 at a coverage of 50% was US$5342 for a village. This strategy was unfavourable compared to other strategies, as it was costly and ineffective in controlling the epidemic. The costs of AV_52 at a coverage of 70% and AV_156 at a coverage of 70% were, respectively, US$3646 and US$3716, equivalent to US$3.00 and US$3.17 per averted dog-rabies case. Increasing the coverage of AV_156 from 50% to 70% reduced the number of cases by 7% and reduced the cost by US$1452, resulting in a cost-effectiveness ratio of US$1.81 per averted dog-rabies case. This simulation model provides an effective tool to explore the public cost-effectiveness of mass dog vaccination strategies in Flores Island. Insights obtained from the simulation results are useful for animal health authorities to support decision-making in rabies

Improved serological response to human diploid cell rabies vaccine when given simultaneously with antirabies hyperimmune globulin.

PubMed

Navarrete-Navarro, S; Aguilar-Setién, A; Avila-Figueroa, C; Hernández-Sierra, F; Santos-Preciado, J I

1999-01-01

The prevention of rabies in Mexico continues to be an important goal for the health sector. Although the prevalence of this disease continues to fall, between 1990 and 1995 a total of 238 cases were registered (an average of 40 cases annually), with a mean annual incidence of 0.04 cases per 100,000 inhabitants and a mortality of almost 100%, so that it is important to rely on highly effective vaccines with few side effects. The objective of this work was to evaluate seroconversion and tolerance to the human diploid cell antirabies vaccine administered to individuals with a history of exposure to rabies, to compare these results with those reported in the literature for the Fuenzalida vaccine, a rabies vaccine produced in the brain tissue of suckling mice, and to find the role antirabies hyperimmune gamma globulin plays in the concentration of post-vaccination antibody concentrations. An analytical transverse study was carried out in 40 children and adults with a history of rabies exposure who were given a complete, five-dose intramuscular schedule of the human diploid cell rabies vaccine. Subjects were followed daily, and local and systemic signs and symptoms were recorded. Two blood samples (at baseline and at the end of the vaccination schedule) were taken and antibody titers against rabies glycoprotein, using the ELISA technique, were measured. Adverse side effects produced by the human diploid cell antirabies vaccine, such as frequency of pain, erythema, itching, and regional adenopathy were fewer than those reported in the literature for the Fuenzalida vaccine (p < 0.05), and of induration and local pain (p < 0.05) in relation to the latter vaccine. All patients seroconverted, producing geometric mean antibody titers of 6.22 IU/mL, an arithmetic mean titer of 9.66 IU/mL with a SD of 9.1 IU/mL. The level of tolerance to the diploid cell vaccine was good and its adverse effects were minimal and fewer than those reported for the Fuenzalida rabies vaccine

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

PubMed

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.

Serologic response in eight alpacas vaccinated by extralabel use of a large animal rabies vaccine during a public health response to a rabid alpaca in South Carolina.

PubMed

Wallace, Ryan M; Niezgoda, Michael; Waggoner, Emily A; Blanton, Jesse Dean; Radcliffe, Rachel A

2016-09-15

CASE DESCRIPTION A female alpaca, kept at pasture with 12 other female alpacas, 2 crias, and 5 goats, was evaluated because of clinical signs of aggression. CLINICAL FINDINGS The clinical signs of aggression progressed to include biting at other animals as well as disorientation. Three days later, the alpaca was euthanized because of suspicion of rabies virus infection. TREATMENT AND OUTCOME No physical injuries were found at necropsy. Brain tissue specimens were confirmed positive for rabies on the basis of direct fluorescent antibody test results. Molecular typing identified the rabies virus variant as one that is enzootic in raccoons. The farm was placed under quarantine, restricting movement of animals on and off the property for 6 months. To prevent further rabies cases, 14 alpacas (12 adults and 2 crias) were vaccinated by extralabel use of a large animal rabies vaccine. Of the 14 vaccinated alpacas, 8 had paired serum samples obtained immediately before and 21 days after vaccination; all 8 alpacas had adequate serum antirabies antibody production in response to rabies vaccination. As a result of an adequate serologic response, the quarantine was reduced to 3 months. In the year after the index rabies case, no other animals on the farm developed rabies. CLINICAL RELEVANCE Extralabel use of rabies vaccines in camelids was used in the face of a public health investigation. This report provides an example of handling of a rabies case for future public health investigations, which will undoubtedly need to develop ad-hoc rabies vaccination recommendations on the basis of the unique characteristics of the event.

Bacillus atrophaeus inactivated spores as a potential adjuvant for veterinary rabies vaccine.

PubMed

Oliveira-Nascimento, L; Caricati, A T P; Abdulack-Lopes, F; Neves, L C M; Caricati, C P; Penna, T C V; Stephano, M A

2012-05-14

Rabies is a viral encephalitis, nearly always fatal, but preventable through vaccines. Rabid animal bite is the prime transmission act, while veterinary vaccination is one of the best strategies for rabies general prevention. Aluminum compounds and saponin are the commercial adjuvants used for this vaccine nowadays. Nevertheless, aluminum compounds can provoke undesired side effects and saponin has a narrow activity range without toxicity. B. atrophaeus inactivated spores (BAIS), with or without saponin, were then used as an alternative to boost the inactivated rabies virus response. BAIS was as effective as saponin in augmenting antibody titers, but combination of both adjuvants doubled the titers raised by them individually. The combined adjuvant formulation maintained viability for 21 months when stored at 4-8°C. Overall, BAIS was demonstrated as a viable alternative to commercial adjuvants, while its combination with saponin resulted in even higher vaccine potency with good stability. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transfer of technology for production of rabies vaccine: Memorandum from a WHO Meeting*

PubMed Central

1985-01-01

The important challenge of prevention and control of rabies in the world will require international efforts to increase the availability and use of high quality cell-culture rabies vaccines for use in man and animals. An important aspect of activities to ensure such availability is transfer of technologies to developing countries for production of these vaccines. This article, which is based on the report of a WHO Consultation, outlines the technical options for vaccine production. The principles and economic aspects of technology transfer are considered, and a WHO assistance programme is outlined. It is concluded that technology transfer should be mediated through a framework of national institutes, expert panels, WHO collaborating centres, production and control laboratories, and other relevant institutions. On this basis, recommendations are made concerning the mechanisms of technology transfer for production of cell-culture rabies vaccines. PMID:3878738

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

PubMed

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

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

PubMed Central

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

2017-01-01

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

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

USGS Publications Warehouse

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

2017-01-01

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

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

PubMed

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

2013-09-13

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

APRIL:TACI axis is dispensable for the immune response to rabies vaccination.

PubMed

Haley, Shannon L; Tzvetkov, Evgeni P; Lytle, Andrew G; Alugupalli, Kishore R; Plummer, Joseph R; McGettigan, James P

2017-08-01

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent

Humoral immune response in dogs and cats vaccinated against rabies in southeastern Brazil

PubMed Central

2013-01-01

Background Brazil holds annual nationwide public campaigns to vaccinate dogs and cats against rabies. The presence of rabies antibodies in these animals, which are among the main transmitters of rabies to humans, is a good indicator that they are immunized and protected. Methods In the present study we analyzed 834 serum samples from dogs and cats from the Southeast of Brazil (Presidente Prudente and Dracena cities), 12 months after the 2009 vaccination campaign. We used the technique known as rapid fluorescent focus inhibition test (RFFIT) and considered reactant those sera with values higher 0.5 IU/mL. Results and discussion Reactant sample results in Presidente Prudente were 153 (51.0%) for dogs and 59 (32.6%) for cats, and in Dracena 110 (52.1%) for dogs and 71 (50.0%) for cats. We discussed vaccine coverage of animals involved in this experiment, and observed low titers < 0.5 IU/mL, especially in cats from Presidente Prudente. Conclusion According to the results presented in our experiment, we suggest that titers below 0.5 IU/mL are worrisome and that, for multiple reasons, animals should be immunized against rabies in the period between public vaccination campaigns. Hence, the desired vaccine coverage was not accomplished, especially among cats from Presidente Prudente. PMID:23899101

Prevalence of immunity presumed using rabies vaccination history and household factors associated with vaccination status among domestic dogs in Japan.

PubMed

Hidano, Arata; Hayama, Yoko; Tsutsui, Toshiyuki

2012-01-01

Rabies was eliminated in Japan over 50 years ago; however, the recent increase in the movement of humans and animals across the world highlights the potential threat of disease reentry into the country. The immune status against rabies among the dog population in Japan is not well known; thus, the purpose of this study was to estimate the prevalence of dogs with effective immunity from the vaccination history using a web-based survey. We found that 76.9% (95% confidence interval, 75.8-78.1) of dogs in this study population belonged to the population in which 90% were assumed to have the internationally accepted antibody titer. We showed that dogs taken less frequently for walks were less likely to be vaccinated. Additionally, the frequency of encounters with other dogs during walks and the number of individuals in households were associated with vaccination history. To our knowledge, this study is the first report estimating the prevalence of dogs in Japan with effective immunity against rabies. Further, we identified the population with low vaccination coverage as well as the heterogeneous characteristics of vaccination history among the dog population. These findings contribute to the implementation of an efficient strategy for improving the overall vaccination coverage in Japan and the development of a quantitative risk assessment of rabies.

Efficacy of rabies vaccines in dogs and cats and protection in a mouse model against European bat lyssavirus type 2.

PubMed

Nokireki, Tiina; Jakava-Viljanen, Miia; Virtala, Anna-Maija; Sihvonen, Liisa

2017-10-02

Rabies is preventable by pre- and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. The success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. Vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. The aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) and cats (n = 722), as well as to investigate the factors influencing the response to vaccination when animals failed to reach a rabies antibody titre of ≥ 0.5 IU/ml. Another aim was to assess the level of protection afforded by a commercial veterinary rabies vaccine against intracerebral challenge in mice with European bat lyssavirus type 2 (EBLV-2) and classical rabies virus (RABV), and to compare this with the protection offered by a vaccine for humans. A significantly higher proportion of dogs (10.7%, 95% confidence interval CI 10.1-11.3) than cats (3.5%; 95% CI 2.3-5.0) had a vaccination antibody titre of < 0.5 IU/ml. In dogs, vaccination with certain vaccines, vaccination over 6 months prior the time of antibody determination and vaccination of dogs with a size of > 60 cm or larger resulted in a higher risk of failing to reach an antibody level of at least 0.5 IU/ml. When challenged with EBLV-2 and RABV, 80 and 100% of mice vaccinated with the veterinary rabies vaccine survived, respectively. When mice were vaccinated with the human rabies vaccine and challenged with EBLV-2, 75-80% survived, depending on the booster. All vaccinated mice developed sufficient to high titres of virus-neutralising antibodies (VNA) against RABV 21-22 days post-vaccination, ranging from 0.5 to 128 IU/ml. However, there was significant difference between antibody titres after vaccinating once in comparison to vaccinating twice (P < 0.05). There was a significant difference

Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.

PubMed

Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence; Tsai, Hsiang-Jung

2017-01-01

Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.

From brain passage to cell adaptation: the road of human rabies vaccine development.

PubMed

Wu, Xianfu; Smith, Todd G; Rupprecht, Charles E

2011-11-01

A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.

Tactics and Economics of Wildlife Oral Rabies Vaccination, Canada and the United States

PubMed Central

Meltzer, Martin I.; Shwiff, Stephanie A.; Slate, Dennis

2009-01-01

Progressive elimination of rabies in wildlife has been a general strategy in Canada and the United States; common campaign tactics are trap–vaccinate–release (TVR), point infection control (PIC), and oral rabies vaccination (ORV). TVR and PIC are labor intensive and the most expensive tactics per unit area (≈$616/km2 [in 2008 Can$, converted from the reported $450/km2 in 1991 Can$] and ≈$612/km2 [$500/km2 in 1999 Can$], respectively), but these tactics have proven crucial to elimination of raccoon rabies in Canada and to maintenance of ORV zones for preventing the spread of raccoon rabies in the United States. Economic assessments have shown that during rabies epizootics, costs of human postexposure prophylaxis, pet vaccination, public health, and animal control spike. Modeling studies, involving diverse assumptions, have shown that ORV programs can be cost-efficient and yield benefit:cost ratios >1.0. PMID:19757549

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

PubMed

Vodopija, I; Sureau, P; Smerdel, S; Lafon, M; Baklaic, Z; Ljubicic, M; Svjetlicic, M

1988-12-01

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

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

PubMed

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.

Rabies preexposure vaccination among veterinarians and at-risk staff.

PubMed

Trevejo, R T

2000-12-01

To measure rabies preexposure vaccination rate and identify factors potentially associated with lack of vaccination among veterinarians and at-risk staff. Cross-sectional survey. At-risk veterinary medical association (VMA) members, their staff members, and animal shelter and wildlife rehabilitation center personnel located in a California county. A questionnaire was mailed to VMA members and managers of animal shelters and wildlife rehabilitation centers. Respondents were requested to provide data on vaccination history and potential factors associated with vaccination status for themselves and their at-risk staff members. Vaccinated and unvaccinated individuals were compared by use of univariate and logistic regression analyses to identify factors associated with vaccination status. Fifty-eight percent (79/137) of persons who received questionnaires responded; 74 were eligible for the study. Respondents provided data for 47.6% (219/460) of their staff members. The vaccination rate was greater among respondents (85.1 %) than among their staff members (17.5%). Among staff members, age and duration of employment were significantly associated with vaccination status. A large proportion of at-risk staff members working in veterinary clinics, animal shelters, and wildlife rehabilitation centers in the study area did not receive rabies preexposure vaccination per the Centers for Disease Control and Prevention's published recommendations of the Advisory Committee on Immunization Practices (ACIP). The cost of the preexposure vaccine series may be a barrier, particularly for young employees who are commonly short-term, part-time, or volunteer workers. Efforts are needed to increase awareness of the ACIP recommendations and to increase access to vaccination through agencies such as public health clinics.

Survey of rabies vaccination status of Queensland veterinarians and veterinary students.

PubMed

Mendez, D; Foyle, L; Cobbold, R; Speare, R

2018-05-01

To determine the rabies vaccination status of Queensland veterinarians and veterinary students and their perception of zoonotic risk from Australian bat lyssavirus (ABLV). Cross-sectional questionnaire surveys. Questionnaires were sent by post in 2011 to veterinary surgeons registered in Queensland, to final-year veterinary students at James Cook University via SurveyMonkey® in 2013 and to final-year veterinary students at James Cook University and University of Queensland via SurveyMonkey® in 2014. The response rate for registered veterinarians was 33.5% and for veterinary students 33.3% and 30% in 2013 and 2014, respectively. Of the 466 registered veterinary surgeons, 147 (31.5%) had been vaccinated, with 72 (15.5%) currently vaccinated. For veterinary students the rabies vaccination rate was 20.0% (4/20) and 13.0% (6/46) in the 2013 and 2014 surveys, respectively. More than 95% of veterinary students had received the mandatory Q fever vaccine. Both veterinarians and students regarded bats and horses as high-risk species for zoonoses. Queensland veterinarians and veterinary students have low levels of protection against ABLV. Although incidents of ABLV spilling over from a bat to a domestic mammal are likely to remain rare, they pose a significant human health and occupational risk given the outcome of infection in humans is high consequence. Principals of veterinary practices and veterinary authorities in Australia should implement a policy of rabies vaccination for clinical staff and veterinary students. © 2018 Australian Veterinary Association.

Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers

PubMed Central

Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence

2017-01-01

Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1–7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan. PMID:28977009

Newcastle disease virus-vectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats.

PubMed

Ge, Jinying; Wang, Xijun; Tao, Lihong; Wen, Zhiyuan; Feng, Na; Yang, Songtao; Xia, Xianzhu; Yang, Chinglai; Chen, Hualan; Bu, Zhigao

2011-08-01

Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10⁹·⁸ 50% egg infective doses (EID₅₀)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10⁸·³ EID₅₀ completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.

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

PubMed

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.

Rabies control in rural Africa: Evaluating strategies for effective domestic dog vaccination

PubMed Central

Kaare, M.; Lembo, T.; Hampson, K.; Ernest, E.; Estes, A.; Mentzel, C.; Cleaveland, S.

2012-01-01

Effective vaccination campaigns need to reach a sufficient percentage of the population to eliminate disease and prevent future outbreaks, which for rabies is predicted to be 70%, at a cost that is economically and logistically sustainable. Domestic dog rabies has been increasing across most of sub-Saharan Africa indicating that dog vaccination programmes to date have been inadequate. We compare the effectiveness of a variety of dog vaccination strategies in terms of their cost and coverage in different community settings in rural Tanzania. Central-point (CP) vaccination was extremely effective in agro-pastoralist communities achieving a high coverage (>80%) at a low cost (vaccination was costly (>US$5/dog) and inadequate (<20% coverage); combined approaches using CP and either house-to-house vaccination or trained community-based animal health workers were most effective with coverage exceeding 70%, although costs were still high (>US$6 and >US$4/dog, respectively). No single vaccination strategy is likely to be effective in all populations and therefore alternative approaches must be deployed under different settings. CP vaccination is cost-effective and efficient for the majority of dog populations in rural Tanzania and potentially elsewhere in sub-Saharan Africa, whereas a combination strategy is necessary in remote pastoralist communities. These results suggest that rabies control is logistically feasible across most of the developing world and that the annual costs of effective vaccination campaigns in Tanzania are likely to be affordable. PMID:18848595

The effect of age on serum antibody titers after rabies and influenza vaccination in healthy horses.

PubMed

Muirhead, T L; McClure, J T; Wichtel, J J; Stryhn, H; Frederick Markham, R J; McFarlane, D; Lunn, D P

2008-01-01

The proportion of geriatric horses within the equine population has increased in the past decade, but there is limited information on the immune function of these animals. Aged horses will have a lesser increase in serum antibody response to vaccination. Thirty-four aged healthy horses (> or = 20 years) and 29 younger adult horses (4-12 years) of various breeds. All horses were vaccinated with vaccines of killed rabies and influenza virus. Horses in each age group were allocated to receive either rabies or influenza booster vaccine 4 weeks after the initial vaccination. Serum samples were taken at 0, 4, 8, and 24 weeks. Rabies serum neutralization titers and equine influenza virus specific antibody sub-isotypes (IgGa, IgGb, IgG(T), and IgA) as well as single radial hemolysis (SRH) titers were determined. Rabies antibody titers were similar in the 2 age groups at all sampling times. Aged horses had higher IgGa and IgGb influenza antibody titers before vaccination than younger horses but similar titers after vaccination (P= .004 and P= .0027, respectively). Younger horses had significantly greater increases in titer than aged horses at all sampling times for IgGa (P= .001) and at 8 and 24 weeks for IgGb (P= .041 and .01, respectively). There was no detectable serum IgG(T) at any time point. A significant booster vaccine effect was seen for both antirabies and anti-influenza titers. Anti-influenza titer before vaccination also had a significant effect on subsequent antibody response. Healthy aged horses generated a primary immune response to a killed rabies vaccine similar to that of younger adult horses. Aged horses had a significantly reduced anamnestic response to influenza vaccine.

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

PubMed

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.

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

PubMed

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.

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination.

PubMed

Li, Yingying; Zhou, Ming; Luo, Zhaochen; Zhang, Yachun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling

2017-04-01

Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization. IMPORTANCE Extending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological

Production and evaluation of a chromatographically purified Vero cell rabies vaccine (PVRV) in China using microcarrier technology

PubMed Central

Yu, Pengcheng; Huang, Ying; Zhang, Yibin; Tang, Qing; Liang, Guodong

2012-01-01

China is a high population country with millions of animal bite cases every year; thus, it is necessary to explore and develop more effective and productive rabies vaccines for human use. To establish a safe, effective, inexpensive and high-yield rabies vaccine, a non-adjuvant purified Vero cell rabies vaccine produced in the SPEEDA PVRV microcarrier bioreactor was developed by Liaoning Chengda Biology Co. Ltd. in China. This vaccine was produced using Vero cells that were cultured in a microcarrier bioreactor. A microcarrier bioreactor containing 25 g/L of Cytodex-1 was used for perfusion culture. The Vero cell culture density was up to 1.2–1.5 × 107 cells/ml, viruses could be constantly harvested for 18–22 days, and the resulting vaccine immunizing potency was ≥ 4.5 IU/ml. Vaccine safety and immunogenicity post-immunization were also assessed. A total of 602 volunteers were enrolled and divided into two groups that were vaccinated with either SPEEDA PVRV or VERORAB PVRV on days 0, 3, 7, 14 and 28. All subjects vaccinated with SPEEDA PVRV showed no serious local or systemic adverse effects. The positive conversion rate of serum neutralizing antibodies against the rabies virus reached 100% in both the test and control groups (inoculated with VERORAB PVRV) at 14 days and 45 days after vaccination, and no significant difference was found between the neutralizing antibody geometric mean titers (GMTs) of the two groups. SPEEDA PVRV is appropriate for mass production and shows satisfactory clinical safety and immunogenicity for human post-exposure prophylaxis of rabies. PMID:22894963

A quantitative indirect ELISA to monitor the effectiveness of rabies vaccination in domestic and wild carnivores.

PubMed

Servat, A; Feyssaguet, M; Blanchard, I; Morize, J L; Schereffer, J L; Boue, F; Cliquet, F

2007-01-10

This paper reports a new ELISA to measure the level of rabies anti-glycoprotein G antibodies after vaccination. The Platelia Rabies II kit was evaluated on different populations of dogs, cats and foxes. For each target species, sera from naive, unvaccinated and vaccinated animals were tested. Platelia Rabies II results were compared to the reference fluorescent antibody virus neutralisation test (for dogs and cats) and to a published in house ELISA test (for foxes). The Platelia Rabies II test was found to be highly specific whatever the species (more than 98%) using a cut-off value of 0.5 EU/ml. The index of sensitivity was between 92.4% and 94.5% for fox samples, and reached 83% for domestic carnivores. Data collected by testing field samples revealed that the rate of false negative results ranged between 8.9% and 11.1% and the rate of false positive results ranged between 1% and 2% for the dog/cat population. Therefore, the Platelia Rabies II test described here would be a good candidate for routine detection of rabies antibodies not only in domestic carnivores (within the framework of international trade) but also in foxes for the follow up of rabies oral vaccination programs.

Elimination of terrestrial rabies in Germany using oral vaccination of foxes.

PubMed

Müller, Thomas; Bätza, Hans-Joachim; Freuling, Conrad; Kliemt, Anke; Kliemt, Jeannette; Heuser, Rolf; Schlüter, Hartmut; Selhorst, Thomas; Vos, Adriaan; Mettenleiter, Thomas C

2012-01-01

Oral rabies vaccination (ORV) has become the method of choice in fox rabies control in Europe. During the past three decades fox-mediated rabies virtually disappeared from Western and Central Europe. Following Switzerland, Germany was the second European country to launch ORV field trials on its territory in 1983. This paper provides a historical overview on the emergence of fox rabies in Germany; describing the basic principles and milestones of the German rabies eradication programme and presenting results of two decades of efforts to control the disease in foxes. Also, setbacks as well as country-specific differences and particularities on Germany's long way to rabies elimination in comparison to other European countries are addressed. Since the first field trials in Germany the number of rabies cases steadily decreased from 10 484 in 1983 to three cases recorded in 2006. On February 3rd 2006 the last case of terrestrial rabies in Germany was detected in a fox near the town of Mainz, Rhineland-Palatinate. In 2008, ORV ceased after 25 years and Germany was officially declared as free from terrestrial rabies. The German rabies eradication programme did cost approximately 100 million euro of which 37 million euro were covered by the EU. For the future, efforts should focus on maintaining a rabies free status by implementing measures to prevent reintroduction of terrestrial rabies from endemic countries.

Rabies in Poland in 2011.

PubMed

Sadkowska-Todys, Malgorzata; Kucharczyk, Bozena

2013-01-01

To assess epidemiological situation of rabies in Poland in 2011. The assessment was based on the results of the data analysis from questionnaires (People vaccinated against rabies post-exposure surveys in Poland and people vaccinated against rabies after exposure in other countries) submitted by the Sanitary-Epidemiological Stations and data from the annual newsletter "Infectious diseases and poisonings in Poland in 2011" (Czarkowski MP et al., Warsaw, NIZP-PZH and GIS) and epizootic data provided by the General Veterinary Inspectorate. In 2011, in Poland, 160 cases of rabies (in 2010 - 152 cases) were reported. Animal cases occurred primarily in the Malopolska province, where an increase in animal rabies cases has been observed since September 2010 and in Podkarpackie province. A single case of fox rabies was reported in Silesia, where there was no disease for many years. Rabies among terrestrial animals also occurred in the provinces ofLubelskie, Warmińsko-Mazurskie and Podlaskie. In other regions of the country there were recorded only isolated cases of bat rabies. In 2011, number of people vaccinated against rabies was 7 543 (in 2010 - 7,243), of which 300 (4%) due to exposure to the animals that were confirmed to have rabies. Among those vaccinated because of contact with the rabid animal, 68 people (over 22%) were vaccinated after contact with fox. As in previous years, people were mainly vaccinated after exposure to dogs and cats in which rabies could not be ruled out - 5 874 persons (78%). The number of registered animals with confirmed rabies remains at the same level and the disease epizootic situation is good. This is a consequence of the implementation of the oral vaccination of wild animals introduced in the country in 1993. Epizootic situation in the country has a small influence on the number of people vaccinated against rabies who have come into contact with the animal potentially infected with the rabies. Serum is given in a few cases, including a

Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route

PubMed Central

Bilagumba, Gangaboraiah; Ravish, Haradanahalli Shankarappa; Narayana, Hanumanthappa Ashwath Doddabele

2010-01-01

The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986–2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India and Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) and human diploid cell vaccine (MIRV, France). The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route (p > 0.230 and p > 0.568). PMID:20523131

Feasibility and efficacy of oral rabies vaccine SAG2 in endangered Ethiopian wolves.

PubMed

Sillero-Zubiri, Claudio; Marino, Jorgelina; Gordon, Christopher H; Bedin, Eric; Hussein, Alo; Regassa, Fekede; Banyard, Ashley; Fooks, Anthony R

2016-09-14

Diseases are a major cause of population declines in endangered populations of several canid species. Parenteral vaccination efforts to protect Ethiopian wolves (Canis simensis) from rabies have targeted the domestic dog reservoir, or the wolves themselves in response to confirmed outbreaks. Oral vaccination offers a more cost-efficient, safe and proactive approach to protect Ethiopian wolves and other threatened canids from rabies. Field trials of the oral vaccine Rabigen® SAG2Dog were undertaken in the Bale Mountains of southeastern Ethiopia. Four different bait types and three delivery methods were tested in twelve Ethiopian wolf packs, and the oral vaccine (using the preferred bait) was trialled in three packs. Vaccine uptake and immunization rates were measured through direct observations and in live-trapped animals through the assessment of biomarker levels and serological status. Commercial baits were never taken by wolves; goat meat baits had the highest uptake, compared to rodent and intestine baits. Targeted delivery from horseback and nocturnal delivery within a pack's territory performed favourably compared to random bait distribution. Bait uptake by non-target species was lowest during the nocturnal blind distribution. Of 21 wolves trapped after vaccination, 14 were positive for the biomarker iophenoxic acid (i.e. ingested the bait and most likely pierced the sachet with the vaccine). Of these, 86% (n=12/14) had levels considered sufficient to provide protective immunity to wildlife (⩾0.20IU/ml), and 50% (n=7/14) demonstrated antibody titres above the universally recognised threshold (⩾0.5IU/ml) -the baseline average was 0.09IU/ml (n=12 wolves). All but one of the wolves vaccinated in 2014 were alive 14months later. Our trials confirm the potential for SAG2, delivered in a goat meat bait, to effectively protect Ethiopian wolves against rabies, supporting the initiative for a more efficient and proactive approach to manage and eventually eliminate

Coverage of pilot parenteral vaccination campaign against canine rabies in N'Djaména, Chad.

PubMed Central

Kayali, U.; Mindekem, R.; Yémadji, N.; Vounatsou, P.; Kaninga, Y.; Ndoutamia, A. G.; Zinsstag, J.

2003-01-01

Canine rabies, and thus human exposure to rabies, can be controlled through mass vaccination of the animal reservoir if dog owners are willing to cooperate. Inaccessible, ownerless dogs, however, reduce the vaccination coverage achieved in parenteral campaigns. This study aimed to estimate the vaccination coverage in dogs in three study zones of N'Djaména, Chad, after a pilot free parenteral mass vaccination campaign against rabies. We used a capture-mark-recapture approach for population estimates, with a Bayesian, Markov chain, Monte Carlo method to estimate the total number of owned dogs, and the ratio of ownerless to owned dogs to calculate vaccination coverage. When we took into account ownerless dogs, the vaccination coverage in the dog populations was 87% (95% confidence interval (CI), 84-89%) in study zone I, 71% (95% CI, 64-76%) in zone II, and 64% (95% CI, 58-71%) in zone III. The proportions of ownerless dogs to owned dogs were 1.1% (95% CI, 0-3.1%), 7.6% (95% CI, 0.7-16.5%), and 10.6% (95% CI, 1.6-19.1%) in the three study zones, respectively. Vaccination coverage in the three populations of owned dogs was 88% (95% CI, 84-92%) in zone I, 76% (95% CI, 71-81%) in zone II, and 70% (95% CI, 66-76%) in zone III. Participation of dog owners in the free campaign was high, and the number of inaccessible ownerless dogs was low. High levels of vaccination coverage could be achieved with parenteral mass vaccination. Regular parenteral vaccination campaigns to cover all of N'Djaména should be considered as an ethical way of preventing human rabies when post-exposure treatment is of limited availability and high in cost. PMID:14758434

78 FR 49444 - Oral Rabies Vaccine Trial; Availability of a Supplement to an Environmental Assessment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

...] Oral Rabies Vaccine Trial; Availability of a Supplement to an Environmental Assessment and Finding of... supplement to an environmental assessment and finding of no significant impact relative to an oral rabies.... Richard Chipman, Rabies Program Coordinator, Wildlife Services, APHIS, 59 Chennell Drive, Suite 7, Concord...

First Report on the Efficiency of Oral Vaccination of Foxes against Rabies in Serbia.

PubMed

Lupulovic, D; Maksimovic Zoric, J; Vaskovic, N; Bugarski, D; Plavsic, B; Ivanovic, N; Petrovic, T; Pusic, I; Marcic, D; Grgic, Z; Lazic, S

2015-12-01

Rabies is one of the oldest known zoonotic diseases that has significant impact on public health, but still remains neglected in Serbia. Rabies virus can infect humans and other mammals and causes inflammation of the brain associated with encephalomyelitis and neurological symptoms. In 2010, Veterinary Directorate (national Competent Authority for animal health in Serbia) has started multi-annual project of oral rabies vaccination of foxes and other wild carnivores (e.g. jackals), as support of long-term programme of eradication of rabies in Serbia, co-funded by EU (financed by Instrument for Pre-Accession Assistance). Monitoring of the effectiveness of oral vaccination campaigns has been carried out in continuation from 2011 and was based on: (i) post-mortem laboratory examination of brain tissue of target animals (foxes, jackals and other carnivores) by fluorescent antibody test (FAT), (ii) detection of antibodies against rabies virus in serum samples by ELISA and (iii) detection of tetracycline biomarker in the mandibles for the evaluation of vaccine bait uptake. From September 2011 to May 2014, the total number of 4943 brain tissue samples, 4241 sera and 4971 mandibles were analysed. Confirmed rabies-positive brains decreased from 10 in 2011/2012 to 6 in 2012/2013 and eventually to 1 positive case in 2013/2014. The seroconversion rate increased from 10.48% (133/1269) in 2011/2012 to 20.11% (362/1800) in 2012/2013 and 42.23% (495/1172) in 2013/2014. Along with the seroconversion, the number of detected tetracycline-positive mandibles demonstrated an increasing tendency in the same period, being 49.67% (682/1373) in 2011/2012, 62.60% (1294/2067) in 2012/2013 and 90.33% (1383/1531) in the monitoring programme carried out in 2013/2014. Presented results confirmed that ORV of foxes and other wildlife in Serbia against rabies was successful and characterized by steady increase of vaccine baits uptake and immunization of animals. © 2015 Blackwell Verlag GmbH.

Epidemiology of animal bites and other potential rabies exposures and anti-rabies vaccine utilization in a rural area in Southern Ethiopia.

PubMed

Ramos, José M; Melendez, Napoleón; Reyes, Francisco; Gudiso, Ganamo; Biru, Dejene; Fano, Gamadi; Aberra, Gulelat; Tessema, Dalu; Tesfamariam, Abraham; Balcha, Seble; Gutiérrez, Félix

2015-01-01

The presented report describes the epidemiology of potential rabies exposures and examines the utilization of anti-rabies vaccine in a rural area of Ethiopia during a period of 43 months. A total of 683 persons (51.1% females, 73% children) with animal- related bites were included in the retrospective, registry-based study. The most common site of exposure was the leg (66.8%). In children under 8 years of age the face was more often involved than in adults (9.5% vs. 4.8%; p=0.03). The main type of exposure was a bite with bleeding (66.3%) followed by contamination of mucous membranes with saliva (19.7%). The primary sources were dogs (93.4%) followed by cats (2.6%). Children under 15 years were more likely to be exposed to dogs (94.9%) than adults (88.7%) (p=0.01). The most common way of coming in contact with animals was 'walking by' (83.9%). Children came in contact with animals while 'playing with' (10.7%) more often than adults (1.1%) (p<0.001). All the patients received an anti-rabies nervous-tissue vaccine, 99% of whom completed the vaccination course. Animal bites continue to be a problem in rural Ethiopia, mainly among children. Efforts to protect children against animal bites must be of paramount importance in preventing rabies in this population.

A modelling approach to vaccination and contraception programmes for rabies control in fox populations.

PubMed Central

Suppo, C; Naulin, J M; Langlais, M; Artois, M

2000-01-01

In a previous study, three of the authors designed a one-dimensional model to simulate the propagation of rabies within a growing fox population; the influence of various parameters on the epidemic model was studied, including oral-vaccination programmes. In this work, a two-dimensional model of a fox population having either an exponential or a logistic growth pattern was considered. Using numerical simulations, the efficiencies of two prophylactic methods (fox contraception and vaccination against rabies) were assessed, used either separately or jointly. It was concluded that far lower rates of administration are necessary to eradicate rabies, and that the undesirable side-effects of each programme disappear, when both are used together. PMID:11007334

Willingness to Pay for Dog Rabies Vaccine and Registration in Ilocos Norte, Philippines (2012).

PubMed

Birhane, Meseret G; Miranda, Mary Elizabeth G; Dyer, Jessie L; Blanton, Jesse D; Recuenco, Sergio

2016-03-01

The Philippines is one of the developing countries highly affected by rabies. Dog vaccination campaigns implemented through collaborative effort between the government and NGOs have played an important role in successfully reducing the burden of disease within the country. Nevertheless, rabies vaccination of the domestic animal population requires continuous commitment not only from governments and NGOs, but also from local communities that are directly affected by such efforts. To create such long-term sustained programs, the introduction of affordable dog vaccination and registration fees is essential and has been shown to be an important strategy in Bohol, Philippines. The aim of this study, therefore, was to estimate the average amount of money that individuals were willing to pay for dog vaccination and registration in Ilocos Norte, Philippines. This study also investigated some of the determinants of individuals' willingness to pay (WTP). A cross-sectional questionnaire was administered to 300 households in 17 municipalities (out of a total of 21) selected through a multi-stage cluster survey technique. At the time of the survey, Ilocos Norte had a population of approximately 568,017 and was predominantly rural. The Contingent Valuation Method was used to elicit WTP for dog rabies vaccination and registration. A 'bidding game' elicitation strategy that aims to find the maximum amount of money individuals were willing to pay was also employed. Data were collected using paper-based questionnaires. Linear regression was used to examine factors influencing participants' WTP for dog rabies vaccination and registration. On average, Ilocos Norte residents were willing to pay 69.65 Philippine Pesos (PHP) (equivalent to 1.67 USD in 2012) for dog vaccination and 29.13PHP (0.70 USD) for dog registration. Eighty-six per cent of respondents were willing to pay the stated amount to vaccinate each of their dogs, annually. This study also found that WTP was influenced by

Willingness to Pay for Dog Rabies Vaccine and Registration in Ilocos Norte, Philippines (2012)

PubMed Central

Birhane, Meseret G.; Miranda, Mary Elizabeth G.; Dyer, Jessie L.; Blanton, Jesse D.; Recuenco, Sergio

2016-01-01

Background The Philippines is one of the developing countries highly affected by rabies. Dog vaccination campaigns implemented through collaborative effort between the government and NGOs have played an important role in successfully reducing the burden of disease within the country. Nevertheless, rabies vaccination of the domestic animal population requires continuous commitment not only from governments and NGOs, but also from local communities that are directly affected by such efforts. To create such long-term sustained programs, the introduction of affordable dog vaccination and registration fees is essential and has been shown to be an important strategy in Bohol, Philippines. The aim of this study, therefore, was to estimate the average amount of money that individuals were willing to pay for dog vaccination and registration in Ilocos Norte, Philippines. This study also investigated some of the determinants of individuals’ willingness to pay (WTP). Methods A cross-sectional questionnaire was administered to 300 households in 17 municipalities (out of a total of 21) selected through a multi-stage cluster survey technique. At the time of the survey, Ilocos Norte had a population of approximately 568,017 and was predominantly rural. The Contingent Valuation Method was used to elicit WTP for dog rabies vaccination and registration. A ‘bidding game’ elicitation strategy that aims to find the maximum amount of money individuals were willing to pay was also employed. Data were collected using paper-based questionnaires. Linear regression was used to examine factors influencing participants’ WTP for dog rabies vaccination and registration. Key Results On average, Ilocos Norte residents were willing to pay 69.65 Philippine Pesos (PHP) (equivalent to 1.67 USD in 2012) for dog vaccination and 29.13PHP (0.70 USD) for dog registration. Eighty-six per cent of respondents were willing to pay the stated amount to vaccinate each of their dogs, annually. This study

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

PubMed

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

Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine.

PubMed

Asgary, Vahid; Shoari, Alireza; Baghbani-Arani, Fahimeh; Sadat Shandiz, Seyed Ataollah; Khosravy, Mohammad Sadeq; Janani, Alireza; Bigdeli, Razieh; Bashar, Rouzbeh; Cohan, Reza Ahangari

2016-01-01

Green synthesis of nanoparticles by plant extracts plays a significant role in different applications. Recently, several studies were conducted on the use of nanoparticles as adjuvant. The main aim of this study was to evaluate green synthesized silver nanoparticles (AgNPs) as adjuvant in rabies veterinary vaccine and compare the results with the existing commercially available alum adjuvant. In the current study, AgNPs were prepared by the reduction of aqueous silver nitrate by leaf extract of Eucalyptus procera. The formation of AgNPs was confirmed by ultraviolet (UV)-visible spectrophotometer, scanning electron microscopy, dynamic light scattering, and X-ray diffraction analysis. Then, different amounts of AgNPs (200 µg, 400 µg, 600 µg, and 800 µg) were added to 1 mL of inactivated rabies virus. The loaded vaccines (0.5 mL) were injected intraperitoneally into six Naval Medical Research Institute mice in each group on days 1 and 7. On the 15th day, the mice were intracerebrally challenged with 0.03 mL of challenge rabies virus (challenge virus strain-11, 20 lethal dose [20 LD50]), and after the latency period of rabies disease in mice (5 days), the mice were monitored for 21 days. Neutralizing antibodies against rabies virus were also investigated using the rapid fluorescent focus inhibition test method. The National Institutes of Health test was performed to determine the potency of optimum concentration of AgNPs as adjuvant. In vitro toxicity of AgNPs was assessed in L929 cell line using MTT assay. In addition, in vivo toxicity of AgNPs and AgNPs-loaded vaccine was investigated according to the European Pharmacopeia 8.0. AgNPs were successfully synthesized, and the identity was confirmed by UV-visible spectrophotometry and X-ray diffraction analysis. The prepared AgNPs were spherical in shape, with an average size of 60 nm and a negative zeta potential of -14 mV as determined by dynamic light scattering technique. The highest percentage of viability was

Rationale and support for a One Health program for canine vaccination as the most cost-effective means of controlling zoonotic rabies in endemic settings.

PubMed

Lavan, Robert P; King, Alasdair I MacG; Sutton, David J; Tunceli, Kaan

2017-03-23

Although dog vaccination has been demonstrated to reduce and eliminate rabies in humans, during meetings there are often calls for further pilot studies. The assembled data proves that a widespread approach is now required. While zoonotic rabies has a minimal presence in developed nations, it is endemic throughout most of Asia and Africa, where it is considered to be a neglected tropical disease. In these areas, rabies causes an estimated annual mortality of at least 55,000 human deaths. Worldwide rabid dogs are the source of the vast majority of human rabies exposures. The World Health Organization (WHO), the Food and Agriculture Organization (FAO) of the United Nations and the World Organization for Animal Health (OIE) advocate a collaborative One Health approach involving human public health and veterinary agencies, with mass canine vaccination programs in endemic areas being the mainstay of strategies to eliminate dog-mediated human rabies. While post-exposure prophylaxis (PEP) is effective in preventing deaths in people exposed to rabies, it is comparatively expensive and has little impact on the canine reservoir that is the primary source of zoonotic rabies. Indiscriminate culling of the dog population is expensive and there is little evidence that it is effective in controlling rabies in non-island locations. Mass canine vaccination programs using a One Health framework that achieves a minimum 70% vaccination coverage during annual campaigns have proven to be cost-effective in controlling zoonotic rabies in endemic, resource-poor regions. Case studies, such as in Tanzania and Bhutan, illustrate how an approach based on mass canine rabies vaccination has effectively reduced both canine and human rabies to minimal levels. The multiple benefits of mass canine rabies vaccination in these cases included eliminating rabies in the domestic dog reservoirs, eliminating human rabies cases, and decreasing the rabies economic burden by reducing expenditures on PEP

Rabies in South Asia: fighting for elimination.

PubMed

Chowdhury, Fazle-Rabbi; Basher, Ariful; Amin, Mohammad R; Hassan, Nazia; Patwary, Mohammad I

2015-01-01

South Asia is regarded as the hot spot for the tourist and travelers. Unfortunately, three big countries (India, Pakistan and Bangladesh) of this region belong to top five rabies endemic countries of the world. Around 55,000 people die of rabies every year globally and 45% of them belong to South and South East Asia. Countries are now working on the elimination of rabies by the year 2020. Elimination of animal rabies is the pivotal of controlling human rabies. Dog (primary source) registration, population control and mass vaccination are the different ways of eliminating animal rabies. Pre (for risk groups including travelers) and post-exposure vaccine is the core for controlling human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue culture vaccine. Due to low antigenicity and post-vaccine neurological complications all countries of South Asia except Pakistan have phased out the production and use of nerve tissue vaccine. To reduce the cost intramuscular regimen is now largely replaced by intradermal regimen and equine rabies immunoglobulin will probably replace human immunoglobulin in future for category III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC development fund' which would hopefully play a vital role in regional collaboration to make the region rabies free.

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi.

PubMed

Burdon Bailey, Jordana L; Gamble, Luke; Gibson, Andrew D; Bronsvoort, Barend M deC; Handel, Ian G; Mellanby, Richard J; Mazeri, Stella

2018-03-01

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children's knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren.

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi

PubMed Central

Burdon Bailey, Jordana L.; Gamble, Luke; Gibson, Andrew D.; Bronsvoort, Barend M. deC.; Handel, Ian G.; Mellanby, Richard J.; Mazeri, Stella

2018-01-01

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren. PMID:29522517

Should travellers to rabies-endemic countries be pre-exposure vaccinated? An assessment of post-exposure prophylaxis and pre-exposure prophylaxis given to Danes travelling to rabies-endemic countries 2000-12.

PubMed

Christiansen, Annette H; Rodriguez, Anna B; Nielsen, Jens; Cowan, Susan A

2016-04-01

Since 2000, a steady increase of vaccines used for both rabies Post-exposure prophylaxis (PEP) and rabies Pre-exposure prophylaxis (PrEP) given to Danish travellers was observed. This study aims to evaluate whether the increase of PEP and PrEP was due to increased travelling, increased awareness of the need for PrEP, or more animal bites per travel, leading to more PEP being administered, in order to assess the need for changing the recommendations. We also described in which countries Danish travelers most frequently reported possible exposure to rabies, and evaluated the timeliness of rabies PEP, including rabies immunoglobulin (RIG). We included all Danes reported to the National Database for Rabies Treatment as having started rabies PEP either abroad or after returning to Denmark, between 2000 and 2012. Data on the yearly number of Danish travelers from 2004 to 2012 to Thailand were collected to calculate the incidence of animal bites at this destination. We also included data on rabies vaccines sold for PrEP or for booster vaccination in Denmark. PEP after possible exposure to rabies abroad increased yearly by 8.8 %. Likewise vaccines sold for PrEP increased by 8.2% annually. The number of Danish travelers to Thailand increased by 7.3% per year, resulting in a stable incidence of animal bites per 100,000 travelers. Seventy-five % started PEP in the country of exposure, while only 10 % received RIG. The yearly increase in PEP and PrEP are parallel to the yearly increase in number of travelers, and can thus be explained by the increased rate of traveling, and not by a rise in awareness of rabies risk or more bites per traveler.Even short term travelers should be given the option of including PrEP in their travel immunisation program, as PEP and especially RIG is not always available in rabies-endemic countries. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

[Rabies].

PubMed

Nishizono, Akira

2009-02-01

Rabies is a fetal viral encephalitis caused by the rabies virus, that is mainly transmitted through the saliva of infected domestic or wild animals. Rabies remains an important public health issue worldwide due to the prevalence of endemic dog rabies in developing countries. The epidemiological impact is particularly still high in Asian and African countries. In contrast, in the developed countries, including Japan, rabies is a re-emerging disease. The Lyssaviruses (types EBLV and ABL) and rabies virus infections via bats have recently emerged in Europe and the United States. Although the incubation period averages 1-3 months, there is no known treatment once the symptoms of rabies appear. On the basis of clinical manifestations, rabies can be classified into 2 types: furious and paralytic rabies. The former is characterized by the well-known symptoms of hydrophobia, aerophobia, and hypersalivation. However the latter type is likely to be misdiagnosed because of its similarity to Guillian-Barré syndrome and neuropsychiatric illnesses. Therefore, post-exposure treatment (PET) using a tissue-culture vaccine is the only way to prevent the disease. In the case of exposure to severe bites (WHO category III), rabies immunoglobulin (RIG) is essential for PET. Although the mechanism underlying the pathogenesis of rabies remains poorly understood, the recent technique of reverse genetics can be a useful tool for understanding rabies pathogenesis at a genetic level. Japan has been free of rabies for over 50 years because of the proper registration of domestic animals and control over their vaccinations. However, it is necessary to always remember that rabies is still a global burden as a representative of a re-emerging disease.

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs.

PubMed

Touihri, Leila; Ahmed, Sami Belhaj; Chtourou, Yacine; Daoud, Rahma; Bahloul, Chokri

2012-12-27

During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an "Internal Ribosome Entry Site" (IRES) domain. The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent

Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies.

PubMed

van Heerden, J; Bingham, J; van Vuuren, M; Burroughs, R E J; Stylianides, E

2002-03-01

Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

Rabies in Poland in 2012.

PubMed

Sadkowska-Todys, Małgorzata; Kucharczyk, Bożena

2014-01-01

Evaluation of the epidemiological situation of rabies in Poland in 2012. Evaluation was based on the analysis of data from questionnaires sent by the Epidemiological-Sanitary Stations. The data are from questionnaires of persons who were administered vaccine against rabies following exposure in Poland and beyond its territory and data from annual bulletin "Infectious diseases and poisonings in Poland in 2012"(Czarkowski MP et al., Warsaw, NIH and CSI) and epizootic data provided by the General Veterinary Inspectorate. In 2012, a total of 257 animal rabies cases were registered in Poland, i.e. nearly 60% more compared to 2011. More than 83% of these cases were reported in Podkarpackie province. Compared to 2011, more than 3.5 increase was noted there. One rabid dog was reported in Śląskie province where one rabies infection in fox was noted there a year ago. Rabies infections in terrestrial animals were also reported in the following provinces: Małopolskie, Lubelskie, Warmińsko-mazurskie and Podlaskie. Single rabies infections in bats were registered in other regions of Poland. In 2012, a total of 7,753 persons were vaccinated against rabies, including 315, i.e. more than 4% due to the exposure to animals infected with rabies virus. Of persons vaccinated due to contact with a rabid animal, nearly 40% and more than 44% were vaccinated following contact with rabid fox and domestic animal, respectively. As with the previous years, humans were vaccinated mostly due to contact with dogs and cats in which rabies could not be excluded - 5,974 persons (77%). A reason for concern is an increase in the number of animal rabies cases reported in 2012, especially in Podkarpackie province. Epizootic situation in Poland affects slightly the number of persons vaccinated against rabies who had contact with an animal which potentially is a source of rabies virus. Since many years, this number remains stable, amounting to 7-8,000 annually.

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

PubMed Central

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

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

PubMed

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.

Protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization.

PubMed

Zhugunissov, K; Bulatov, Ye; Taranov, D; Yershebulov, Z; Koshemetov, Zh; Abduraimov, Ye; Kondibayeva, Zh; Samoltyrova, A; Amanova, Zh; Khairullin, B; Sansyzbay, A

2017-11-01

In this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain VRC-RZ2, was examined in stray dogs (Canis Sp.), corsacs (Vulpes corsac) and steppe wolves (Canis lupus campestris). In the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in the negative control group. Saliva samples taken from animals prior and post (5 th and 10 th days) vaccination failed to demonstrate rabies virus antigen. Observations of immunogenicity in vaccinated carnivores (dogs, corsacs and wolves) during a 180 day period showed the titers of virus neutralizing antibodies (VNA) in the blood sera of vaccinated dogs to be within 0.59-1.37 IU/mL. On 14 days post vaccination (dpv), all the wild carnivores had detectable levels of neutralizing antibodies, with mean titers ranging from 0.50 ± 0.07 IU/mL (for wolves) to 0.59 ± 0.10 IU/mL (for corsacs). Weeks after vaccination, all the vaccinated wolves and corsacs had higher levels of neutralizing antibodies: 0.70 ± 0.10 - 0.71 ± 0.08 IU/mL at 30 dpv, 1.06 ± 0.08 - 1.28 ± 0.21 IU/mL at 60 dpv and 0.41 ± 0.09 - 047 ± 0.06 at 180 dpv. The highest level of VNA (˃1.0 IU/ml) was detected at 60 dpv, in all vaccinated animals. After challenge all vaccinated dogs remained healthy for 180 days. Control animals (unvaccinated dogs) developed symptoms of rabies on day 6 post administration of a virulent virus and died of rabies on days 11-13. Of note, the VNA titers in all the wild carnivores (corsacs and wolves) immunized with VRC-RZ2 were higher than 0.5 IU/ml (0.59 ± 0.11 IU/ml), even as early as 14 days post vaccination. These, presumably protective, titers of antibodies to rabies virus were present in the dogs and wild carnivores examined in this study for at

Spatial control of rabies on heterogeneous landscapes.

PubMed

Russell, Colin A; Real, Leslie A; Smith, David L

2006-12-20

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

[Rabies].

PubMed

Ribadeau-Dumas, Florence; Dacheux, Laurent; Bourhy, Hervé

2013-01-01

Rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of broken skin or a mucous membrane. Infection can be prevented by timely prevention (wash for several minutes, antisepsis and vaccination completed by antirabies immunoglobulins [Ig] according to the severity of exposure). The 55,000 human deaths estimated annually worldwide result mainly from uncontrolled canine rabies in enzootic countries (particularly in Africa and in Asia), attributable to a lack of resources or interest for this disease. Bat rabies, henceforth first cause of human's rabies in many countries in America, affects a very small number of individuals but seems more difficult to control. Shortened vaccine protocols, rationalized use of Ig and development of products of substitution should enhance access of exposed patients to prevention. Finally, research on the biological cycle, the pathogeny and on escape of virus-induced mechanisms from the immune system should continue to pave the way for presently unknown treatments of clinical rabies. © 2013 médecine/sciences – Inserm / SRMS.

Effects of homologous and heterologous antiserum on neutralizing-antibody response to rabies vaccine*

PubMed Central

Archer, B. G.; Dierks, R. E.

1968-01-01

Heterologous antirabies serum is commonly used in the treatment of persons exposed to rabies. However, the high incidence of serum sickness which accompanies its use has prompted work to develop a homologous human product. As human antirabies serum is expensive and difficult to obtain in large quantities, a series of experiments was done on guinea-pigs to test the effects of homologous and heterologous antirabies serum. Similar amounts of homologous and heterologous antisera administered to guinea-pigs produced similar circulating neutralization titres one day later. The homologous antibody titres, however, decreased more slowly than the heterologous antibody titres. When homologous antiserum was given, followed by duck-embryo rabies vaccine, an apparent response to the vaccine was suppressed or delayed longer than when heterologous antiserum and vaccine were administered. However, when homologous antiserum was given with suckling-mouse-brain vaccine, of a much higher potency, the response to vaccine was apparent in the presence of a passive titre of 1:120. If a similar relationship is seen in man with the use of a homologous antirabies product, it will be essential to use high potency vaccines or alter the established vaccination schedules in order to overcome the inherent interference problems. PMID:5303907

Raccoon contact networks predict seasonal susceptibility to rabies outbreaks and limitations of vaccination.

PubMed

Reynolds, Jennifer J H; Hirsch, Ben T; Gehrt, Stanley D; Craft, Meggan E

2015-11-01

Infectious disease transmission often depends on the contact structure of host populations. Although it is often challenging to capture the contact structure in wild animals, new technology has enabled biologists to obtain detailed temporal information on wildlife social contacts. In this study, we investigated the effects of raccoon contact patterns on rabies spread using network modelling. Raccoons (Procyon lotor) play an important role in the maintenance of rabies in the United States. It is crucial to understand how contact patterns influence the spread of rabies in raccoon populations in order to design effective control measures and to prevent transmission to human populations and other animals. We constructed a dynamic system of contact networks based on empirical data from proximity logging collars on a wild suburban raccoon population and then simulated rabies spread across these networks. Our contact networks incorporated the number and duration of raccoon interactions. We included differences in contacts according to sex and season, and both short-term acquaintances and long-term associations. Raccoons may display different behaviours when infectious, including aggression (furious behaviour) and impaired mobility (dumb behaviour); the network model was used to assess the impact of potential behavioural changes in rabid raccoons. We also tested the effectiveness of different vaccination coverage levels. Our results demonstrate that when rabies enters a suburban raccoon population, the likelihood of a disease outbreak affecting the majority of the population is high. Both the magnitude of rabies outbreaks and the speed of rabies spread depend strongly on the time of year that rabies is introduced into the population. When there is a combination of dumb and furious behaviours in the rabid raccoon population, there are similar outbreak sizes and speed of spread to when there are no behavioural changes due to rabies infection. By incorporating detailed data

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

PubMed

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N’Djamena, Chad

PubMed Central

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N’Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for

Antibody response to rabies vaccination in captive and freeranging wolves (Canis lupus)

USGS Publications Warehouse

Federoff, N.E.

2001-01-01

Fourteen captive and five free-ranging Minnesota gray wolves (Canis lupus) were tested for the presence of rabies virus neutralizing antibodies (RVNA) after vaccination with an inactivated canine rabies vaccine. Blood was collected from all wolves prior to vaccination and at 1 mo postvaccination (PV) and from all captive and three wild wolves at 3 mo PV. In addition, one free-ranging wolf was sampled at 4 mo PV, and two free-ranging wolves were sampled at 6 mo PV. All wolves were seronegative prior to vaccination. RVNA were detected in 14 (100%) captive wolves and in four of five (80%) free-ranging wolves. The geometric mean titer of the captive wolves at 1 mo PV was significantly higher (P = 0.023) than in the free-ranging wolves. Five of 13 (38.5%) captive wolves and none of the three (0%) free-ranging wolves had measurable RVNA at 3 mo PV. No measurable RVNA were detected in the serum samples collected from the free-ranging wolves at 4 and 6 mo PV. These results should be interpreted with caution because of the small number of free-ranging wolves tested. Further research is needed to properly assess immune function and antibody response to vaccination in captive wolves in comparison with their free-ranging counterparts.

The control of rabies in Malaya through compulsory mass vaccination of dogs.

PubMed

WELLS, C W

1954-01-01

A fulminating extension of rabies-which has been enzootic in northern Malaya since 1924-occurred in Kuala Lumpur in April 1952. The outbreak was suppressed by the compulsory mass vaccination of dogs, stringent legislation, and intensive stray-dog destruction. Similar measures are being employed in the current campaign, the aim of which is the complete eradication of the disease.From an average annual incidence of 112 confirmed canine cases prior to 1952-when a total of 198 cases was reported-the incidence fell to 15 cases (all in unvaccinated dogs) for the period January-November 1953, during the last 5(1/2) months of which no case in either animals or man was reported. It is considered that the extensive publicity campaign and strict enforcement of the control measures have contributed measurably to the present improved position.Statistics relating to confirmed cases in dogs previously vaccinated with (a) phenolized 20% brain-tissue suspension vaccine (buffalo origin) and (b) chicken-embryo vaccine (Flury strain) are quoted and their probable significance in favour of the latter under Malayan conditions is discussed. The hypothesis that the development of rabies may, in many instances, have been blocked by the vaccine is advanced.The plan for a pan-Federation compulsory vaccination campaign in 1954, to consolidate the 1952-3 improvements, is outlined.

[Results of preventive rabies vaccination with a concentrated vaccine of the PM/WI38-1503-3M rabies strain cultured on human diploid cells. Preparation of mixed antirabies-antitetanus hyperimmune immunoglobulin by plasmapheresis of blood taken from vaccinated veterinary students].

PubMed

Ajjan, N; Soulebot, J P; Stellmann, C; Biron, G; Charbonnier, C; Triau, R; Mérieux, C

1978-01-01

Many thousands of people in France and abroad have already benefited from preventive rabies vaccination by means of a vaccine obtained from culture on human diploid cells, perfected ten years ago by R. Lang, the Institut Mérieux and the Wistar Institute. In addition to being well tolerated, the serological efficacy of this vaccine is such that 100% of the vaccines observed had a seroconversion after only two injections at an interval of one month. However, a booster dose should be given 6 to 12 months after the first injection, and a further booster 3 to 5 years later or on request in case of known contamination. These boosters, combined with an anti-tetanus booster, induce such high antibody titers--between 10-100 and even 1000 I.U./ml--that it is easy to obtain substantial batches of combined anti-rabies and anti-tetanus immunoglobulin from a small number of volunteers. The complete efficacy of this new vaccine reduces the number of systematic post-vaccinal serologic controls and its innocuity is such that an extended preventive vaccination programme may be carried out, for instance in the case of children living in areas known to be dangerous.

Antibody response in cattle after vaccination with inactivated and attenuated rabies vaccines.

PubMed

Rodrigues da Silva, A C; Caporale, G M; Gonçalves, C A; Targueta, M C; Comin, F; Zanetti, C R; Kotait, I

2000-01-01

Despite the absence of current official reports showing the number of cattle infected by rabies, it is estimated that nearly 30,000 bovines are lost each year in Brazil. In order to minimize the important economic losses, control of the disease is achieved by eliminating bat colonies and by herd vaccination. In this study, we compare the antibody response in cattle elicited by vaccination with an attenuated ERA vaccine (AEvac) and an inactivated-adjuvanted PV (IPVvac) vaccine. The antibody titers were appraised by cell-culture neutralization test and ELISA, and the percentage of seropositivity was ascertained for a period of 180 days. IPVvac elicited complete seropositivity rates from day 30 to day 150, and even on day 180, 87% of the sera showed virus-neutralizing antibody titers (VNA) higher than 0.5IU/ml. There were no significant differences between the VNA titers and seropositivity rates obtained with IPVvac in the two methods tested. AEvac, however, elicited significantly lower titers than those observed in the group receiving inactivated vaccine. In addition, the profiles of antirabies IgG antibodies, evaluated by ELISA, and VNA, appraised by cell-culture neutralization test, were slightly different, when both vaccines were compared.

Rabies in Thailand.

PubMed Central

Mitmoonpitak, C.; Tepsumethanon, V.; Wilde, H.

1998-01-01

The prevalence of canine and human rabies in Thailand has decreased significantly during the last decade. This has been associated with an increasing number of human post-exposure treatments. Educational efforts, mass vaccination of dogs and cats and the use of safe and effective vaccines have all made an impact. The proportion of fluorescent antibody positive dogs, among those examined for rabies averaged 54% indicating that rabies is still a major public health threat. Canine rabies vaccination is not usually performed in animals < 3 months old. However, this study revealed that 14% of rabid dogs were < 3 months old and 42% were < or = 6 months old. This is the age group most likely to interact with humans and other dogs. Our study also supports the World Health Organization's recommendation that observing suspected rabid dogs for 10 days is an adequate and safe practice. PMID:9593486

Rabies Epidemiology and Control in Ecuador.

PubMed

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 (p<0.01) between annual cases of dog and human rabies. In 2011, there was an epidemic of sylvatic rabies transmitted to people by vampire bats (Desmodus rotundus) in the Amazon region, specifically in Morona Santiago, leading to 11 fatalities. Phylogenetic analyses of the CVS vaccine N gene showed an association with urban canine rabies strains (the Cosmopolitan lineage and Asian strains), whereas sylvatic rabies, like those reported in the Amazon region, were found to be grouped in a different clade represented mainly by bat-derived strains. This study presents the first compilation of epidemiological data on rabies in Ecuador. 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

Rabies Epidemiology and Control in Ecuador

PubMed Central

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 (p<0.01) between annual cases of dog and human rabies. In 2011, there was an epidemic of sylvatic rabies transmitted to people by vampire bats (Desmodus rotundus) in the Amazon region, specifically in Morona Santiago, leading to 11 fatalities. Phylogenetic analyses of the CVS vaccine N gene showed an association with urban canine rabies strains (the Cosmopolitan lineage and Asian strains), whereas sylvatic rabies, like those reported in the Amazon region, were found to be grouped in a different clade represented mainly by bat-derived strains. Conclusions: This study presents the first compilation of epidemiological data on rabies in Ecuador. 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

Restoration of the antibody response upon rabies vaccination in HIV-infected patients treated with HAART.

PubMed

Gelinck, Luc B S; Jol-van der Zijde, Cornelia M; Jansen-Hoogendijk, Anja M; Brinkman, Daniëlle M C; van Dissel, Jaap T; van Tol, Maarten J D; Kroon, Frank P

2009-11-27

Rabies vaccine was used as a T-cell-dependent neoantigen to investigate several aspects of the primary and booster immune response in vivo in HIV-infected individuals receiving antiretroviral treatment. Study participants received rabies vaccination twice, within a 3-month interval. Serum samples were taken before and 1, 2 and 4 weeks after both vaccinations and 1 and 5 years after the primary vaccination. Antirabies antibodies [immunoglobulin G (IgG), IgG subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM)] were determined; antibody avidity was measured after both vaccinations. T-cell subsets were characterized by flow cytometry. Eighteen healthy controls and 30 HIV-infected adults, treated with HAART for almost 4 years, with a median CD4(+) T-cell count of 537 cells/microl, were immunized. The postvaccination concentrations of antirabies IgG and IgM were significantly lower in HIV-infected individuals as compared with controls. Three T-cell-dependent processes, a true booster response, a class switch from IgM to IgG and avidity maturation were present in both healthy controls and HIV-infected individuals. Higher age was associated with lower postvaccination antirabies IgG and IgM titers. Five years after the primary vaccination, 63% of the HIV-infected individuals still had antibody titers above the protection threshold. Immune restoration in HIV-infected individuals treated with HAART, resulting in a CD4(+) T-cell count greater than 500 cells/microl, is incomplete. However, the majority of HIV-infected individuals are capable of mounting a long-lasting immune response, including several pivotal T-cell-dependent processes, upon vaccination with a neoantigen such as the rabies vaccine.

Low coverage of central point vaccination against dog rabies in Bamako, Mali.

PubMed

Muthiani, Yvonne; Traoré, Abdallah; Mauti, Stephanie; Zinsstag, Jakob; Hattendorf, Jan

2015-06-15

Canine rabies remains an important public-health problem in Africa. Dog mass vaccination is the recommended method for rabies control and elimination. We report on the first small-scale mass dog vaccination campaign trial in Bamako, Mali. Our objective was to estimate coverage of the vaccination campaign and to quantify determinants of intervention effectiveness. In September 2013, a central point vaccination campaign--free of cost for dog owners--was carried out in 17 posts on three consecutive days within Bamako's Commune 1. Vaccination coverage and the proportion of ownerless dogs were estimated by combining mark-recapture household and transect surveys using Bayesian modeling. The estimated vaccination coverage was 17.6% (95% Credibility Interval, CI: 14.4-22.1%) which is far below the World Health Organization (WHO) recommended vaccination coverage of 70%. The Bayesian estimate for the owned dog population of Commune 1 was 3459 dogs (95% CI: 2786-4131) and the proportion of ownerless dogs was about 8%. The low coverage observed is primarily attributed to low participation by dog owners. Dog owners reported several reasons for not bringing their dogs to the vaccination posts. The most frequently reported reasons for non-attendance were lack of information (25%) and the inability to handle the dog (16%). For 37% of respondents, no clear reason was given for non-vaccination. Despite low coverage, the vaccination campaign in Bamako was relatively easy to implement, both in terms of logistics and organization. Almost half of the participating dog owners brought their pets on the first day of the campaign. Participatory stakeholder processes involving communities and local authorities are needed to identify effective communication channels and locally adapted vaccination strategies, which could include both central-point and door-to-door vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Rabies Vaccine Hesitancy and Deaths Among Pregnant and Breastfeeding Women - Vietnam, 2015-2016.

PubMed

Nguyen, Huong T T; Tran, Cuc H; Dang, Anh D; Tran, Huong G T; Vu, Thiem D; Pham, Thach N; Nguyen, Hoang V; Nguyen, Anh N K; Pieracci, Emily G; Tran, Duong N

2018-03-02

Human rabies deaths are preventable through prompt administration of postexposure prophylaxis (PEP) with rabies immune globulin and rabies vaccine after exposure to a rabid animal (1); there are no known contraindications to receiving PEP (1,2). Despite widespread availability of PEP in Vietnam, in 2015 the Ministry of Health (MoH) received reports of pregnant and breastfeeding women with clinically diagnosed rabies. MoH investigated factors associated with these rabies cases. MoH found that, during 2015-2016, among 169 cases reported in Vietnam, two probable cases of rabies were reported in breastfeeding mothers and four in pregnant women, all of whom had been bitten by dogs. All six patients died. Three of the four pregnant women had cesarean deliveries. One of the three newborns died from complications believed to be unrelated to rabies; the fourth pregnant woman contracted rabies too early in pregnancy for the fetus to be viable. Two of the patients sought care from a medical provider or traditional healer; however, none sought PEP after being bitten. In each case, families reported the patient's fear of risk to the fetus or breastfed child as the primary barrier to receiving PEP. These findings highlight the need for public health messaging about the safety and effectiveness of PEP in preventing rabies among all persons with exposures, including pregnant and breastfeeding women.

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

PubMed

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.

Insights and efforts to control rabies in Zambia: Evaluation of determinants and barriers to dog vaccination in Nyimba district.

PubMed

Mulipukwa, Carolyn Patricia; Mudenda, Boyd; Mbewe, Allan Rabson

2017-10-01

The current rabies control strategy in Zambia is based on dog vaccination, dog population control and dog movement restrictions. In Nyimba district of Zambia, dog vaccination coverage is low but the incidence of dog bites is high which places the community at risk of rabies infection. The renewed global interest eliminating rabies in developing countries has spurred interest to identify determinants and barriers of dog vaccination in an effort to reduce the overall disease burden. A mixed methods cross sectional design was used in the study. This consisted of three parts: Evaluation of medical records regarding dog bite injuries, implementation and analysis of a household survey and in-depth review of key informant interviews. Data was collected into a Microsoft Excel database and subsequently transferred to STATA for descriptive, inferential and thematic analysis. Dog vaccination coverage overall was 8.7% (57/655), with 3.4% (22/655) in urban areas, 1.8% (12/655) in peri-urban and 3.5 (23/655) in the rural regions. Financially stable households were more likely to have their dogs vaccinated. Only 10.3% (31/300) of the respondents had vaccinated their dogs and these had a reliable source of income as 6% (18/300) were peasant farmers, 2% (6/300) were dependants whose guardians were financially stable and 2.3% (7/300) were in steady employment. Important barriers to dog vaccination included cost, limited awareness of vaccination program and access. Current rabies control strategies in Nyimba district, Zambia, appear quite limited. Improvements in the regional dog vaccination program may provide benefits. Enhancement of educational efforts targeting behavioural factors may also prove useful. Finally, the cost of dog vaccination can be reduced with scaled up production of a local vaccine.

Insights and efforts to control rabies in Zambia: Evaluation of determinants and barriers to dog vaccination in Nyimba district

PubMed Central

Mudenda, Boyd; Mbewe, Allan Rabson

2017-01-01

Background The current rabies control strategy in Zambia is based on dog vaccination, dog population control and dog movement restrictions. In Nyimba district of Zambia, dog vaccination coverage is low but the incidence of dog bites is high which places the community at risk of rabies infection. The renewed global interest eliminating rabies in developing countries has spurred interest to identify determinants and barriers of dog vaccination in an effort to reduce the overall disease burden. Methodology A mixed methods cross sectional design was used in the study. This consisted of three parts: Evaluation of medical records regarding dog bite injuries, implementation and analysis of a household survey and in-depth review of key informant interviews. Data was collected into a Microsoft Excel database and subsequently transferred to STATA for descriptive, inferential and thematic analysis. Results Dog vaccination coverage overall was 8.7% (57/655), with 3.4% (22/655) in urban areas, 1.8% (12/655) in peri-urban and 3.5 (23/655) in the rural regions. Financially stable households were more likely to have their dogs vaccinated. Only 10.3% (31/300) of the respondents had vaccinated their dogs and these had a reliable source of income as 6% (18/300) were peasant farmers, 2% (6/300) were dependants whose guardians were financially stable and 2.3% (7/300) were in steady employment. Important barriers to dog vaccination included cost, limited awareness of vaccination program and access. Conclusion Current rabies control strategies in Nyimba district, Zambia, appear quite limited. Improvements in the regional dog vaccination program may provide benefits. Enhancement of educational efforts targeting behavioural factors may also prove useful. Finally, the cost of dog vaccination can be reduced with scaled up production of a local vaccine. PMID:28991898

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

PubMed

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.

Rabies in Poland in 2013 and 2014

PubMed

Sadkowska-Todys, Małgorzata; Kucharczyk, Bożena

Evaluation of the epidemiological situation of rabies in Poland in 2013 and 2014 in comparison to the previous years. The evaluation was based on analysis of the data from individual report sent by the Epidemiological-Sanitary Stations. The data are from questionnaires of persons who were administered vaccine against rabies following exposure in Poland and beyond its territory, data from annual bulletin “Infectious diseases and poisonings in Poland in 2012-2014”(Czarkowski MP et al., Warsaw, NIH and CSI) and epizootic data provided by the General Veterinary Inspectorate. Number of animal rabies cases reported in Poland in 2013 and in 2014 was 204 and 105, respectively. This was 30% and 60% less compared to 2012. In 2013 more than 59% of animal rabies cases occurred in Podkarpackie veivodeship and more than 28% in Malopolskie. In 2014 more than 77% of rabid animals were found in the Małopolskie veivodeship, but Podkarpackie accounted for less than 9%. Rabies in terrestrial animals in 2013-2014 was also found in Lubelskie, Podlaskie and Świętokrzyskie veivodeships. In other regions of the country there were reported only single cases of rabies in bats. In 2013, a total of 7 317 people were vaccinated against rabies in 2013 and 7 679 in 2014 including 295 (4%) and 145 (1.9%) persons vaccinated due to exposure to the animals with confirmed rabies, respectively. Among those vaccinated after contact with rabid animal 26% and 29% were vaccinated after contact with a fox in 2013 and 2014, respectively and 64% and 57% as a result of exposure to the domestic animals with confirmed rabies. As with the previous years, people were vaccinated mostly due to exposure to dogs and cats, in which rabies could not be excluded - 5 725 people in 2013 (88%) and 6 057 (87%) in 2014. After the increase in the number of animal rabies cases that occurred in 2012, in the next two years there has been a gradual decline in its number. In 2014 the number of animal rabies cases was lower

Rabies in the Americas: 1998-2014

PubMed Central

Vigilato, Marco A. N.; Pompei, Julio A.; Rocha, Felipe; Vokaty, Alexandra; Molina-Flores, Baldomero; Cosivi, Ottorino; Del Rio Vilas, Victor J.

2018-01-01

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998–2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence. PMID:29558465

Rabies in the Americas: 1998-2014.

PubMed

Freire de Carvalho, Mary; Vigilato, Marco A N; Pompei, Julio A; Rocha, Felipe; Vokaty, Alexandra; Molina-Flores, Baldomero; Cosivi, Ottorino; Del Rio Vilas, Victor J

2018-03-01

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998-2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence.

Cost-estimate and proposal for a development impact bond for canine rabies elimination by mass vaccination in Chad.

PubMed

Anyiam, Franziska; Lechenne, Monique; Mindekem, Rolande; Oussigéré, Assandi; Naissengar, Service; Alfaroukh, Idriss Oumar; Mbilo, Celine; Moto, Daugla Doumagoum; Coleman, Paul G; Probst-Hensch, Nicole; Zinsstag, Jakob

2017-11-01

Close to 69,000 humans die of rabies each year, most of them in Africa and Asia. Clinical rabies can be prevented by post-exposure prophylaxis (PEP). However, PEP is commonly not available or not affordable in developing countries. Another strategy besides treating exposed humans is the vaccination of vector species. In developing countries, the main vector is the domestic dog, that, once infected, is a serious threat to humans. After a successful mass vaccination of 70% of the dogs in N'Djaména, we report here a cost-estimate for a national rabies elimination campaign for Chad. In a cross-sectional survey in four rural zones, we established the canine : human ratio at the household level. Based on human census data and the prevailing socio-cultural composition of rural zones of Chad, the total canine population was estimated at 1,205,361 dogs (95% Confidence interval 1,128,008-1,736,774 dogs). Cost data were collected from government sources and the recent canine mass vaccination campaign in N'Djaména. A Monte Carlo simulation was used for the simulation of the average cost and its variability, using probability distributions for dog numbers and cost items. Assuming the vaccination of 100 dogs on average per vaccination post and a duration of one year, the total cost for the vaccination of the national Chadian canine population is estimated at 2,716,359 Euros (95% CI 2,417,353-3,035,081) for one vaccination round. A development impact bond (DIB) organizational structure and cash flow scenario were then developed for the elimination of canine rabies in Chad. Cumulative discounted cost of 28.3 million Euros over ten years would be shared between the government of Chad, private investors and institutional donors as outcome funders. In this way, the risk of the investment could be shared and the necessary investment could be made available upfront - a key element for the elimination of canine rabies in Chad. Copyright © 2016 The Authors. Published by Elsevier B

[Safety and efficacy of an antirabies vaccine consisting of recombinant vaccinia-rabies virus administered orally to the fox, dog and cat].

PubMed

Blancou, J; Artois, M; Brochier, B; Thomas, I; Pastoret, P P; Desmettre, P; Languet, B; Kiény, M P

1989-01-01

One of the most promising ways to control rabies in wildlife seems to be the distribution of bait containing an anti-rabies vaccine. So far, the most widely used vaccines were modified live viruses (SAD strain or derivatives). Nevertheless, these strains retain some pathogenicity for non-target species. A novel vaccine was proposed consisting of genetically modified vaccinia virus (strain Copenhagen, thermosensitive ts 26) expressing the foreign glycoprotein G for the rabies virus (strain ERA). Different doses of this recombinant virus were administered orally to 59 foxes (Vulpes vulpes) and their antibodies were titrated before challenge. Foxes (8/8) resisted 1 month after vaccination with 10(7) plaque forming units (PFU), or 4/4 after 18 months. Seroconversion among dogs was 4/4 after vaccination with 10(9,6) PFU and 4/4 among cats after vaccination with 10(8) PFU. These dogs (4/4) and cats (3/4) resisted the challenge 2-3 months after vaccination. This vaccine thus appears to be potent and safe in these species. Its properties are discussed.

An electrochemiluminescence assay for analysis of rabies virus glycoprotein content in rabies vaccines

PubMed Central

Smith, Todd G.; Ellison, James A.; Ma, Xiaoyue; Kuzmina, Natalia; Carson, William C.; Rupprecht, Charles E.

2015-01-01

Vaccine potency testing is necessary to evaluate the immunogenicity of inactivated rabies virus (RABV) vaccine preparations before human or veterinary application. Currently, the NIH test is recommended by the WHO expert committee to evaluate RABV vaccine potency. However, numerous disadvantages are inherent concerning cost, number of animals and biosafety requirements. As such, several in vitro methods have been proposed for the evaluation of vaccines based on RABV glycoprotein (G) quality and quantity, which is expected to correlate with vaccine potency. In this study an antigen-capture electrochemiluminescent (ECL) assay was developed utilizing anti-RABV G monoclonal antibodies (MAb) to quantify RABV G. One MAb 2-21-14 was specific for a conformational epitope so that only immunogenic, natively-folded G was captured in the assay. A second MAb (62-80-6) that binds a linear epitope or MAb 2-21-14 was used for detection of RABV G. Vaccine efficacy was also assessed in vivo using pre-exposure vaccination of mice. Purified native RABV G induced a RABV neutralizing antibody (rVNA) response with a geometric mean titer of 4.2 IU/ml and protected 100% of immunized mice against RABV challenge, while an experimental vaccine with a lower quality and quantity of G induced a rVNA titer <0.05 IU/ml and protected <50% of immunized mice. These preliminary results support the hypothesis that in vivo immunogenicity may be predicted from the in vitro measurement of RABV G using an ECL assay. Based upon these results, the ECL assay may have utility in replacement of the NIH test. PMID:23742991

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

PubMed

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.

Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

PubMed

Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

2017-03-01

Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Rabies

MedlinePlus

... and remove any foreign objects. Most of the time, stitches should not be used for animal bite wounds. If there is any risk of rabies, you will be given a series of a preventive vaccine . The vaccine is generally ...

Economic evaluation of an oral rabies vaccination program for control of a domestic dog-coyote rabies epizootic: 1995-2006.

PubMed

Shwiff, Stephanie A; Kirkpatrick, Katy N; Sterner, Ray T

2008-12-01

To conduct a benefit-cost analysis of the results of the domestic dog and coyote (DDC) oral rabies vaccine (ORV) program in Texas from 1995 through 2006 by use of fiscal records and relevant public health data. Retrospective benefit-cost analysis. Procedures-Pertinent economic data were collected in 20 counties of south Texas affected by a DDC-variant rabies epizootic. The costs and benefits afforded by a DDC ORV program were then calculated. Costs were the total expenditures of the ORV program. Benefits were the savings associated with the number of potentially prevented human postexposure prophylaxis (PEP) treatments and animal rabies tests for the DDC-variant rabies virus in the epizootic area and an area of potential disease expansion. Total estimated benefits of the program approximately ranged from $89 million to $346 million, with total program costs of $26,358,221 for the study period. The estimated savings (ie, damages avoided) from extrapolated numbers of PEP treatments and animal rabies tests yielded benefit-cost ratios that ranged from 3.38 to 13.12 for various frequen-cies of PEP and animal testing. In Texas, the use of ORV stopped the northward spread and led to the progressive elimination of the DDC variant of rabies in coyotes (Canis latrans). The decision to implement an ORV program was cost-efficient, although many unknowns were involved in the original decision, and key economic variables were identified for consideration in future planning of ORV programs.

Assessment of 200 pediatric patients exposed to rabies risk.

PubMed

Koksal, Ali Osman; Yilmaz, Aslihan Arasli; Ozdemir, Osman; Cicek, Seyma; Yilmaz, Serife

2015-10-01

Rabies is still an important health problem particularly in underdeveloped or developing countries. In this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the Pediatric Emergency Clinic of our hospital, which serves as one of the Rabies Vaccination Centers in our province. In our study, medical records of 200 patients admitted to the Pediatric Emergency Clinic with suspicion of risk of contact with the rabies virus were retrospectively analyzed. Of those 200 cases, rabies risk was found to be greater in the 5-9 year old group. There was a history of having been bitten by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals in 2%. While 76% of animals were stray animals, only 11% of them had an owner and had been vaccinated, and were under supervision. Rabies vaccination only had been administered to 42.5% of admitted patients, tetanus and rabies vaccination to 51.5%, tetanus; rabies vaccination and human rabies immune globulin were administered to 6%. Post-exposure prophylaxis was found to have been given as recommended to 83.5% of cases. Rabies remains an important public health problem in developing countries Like ours. We consider that public awareness should be raised; local authorities should devote efforts to control stray animals and supervise such services, and updated guidance and training should be provided to the concerned health staff to reduce the risk of rabies.

Bilateral neuro-retinitis following chick embryo cell anti-rabies vaccination – a case report

PubMed Central

Saxena, Rohit; Sethi, Harinder Singh; Rai, Harminder Kumar; Menon, Vimla

2005-01-01

Background The Optic nerve is rarely involved after sheep brain anti-rabies vaccination in the form of retrobulbar neuritis or papillitis. Bilateral neuroretinitis after chick embryo cell antirabies vaccination has not been reported. Case presentation We report the case of a 56 year old male who developed bilateral neuro-retinitis following three injections of antirabies vaccine prepared from the chick embryo. Conclusion The chick embryo cell antirabies vaccine can cause bilateral neuroretinits which has not been reported previously. PMID:16105182

Safety comparison of four types of rabies vaccines in patients with WHO category II animal exposure

PubMed Central

Peng, Jun; Lu, Sha; Zhu, Zhenggang; Zhang, Man; Hu, Quan; Fang, Yuan

2016-01-01

Abstract To evaluate the safeties of 4 types of rabies vaccines for patients with WHO category II animal exposure, especially in different age groups. A total of 4000 patients with WHO category II animal exposure were randomly divided into 4 vaccine groups, and were respectively given with Vaccines A, B, C, and D. And subjects in each vaccine group were divided into 4 age groups (≤5, 5–18, 19–60, and ≥60-year-old groups). Then adverse events (including local and systemic ones) were recorded and compared. Consequently, except for Vaccine B, patients under the age of 5 in Groups A, C, and D suffered from more adverse reactions than those in other age groups. Furthermore, for the children aged less than 5 years, incidence of adverse events following administration of Vaccine B, with the dose of 0.5 mL and production of bioreactor systems, was significantly lower than Vaccines A and D. Our data showed that rabies vaccines with smaller doses and more advanced processing techniques are of relatively high safety for the patients, especially for the young children. PMID:27893654

Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar

2014-01-01

Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Incentives Increase Participation in Mass Dog Rabies Vaccination Clinics and Methods of Coverage Estimation Are Assessed to Be Accurate

PubMed Central

Steinmetz, Melissa; Czupryna, Anna; Bigambo, Machunde; Mzimbiri, Imam; Powell, George; Gwakisa, Paul

2015-01-01

In this study we show that incentives (dog collars and owner wristbands) are effective at increasing owner participation in mass dog rabies vaccination clinics and we conclude that household questionnaire surveys and the mark-re-sight (transect survey) method for estimating post-vaccination coverage are accurate when all dogs, including puppies, are included. Incentives were distributed during central-point rabies vaccination clinics in northern Tanzania to quantify their effect on owner participation. In villages where incentives were handed out participation increased, with an average of 34 more dogs being vaccinated. Through economies of scale, this represents a reduction in the cost-per-dog of $0.47. This represents the price-threshold under which the cost of the incentive used must fall to be economically viable. Additionally, vaccination coverage levels were determined in ten villages through the gold-standard village-wide census technique, as well as through two cheaper and quicker methods (randomized household questionnaire and the transect survey). Cost data were also collected. Both non-gold standard methods were found to be accurate when puppies were included in the calculations, although the transect survey and the household questionnaire survey over- and under-estimated the coverage respectively. Given that additional demographic data can be collected through the household questionnaire survey, and that its estimate of coverage is more conservative, we recommend this method. Despite the use of incentives the average vaccination coverage was below the 70% threshold for eliminating rabies. We discuss the reasons and suggest solutions to improve coverage. Given recent international targets to eliminate rabies, this study provides valuable and timely data to help improve mass dog vaccination programs in Africa and elsewhere. PMID:26633821

Safety and Serological Response to a Matrix Gene-deleted Rabies Virus-based Vaccine Vector in Dogs

PubMed Central

McGettigan, James P.; David, Frederic; Figueiredo, Monica Dias; Minke, Jules; Mebatsion, Teshome; Schnell, Matthias J.

2014-01-01

Dogs account for the majority of human exposures and deaths due to rabies virus (RABV) worldwide. In this report, we show that a replication-deficient RABV-based vaccine in which the matrix gene is deleted (RABV- M) is safe and induces rapid and potent VNA titers after a single inoculation in dogs. Average VNA titers peaked at 3.02 or 5.11 International Units (IU/ml) by 14 days post-immunization with a single dose of 106 or 107 focus forming units (ffu), respectively, of RABV- M. By day 70 post immunization, all dogs immunized with either dose of vaccine showed VNA titers >0.5 IU/ml, the level indicative of a satisfactory immunization. Importantly, no systemic or local reactions were noted in any dog immunized with RABV- M. The elimination of dog rabies through mass vaccination is hindered by limited resources, requirement for repeat vaccinations often for the life of a dog, and in some parts of the world, inferior vaccine quality. Our preliminary safety and immunogenicity data in dogs suggest that RABV- M might complement currently used inactivated RABV-based vaccines in vaccination campaigns by helping to obtain 100% response in vaccinated dogs, thereby increasing overall vaccination coverage. PMID:24508037

The impact of poverty on dog ownership and access to canine rabies vaccination: results from a knowledge, attitudes and practices survey, Uganda 2013.

PubMed

Wallace, Ryan MacLaren; Mehal, Jason; Nakazawa, Yoshinori; Recuenco, Sergio; Bakamutumaho, Barnabas; Osinubi, Modupe; Tugumizemu, Victor; Blanton, Jesse D; Gilbert, Amy; Wamala, Joseph

2017-06-01

Rabies is a neglected disease despite being responsible for more human deaths than any other zoonosis. A lack of adequate human and dog surveillance, resulting in low prioritization, is often blamed for this paradox. Estimation methods are often employed to describe the rabies burden when surveillance data are not available, however these figures are rarely based on country-specific data. In 2013 a knowledge, attitudes, and practices survey was conducted in Uganda to understand dog population, rabies vaccination, and human rabies risk factors and improve in-country and regional rabies burden estimates. Poisson and multi-level logistic regression techniques were conducted to estimate the total dog population and vaccination coverage. Twenty-four villages were selected, of which 798 households completed the survey, representing 4 375 people. Dog owning households represented 12.9% of the population, for which 175 dogs were owned (25 people per dog). A history of vaccination was reported in 55.6% of owned dogs. Poverty and human population density highly correlated with dog ownership, and when accounted for in multi-level regression models, the human to dog ratio fell to 47:1 and the estimated national canine-rabies vaccination coverage fell to 36.1%. This study estimates there are 729 486 owned dogs in Uganda (95% CI: 719 919 - 739 053). Ten percent of survey respondents provided care to dogs they did not own, however unowned dog populations were not enumerated in this estimate. 89.8% of Uganda's human population was estimated to reside in a community that can support enzootic canine rabies transmission. This study is the first to comprehensively evaluate the effect of poverty on dog ownership in Africa. These results indicate that describing a dog population may not be as simple as applying a human: dog ratio, and factors such as poverty are likely to heavily influence dog ownership and vaccination coverage. These modelled estimates should be confirmed through

Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis

PubMed Central

Haley, Shannon L.; Tzvetkov, Evgeni P.; Meuwissen, Samantha; Plummer, Joseph R.

2017-01-01

ABSTRACT Vaccine-induced B cells differentiate along two pathways. The follicular pathway gives rise to germinal centers (GCs) that can take weeks to fully develop. The extrafollicular pathway gives rise to short-lived plasma cells (PCs) that can rapidly secrete protective antibodies within days of vaccination. Rabies virus (RABV) postexposure prophylaxis (PEP) requires rapid vaccine-induced humoral immunity for protection. Therefore, we hypothesized that targeting extrafollicular B cell responses for activation would improve the speed and magnitude of RABV PEP. To test this hypothesis, we constructed, recovered, and characterized a recombinant RABV-based vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF). BAFF is an ideal molecule to improve early pathways of B cell activation, as it links innate and adaptive immunity, promoting potent B cell responses. Indeed, rRABV-mBAFF induced a faster, higher antibody response in mice and enhanced survivorship in PEP settings compared to rRABV. Interestingly, rRABV-mBAFF and rRABV induced equivalent numbers of GC B cells, suggesting that rRABV-mBAFF augmented the extrafollicular B cell pathway. To confirm that rRABV-mBAFF modulated the extrafollicular pathway, we used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model. In response to antigen, SAP-deficient mice form extrafollicular B cell responses but do not generate GCs. rRABV-mBAFF induced similar anti-RABV antibody responses in SAP-deficient and wild-type mice, demonstrating that BAFF modulated immunity through the extrafollicular and not the GC B cell pathway. Collectively, strategies that manipulate pathways of B cell activation may facilitate the development of a single-dose RABV vaccine that replaces current complicated and costly RABV PEP. IMPORTANCE Effective RABV PEP is currently resource- and cost-prohibitive in regions of the world where RABV is most prevalent. In order to diminish the

Effective protection of monkeys against death from street virus by post-exposure administration of tissue-culture rabies vaccine

PubMed Central

Sikes, R. K.; Cleary, W. F.; Koprowski, H.; Wiktor, T. J.; Kaplan, M. M.

1971-01-01

Three series of experiments on rabies vaccines were carried out on rhesus monkeys using suckling-mouse-brain vaccine, rabbit-brain vaccine, duck-embryo vaccine, and purified, concentrated tissue-culture vaccine. The latter was prepared in a human diploid cell strain and inactivated with β-propiolactone, and consisted of tissue-culture fluid concentrated 200-fold with a final infectivity titre of 109.8 plaque-forming units per ml before inactivation. In the first two series of experiments, several vaccines were tested for relative immunogenicity on a pre-exposure basis. In the third series, a successful model was developed in which a single inoculation of the tissue-culture vaccine administered after exposure to rabies virus, with or without accompanying standard doses of antirabies serum, was evaluated as a method of prevention. A single dose of the tissue-culture vaccine protected 7 out of 8 monkeys from death by street virus. Homologous or heterologous antirabies serum alone gave poor results. The results indicate great promise for prophylaxis in man with one dose, or perhaps a few doses, of highly concentrated, purified tissue-culture vaccine. PMID:5004004

Expression of rabies glycoprotein and ricin toxin B chain (RGP-RTB) fusion protein in tomato hairy roots: a step towards oral vaccination for rabies.

PubMed

Singh, Ankit; Srivastava, Subhi; Chouksey, Ankita; Panwar, Bhupendra Singh; Verma, Praveen C; Roy, Sribash; Singh, Pradhyumna K; Saxena, Gauri; Tuli, Rakesh

2015-04-01

Transgenic hairy roots of Solanum lycopersicum were engineered to express a recombinant protein containing a fusion of rabies glycoprotein and ricin toxin B chain (rgp-rtxB) antigen under the control of constitutive CaMV35S promoter. Asialofetuin-mediated direct ELISA of transgenic hairy root extracts was performed using polyclonal anti-rabies antibodies (Ab1) and epitope-specific peptidal anti-RGP (Ab2) antibodies which confirmed the expression of functionally viable RGP-RTB fusion protein. Direct ELISA based on asialofetuin-binding activity was used to screen crude protein extracts from five transgenic hairy root lines. Expressions of RGP-RTB fusion protein in different tomato hairy root lines varied between 1.4 and 8 µg in per gram of tissue. Immunoblotting assay of RGP-RTB fusion protein from these lines showed a protein band on monomeric size of ~84 kDa after denaturation. Tomato hairy root line H03 showed highest level of RGP-RTB protein expression (1.14 %) and was used further in bench-top bioreactor for the optimization of scale-up process to produce large quantity of recombinant protein. Partially purified RGP-RTB fusion protein was able to induce the immune response in BALB/c mice after intra-mucosal immunization. In the present investigation, we have not only successfully scaled up the hairy root culture but also established the utility of this system to produce vaccine antigen which subsequently will reduce the total production cost for implementing rabies vaccination programs in developing nations. This study in a way aims to provide consolidated base for low-cost preparation of improved oral vaccine against rabies.

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

PubMed Central

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

[Rabies is a risk for travelling children].

PubMed

Rotivel, Y; Goudal, M; Wirth, S; Tsiang, H

1998-05-01

Rabies remains a dreadful disease which kills about 50,000 people per year, mostly in Asia, Africa, South America and Central Europe. Between 30% an 50% of the victims are young children. Modern rabies vaccines are safe and immunogenic. Therefore parents must be informed on the risk of rabies, and pre-exposure vaccination must be performed for children traveling often or for periods longer than one month in canine enzootic countries. Post-exposure treatment must be initiated without delay with modern vaccines wherever available, according to approved schedules. Pre-exposure vaccination is particularly useful in remote places where modern vaccines and immunoglobulins are not readily available.

Possible rabies exposures in Peace Corps volunteers, 2011.

PubMed

Harvey, Kira; Jentes, Emily S; Charles, Myrna; Johnson, Katherine J; Petersen, Brett; Lamias, Mark J; Blanton, Jesse D; Sotir, Mark J; Brunette, Gary W

2014-05-01

We surveyed Peace Corps Medical Officers (PCMOs) to determine the frequency of and responses to possible rabies exposures of U.S. Peace Corps volunteers (PCVs). Surveys were sent to 56 PCMOs serving in countries with moderate or high rabies vaccine recommendations from the U.S. Centers for Disease Control and Prevention (CDC), of which 38 (68%) responded. Thirty-seven PCMOs reported that, of 4,982 PCVs, 140 (3%) experienced possible rabies exposures. Of these, 125 (89%) had previously received rabies vaccination, 129 (92%) presented with adequately cleansed wounds, and 106 (76%) were deemed to require and were given post-exposure prophylaxis (PEP). Of 35 respondents, 30 (86%) reported that rabies vaccine was always accessible to PCVs in their country within 24 hours. Overall, the Peace Corps is successful at preventing and treating possible rabies exposures. However, this study identified a few gaps in policy implementation. The Peace Corps should continue and strengthen efforts to provide education, preexposure vaccination, and PEP to PCVs.

Possible Rabies Exposures in Peace Corps Volunteers, 2011

PubMed Central

Harvey, Kira; Jentes, Emily S.; Charles, Myrna; Johnson, Katherine J.; Petersen, Brett; Lamias, Mark J.; Blanton, Jesse D.; Sotir, Mark J.; Brunette, Gary W.

2014-01-01

We surveyed Peace Corps Medical Officers (PCMOs) to determine the frequency of and responses to possible rabies exposures of U.S. Peace Corps volunteers (PCVs). Surveys were sent to 56 PCMOs serving in countries with moderate or high rabies vaccine recommendations from the U.S. Centers for Disease Control and Prevention (CDC), of which 38 (68%) responded. Thirty-seven PCMOs reported that, of 4,982 PCVs, 140 (3%) experienced possible rabies exposures. Of these, 125 (89%) had previously received rabies vaccination, 129 (92%) presented with adequately cleansed wounds, and 106 (76%) were deemed to require and were given post-exposure prophylaxis (PEP). Of 35 respondents, 30 (86%) reported that rabies vaccine was always accessible to PCVs in their country within 24 hours. Overall, the Peace Corps is successful at preventing and treating possible rabies exposures. However, this study identified a few gaps in policy implementation. The Peace Corps should continue and strengthen efforts to provide education, preexposure vaccination, and PEP to PCVs. PMID:24639304

Eliminating Rabies in Estonia

PubMed Central

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

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

PubMed

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.

New Japanese encephalitis vaccines: alternatives to production in mouse brain.

PubMed

Halstead, Scott B; Thomas, Stephen J

2011-03-01

Japanese encephalitis virus (JEV), a flavivirus maintained in a zoonotic cycle and transmitted by the mosquito Culex tritaeniorhynchus, causes epidemics of encephalitis throughout much of Asia. Resident populations, including short- or long-term visitors to enzootic regions, are at risk of infection and disease. For the past several decades, killed viral vaccines prepared in tissue culture or mouse brain have been used effectively to immunize travelers and residents of enzootic countries. Cost, efficacy and safety concerns led to the development of a live-attenuated virus vaccine (SA14-14-2) and more recently, to the licensure in the USA, Europe, Canada, and Australia of a purified inactivated, tissue culture-based Japanese encephalitis vaccine (IXIARO(®), referred to as IC51; Intercell AG, Vienna, Austria). In addition, a live-attenuated yellow fever-Japanese encephalitis chimeric vaccine (IMOJEV™, referred to as Japanese encephalitis-CV; Sanofi Pasteur, Lyon, France) was recently licensed in Australia and is under review in Thailand. A broad portfolio of safe and effective Japanese encephalitis vaccines has become available to meet the needs of at-risk populations; when appropriately delivered, these new vaccines should greatly diminish the burden of disease.

Spatial accessibility to vaccination sites in a campaign against rabies in São Paulo city, Brazil.

PubMed

Polo, Gina; Acosta, Carlos Mera; Dias, Ricardo Augusto

2013-08-01

It is estimated that the city of São Paulo has over 2.5 million dogs and 560 thousand cats. These populations are irregularly distributed throughout the territory, making it difficult to appropriately allocate health services focused on these species. To reasonably allocate vaccination sites, it is necessary to identify social groups and their access to the referred service. Rabies in dogs and cats has been an important zoonotic health issue in São Paulo and the key component of rabies control is vaccination. The present study aims to introduce an approach to quantify the potential spatial accessibility to the vaccination sites of the 2009 campaign against rabies in the city of São Paulo and solve the overestimation associated with the classic methodology that applies buffer zones around vaccination sites based on Euclidean (straight-line) distance. To achieve this, a Gaussian-based two-step floating catchment area method with a travel-friction coefficient was adapted in a geographic information system environment, using distances along a street network based on Dijkstra's algorithm (short path method). The choice of the distance calculation method affected the results in terms of the population covered. In general, areas with low accessibility for both dogs and cats were observed, especially in densely populated areas. The eastern zone of the city had higher accessibility values compared with peripheral and central zones. The Gaussian-based two-step floating catchment method with a travel-friction coefficient was used to assess the overestimation of the straight-line distance method, which is the most widely used method for coverage analysis. We conclude that this approach has the potential to improve the efficiency of resource use when planning rabies control programs in large urban environments such as São Paulo. The findings emphasize the need for surveillance and intervention in isolated areas. Copyright © 2013 Elsevier B.V. All rights reserved.

Compendium of Animal Rabies Control, 1998. Vol. 47, No. RR-9

DTIC Science & Technology

1998-05-29

as necessary. Recommendations for parenteral immu- nization procedures are contained in Part I; all animal rabies vaccines licensed by the United...Part I: Recommendations for Parenteral Immunization Procedures A. Vaccine Administration All animal rabies vaccines should be restricted to use by...or under the direct super- vision of, a veterinarian. B. Vaccine Selection In comprehensive rabies-control programs, only vaccines with a 3-year

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

PubMed

Manning, Susan E; Rupprecht, Charles E; Fishbein, Daniel; Hanlon, Cathleen A; Lumlertdacha, Boonlert; Guerra, Marta; Meltzer, Martin I; Dhankhar, Praveen; Vaidya, Sagar A; Jenkins, Suzanne R; Sun, Benjamin; Hull, Harry F

2008-05-23

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning

Update on human rabies in a dog- and fox-rabies-free country.

PubMed

Stahl, J-P; Gautret, P; Ribadeau-Dumas, F; Strady, C; Le Moal, G; Souala, F; Maslin, J; Fremont, B; Bourhy, H

2014-07-01

Rabies is responsible for 50,000 deaths per year worldwide. Mainland France has been officially freed from rabies in non-flying animals since 2001. We wanted to provide an update on the French situation, using published data, and describe possible options since official guidelines are lacking. Post-exposure prophylaxis (PEP) (early and careful cleaning and dressing of the wound, vaccination, and in case of high-risk exposure, injection of specific anti-rabies immunoglobulins) is known to be efficient except in rare cases. It is recommended after grade II contact (+specific immunoglobulins in immunodepressed patients), or grade III contact (vaccination+immunoglobulins). Mainland France being rabies-free, 3 options may be considered in case of bite by a dog or a cat that cannot be monitored in France: (a) consider the risk of rabies as null, so no PEP should be administrated, whatever the severity of bites; (b) consider there is a weak but lethal risk, so the international recommendations should be applied, using immunoglobulins in some cases; (c) consider that the risk is extremely low but cannot be excluded, and that the patient should be vaccinated to be protected, but without adding immunoglobulins (whether in case of grade II or III bites). There are no national guidelines for rabies in France, and so the physician managing the patient is the one who will decide to treat or not. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barkhouse, Darryll A.; Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107; Faber, Milosz

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 DRV4more » 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.« less

Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis.

PubMed

Haley, Shannon L; Tzvetkov, Evgeni P; Meuwissen, Samantha; Plummer, Joseph R; McGettigan, James P

2017-04-15

Vaccine-induced B cells differentiate along two pathways. The follicular pathway gives rise to germinal centers (GCs) that can take weeks to fully develop. The extrafollicular pathway gives rise to short-lived plasma cells (PCs) that can rapidly secrete protective antibodies within days of vaccination. Rabies virus (RABV) postexposure prophylaxis (PEP) requires rapid vaccine-induced humoral immunity for protection. Therefore, we hypothesized that targeting extrafollicular B cell responses for activation would improve the speed and magnitude of RABV PEP. To test this hypothesis, we constructed, recovered, and characterized a recombinant RABV-based vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF). BAFF is an ideal molecule to improve early pathways of B cell activation, as it links innate and adaptive immunity, promoting potent B cell responses. Indeed, rRABV-mBAFF induced a faster, higher antibody response in mice and enhanced survivorship in PEP settings compared to rRABV. Interestingly, rRABV-mBAFF and rRABV induced equivalent numbers of GC B cells, suggesting that rRABV-mBAFF augmented the extrafollicular B cell pathway. To confirm that rRABV-mBAFF modulated the extrafollicular pathway, we used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model. In response to antigen, SAP-deficient mice form extrafollicular B cell responses but do not generate GCs. rRABV-mBAFF induced similar anti-RABV antibody responses in SAP-deficient and wild-type mice, demonstrating that BAFF modulated immunity through the extrafollicular and not the GC B cell pathway. Collectively, strategies that manipulate pathways of B cell activation may facilitate the development of a single-dose RABV vaccine that replaces current complicated and costly RABV PEP. IMPORTANCE Effective RABV PEP is currently resource- and cost-prohibitive in regions of the world where RABV is most prevalent. In order to diminish the requirements for

Seroconversion in captive African wild dogs (Lycaon pictus) following administration of a chicken head bait/SAG-2 oral rabies vaccine combination.

PubMed

Knobel, D L; Liebenberg, A; Du Toit, J T

2003-03-01

This study determined the proportion of captive juvenile and adult African wild dogs (Lycaon pictus) that developed protective titres of rabies neutralising antibodies following ingestion of a chicken head bait/SAG-2 oral rabies vaccine combination. A single chicken head containing 1.8 ml of SAG-2 vaccine (10(8.0) TCID50/ml) in a plastic blister was fed to each of eight adult and three juvenile wild dogs. Bait ingestion resulted in a significant rise in serum neutralising antibody titres. Overall seroconversion rate was eight out of 11 (72.7%), and all the puppies and five out of eight (62.5%) adults showed potentially protective levels of antibodies on day 31. The mean post-vaccination neutralising antibody titre was within the range reported to be protective against challenge with virulent rabies virus in other species.

Genetically modified rabies virus-vectored Ebola virus disease vaccines are safe and induce efficacious immune responses in mice and dogs.

PubMed

Shuai, Lei; Wang, Xijun; Wen, Zhiyuan; Ge, Jinying; Wang, Jinliang; Zhao, Dandan; Bu, Zhigao

2017-10-01

Ebola viruses (EBOVs) are zoonotic pathogens that cause EBOV disease (EVD) with high case fatality in humans. Currently, EVD vaccines are still under development in several countries. Here, we generated two recombinant rabies viruses (RABVs), rERAG 333E /ZGP and rERAG 333E /SGP, expressing the Zaire EBOV glycoprotein (ZGP) or Sudan EBOV glycoprotein (SGP) gene based on a modified ERA vaccine strain (rERAG 333E ) vector platform. The recombinant RABVs retained growth properties similar to those of the vector virus in BSR cell culture and efficiently expressed ZGP or SGP. After intracerebral (i.c.) inoculation with rERAG 333E /ZGP or rERAG 333E /SGP, all adult mice showed no signs of disease or weight loss and suckling mice maintained similar survivorship curve as those mice inoculated with control vector rERAG 333E , demonstrating that ZGP or SGP expression did not increase the virulence of the vector. Mouse immunization studies showed that vaccination with rERAG 333E /ZGP and rERAG 333E /SGP induced Zaire or Sudan EBOV neutralizing antibody (VNA) responses and IgG, IgG2a responses to ZGP or SGP, suggesting their potential as oral or inactivated bivalent vaccines against rabies and EVD. Most importantly, all dogs immunized orally with rERAG 333E /ZGP developed long-lasting ZEBOV and RABV VNA responses with or without previous rabies vaccine immunization history. Live rERAG 333E with EBOV GP thus appear to have the potential to be oral vaccines for free-roaming animals in endemic areas of EVD and rabies, and may serve as inactivated vaccines for use in humans. Copyright © 2017. Published by Elsevier B.V.

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

PubMed Central

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

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.

PubMed

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.

Rabies deaths in Pakistan: results of ineffective post-exposure treatment.

PubMed

Parviz, Shehzad; Chotani, Rashid; McCormick, Joseph; Fisher-Hoch, Sue; Luby, Stephen

2004-11-01

To estimate the incidence of rabies and the effectiveness of post-exposure treatment (PET) in Pakistan. Rabies cases admitted from July 1993 to December 1994 to a public rabies isolation hospital were analyzed. Two samples (one sample each from a separate peripheral site) of a single batch of sheep brain vaccine (SBV) were also tested for potency by the National Institute of Health (NIH) test in May 1997. Forty patients were admitted with a history of clinical rabies. The median age was 22 years and 55% were under 15. Thirteen (23%) victims did not receive any vaccine; the remaining 27 (67%) received SBV only, and of these, 16 (40%) received a full course of SBV. No rabies immunoglobulins (RIG) or cell culture vaccines were administered. There were frequent power blackouts and no back-up supply at the public hospital. In-house potency testing of the vaccine batch by the manufacturer was adequate, although it was not tested by the World Health Organization (WHO) recommended NIH test. Samples of SBV of the same batch collected at the peripheral sites showed no potency. Rabies incidence was estimated to range between 7.0 to 9.8 cases per million annually. A multi-sectorial approach is needed to decrease rabies incidence in Pakistan. Public and healthcare practitioner education on prompt and appropriate PET, especially the use of cost-effective cell culture intradermal regimens, is needed urgently. The NIH test should be employed for vaccine potency testing. An independent agency is needed for monitoring vaccine quality and strategies are needed for maintaining cold chain. SBV should be replaced by locally manufactured second-generation cell culture rabies vaccine. Purified equine rabies immunoglobulin (ERIG) should be manufactured locally to meet national needs. Furthermore, effective dog control strategies should be implemented to decrease the rabies reservoir.

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

PubMed Central

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

Rabies (For Parents)

MedlinePlus

... mostly in developing countries where programs for vaccinating dogs against rabies don't exist. But the good ... vaccination programs in the United States, transmission from dogs to people is very rare. Outside the United ...

Compendium of animal rabies prevention and control, 2011.

PubMed

2011-11-04

Rabies has one of the highest case-fatality ratios of any infectious disease. This report provides recommendations for public health officials, veterinarians, animal control officials, and other parties engaged in rabies prevention and control activities and should serve as the basis for standardizing procedures among jurisdictions. The recommendations regarding domestic animal vaccination, management of animals exposed to rabies, and management of animals that bite humans are the core elements of animal rabies control and human rabies prevention. These updated 2011 guidelines include the national case definition for animal rabies and clarify the role of the CDC rabies laboratory in providing confirmatory testing of suspect animals. The table of rabies vaccines licensed and marketed in the United States has been updated, and additional references have been included to provide scientific support for information in this report.

Simultaneous Growth of Rabies and Canine Distemper Viruses in Chick Embryos

PubMed Central

Chang, James C. C.

1965-01-01

Rabies virus and canine distemper virus were grown simultaneously, and possibly symbiotically, in the same chick embryos. There seemed to be no adverse effect on either virus when cultured in such manner. Bivalent vaccines for rabies and canine distemper were produced. The potencies and the virus titers of such vaccines were comparable to those of rabies vaccine and canine distemper vaccine produced separately. PMID:14290942

The value of duck-embryo vaccine and high-egg-passage Flury vaccine in experimental rabies infection in guinea-pigs

PubMed Central

Veeraraghavan, N.; Subrahmanyan, T. P.

1963-01-01

The authors have compared the value of multiple doses of duck-embryo and HEP Flury vaccine with that of pooled 5% sheep-brain vaccine in experimental rabies infection in guinea-pigs. They found that the duck-embryo vaccine given in a dosage corresponding to 14 ml of 10% vaccine (the dosage recommended for human treatment), either alone or with antirabies serum, gave no protection and that, even when administered in a dosage corresponding to 140 ml of 5% pooled vaccine, both the duck-embryo and the HEP Flury vaccines, whether alone or with serum, conferred little protection. Pooled phenolized vaccine under identical conditions gave good results. The immunogenicity of duck-embryo and HEP Flury vaccines, given before infection, was also inferior to that of pooled vaccine; and the duck-embryo vaccine was found to be a poorer antigen than the pooled vaccine in mouse potency tests. The authors conclude that the dosage of duck-embryo vaccine recommended for human treatment is inadequate and that the HEP Flury vaccine in its present form is unsuitable for post-infection treatment. PMID:14065070

Neurological adverse events associated with vaccination.

PubMed

Piyasirisilp, Sucheep; Hemachudha, Thiravat

2002-06-01

Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.

Reemerging Rabies and Lack of Systemic Surveillance in People’s Republic of China

PubMed Central

Hu, Rongliang; Zhang, Yongzhen; Dong, Guanmu; Rupprecht, Charles E.

2009-01-01

Rabies is a reemerging disease in China. The high incidence of rabies leads to numerous concerns: a potential carrier-dog phenomenon, undocumented transmission of rabies virus from wildlife to dogs, counterfeit vaccines, vaccine mismatching, and seroconversion testing in patients after their completion of postexposure prophylaxis (PEP). These concerns are all scientifically arguable given a modern understanding of rabies. Rabies reemerges periodically in China because of high dog population density and low vaccination coverage in dogs. Mass vaccination campaigns rather than depopulation of dogs should be a long-term goal for rabies control. Seroconversion testing after vaccination is not necessary in either humans or animals. Human PEP should be initiated on the basis of diagnosis of biting animals. Reliable national systemic surveillance of rabies-related human deaths and of animal rabies prevalence is urgently needed. A laboratory diagnosis–based epidemiologic surveillance system can provide substantial information about disease transmission and effective prevention strategies. PMID:19751575

Rabies in Kazakhstan.

PubMed

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.

Practical significance of rabies antibodies in cats and dogs.

PubMed

Aubert, M F

1992-09-01

Doubt has sometimes been cast upon the protective effect of rabies antibodies in serum. Animals and humans suffering from fatal rabies often produce high antibody titres, while rabies cases are also observed in vaccinated animals. Cellular immunity is also largely involved in protection. Nevertheless, a large number of laboratory experiments and field observations clearly demonstrate that cats and dogs which develop antibodies after vaccination and before challenge have a very high probability of surviving any challenge, no matter how strong the dose and which virus strain was used. Rabies antibody titration can, therefore, afford a strong additional guarantee to the vaccination certificates accompanying domestic carnivores during transportation between countries. Quarantine rules should also be adapted to the epidemiological features in the exporting country, e.g. statistics of vaccination failure in cats and dogs and host-virus adaptation of the rabies strains circulating in these countries.

Response to a rabies epidemic, Bali, Indonesia, 2008-2011.

PubMed

Putra, Anak Agung Gde; Hampson, Katie; Girardi, Janice; Hiby, Elly; Knobel, Darryn; Mardiana, I Wayan; Townsend, Sunny; Scott-Orr, Helen

2013-04-01

Emergency vaccinations and culling failed to contain an outbreak of rabies in Bali, Indonesia, during 2008-2009. Subsequent island-wide mass vaccination (reaching 70% coverage, >200,000 dogs) led to substantial declines in rabies incidence and spread. However, the incidence of dog bites remains high, and repeat campaigns are necessary to eliminate rabies in Bali.

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

PubMed

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

2016-03-01

Rabies is endemic in the Philippines and dog bites are a major cause of rabies cases in humans. The rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. Therefore, more effective and feasible strategies for rabies control are urgently required in the country. To control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously had no reported cases. Our molecular epidemiological study suggests that inter-island transmission events can occur; therefore, we further investigated these inter-island transmission using phylogenetic and modeling approaches. We investigate inter-island transmission between Luzon and Tablas Islands in the Philippines. Phylogenetic analysis and mathematical modeling demonstrate that there was a time lag of several months to a year from rabies introduction to initial case detection, indicating the difficulties in recognizing the initial rabies introductory event. There had been no rabies cases reported in Tablas Island; however, transmission chain was sustained on this island after the introduction of rabies virus because of low vaccination coverage among dogs. Across the islands, a rabies control program should include control of inter-island dog transportation and rabies vaccination to avoid viral introduction from the outside and to break transmission chains after viral introduction. However, this program has not yet been completely implemented and transmission chains following inter-island virus transmission are still observed. Local government units try to control dog transport; however, it should be more strictly controlled, and a continuous rabies control program should be implemented to prevent rabies spread even in rabies-free areas. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Eliminating rabies in Tanzania? Local understandings and responses to mass dog vaccination in Kilombero and Ulanga districts.

PubMed

Bardosh, Kevin; Sambo, Maganga; Sikana, Lwitiko; Hampson, Katie; Welburn, Susan C

2014-06-01

With increased global attention to neglected diseases, there has been a resurgence of interest in eliminating rabies from developing countries through mass dog vaccination. Tanzania recently embarked on an ambitious programme to repeatedly vaccinate dogs in 28 districts. To understand community perceptions and responses to this programme, we conducted an anthropological study exploring the relationships between dogs, society, geography and project implementation in the districts of Kilombero and Ulanga, Southern Tanzania. Over three months in 2012, we combined the use of focus groups, semi-structured interviews, a household questionnaire and a population-based survey. Willingness to participate in vaccination was mediated by fear of rabies, high medical treatment costs and the threat of dog culling, as well as broader notions of social responsibility. However, differences between town, rural and (agro-) pastoralist populations in livelihood patterns and dog ownership impacted coverage in ways that were not well incorporated into project planning. Coverage in six selected villages was estimated at 25%, well below official estimates. A variety of problems with campaign mobilisation, timing, the location of central points, equipment and staff, and project organisation created barriers to community compliance. Resource-limitations and institutional norms limited the ability for district staff to adapt implementation strategies. In the shadows of resource and institutional limitations in the veterinary sector in Africa, top-down interventions for neglected zoonotic diseases likes rabies need to more explicitly engage with project organisation, capacity and community participation. Greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably.

A mixed methods approach to assess animal vaccination programmes: The case of rabies control in Bamako, Mali.

PubMed

Mosimann, Laura; Traoré, Abdallah; Mauti, Stephanie; Léchenne, Monique; Obrist, Brigit; Véron, René; Hattendorf, Jan; Zinsstag, Jakob

2017-01-01

In the framework of the research network on integrated control of zoonoses in Africa (ICONZ) a dog rabies mass vaccination campaign was carried out in two communes of Bamako (Mali) in September 2014. A mixed method approach, combining quantitative and qualitative tools, was developed to evaluate the effectiveness of the intervention towards optimization for future scale-up. Actions to control rabies occur on one level in households when individuals take the decision to vaccinate their dogs. However, control also depends on provision of vaccination services and community participation at the intermediate level of social resilience. Mixed methods seem necessary as the problem-driven transdisciplinary project includes epidemiological components in addition to social dynamics and cultural, political and institutional issues. Adapting earlier effectiveness models for health intervention to rabies control, we propose a mixed method assessment of individual effectiveness parameters like availability, affordability, accessibility, adequacy or acceptability. Triangulation of quantitative methods (household survey, empirical coverage estimation and spatial analysis) with qualitative findings (participant observation, focus group discussions) facilitate a better understanding of the weight of each effectiveness determinant, and the underlying reasons embedded in the local understandings, cultural practices, and social and political realities of the setting. Using this method, a final effectiveness of 33% for commune Five and 28% for commune Six was estimated, with vaccination coverage of 27% and 20%, respectively. Availability was identified as the most sensitive effectiveness parameter, attributed to lack of information about the campaign. We propose a mixed methods approach to optimize intervention design, using an "intervention effectiveness optimization cycle" with the aim of maximizing effectiveness. Empirical vaccination coverage estimation is compared to the

Sudden onset unilateral sensorineural hearing loss after rabies vaccination.

PubMed

Okhovat, Saleh; Fox, Richard; Magill, Jennifer; Narula, Antony

2015-12-15

A 33-year-old man developed profound sudden onset right-sided hearing loss with tinnitus and vertigo, within 24 h of pretravel rabies vaccination. There was no history of upper respiratory tract infection, systemic illness, ototoxic medication or trauma, and normal otoscopic examination. Pure tone audiograms (PTA) demonstrated right-sided sensorineural hearing loss (thresholds 90-100 dB) and normal left-sided hearing. MRI internal acoustic meatus, viral serology (hepatitis B, C, HIV and cytomegalovirus) and syphilis screen were normal. Positive Epstein-Barr virus IgG, viral capsid IgG and anticochlear antibodies (anti-HSP-70) were noted. Initial treatment involved a course of high-dose oral prednisolone and acyclovir. Repeat PTAs after 12 days of treatment showed a small improvement in hearing thresholds. Salvage intratympanic steroid injections were attempted but failed to improve hearing further. Sudden onset sensorineural hearing loss (SSNHL) is an uncommon but frightening experience for patients. This is the first report of SSNHL following rabies immunisation in an adult. 2015 BMJ Publishing Group Ltd.

The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data

PubMed Central

Lembo, Tiziana; Hampson, Katie; Kaare, Magai T.; Ernest, Eblate; Knobel, Darryn; Kazwala, Rudovick R.; Haydon, Daniel T.; Cleaveland, Sarah

2010-01-01

Background Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. Methodology/Principal Findings This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. Conclusions/Significance We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths. PMID:20186330

Collaborative study to evaluate a new ELISA test to monitor the effectiveness of rabies vaccination in domestic carnivores.

PubMed

Servat, A; Cliquet, F

2006-09-01

To prevent any introduction of rabies, many rabies-free countries have adopted a scheme requiring the rabies vaccination of pets associated with a serological test. FAVN test and RFFIT are the current OIE prescribed techniques to perform this assay. A qualitative indirect ELISA (Serelisa) test has been recently described as a screening test to monitor the effectiveness of rabies vaccination of pets. A lack of sensitivity requires ELISA negative samples to be retested using an OIE confirmatory test. This raised the question whether this new test could be reasonably proposed as an alternative tool in the context of international trades of pets. The Community Reference Institute of Nancy organized a short trial to answer this question. In this study, 16 laboratories tested a panel of their own samples with FAVN test/RFFIT and the Serelisa. The comparison of results revealed that the performance of the Serelisa is highly heterogeneous. A lack of sensitivity was detected in 50% of participants, when 25% of laboratories obtained a significant rate of false positive results. This last point questions the pertinence of using the Serelisa in the context of international trades by preventing any movements of insufficiently or non-protected animals.

Hepatitis B Vaccination Status among Japanese Travelers.

PubMed

Yaita, Kenichiro; Yahara, Koji; Sakai, Yoshiro; Iwahashi, Jun; Masunaga, Kenji; Hamada, Nobuyuki; Watanabe, Hiroshi

2017-05-08

This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organization's payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.

Post-exposure prophylaxis against rabies at two newly designated intradermal rabies vaccination clinics in Kerala, India.

PubMed

J, Teena M; Mathew, T; S, Anish T; M, Sujina C; Philip, R R

2012-01-01

The two-site intradermal rabies vaccination (IDRV) regimen was recently introduced in Kerala. We aimed to determine factors associated with exposure of category III severity among patients seeking prophylaxis against rabies at IDRV clinics. This hospital-based, cross-sectional study was done at two clinics in Thiruvananthapuram district, Kerala. Data were collected using a semi-structured questionnaire by direct interview and 320 patients were included. Bivariate analysis of quantitative variables was done using t-test and that of qualitative variables using chi-square test. The mean (standard deviation) age of patients was 32.4 (19.6) years. Among the 320 cases, 202 (63.1%) had category III exposure. Lower extremities were the most frequent site of exposure (146, 45.6%). The most frequent mode of exposure was being bitten by an animal (214, 66.9%), often a dog. Residence in rural areas, exposure to dogs and wounds on the extremities had a significant association with severity of exposure. Animal exposures were more among people from rural areas. About two-thirds of exposures which necessitated post-exposure prophylaxis were category III. Copyright 2012, NMJI.

Rabies

MedlinePlus

... transdermal bites or scratches, licks on broken skin; contamination of mucous membrane with saliva from licks, contacts ... vaccines and rabies immunoglobulin, to understand the global manufacturing capacity and to explore bulk purchasing options for ...

Human rabies in India: epidemiological features, management and current methods of prevention.

PubMed

Dutta, J K

1999-10-01

In most endemic countries stray dogs are the main source of rabies infection in humans. In India 95-97% of rabies patients are infected by dogs. Most pet dogs do not regularly receive booster doses of vaccine. In Thailand, most rabies patients develop the disease within 1 month of exposure. Rabies immunoglobulin is costly and usually not available. So in India nervous tissue vaccine is commonly used--it is inexpensive and freely available despite frequent neurological complications. The cost of immunization by tissue culture vaccines may be reduced by nearly 60% by intradermal vaccination.

Vaccine immune response and interference of colostral antibodies in calves vaccinated against rabies at 2, 4 and 6 months of age born from antirabies revaccinated females.

PubMed

Filho, O A; Megid, J; Geronutti, L; Ratti, J; Almeida, M F A; Kataoka, A P A G; Martorelli, L F A

2012-06-01

Considering the high prevalence of rabies in cattle, we aimed to evaluate the interference of colostral antibodies transferred to calves after birth and the benefit of administering an antirabies vaccination in two-month-old calves compared to vaccinating at 4 and 6 months of age. Calves born from females revaccinated against rabies during the third trimester of pregnancy were studied. Forty-eight hours after parturition, blood samples from dams and offspring were collected, and antirabies neutralizing antibody titers were analyzed using the Rapid Focus Fluorescent Inhibition Test. We found that all calves had similar titers of antibodies transferred through the colostrum. Furthermore, none of the calves presented a satisfactory serological response after the first vaccination, but all had an appropriate response after revaccination. This study demonstrates that antirabies vaccination should be recommended for calves at two months of age in endemic and epizootic situations. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

Russell, Colin A; Smith, David L; Childs, James E; Real, Leslie A

2005-03-01

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

Could the RTS,S/AS01 meningitis safety signal really be a protective effect of rabies vaccine?

PubMed

Gessner, Bradford D; Knobel, Darryn L; Conan, Anne; Finn, Adam

2017-02-01

The RTS,S/AS01 malaria vaccine has been associated with meningitis and cerebral malaria safety signals. Key characteristics of the meningitis signal include presence, in the 5-17month but not the 6-12week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5-17month old age group control arm had abnormally low incidences while other arms in both age groups had meningitis and cerebral malaria incidences similar to background rates. No single hypothesis postulating an adverse effect from RTS,S/AS01 unites these observations. Unlike the 6-12week group, the control population in the 5-17month old age group received rabies vaccine. This raises the possibility that non-specific rabies vaccine effects had a protective effect against central nervous system infection, a hypothesis consistent with the epidemiologic data. The lack of a confirmed biologic mechanism for such an effect emphasizes the need for additional studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

PubMed

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects

PubMed Central

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-01-01

ABSTRACT Aim: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Methods: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). Results: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Conclusions: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China. PMID:28121231

Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age

PubMed Central

Wallace, Ryan M.; Pees, Anna; Blanton, Jesse B.

2017-01-01

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs’ failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57–1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12–16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8–30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer. PMID:28759602

Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age.

PubMed

Wallace, Ryan M; Pees, Anna; Blanton, Jesse B; Moore, Susan M

2017-07-01

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs' failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57-1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12-16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8-30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

Neutralising antibody titration in 25,000 sera of dogs and cats vaccinated against rabies in France, in the framework of the new regulations that offer an alternative to quarantine.

PubMed

Cliquet, F; Verdier, Y; Sagné, L; Aubert, M; Schereffer, J L; Selve, M; Wasniewski, M; Servat, A

2003-12-01

Regulations governing international movements of domestic carnivores from rabies-infected to rabies-free countries have recently been loosened, with the adoption of a system that combines vaccination against rabies and serological surveillance (neutralising antibody titration test with a threshold of 0.5 UI/ml). Since 1993, the Research Laboratory for Rabies and Wild Animal Pathology in Nancy, France, has analysed over 25,000 sera from dogs and cats using a viral seroneutralisation technique. The statistical analyses performed during this time show that cats respond better than dogs. Although no significant difference in titres was observed between primovaccinated and repeat-vaccinated cats, repeat-vaccinated dogs had titres above 0.5 IU/ml more frequently. In primovaccinated dogs, monovalent vaccines offered a better serological conversion rate than multivalent ones. Finally, the results of these analyses showed a strong correlation between antibody counts and the time that elapsed between the last vaccination and the blood sampling.

Assessing the rabies control and surveillance systems in Brazil: an experience of measures toward bats after the halt of massive vaccination of dogs and cats in Campinas, Sao Paulo.

PubMed

De Lucca, Tosca; Rodrigues, Ricardo Conde Alves; Castagna, Claudio; Presotto, Douglas; De Nadai, Diego Vinicius; Fagre, Anna; Braga, Guilherme Basseto; Guilloux, Aline Gil Alves; e Alves, Ana Júlia Silva; Martins, Camila Marinelli; Amaku, Marcos; Ferreira, Fernando; Dias, Ricardo Augusto

2013-08-01

Bats are less vulnerable to forest fragmentation than any other mammal, and for that reason, some species can disperse to peri-urban or urban areas. Insectivorous bats are abundant in urban areas due to the density of artificial roosts and insects attracted by city lights. Inter-species transmission of the rabies virus between bats can occur, and this is the most probable mechanism of virus circulation in bat populations. Bats can also transmit the rabies virus to other mammal species, like dogs and cats. With the halt of dog and cat vaccination campaigns in 2010, the importance of rabies surveillance in bats has increased in Brazil. A cross-sectional study performed in Campinas, Sao Paulo State, using data from the passive surveillance system for bats showed that rabies-positive bats from the families Molossidae, Phyllostomidae and Vespertilionidae were found in a peri-urban area. In these areas, dog and cat emergency vaccination (vaccination blockage) was recommended after the halt of the massive vaccination campaign in 2010. This control strategy was able to increase the proportion of vaccinated animals around a critical value of 50% and even with a higher probability of infectious contact between bats and dogs or cats in the vaccination blockage areas, no dog or cat rabies case was observed, evidencing the importance of the implementation of strategic rabies control measures in this new epidemiological scenario. Copyright © 2013 Elsevier B.V. All rights reserved.

Rabies vaccine standards: comparison of the 5th and 6th WHO international reference standards to the USDA veterinary reference standard.

PubMed

Hermann, J; Fry, A; Reising, M; Patterson, P; Siev, D; Gatewood, D

2012-11-06

Ensuring rabies vaccines are potent and effective is paramount in preventing transmission of this deadly disease and safeguarding public health. Efficacy of human and veterinary vaccines is ensured by evaluating relative potency estimates of the vaccine compared to a rabies reference standard using the National Institutes of Health (NIH) test. Reference vaccines are based on the International Standard for Rabies Vaccine provided by the World Health Organization (WHO). A comparison study was conducted to determine the relative potency of the 5th WHO, 6th WHO, and United States Department of Agriculture's (USDA) 08-14 reference standards using the NIH test. Results from the study demonstrate that the 6th WHO reference standard is approximately twice as potent as the 5th WHO reference when reconstituted to contain 1 IU per ml. Based on these results, the Center for Veterinary Biologics (CVB) doubled the reconstitution volume of USDA veterinary reference 08-14 from 13 ml to 26 ml, for an initial use dilution of 0.7 IU per ml for use by veterinary biologics manufacturers in the NIH test. This study emphasizes the importance of reference standard calibration for use in the National Institutes of Health test. Published by Elsevier Ltd.

[Antigenic determination of human anti-rabies vaccine against viral street strains common in the wild animal population in Poland].

PubMed

Seroka, D

1994-01-01

The aim of the study was to compare the antigen properties of a vaccine strain with street strains isolated from various animal hosts throughout the country. Investigation was carried out using monoclonal antibodies against NC protein. Also, two tests were carried out: the modified NIH test for potency and the neutralization test using the sera of people vaccinated against rabies (PM vaccine strain). The investigated street strains were used in both tests as the challenge viruses. A suspension of these strains diluted five times made it possible to avoid extreme values of animal survival (0% or 100%) what, consequently, made calculation of the LD50 value easier. A different rabies virus serotype (EBLI virus) in the population of insectivore bats Eptesicus serotinus and antigen variants within the first serotype, having common epitopes with strains of the vaccine virus SAD B19 and the polar rabies virus, were found to be present throughout the country. The concentrated and purified vaccine containing the PM virus did not protect mice against infection with strains of viruses isolated from bats (protection index 10 and lower). For the remaining strains, depending on the animal source of their isolation, the protection index ranged from 10 to 1000 and higher. The properties neutralizing a dose of 5 i.u./ml of serum from the subject inoculated with the vaccine containing the PM strain were similar for all the investigated strains; 0,5 i.u./ml did not neutralize the strain isolated from a racoon dog.

[Current status of animal rabies in France].

PubMed

Aubert, M

1997-01-01

The main host reservoir and vector of rabies in Western Europe is the red fox (Vulpes vulpes). A vaccination strategy for this species has been developed and tested in Switzerland since 1978. Results indicate that the vaccine which is administered in spring and autumn for at least two consecutive years is more effective than destruction by shooting or gassing the animals. The same approach using bait containing increasingly effective and safe vaccines has been in use in France since 1986. By creating an immunological barrier from the English channel to the Swiss border, it has been possible to stop the southern progression of the disease. In the following years the vaccination program was extended to all contaminated areas in France (141,700 km2). From 1989 to 1996 rabies decreased in incidence by 99.7% and disappeared from 95% of the previously contaminated area. Although no case of rabies involving a non-flying mammal has been reported since October 1996, rabies cannot be considered as eradicated as long as places of active disease subsist in neighboring areas of Belgium and the Sarreland. Bat rabies in Europe is caused by two viral genotypes that have never been isolated in any species other than bats and man. A total of four cases of bat rabies have been diagnosed in France since 1989. All four cases occurred in the Serotine community including one in 1997. All cases of canine rabies reported in the last 20 years have been observed in imported animals. The last was in 1995 and could have been prevented by stricter border control.

Rabies and rabies virus in wildlife in mainland China, 1990-2013.

PubMed

Wang, Lihua; Tang, Qing; Liang, Guodong

2014-08-01

The number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland China. To better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland China. In addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (RABVs) were analyzed. Several wildlife species carry rabies including the bat, Chinese ferret badger, raccoon dog, rat, fox, and wolf. RABVs have been isolated or detected in the bat, Chinese ferret badger, raccoon dog, Apodemus, deer, and vole. Among them, the bat, Chinese ferret badger, and raccoon dog may play a role in the ecology of lyssaviruses in mainland China. All wildlife-originated RABVs were found to belong to genotype 1 RABV except for a bat-originated Irkut virus isolated in 2012. Several substitutions were found between the glycoprotein of wildlife-originated RABVs and vaccine strains. Whether these substitutions could affect the efficacy of currently used vaccines against infections caused by these wildlife-originated RABVs needs to be investigated further. Phylogenetic analysis showed that RABVs in the bat, Chinese ferret badger, and raccoon dog were distinct from local dog-originated RABVs, and almost all collected wildlife-originated isolates were associated with older China clades II to V, suggesting the possibility of wildlife reservoirs in mainland China through the ages. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

An evaluation of rabies vaccination rates among canines and felines involved in biting incidents within the Wellington-Dufferin-Guelph Public Health Department.

PubMed

Bottoms, K; Trotz-Williams, L; Hutchison, S; MacLeod, J; Dixon, J; Berke, O; Poljak, Z

2014-11-01

The objectives of this study were to determine the rate of animal bite incidents occurring in the human population of a local health department, and to determine the proportion of these canines and felines that were not up to date on their rabies vaccination at the time the incident occurred. Data were obtained from animal bite incidents reported to Wellington-Dufferin-Guelph Public Health during 2010 and 2011. Descriptive statistics of 718 eligible reports revealed the average rate of animal biting was 1.55 bites per 1000 residents per year. Approximately 54% of these animals were vaccinated against rabies, 32% were not up to date with their rabies vaccination, and the remaining 14.5% were of unknown status. The unit of analysis was the municipality, and the four outcomes of interest were: (i) number of animal bite incidents per 1000 residents, (ii) number of dog bite incidents per 1000 residents, (iii) proportion of animals involved in bite incidents that were not up to date with their rabies vaccination, and (iv) proportion of dogs that were not up to date. Associations between the outcomes and selected demographic variables were investigated using regression analysis. The number of veterinary clinics per 10,000 residents, and whether the municipality was urban or rural were identified as significant predictors for the number of animal bites per 1000 residents, and the number of dog bites. There were no significant predictors for the proportion of unvaccinated animals or dogs. Spatial clustering and the location of spatial clusters were assessed using the empirical Bayes index and spatial scan test. This analysis identified five municipalities within the health department that have a high rate of biting incidents and a high proportion of animals that were not up to date on their rabies vaccination. Such municipalities are ideal for targeted educational campaigns regarding the importance of vaccination in pets. © 2014 Blackwell Verlag GmbH.

Molecular epidemiology of rabies virus in Poland.

PubMed

Orłowska, Anna; Żmudziński, Jan Franciszek

2014-08-01

The paper describes a phylogenetic study of 58 Polish isolates of rabies virus collected between 1992 and 2010. Sequences of the nucleoprotein (N) and glycoprotein (G) genes approximately 600 bp long were compared with reference sequences (GenBank) of European rabies viruses from neighbouring countries. The study confirmed a very high level of homology (94.4-100 %) of the Polish rabies virus strains irrespective of the date of isolation. Two variants of rabies virus: NEE (Northeastern Europe variant) and CE (Central Europe variant), depending on the geographical place of isolation, were circulating in Poland from 1992 to 2010. The Polish rabies virus isolates showed high similarity to European RABV strains, especially those collected in Ukraine and Romania. They were clearly different from vaccine strains SAD B19 and SAD Bern, which have been used for oral vaccination of foxes against rabies in Poland since 1993.

Uptake of Rabies Control Measures by Dog Owners in Flores Island, Indonesia

PubMed Central

Wera, Ewaldus; Mourits, Monique C. M.; Hogeveen, Henk

2015-01-01

Background Rabies has been a serious public health threat in Flores Island, Indonesia since it was introduced in 1997. To control the disease, annual dog vaccination campaigns have been implemented to vaccinate all dogs free of charge. Nevertheless, the uptake rate of the vaccination campaigns has been low. The objective of this paper is to identify risk factors associated with the uptake of rabies control measures by individual dog owners in Flores Island. Methodology/principal findings A total of 450 dog owners from 44 randomly selected villages in the Sikka and Manggarai regencies were interviewed regarding their socio-demographic factors, knowledge of rabies, and their uptake of rabies control measures. The majority of dog owners surveyed (>90%) knew that rabies is a fatal disease and that it can be prevented. Moreover, 68% of the dog owners had a high level of knowledge about available rabies control measures. Fifty-two percent of the dog owners had had at least one of their dogs vaccinated during the 2012 vaccination campaign. Vaccination uptake was significantly higher for dog owners who resided in Sikka, kept female dogs for breeding, had an income of more than one million Rupiah, and had easy access to their village. The most important reasons not to join the vaccination campaign were lack of information about the vaccination campaign schedule (40%) and difficulty to catch the dog during the vaccination campaign (37%). Conclusions/significance Dog owners in Flores Island had a high level of knowledge of rabies and its control, but this was not associated with uptake of the 2012 vaccination campaign. Geographical accessibility was one of the important factors influencing the vaccination uptake among dog owners. Targeted distribution of information on vaccination schedules and methods to catch and restrain dogs in those villages with poor accessibility may increase vaccination uptake in the future. PMID:25782019

Eliminating Rabies in Tanzania? Local Understandings and Responses to Mass Dog Vaccination in Kilombero and Ulanga Districts

PubMed Central

Bardosh, Kevin; Sambo, Maganga; Sikana, Lwitiko; Hampson, Katie; Welburn, Susan C.

2014-01-01

Background With increased global attention to neglected diseases, there has been a resurgence of interest in eliminating rabies from developing countries through mass dog vaccination. Tanzania recently embarked on an ambitious programme to repeatedly vaccinate dogs in 28 districts. To understand community perceptions and responses to this programme, we conducted an anthropological study exploring the relationships between dogs, society, geography and project implementation in the districts of Kilombero and Ulanga, Southern Tanzania. Methodology/Principal Findings Over three months in 2012, we combined the use of focus groups, semi-structured interviews, a household questionnaire and a population-based survey. Willingness to participate in vaccination was mediated by fear of rabies, high medical treatment costs and the threat of dog culling, as well as broader notions of social responsibility. However, differences between town, rural and (agro-) pastoralist populations in livelihood patterns and dog ownership impacted coverage in ways that were not well incorporated into project planning. Coverage in six selected villages was estimated at 25%, well below official estimates. A variety of problems with campaign mobilisation, timing, the location of central points, equipment and staff, and project organisation created barriers to community compliance. Resource-limitations and institutional norms limited the ability for district staff to adapt implementation strategies. Conclusions and Significance In the shadows of resource and institutional limitations in the veterinary sector in Africa, top-down interventions for neglected zoonotic diseases likes rabies need to more explicitly engage with project organisation, capacity and community participation. Greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably. PMID:24945697

Response to a Rabies Epidemic, Bali, Indonesia, 2008–2011

PubMed Central

Hampson, Katie; Girardi, Janice; Hiby, Elly; Knobel, Darryn; Mardiana, Wayan; Townsend, Sunny; Scott-Orr, Helen

2013-01-01

Emergency vaccinations and culling failed to contain an outbreak of rabies in Bali, Indonesia, during 2008–2009. Subsequent island-wide mass vaccination (reaching 70% coverage, >200,000 dogs) led to substantial declines in rabies incidence and spread. However, the incidence of dog bites remains high, and repeat campaigns are necessary to eliminate rabies in Bali. PMID:23632033

Single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.

PubMed

Jonker, Emile F F; Visser, Leonardus G

2017-09-01

The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N  = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P  < 0.03). This dose finding study demonstrates that priming with a single dose of rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Rabies: the clinical features, management and prevention of the classic zoonosis.

PubMed

Warrell, Mary J; Warrell, David A

2015-02-01

The diagnosis of rabies encephalitis relies on awareness of the varied clinical features and eliciting a history of unusual contact with a mammal throughout the endemic area. The diagnosis is easily missed. Laboratory tests are not routine and only confirm clinical suspicion. Rabies infection carries a case fatality exceeding 99.9%. Palliation is appropriate, except for previously-vaccinated patients or those infected by American bats, for whom intensive care is probably indicated. However, as rabies vaccines are outstandingly effective, no one should die of dog-transmitted infection. Vaccines and rabies immunoglobulin are expensive and usually scarce in Asia and Africa. All travellers to dog rabies enzootic areas should be strongly encouraged to have pre-exposure immunisation before departure. There is no contraindication to vaccination but the cost can be prohibitive. Intradermal immunisation, using 0.1 ml and sharing vials of vaccine, is cheaper and is now permitted by UK regulations. Returning travellers may need post-exposure prophylaxis. Economical intradermal post-exposure vaccination is practicable and should be introduced into rural areas of Africa and Asia immediately. Eliminating rabies in dogs is now feasible and would dramatically reduce human mortality, if funds were made available. The high current economic burden of human prophylaxis would then be largely relieved. © 2015 Royal College of Physicians.

One Health approach to cost-effective rabies control in India.

PubMed

Fitzpatrick, Meagan C; Shah, Hiral A; Pandey, Abhishek; Bilinski, Alyssa M; Kakkar, Manish; Clark, Andrew D; Townsend, Jeffrey P; Abbas, Syed Shahid; Galvani, Alison P

2016-12-20

Over 20,000 rabies deaths occur annually in India, representing one-third of global human rabies. The Indian state of Tamil Nadu has pioneered a "One Health" committee to address the challenge of rabies in dogs and humans. Currently, rabies control in Tamil Nadu involves postexposure vaccination of humans after dog bites, whereas potential supplemental approaches include canine vaccination and sterilization. We developed a data-driven rabies transmission model fit to human rabies autopsy data and human rabies surveillance data from Tamil Nadu. Integrating local estimates for canine demography and costs, we predicted the impact of canine vaccination and sterilization on human health outcomes and evaluated cost-effectiveness according to the WHO criteria for India, which correspond to thresholds of $1,582 and $4,746 per disability-adjusted life-years (DALYs) for very cost-effective and cost-effective strategies, respectively. We found that highly feasible strategies focused on stray dogs, vaccinating as few as 7% of dogs annually, could very cost-effectively reduce human rabies deaths by 70% within 5 y, and a modest expansion to vaccinating 13% of stray dogs could cost-effectively reduce human rabies by almost 90%. Through integration over parameter uncertainty, we find that, for a cost-effectiveness threshold above $1,400 per DALY, canine interventions are at least 95% likely to be optimal. If owners are willing to bring dogs to central point campaigns at double the rate that campaign teams can capture strays, expanded annual targets become cost-effective. This case study of cost-effective canine interventions in Tamil Nadu may have applicability to other settings in India and beyond.

One Health approach to cost-effective rabies control in India

PubMed Central

Shah, Hiral A.; Pandey, Abhishek; Bilinski, Alyssa M.; Kakkar, Manish; Clark, Andrew D.; Galvani, Alison P.

2016-01-01

Over 20,000 rabies deaths occur annually in India, representing one-third of global human rabies. The Indian state of Tamil Nadu has pioneered a “One Health” committee to address the challenge of rabies in dogs and humans. Currently, rabies control in Tamil Nadu involves postexposure vaccination of humans after dog bites, whereas potential supplemental approaches include canine vaccination and sterilization. We developed a data-driven rabies transmission model fit to human rabies autopsy data and human rabies surveillance data from Tamil Nadu. Integrating local estimates for canine demography and costs, we predicted the impact of canine vaccination and sterilization on human health outcomes and evaluated cost-effectiveness according to the WHO criteria for India, which correspond to thresholds of $1,582 and $4,746 per disability-adjusted life-years (DALYs) for very cost-effective and cost-effective strategies, respectively. We found that highly feasible strategies focused on stray dogs, vaccinating as few as 7% of dogs annually, could very cost-effectively reduce human rabies deaths by 70% within 5 y, and a modest expansion to vaccinating 13% of stray dogs could cost-effectively reduce human rabies by almost 90%. Through integration over parameter uncertainty, we find that, for a cost-effectiveness threshold above $1,400 per DALY, canine interventions are at least 95% likely to be optimal. If owners are willing to bring dogs to central point campaigns at double the rate that campaign teams can capture strays, expanded annual targets become cost-effective. This case study of cost-effective canine interventions in Tamil Nadu may have applicability to other settings in India and beyond. PMID:27994161

Animal bites and rabies exposure in Australian travellers.

PubMed

Mills, Deborah J; Lau, Colleen L; Weinstein, Philip

2011-12-19

To examine the circumstances of animal exposure in a case series of Australian travellers who required rabies postexposure prophylaxis, and to assess the appropriateness of current guidelines for rabies pre-exposure vaccination. Prospective case series of 65 returned travellers who presented to four Australian travel medicine clinics between 1 April 2009 and 31 July 2010 for rabies post-exposure prophylaxis. Demographic characteristics associated with risk of injury; countries where injuries occurred; circumstances of the injuries; and travellers' experiences of obtaining postexposure prophylaxis overseas. Animal bites and scratches occurred most commonly among travellers aged 20-29 years. Most injuries occurred in Bali, Indonesia (30 [46%]) and Thailand (21 [32%]), and the most common animals responsible for the injuries to the 65 travellers were monkeys (29 travellers [45%]) and dogs (27 [42%]). Thirty-nine of the travellers (60%) initiated contact with the animal. Forty travellers (62%) were able to commence rabies vaccination overseas, but only nine (14%) were able to obtain rabies immunoglobulin overseas. Most travellers had difficulty obtaining rabies postexposure prophylaxis overseas, resulting in significant delays in appropriate treatment. We recommend that current National Health and Medical Research Council guidelines for at-risk persons be broadened, and that the risk of rabies and the option of pre-exposure vaccination be discussed with all travellers to rabies-endemic areas.

Acute Transverse Myelitis at the Conus Medullaris Level After Rabies Vaccination in a Patient With Behçet's Disease

PubMed Central

Bir, Levent Sinan; Özdemir Eşmeli, Fatma; Cenikli, Utku; Erdoğan, Çağgdaş; Değirmenci, Eylem

2007-01-01

Case report: A 25-year-old man with Behçet's disease was admitted because of weakness of the lower limbs and difficulty in urination. He had received a rabies vaccination 2 months previous because he had been bitten by a dog. Findings: Clinical and laboratory findings supported acute transverse myelitis. A hyperintense lesion and expansion at the level of conus medullaris was detected on spinal magnetic resonance imaging. Conclusion: Although neurologic involvement is one of the main causes of mortality and morbidity in Behçet's disease, the factors that aggravate the involvement of the nervous system are still unclear. Vaccination may have been the factor that had activated autoimmune mechanisms in this case. To our knowledge, involvement of the conus medullaris in Behçet's disease after rabies vaccination has not been reported. PMID:17684898

[Acute renal pain as an adverse reaction of the rabies immunization].

PubMed

Lalosević, Dusan

2009-01-01

HRIG is the best preparate in rabies prophylaxis, and it's considered that optimal dose is 20 international units per kilogram and must not been reduced or overdosed. HRIG have to be injected infiltrative around bite wounds, and if after that remains a part of the dose, it has to be given in gluteal muscle. Application only in gluteus is vitium artis. At one patient immunized against rabies has occured acute bilateral renal pain and fever at time of immunization against rabies, and because of that vaccination must been stopped after the 3rd dose of vaccine. Patient was a 26-year-old female without significant pre-existing disease, bitten by stray dog. After the start of immunization, because the wrong direction, she received about 2.5 more amount of human rabies immunoglobuline (HRIG) then is recommended on declaration at etiquette of ampoule, and only in gluteus in quantity of 10.5 ml. Glomerulonephritis after rabies vaccination until now was described just once by Singhal et al. in 1981. year. Acute renal pain, after rabies vaccine, which aggravated after repeated vaccine doses in our patient who received overdosed HRIG, may be explained by immunopathological mechanism, rather with formation of circulating immune complexes, their precipitation on the glomerular basement membrane and developing glomerulonephritis. Low weight soluble molecular immune complexes formed when antigen is in excess, as in case after repeated doses of rabies vaccine, circulate and precipitate on glomerular membrane and causes glomerulonephritis. As contribution to this explanation, is that symptoms as renal pain disappeared after interrupting vaccination protocol in our patient.

Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan

PubMed Central

Wallace, Ryan M.; Lai, Yuching; Doty, Jeffrey B.; Chen, Chen-Chih; Vora, Neil M.; Blanton, Jesse D.; Chang, Susan S.; Pei, Kurtis J. C.

2018-01-01

Background Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca) in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described. Methodology/Principle findings As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV) baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%), 1 of 21 fishmeal baits (4.8%), 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait. Conclusions/Significance Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent ‘dog to ferret-badger’ host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals’ competition for baits, ants, bait design, and dense tropical landscape represent potential

Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan.

PubMed

Wallace, Ryan M; Lai, Yuching; Doty, Jeffrey B; Chen, Chen-Chih; Vora, Neil M; Blanton, Jesse D; Chang, Susan S; Cleaton, Julie M; Pei, Kurtis J C

2018-01-01

Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca) in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described. As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV) baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%), 1 of 21 fishmeal baits (4.8%), 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait. Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent 'dog to ferret-badger' host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals' competition for baits, ants, bait design, and dense tropical landscape represent potential challenges to effective ORV programs that will need to be considered in future

[Rabies in a cat in Greenland].

PubMed

Christensen, Laurids Siig; Jacobsen, Keld; Maersk-Møller, Elisabeth

2008-08-18

We describe the first case of rabies diagnosed in a cat in Greenland. The cat showed aggressive behaviour one month after the visit of a rabid fox on the premises. Rabies is enzootic in Greenland, the arctic fox being the natural host of rabies virus. Cats are imported in increasing numbers to Greenland and the reported case stresses the need for concern in relation to a hitherto unrecognised risk of exposure to rabies virus and stresses the need to comply with the obligatory anti-rabies vaccination regimes for cats in Greenland.

Dog-transmitted Rabies in Beijing, China.

PubMed

Zhang, Jing Yuan; Zhang, Bi; Zhang, Shou Feng; Zhang, Fei; Li, Nan; Liu, Ye; Hu, Rong Liang

2017-07-01

Rabies remains a continuous threat to public health in Beijing. In this study, a total of 224 brain tissues were collected from suspected infected stray dogs within Beijing between January 2015 and December 2016. Among them, total of 67 samples were diagnosed positive for rabies. In the phylogenetic analysis, rabies in Beijing is currently a relatively independent public health issue originating from local rabid dogs apart from the imported cases from elsewhere in the country. Because vaccination of unregistered dogs against rabies is still neglected in Beijing and other regions of China, national and local authorities should play central roles in all related aspects, such as development of policies, engagement of stakeholders for public and professional education, entire vaccination process, and animal management. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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

PubMed

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

Rabies elimination research: juxtaposing optimism, pragmatism and realism

PubMed Central

Hampson, Katie

2017-01-01

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. PMID:29263285

Seroprevalence of tetanus toxoid antibody and booster vaccination efficacy in Japanese travelers.

PubMed

Mizuno, Yasutaka; Yamamoto, Akihiko; Komiya, Takako; Takeshita, Nozomi; Takahashi, Motohide

2014-01-01

Tetanus can be prevented by vaccination, which is especially important for overseas travelers. However, despite booster vaccination every 10 years being recommended, most Japanese adults do not receive it in the absence of physical injury or overseas travel. We aimed to investigate the level of protective immunity against tetanus among Japanese travelers, which may provide valuable information for formulating booster vaccination recommendations. 113 Japanese travelers given tetanus toxoid were recruited. The collected samples included paired samples prior to and 3-5 weeks after receiving the booster vaccination. Travelers who did not return and those lacking sample collection at the second visit were excluded. Finally, 96 paired blood samples were collected. History of immunization against tetanus, including DPT and DT vaccines, was determined from interviews or immunization records. The pre-vaccination geometric mean titer for the 96 participants was 1.07 IU/mL; 76% had a protective antitoxin level (>0.1 IU/mL), and 50% had a long-term protective antitoxin level (>1.0 IU/mL). Most participants <40 years old had protective immunity without receiving booster vaccination, whereas only 30.8% of those >50 years of age had protective immunity. Among the 23 participants without protective antitoxin levels (<0.1 IU/mL), booster vaccination was efficient in 100% of those <40 years but in only 28.6% of those >50 years of age. Although the tetanus antitoxin level decreases with age, booster vaccination helped to achieve an adequate protective antitoxin levels in Japanese travelers <40 years of age. Furthermore, the individuals who have never been vaccinated against tetanus especially in those >50 years old need to obtain protective immunity against tetanus according to a basic immunization schedule to prevent tetanus in travelers and residents of Japan. Copyright © 2013 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by

Antibody response to vaccines for rhinotracheitis, caliciviral disease, panleukopenia, feline leukemia, and rabies in tigers (Panthera tigris) and lions (Panthera leo).

PubMed

Risi, Emmanuel; Agoulon, Albert; Allaire, Franck; Le Dréan-Quénec'hdu, Sophie; Martin, Virginie; Mahl, Philippe

2012-06-01

This article presents the results of a study of captive tigers (Panthera tigris) and lions (Panthera leo) vaccinated with a recombinant vaccine against feline leukemia virus; an inactivated adjuvanted vaccine against rabies virus; and a multivalent modified live vaccine against feline herpesvirus, calicivirus, and panleukopenia virus. The aim of the study was to assess the immune response and safety of the vaccines and to compare the effects of the administration of single (1 ml) and double (2 ml) doses. The animals were separated into two groups and received either single or double doses of vaccines, followed by blood collection for serologic response for 400 days. No serious adverse event was observed, with the exception of abortion in one lioness, potentially caused by the incorrect use of the feline panleukopenia virus modified live vaccine. There was no significant difference between single and double doses for all vaccines. The recombinant vaccine against feline leukemia virus did not induce any serologic response. The vaccines against rabies and feline herpesvirus induced a significant immune response in the tigers and lions. The vaccine against calicivirus did not induce a significant increase in antibody titers in either tigers or lions. The vaccine against feline panleukopenia virus induced a significant immune response in tigers but not in lions. This report demonstrates the value of antibody titer determination after vaccination of nondomestic felids.

Incidence of canine rabies in N'Djaména, Chad.

PubMed

Kayali, U; Mindekem, R; Yémadji, N; Oussiguéré, A; Naïssengar, S; Ndoutamia, A G; Zinsstag, J

2003-11-12

This work describes for the first time the incidence risk of passively reported canine rabies, and quantifies reported human exposure in N'Djaména (the capital of Chad). To diagnose rabies, we used a direct immunofluorescent-antibody test (IFAT). From January 2001 to March 2002, we were brought 34 rabies cases in dogs and three cases in cats. Canine cases were geographically clustered. The annual incidence risk of canine rabies was 1.4 (95% CI: 1.2, 1.7) per 1000 unvaccinated dogs. Most of the rabid dogs were owned-although free-roaming and not vaccinated against rabies. Most showed increased aggressiveness and attacked people without being provoked. Eighty-one persons were exposed to rabid dogs and four persons to rabid cats (mostly children<15 years old). Most of the exposed persons were neighbours or family members of the animal owner. Most exposures were transdermal bites, but nearly half of all exposed persons did not apply any first wound care or only applied a traditional treatment. In N'Djaména, humans are often exposed to canine rabies but do not use the full-course post-exposure treatment and wound care is insufficient. Most rabid dogs would be accessible to parenteral vaccination. Pilot vaccination campaigns are needed to determine the success of dog mass vaccination in N'Djaména as a way to prevent animal and human rabies.

Impact of community-delivered SMS alerts on dog-owner participation during a mass rabies vaccination campaign, Haiti 2017.

PubMed

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.

Achieving Population-Level Immunity to Rabies in Free-Roaming Dogs in Africa and Asia

PubMed Central

Morters, Michelle K.; McKinley, Trevelyan J.; Horton, Daniel L.; Cleaveland, Sarah; Schoeman, Johan P.; Restif, Olivier; Whay, Helen R.; Goddard, Amelia; Fooks, Anthony R.; Damriyasa, I. Made; Wood, James L. N.

2014-01-01

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 two years to ensure

Rabies postexposure prophylaxis. Human and domestic animal considerations.

PubMed

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.

Exposure time of oral rabies vaccine baits relative to baiting density and raccoon population density.

PubMed

Blackwell, Bradley F; Seamans, Thomas W; White, Randolph J; Patton, Zachary J; Bush, Rachel M; Cepek, Jonathan D

2004-04-01

Oral rabies vaccination (ORV) baiting programs for control of raccoon (Procyon lotor) rabies in the USA have been conducted or are in progress in eight states east of the Mississippi River. However, data specific to the relationship between raccoon population density and the minimum density of baits necessary to significantly elevate rabies immunity are few. We used the 22-km2 US National Aeronautics and Space Administration Plum Brook Station (PBS) in Erie County, Ohio, USA, to evaluate the period of exposure for placebo vaccine baits placed at a density of 75 baits/km2 relative to raccoon population density. Our objectives were to 1) estimate raccoon population density within the fragmented forest, old-field, and industrial landscape at PBS: and 2) quantify the time that placebo, Merial RABORAL V-RG vaccine baits were available to raccoons. From August through November 2002 we surveyed raccoon use of PBS along 19.3 km of paved-road transects by using a forward-looking infrared camera mounted inside a vehicle. We used Distance 3.5 software to calculate a probability of detection function by which we estimated raccoon population density from transect data. Estimated population density on PBS decreased from August (33.4 raccoons/km2) through November (13.6 raccoons/km2), yielding a monthly mean of 24.5 raccoons/km2. We also quantified exposure time for ORV baits placed by hand on five 1-km2 grids on PBS from September through October. An average 82.7% (SD = 4.6) of baits were removed within 1 wk of placement. Given raccoon population density, estimates of bait removal and sachet condition, and assuming 22.9% nontarget take, the baiting density of 75/ km2 yielded an average of 3.3 baits consumed per raccoon and the sachet perforated.

Serologic response of domestic ferrets (Mustela putorius furo) to canine distemper and rabies virus vaccines.

PubMed

Hoover, J P; Baldwin, C A; Rupprecht, C E

1989-01-15

Nine unrelated 12-week-old naive domestic ferrets (Mustela putorius furo) were used to evaluate the serologic responses to commercial canine distemper virus (CDV) and rabies virus (RV) vaccines. Five of the ferrets (group 1) were inoculated 3 times at 2-week intervals with a multivalent modified-live virus vaccine of canine cell-line origin, containing CDV and an inactivated RV vaccine. Four of the ferrets (group 2) were inoculated once with the multivalent modified-live virus vaccine containing CDV and were not inoculated with the RV vaccine. Both group-1 and group-2 ferrets seroconverted to the CDV component of the vaccine. Group-1 ferrets also seroconverted after RV vaccination and maintained serum antibody titers to both CDV and RV for at least 7 months. Domestic ferret sera were found to have IgG epitopes similar to sera of domestic dogs and cats. Domestic ferret sera did not contain antibodies to feline coronavirus or FeLV antigens.

First international collaborative study to evaluate rabies antibody detection method for use in monitoring the effectiveness of oral vaccination programmes in fox and raccoon dog in Europe.

PubMed

Wasniewski, M; Almeida, I; Baur, A; Bedekovic, T; Boncea, D; Chaves, L B; David, D; De Benedictis, P; Dobrostana, M; Giraud, P; Hostnik, P; Jaceviciene, I; Kenklies, S; König, M; Mähar, K; Mojzis, M; Moore, S; Mrenoski, S; Müller, T; Ngoepe, E; Nishimura, M; Nokireki, T; Pejovic, N; Smreczak, M; Strandbygaard, B; Wodak, E; Cliquet, F

2016-12-01

The most effective and sustainable method to control and eliminate rabies in wildlife is the oral rabies vaccination (ORV) of target species, namely foxes and raccoon dogs in Europe. According to WHO and OIE, the effectiveness of oral vaccination campaigns should be regularly assessed via disease surveillance and ORV antibody monitoring. Rabies antibodies are generally screened for in field animal cadavers, whose body fluids are often of poor quality. Therefore, the use of alternative methods such as the enzyme-linked immunosorbent assay (ELISA) has been proposed to improve reliability of serological results obtained on wildlife samples. We undertook an international collaborative study to determine if the commercial BioPro ELISA Rabies Ab kit is a reliable and reproducible tool for rabies serological testing. Our results reveal that the overall specificity evaluated on naive samples reached 96.7%, and the coefficients of concordance obtained for fox and raccoon dog samples were 97.2% and 97.5%, respectively. The overall agreement values obtained for the four marketed oral vaccines used in Europe were all equal to or greater than 95%. The coefficients of concordance obtained by laboratories ranged from 87.2% to 100%. The results of this collaborative study show good robustness and reproducibility of the BioPro ELISA Rabies Ab kit. Copyright © 2016 Elsevier B.V. All rights reserved.

A recombinant pseudorabies virus expressing rabies virus glycoprotein: safety and immunogenicity in dogs.

PubMed

Yuan, Ziguo; Zhang, Shoufeng; Liu, Ye; Zhang, Fei; Fooks, Anthony R; Li, Qianxue; Hu, Rongliang

2008-03-04

Several recombinant vaccines expressing the rabies virus glycoprotein have been developed, particularly for the oral vaccination of wildlife. While these vaccines induce protective immunity in some animal species such as foxes, they are less effective in others. Pseudorabies virus (PRV) has been licensed for use as a live vaccine in pigs and possesses an excellent safety and efficacy record. We have used it to construct a recombinant virus, rPRV/eGFP/rgp, expressing the rabies virus glycoprotein. This recombinant virus has been shown to be safe for dogs by oral and intramuscular routes of inoculation and was demonstrated to induce immune responses against both pseudorabies and rabies in dogs after a single oral dose of 2 x 10(7.0) plaque forming units (PFU). Neutralizing antibody titers against rabies reached > 0.5 IU/ml and 1:64-1:128 against pseudorabies by 5 weeks post-vaccination in all dogs, indicating that the pseudorabies virus vector infected dogs and replicated in vivo, and that the rabies virus glycoprotein had been expressed and an effective immune response elicited. Antibody titers were maintained for over 6 months. This suggests that pseudorabies virus could be an effective live vector for recombinant rabies oral vaccination.

Rabies neutralizing antibody response to different schedules of serum and vaccine inoculations in non-exposed persons

PubMed Central

Atanasiu, P.; Bahmanyar, M.; Baltazard, M.; Fox, J. P.; Habel, K.; Kaplan, M. M.; Kissling, R. E.; Komarov, A.; Koprowski, H.; Lépine, P.; Gallardo, F. Pérez; Schaeffer, M.

1957-01-01

Further studies were made on groups of adult humans, previously unexposed to rabies and with no history of rabies vaccination, who were inoculated with different schedules of phenolized inactivated vaccine given subcutaneously and high egg passage (HEP) Flury strain vaccine given intradermally, with and without inoculation of antirabies serum. Serum specimens of the inoculated individuals were studied for antibody up to the 60th day after the first inoculation of the vaccines and serum. Studies were also made on the effect of “booster” doses of HEP Flury strain vaccine given 6 months after preparatory inoculations. The results can be summarized as follows: 1. Fourteen daily inoculations of phenolized vaccine produced a superior antibody response to that obtained with 3 inoculations given 5 days apart. 2. Three intradermal inoculations of HEP Flury vaccine given 5 days apart gave a low level of antibody response, but these individuals responded efficiently by producing antibody to a “booster” dose of the same vaccine given 6 months later. 3. Administration of phenolized vaccine or of HEP Flury vaccine alone did not produce detectable antibody in most individuals until between the 10th and the 15th day after the first inoculation of the vaccine. 4. Passive antibody following inoculation of antirabies serum persisted in some individuals for as long as 42 days. Two inoculations of serum administered 5 days apart did not give levels of antibody higher than those obtained with one inoculation. 5. One inoculation of serum completely suppressed antibody response to 3 inoculations of Flury vaccine given intradermally 5 days apart, and also prevented the preparation of the individuals to respond to a later “booster” dose of this vaccine. 6. Three inoculation of phenolized vaccine given 5 days apart acted efficiently in producing antibody by the 60th day. However, the interfering action of one and two inoculations of serum was clearly defined in this schedule. 7

Rabies in an Arctic fox on the Svalbard archipelago, Norway, January 2011.

PubMed

Orpetveit, I; Ytrehus, B; Vikoren, T; Handeland, K; Mjos, A; Nissen, S; Blystad, H; Lund, A

2011-02-17

We report a case of rabies in an Arctic fox. In January 2011 a fox attacked dogs belonging to a meteorological station in the Svalbard archipelago, Norway. Rabies virus was detected in the fox's brain post-mortem. The dogs had been vaccinated against rabies and their antibody levels were protective. Post-exposure prophylaxis was administered to staff at the station. Rabies vaccination is recommended for inhabitants and visitors to the Arctic who may be in contact with wild animals.

One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus.

PubMed

Wirblich, Christoph; Coleman, Christopher M; Kurup, Drishya; Abraham, Tara S; Bernbaum, John G; Jahrling, Peter B; Hensley, Lisa E; Johnson, Reed F; Frieman, Matthew B; Schnell, Matthias J

2017-01-15

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic. Rabies virus-based vectors have been proven to be efficient dual vaccines against rabies and emergent infectious diseases such as Ebola virus. Here we show that inactivated rabies virus particles containing the MERS-CoV S1 protein induce potent immune

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

PubMed

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

2017-01-01

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

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

PubMed

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.

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

DTIC Science & Technology

2012-08-13

vaccination program (Meslin 2007). Mixed populations of free-ranging dogs, cats, foxes, jackals , or other wildlife species makes U.S. FOBs in JOAs a...prime venue for oral rabies vaccination. Species that are difficult to trap, such as jackals , can be specifically targeted for oral rabies...vaccination. Anecdotal reports from various vector control and preventive medicine groups in Iraq indicate that packs of jackals exist in particular

Transmission of rabies by bats in Latin America

PubMed Central

Carneiro, Victor

1954-01-01

This article reviews the literature dealing with the role of haematophagous bats in the spread of rabies among cattle in Latin America since 1911, when the association between Desmodontidae and rabies epizootics in Brazil was first suspected. Efforts to control the problem by destruction of the vectors and vaccination of bovines are described, and the suitability of chick-embryo vaccine is considered. PMID:13182599

Comparing Methods of Assessing Dog Rabies Vaccination Coverage in Rural and Urban Communities in Tanzania

PubMed Central

Sambo, Maganga; Johnson, Paul C. D.; Hotopp, Karen; Changalucha, Joel; Cleaveland, Sarah; Kazwala, Rudovick; Lembo, Tiziana; Lugelo, Ahmed; Lushasi, Kennedy; Maziku, Mathew; Mbunda, Eberhard; Mtema, Zacharia; Sikana, Lwitiko; Townsend, Sunny E.; Hampson, Katie

2017-01-01

Rabies can be eliminated by achieving comprehensive coverage of 70% of domestic dogs during annual mass vaccination campaigns. Estimates of vaccination coverage are, therefore, required to evaluate and manage mass dog vaccination programs; however, there is no specific guidance for the most accurate and efficient methods for estimating coverage in different settings. Here, we compare post-vaccination transects, school-based surveys, and household surveys across 28 districts in southeast Tanzania and Pemba island covering rural, urban, coastal and inland settings, and a range of different livelihoods and religious backgrounds. These approaches were explored in detail in a single district in northwest Tanzania (Serengeti), where their performance was compared with a complete dog population census that also recorded dog vaccination status. Post-vaccination transects involved counting marked (vaccinated) and unmarked (unvaccinated) dogs immediately after campaigns in 2,155 villages (24,721 dogs counted). School-based surveys were administered to 8,587 primary school pupils each representing a unique household, in 119 randomly selected schools approximately 2 months after campaigns. Household surveys were conducted in 160 randomly selected villages (4,488 households) in July/August 2011. Costs to implement these coverage assessments were $12.01, $66.12, and $155.70 per village for post-vaccination transects, school-based, and household surveys, respectively. Simulations were performed to assess the effect of sampling on the precision of coverage estimation. The sampling effort required to obtain reasonably precise estimates of coverage from household surveys is generally very high and probably prohibitively expensive for routine monitoring across large areas, particularly in communities with high human to dog ratios. School-based surveys partially overcame sampling constraints, however, were also costly to obtain reasonably precise estimates of coverage. Post-vaccination

Bovine rabies in Turkey: patterns of infection and implications for costs and control.

PubMed

Vos, A; Un, H; Hampson, K; De Balogh, K; Aylan, O; Freuling, C M; Müller, T; Fooks, A R; Johnson, N

2014-09-01

The incidence of rabies in livestock is an important factor for estimating the economic impact of the disease, but obtaining reliable data is hindered by inadequate surveillance. In order to understand the contribution of livestock rabies to the overall burden of disease, the rabies incidence in cattle was investigated in detail for Turkey between 2008 and 2011. Data were compiled on cattle numbers, samples submitted for rabies diagnosis, vaccinated animals and positive rabies cases in animals for seven regions in Turkey. Rabies incidence in cattle fluctuated annually and differed between regions from 0·10 to 3·87 cases/100 000 animals. The positive influence of compensation schemes was observed. Livestock losses were conservatively estimated at around $250 000 international dollars per annum, although in areas where compensation schemes are not operating this could be an underestimate of the economic burden. Vaccination of cattle remains an option for disease prevention, although oral rabies vaccination through aerially distributed baits should be implemented to prevent the further spread of fox-mediated rabies, which could result in much greater economic costs.

National surveillance for human and pet contact with oral rabies vaccine baits, 2001-2009.

PubMed

Roess, Amira A; Rea, Nancy; Lederman, Edith; Dato, Virginia; Chipman, Richard; Slate, Dennis; Reynolds, Mary G; Damon, Inger K; Rupprecht, Charles E

2012-01-15

To determine the rate and absolute number of human and pet exposures to oral rabies vaccine (ORV) bait containing liquid vaccinia rabies glycoprotein recombinant vaccine and to evaluate factors that might affect human contact with bait to modify the program and reduce human exposure to the vaccine. Retrospective analysis of surveillance data (2001 to 2009). Reports on human and pet contact with ORV baits in states with ORV surveillance programs. Data were collected from passive, multistate ORV surveillance systems in Alabama, Arizona, Florida, Georgia, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Texas, Vermont, Virginia, and West Virginia. Data collected included the nature of human or pet contact with bait and vaccine, the caller's knowledge of the ORV bait program, local human population density, and other relevant demographic data. All 18 states participated in the surveillance program for at least 1 year, for a combined 68 years of observation. One thousand four hundred thirty-six calls were reported, representing 3,076 found baits (6.89/100,000 baits dropped); 296 (20%) calls were related to human contact with ruptured bait, and 550 (38%) involved pet contact with the bait. Six adverse events in humans were reported, one of which required hospitalization. Fifty-nine adverse events in pets were noted, all of which were nonserious. Findings from surveillance activities have been used to improve baiting strategies and minimize human and pet contact with ORV baits. Overall, human and pet contact with ORV baits was infrequent. Surveillance has led to early identification of persons exposed to ORV and rapid intervention.

Animal-associated exposure to rabies virus among travelers, 1997-2012.

PubMed

Gautret, Philippe; Harvey, Kira; Pandey, Prativa; Lim, Poh Lian; Leder, Karin; Piyaphanee, Watcharapong; Shaw, Marc; McDonald, Susan C; Schwartz, Eli; Esposito, Douglas H; Parola, Philippe

2015-04-01

Among travelers, rabies cases are rare, but animal bites are relatively common. To determine which travelers are at highest risk for rabies, we studied 2,697 travelers receiving care for animal-related exposures and requiring rabies postexposure prophylaxis at GeoSentinel clinics during 1997-2012. No specific demographic characteristics differentiated these travelers from other travelers seeking medical care, making it challenging to identify travelers who might benefit from reinforced pretravel rabies prevention counseling. Median travel duration was short for these travelers: 15 days for those seeking care after completion of travel and 20 days for those seeking care during travel. This finding contradicts the view that preexposure rabies vaccine recommendations should be partly based on longer travel durations. Over half of exposures occurred in Thailand, Indonesia, Nepal, China, and India. International travelers to rabies-endemic regions, particularly Asia, should be informed about potential rabies exposure and benefits of pretravel vaccination, regardless of demographics or length of stay.

A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.

PubMed

Yendo, Anna Carolina A; de Costa, Fernanda; Cibulski, Samuel P; Teixeira, Thais F; Colling, Luana C; Mastrogiovanni, Mauricio; Soulé, Silvia; Roehe, Paulo M; Gosmann, Grace; Ferreira, Fernando A; Fett-Neto, Arthur G

2016-04-29

Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P ≤ 0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

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

PubMed Central

da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping

2017-01-01

ABSTRACT 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

[Research of Odo Bujwid (1857-1942) concerning the vaccine against rabies-historical characterisation].

PubMed

Wasiewicz, Barbara

2016-01-01

The present article refers to the historical characterisation of Odo Bujwid's (1857-1942) research concerning the vaccine against rabies. The introduction refers to the treatment methods applied before Ludwik Pasteur's discovery. The following part refers to Odo Bujwid's own research including diagnostics, characterisation of the symptoms of disease, modification of the original Ludwik Pasteur's method and statistical information. The resume emphasizes that Odo Bujwid's scientific research was the introduction and generalisation the worldwide microbiology knowledge at the polish lands.

[A historical view of rabies in Chile].

PubMed

Laval R, Enrique; Lepe I, Paulina

2008-04-01

In this review international and national historical features of rabies are presented remarking the start of preventive immunization in Chile, at year 1896, with the creation of the first service for rabies vaccination and la descentralización of preventive treatment from year 1929. Figures of human cases produced by this zoonosis between 1950 and 1986 are described, señalándose changes that occurred in local epidemiology of rabies since 1990, with an endemic pattern in bats and almost disappearance of canine rabies.

An important date in rabies history.

PubMed

Dodet, Betty

2007-12-17

Rabies is estimated to cause 31,000 human deaths in Asia annually. Several recent events, including World Rabies Day have brought this neglected disease to the attention of the scientific community, governmental authorities, the media and the public. It is hoped that this will result in an increased collaboration between veterinary and human health authorities, and an involvement at all levels necessary for the control and elimination of rabies in dogs, the main reservoir and vector of rabies in Asia. Dog rabies elimination is considered as the most cost-effective solution to prevent rabies deaths in humans. Asian countries such as India and the Philippines have recently adopted the objective of eliminating rabies by 2020. To support World Rabies Day, the Asian Rabies Expert Bureau (AREB) had its 4th annual meeting from 5 to 7 September 2007, with the objective of debating strategies for lowering the human rabies toll. Human rabies deaths can already be prevented by improving the compliance to WHO post-exposure prophylaxis recommendations. In addition, in regions with a high incidence of canine rabies and where rabies control in dogs is not yet achieved or not effective, systematic pre-exposure vaccination of children who are the main victims of rabies, may prevent their premature deaths.

Evaluation of ELISA for detection of rabies antibodies in domestic carnivores.

PubMed

Wasniewski, Marine; Cliquet, Florence

2012-01-01

Serological tests of pets have increased as many rabies-free countries have amended their quarantine measures and adopted a scheme requiring rabies vaccination followed by a serological test. A European directive requires the measurement of neutralising antibodies as proof of protection to allow the free movement of pets within the European Union and between third countries non listed in the list C of regulation 998/2003 and European countries. At present, the recommended neutralisation tests (FAVN test or RFFIT) are time-consuming, expensive and require highly trained technicians as well as special laboratory facilities. The rabies ELISA designed by BioPro was developed initially for use for field samples from foxes to check the efficacy of oral vaccination campaigns in Europe. In this study, the specificity, sensitivity and reliability of this commercial rabies ELISA was evaluated for testing sera from dogs and cats involved in international trade. The specificity evaluated in 315 unvaccinated animals was 100%. Concordance of 86.2% was obtained when comparing BioPro ELISA to the gold standard FAVN test in 701 samples from vaccinated dogs and cats. The rabies ELISA developed recently can be considered a valuable method for the assessment of rabies antibodies in vaccinated domestic carnivores in combination with neutralisation tests. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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.

Towards Canine Rabies Elimination in Cebu, Philippines: Assessment of Health Economic Data.

PubMed

Miranda, L M; Miranda, M E; Hatch, B; Deray, R; Shwiff, S; Roces, M C; Rupprecht, C E

2017-02-01

Rabies is endemic in the Philippines. In 2010, with support from the Bill and Melinda Gates Foundation, a canine rabies elimination project was initiated in the Philippine Archipelago of Visayan. We conducted an analysis of dog vaccination and human PEP costs for dog bite patients in a highly urbanized area and a low-income rural municipality in Cebu Province, Philippines, from 2010 to 2012. Our findings indicated that eliminating rabies in dogs through mass vaccination is more cost-effective than treating rabies exposures in humans. The average costs (in USD) per human life saved through PEP were $1620.28 in Cebu City and $1498 in Carmen. Costs per dog vaccinated ranged from $1.18 to $5.79 in Cebu City and $2.15 to $3.38 in Carmen. Mass dog vaccination campaigns conducted in each village were more cost-effective than fixed-site campaigns. The costs of dog vaccination can be reduced further through bulk vaccine purchase by the national government or large donor agency, for example the BMGF. As communities achieve canine rabies elimination, more judicious use of PEP will result in significant public savings. The study affirms the willingness of local governments to invest and reassure donors of their cooperation and resource contribution to sustain disease elimination efforts. © 2015 Blackwell Verlag GmbH.

Current and future trends in the prevention, treatment and control of rabies.

PubMed

Rupprecht, Charles E; Willoughby, Rodney; Slate, Dennis

2006-12-01

Rabies remains a global zoonosis of major public health, agricultural and economic significance. Dogs are the major animal reservoirs in developing regions, wildlife maintain cycles of infection even in developed countries and new viral etiological agents continue to emerge. Nearly all human rabies cases are related directly to animal bite and thus, primary disease prevention requires minimization of suspected exposures. Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. Pre-exposure vaccination should occur in selected population groups at risk of occupational exposure. Historically, survival from fatal rabies by at least five human patients, vaccinated prior to the onset of clinical signs, signaled initial optimism as to the theoretical utility of medical intervention. Recently, the heroic recovery of an unvaccinated teenager from clinical rabies offers hope of future specific therapy. Canine rabies elimination is the key towards ultimate reduction of the disease burden, as first illustrated in developed countries. Implementation of oral vaccination in free-ranging carnivore hosts demonstrates the feasibility of disease abatement in particular wildlife populations, such as demonstrated in Europe and North America, with an enhanced need for application to developing countries in the Americas, Africa and Eurasia.

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

PubMed

Kurosawa, Aiko; Tojinbara, Kageaki; Kadowaki, Hazumu; Hampson, Katie; Yamada, Akio; Makita, Kohei

2017-03-01

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 to

Strategic model of national rabies control in Korea.

PubMed

Cheong, Yeotaek; Kim, Bongjun; Lee, Ki Joong; Park, Donghwa; Kim, Sooyeon; Kim, Hyeoncheol; Park, Eunyeon; Lee, Hyeongchan; Bae, Chaewun; Oh, Changin; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Choi, In-Soo; Lee, Joong-Bok

2014-01-01

Rabies is an important zoonosis in the public and veterinary healthy arenas. This article provides information on the situation of current rabies outbreak, analyzes the current national rabies control system, reviews the weaknesses of the national rabies control strategy, and identifies an appropriate solution to manage the current situation. Current rabies outbreak was shown to be present from rural areas to urban regions. Moreover, the situation worldwide demonstrates that each nation struggles to prevent or control rabies. Proper application and execution of the rabies control program require the overcoming of existing weaknesses. Bait vaccines and other complex programs are suggested to prevent rabies transmission or infection. Acceleration of the rabies control strategy also requires supplementation of current policy and of public information. In addition, these prevention strategies should be executed over a mid- to long-term period to control rabies.

Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16–December 28, 2013

PubMed Central

Huang, Angela Song-En; Chen, Wan-Chin; Huang, Wan-Ting; Huang, Shih-Tse; Lo, Yi-Chun; Wei, Sung-Hsi; Kuo, Hung-Wei; Chan, Pei-Chun; Hung, Min-Nan; Liu, Yu-Lun; Mu, Jung-Jung; Yang, Jyh-Yuan; Liu, Ding-Ping; Chou, Jih-Haw; Chuang, Jen-Hsiang; Chang, Feng-Yee

2015-01-01

Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010–July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial

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

PubMed

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.

Animal-Associated Exposure to Rabies Virus among Travelers, 1997–2012

PubMed Central

Harvey, Kira; Pandey, Prativa; Lim, Poh Lian; Leder, Karin; Piyaphanee, Watcharapong; Shaw, Marc; McDonald, Susan C.; Schwartz, Eli; Esposito, Douglas H.; Parola, Philippe

2015-01-01

Among travelers, rabies cases are rare, but animal bites are relatively common. To determine which travelers are at highest risk for rabies, we studied 2,697 travelers receiving care for animal-related exposures and requiring rabies postexposure prophylaxis at GeoSentinel clinics during 1997–2012. No specific demographic characteristics differentiated these travelers from other travelers seeking medical care, making it challenging to identify travelers who might benefit from reinforced pretravel rabies prevention counseling. Median travel duration was short for these travelers: 15 days for those seeking care after completion of travel and 20 days for those seeking care during travel. This finding contradicts the view that preexposure rabies vaccine recommendations should be partly based on longer travel durations. Over half of exposures occurred in Thailand, Indonesia, Nepal, China, and India. International travelers to rabies-endemic regions, particularly Asia, should be informed about potential rabies exposure and benefits of pretravel vaccination, regardless of demographics or length of stay. PMID:25811076

Intention of dog owners to participate in rabies control measures in Flores Island, Indonesia.

PubMed

Wera, Ewaldus; Mourits, Monique C M; Hogeveen, Henk

2016-04-01

The success of a rabies control strategy depends on the commitment and collaboration of dog owners. In this study the theory of planned behaviour (TPB) was used to identify the factors, which are associated with the intention of dog owners to participate in rabies control measures in the Manggarai and Sikka regencies of Flores Island, Indonesia. Questionnaires were administered to 450 dog owners from 44 randomly selected villages in the two regencies. Ninety-six percent of the dog owners intended to participate in a free-of-charge vaccination campaign. The intention decreased to 24% when dog owners were asked to pay a vaccination fee equal to the market price of the vaccine (Rp 18.000 per dose=US$2). Approximately 81% of the dog owners intended to keep their dogs inside their house or to leash them day and night during a period of at least three months in case of an incidence of rabies in the dog population within their village. Only 40% intended to cull their dogs in case of a rabies incident within their village. Using multivariable logistic regression analysis, the attitude item 'vaccinating dogs reduces rabies cases in humans', and the perceived behavioural control items 'availability of time' and 'ability to confine dogs' were shown to be significantly associated with the intention to participate in a free-of-charge vaccination campaign. The attitude item 'culling dogs reduces rabies cases in humans' was significantly associated with the intention to participate in a culling measure. The attitude item 'leashing of dogs reduces human rabies cases' and perceived behavioural controls 'availability of time' and 'money to buy a leash' were associated with the intention to leash dogs during a rabies outbreak. As the attitude variables were often significantly associated with intention to participate in a rabies control measure, an educational rabies campaign focusing on the benefit of rabies control measures is expected to increase the intention of dog owners to

Human rabies: still a neglected preventable disease in Nigeria.

PubMed

Eke, C B; Omotowo, I B; Ukoha, O M; Ibe, B C

2015-01-01

Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies infections among patients presenting to University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. This was a 10-year (January 1, 2004 to December 31, 2013) observational retrospective study. Case definition of rabies was based on ICD 10 criteria, while relevant clinical data were retrieved from individual folders of registered victims using a semi-structured questionnaire. Data were analyzed using SPSS version 17.0 while the level of statistical significance was set at P < 0.05. A total of 149 cases of dog bites were reported during the period under review, of which 6 (4.0%) had confirmed rabies. Ninety-six (64.4%) cases presented more than 24 h after the bites. Majority of the offending dogs were stray dogs 86 (57.7%), which attacked their victims unprovoked, in 54.6% of cases. Furthermore, most of the bites were from dogs with unknown history of rabies vaccination 72 (52.3%), while the case fatality rate was 100%. All the cases of rabies reported were as a result of bites from stray dogs with unknown history of rabies vaccinations, and the outcome was 100% fatality in all cases. Efforts should be made to create and strengthen awareness campaigns on control of rabies infections through responsible dog ownership including their regular vaccinations as well as provision and use of prompt postexposure prophylaxis in human cases of dog bites at all levels of health care.

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

PubMed

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

2006-03-01

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

Japanese anti- versus pro-influenza vaccination websites: a text-mining analysis.

PubMed

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masafumi; Kato, Mio; Kiuchi, Takahiro

2018-03-23

Anti-vaccination sentiment exists worldwide and Japan is no exception. Health professionals publish pro-influenza vaccination messages online to encourage proactive seeking of influenza vaccination. However, influenza vaccine coverage among the Japanese population is less than optimal. The contents of pro- and anti-influenza vaccination websites may contribute to readers' acceptance of one or the other position. We aimed to use a text-mining method to examine frequently appearing content on websites for and against influenza vaccination. We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan). Targeted websites were classified as 'pro', 'anti' or 'neutral' depending on their claims, with author(s) classified as 'health professionals', 'mass media' or 'laypersons'. Text-mining analysis was conducted, and statistical analysis was performed using a chi-squared test. Of the 334 websites analyzed, 13 content topics were identified. The three most frequently appearing content topics on pro-vaccination websites were vaccination effect for preventing serious cases of influenza, side effects of vaccination, and efficacy rate of vaccination. The three most frequent topics on anti-vaccination websites were ineffectiveness of influenza vaccination, toxicity of vaccination, and side effects of vaccination. The main disseminators of each topic, by author classification, were also revealed. We discuss possible tactics of online influenza vaccination promotion to counter anti-vaccination websites.

[Rabies contingency plan in Japan].

PubMed

Inoue, Satoshi

2005-12-01

In Japan, rabies has been culled out since 1957 thanks to the strong implementation of measures against rabies, such as vaccination of dogs, quarantine and control of wild dogs under the 'Rabies Prevention Law' enacted in 1950. Nevertheless one cannot deny the possibility of introduction of rabies into Japan in view of the recent increase in the international movements of people and animals. Should an outbreak of rabies be suspected now in Japan, the society would probably overreact due to a decreased awareness of risks and a lack of correct knowledge about this disease. Officials of the government and the municipalities, veterinarians and doctors should exchange correct information on rabies and on prevention control and raise their awareness, while providing also information to the public on a timely basis. Besides it is needless to say that it is important to set up a crisis management system allowing a quick and adequate response in case of an outbreak of rabies and to continue to implement appropriate prevention measures in normal times.

Human rabies in Tianjin, China.

PubMed

Montgomery, J P; Zhang, Y; Wells, E V; Liu, Y; Clayton, J L; Wang, X; Boulton, M L

2012-12-01

Human rabies has recently re-emerged as a significant public health threat in Tianjin, China. Using surveillance data compiled by the Tianjin Centers for Disease Control and Prevention, we describe 60 cases of human rabies reported from 2005 to 2011 in the municipality of Tianjin, China. All 60 cases of human rabies resulted in death. Cases were primarily male (80%), middle aged (mean 40.6 years), and exposed to rabies in a rural setting (82%). Most exposures were associated with dog bites (93%) and no animal had a history of rabies vaccination; no cases were laboratory confirmed. Fifteen percent of patients sought medical attention for their wound, and none received a complete regimen of WHO-recommended post-exposure prophylaxis (PEP). These findings suggest the need for China's public health authority to improve animal rabies surveillance and control strategies through laboratory case confirmation, more rapid response to potential exposures with provision of appropriate PEP, and education to the public and to health care providers on identifying and reducing rabies risk.

Canine Rabies: A Looming Threat to Public Health

PubMed Central

Burgos-Cáceres, Sigfrido

2011-01-01

Simple Summary This review is guided by three questions: What is canine rabies? Why is it a looming threat to public health? Why should we care about canine rabies being a public health threat? It seeks to answer these questions and notes that canine rabies is viral zoonosis with dogs being the major vectors. The disease is a looming threat to public health because rabid dogs bite humans, resulting in thousands of deaths every year. We should care about this evolving situation because, in general, rabies is a neglected disease for which there are vaccines, preventive measures, post-exposure prophylaxis, and control protocols. Abstract 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. PMID:26486619

Characterization of rabies pDNA nanoparticulate vaccine in poloxamer 407 gel.

PubMed

Bansal, Amit; Wu, Xianfu; Olson, Victoria; D'Souza, Martin J

2018-07-10

Plasmid DNA (pDNA) vaccines have the potential for protection against a wide range of diseases including rabies but are rapid in degradation and poor in uptake by antigen-presenting cells. To overcome the limitations, we fabricated a pDNA nanoparticulate vaccine. The negatively charged pDNA was adsorbed onto the surface of cationic PLGA (poly (d, l-lactide-co-glycolide))-chitosan nanoparticles and were used as a delivery vehicle. To create a hydrogel for sustainable vaccine release, we dispersed the pDNA nanoparticles in poloxamer 407 gel which is liquid at 4 °C and turns into soft gels at 37 °C, providing ease of administration and preventing burst release of pDNA. Complete immobilization of pDNA to cationic nanoparticles was achieved at a pDNA to nanoparticles ratio (P/N) of 1/50. Cellular uptake of nanoparticles was both time and concentration dependent and followed a saturation kinetics with V max of 11.389 µg/mL h and K m of 139.48 µg/mL. The in vitro release studies showed the nanoparticulate vaccine has a sustained release for up to 24 days. In summary, pDNA PLGA-chitosan nanoparticles were non-cytotoxic, their buffering capacity and cell uptake were enhanced, and sustained the release of pDNA. We expect our pDNA vaccine's potency will be greatly improved in the animal studies. Copyright © 2018 Elsevier B.V. All rights reserved.

[Human contamination by baits for vaccinating foxes against rabies in France].

PubMed

Masson, E; Aubert, M F; Rotivel, Y

1997-09-01

During 1992 and 1993, 4.4 million of baits have been distributed in France over 121,381 km2 for vaccinating foxes against rabies. Phone calls and visits addressed to the local veterinary authorities and to the centres for human antirabies treatment have been recorded according to an appropriate questionnaire. 70 persons declared to have found and sometimes to have touch a bait, 38 of them received a antirabies treatment. Only 9 children (less than 10 year old) handled a bait. Activities that led to find a bait have been: walking in the countryside or hunting (50% of cases), gardening or playing in the garden or near home (35%) and farming (13%). Often dogs were the first to discover the baits and led to a contact of humans with the vaccine in 54% of cases. No casualty occurred. The frequency of these reports decrease by 80% during the period which is considered to be the result of a better information and awareness of the public.

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

PubMed

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

2006-01-01

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

[Vaccination for international travelers].

PubMed

Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

2016-05-01

Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Sylvatic rabies epidemic in Italy: implementation of a data management system to assess the level of application of preventive dog vaccination.

PubMed

Bortolotti, Laura; Cobianchi, Mario; Breda, Tatiana; Favero, Laura; Ruocco, Luigi; Marangon, Stefano

2013-10-01

After 20 years of absence, rabies re-emerged in wild animals in north-eastern Italy in October 2008. Besides measures undertaken to fight the spread of infection in wildlife, vaccination against rabies was made compulsory for dogs living in the risk area. In the last 15 years, the veterinary authorities have focused on implementing computerized data collection systems in animal health, to serve as working tools for epidemiological surveillance activities and emergencies management. The prerequisite for implementing any data collection system is knowledge of the animal population. This also applies to the Canine Registry Data Bank, in which data on dogs and their movements, together with personal data on each owner and keeper, have been stored since 2003. The management information system has been updated and specific functions have been integrated in order to support the activity of both the veterinary services and the veterinary practitioners involved in the dog vaccination program. Vaccination became voluntary in February 2013. This paper describes implementation of the software and organization of data gathering, highlighting the benefits of computerized data compared to previously used paper-based data collection systems. The new functions, designed to centralize collection of uniform, updated vaccination data, have led to more efficient organization and better control of the vaccination plan. Automated information processing allowed vaccination operations to be supervised, incurred costs to be calculated, and vaccination coverage of the dog population to be monitored during the 3 years of compulsory vaccination.

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

PubMed Central

Kurosawa, Aiko; Tojinbara, Kageaki; Kadowaki, Hazumu; Hampson, Katie; Yamada, Akio

2017-01-01

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 to

[Rabies in France: an update].

PubMed

Jaussaud, R; Strady, C; Liénard, M; Strady, A

2000-08-01

In 1996, rabies was responsible for more than 35,000 deaths worldwide. Three cases of human rabies that had been contracted abroad were diagnosed in France during the same year. Cases notified in 1997 followed exposure outside the country. Fox, bat, and dog rabies are reviewed on the basis of the latest epidemiological data obtained in France. Two cases of fox rabies diagnosed in 1998 occurred at the border between France and Germany, thus preventing five French departments bordering Germany from being officially declared rabies-free in 1999. The campaigns for oral immunization of foxes that are led since 1986 are responsible for the decrease in rabies incidence. Though not well known, bat rabies is a reality in France, involving either European virus strains (five cases all over the country) or African virus strains that are carried along by imported tropical bats. Dogs rabies is also today an imported disease. The decrease in risk for rabies has resulted from the conjunction of multiple efforts: extensive programs aimed at oral vaccination of foxes in France and its neighboring countries, efficient epidemiological survey, sanitary controls at borders, ban on importing tropical bats. Furthermore, recommendations for preventive pre-exposure immunization have recently been changed, leading to modifications of the French licensing form.

A rapid immunochromatographic test strip for detecting rabies virus antibody.

PubMed

Wang, Hualei; Feng, Na; Yang, Songtao; Wang, Chengyu; Wang, Tiecheng; Gao, Yuwei; Su, Jianqing; Zheng, Xuexing; Hou, Xiaoqiang; Huang, Hainan; Yang, Ruimei; Zou, Xiaohuan; Huang, Geng; Xia, Xianzhu

2010-12-01

An immunochromatographic test strip (ICTS) for detecting antibodies to rabies virus was developed, using colloidal gold particles labeled with rabies virus glycoprotein as the tracer. The assay was evaluated using sera from dogs immunized with various commercial rabies vaccines, or from dogs in the clinics and sera from dogs immunized with vaccines against pathogens other than rabies virus, and negative sera from a wide variety of animal sources, including dogs, mice, and cats which had never been vaccinated. The ICTS was found to be highly specific for antibodies against rabies virus, with a detection limit of 0.5IU/ml as measured by the fluorescent antibody virus neutralization (FAVN) test. Compared with the FAVN test, the specificity and sensitivity of ICTS were 98.2% and 90.4%, respectively. There was an excellent agreement between results obtained by the ICTS and FAVN tests (kappa=0.888). Strips stored at 4°C in a plastic bag with a desiccant retained their specificity and sensitivity for at least 15 months, and strips stored at ambient temperature remained stable for 12 months. The immunochromatographic test strip may therefore be useful for clinical laboratories lacking specialized equipment and for diagnosis in the field for rapid detection of rabies virus-specific antibodies. Copyright © 2010 Elsevier B.V. All rights reserved.

Animal and human rabies in Mongolia.

PubMed

Odontsetseg, N; Uuganbayar, D; Tserendorj, Sh; Adiyasuren, Z

2009-12-01

The prevalence of animal rabies differs in each area of Mongolia. Wolves (Canis lupus Linnaeus, 1758), foxes ( Vulpes vulpes Linnaeus, 1758), corsac foxes (Vulpes corsac Linnaeus, 1768) and manuls (Felis manul Pallas, 1778) are considered to be the infective wild animals in natural foci. Amongst livestock, cattle have had the most rabies cases, followed by camels, sheep, goats and horses. The peak prevalence of animal rabies occurred in the 1970s. Dundgovi Province had the highest incidence during that period. The number of rabies cases in animals decreased during the 1980s. This may have been due to a decrease in the number of wild reservoir animals and the improvement of appropriate veterinary measures. In recent years, animal rabies has prevailed in the Khangai and western provinces. The infection source of most human rabies cases is the dog. In order to minimise the incidence of human rabies, canine vaccination programmes need to be improved. This paper describes the epizootiology and epidemiology of animal and human rabies in Mongolia. It describes rabies control programmes, including diagnosis, conducted in Mongolia in an effort to control the disease.

Development of a qualitative indirect ELISA for the measurement of rabies virus-specific antibodies from vaccinated dogs and cats.

PubMed

Cliquet, F; McElhinney, L M; Servat, A; Boucher, J M; Lowings, J P; Goddard, T; Mansfield, K L; Fooks, A R

2004-04-01

A protocol suitable for the detection of rabies virus-specific antibodies in serum samples from companion animals using an enzyme linked immunosorbent assay (ELISA) is described. This method has been used successfully for the qualitative assessment of rabies virus-specific antibodies in serum samples from a cohort of vaccinated dogs and cats. In two initial field studies, a variable population of field samples from the Veterinary Laboratories Agency (VLA), United Kingdom were tested. In the first study (n = 1000), the number of false-positive and false-negative results was 11 samples (1.1%) and 67 samples (6.7%), respectively. In the second study (n = 920), the number of false-positive and false-negative results was 7 samples (0.8%) and 52 samples (5.7%). In a third study, undertaken at l'Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Nancy, France (n = 440), 1 false-positive sample (0.23%) and 91 (20.7%) false-negative samples were identified. Data generated using this prototype ELISA indicate a strong correlation for specificity when compared to the gold standard fluorescent antibody virus neutralisation (FAVN) test. Although the ELISA has a lower sensitivity than the FAVN test, it is a useful tool for rapidly screening serum samples from vaccinated companion animals. Using a cut-off value of 0.6 EU/ml, the sensitivity (R = % from VLA and 79% from AFSSA) and specificity (R = 97.3%) indices between the ELISA compared favourably with data generated using the FAVN test. The major advantages of the ELISA test are that it is a qualitative tool that can be completed in four hours, does not require the use of live virus and can be performed without the need for specialised laboratory containment. This contrasts with 4 days using conventional rabies antibody virus neutralisation assays. Using the current format, the ELISA assay described would be a valuable screening tool for the detection of rabies antibodies from vaccinated domestic animals in

The role of risk communication planning in the release of the oral rabies vaccine in New Jersey: An evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pflugh, K.K.

1995-12-01

Communicating health risk information is a complicated task. Citizen reaction to such information is difficult to predict, which makes it hard to plan an appropriate response. Research indicates that the way citizens respond to risk information often depends on whether the risk is familiar or unfamiliar, whether it is seen as imposed on them, whether it is man made or natural, or whether they have control over the risk. Potentially controversial cases that deal with delivering risk information have a special need for a well planned communication effort. Natural resource issues with an impact on public health are no exception.more » In New Jersey, a proposal to release an experimental bioengineered oral rabies vaccine for raccoons to test the effectiveness of the vaccine in halting the spread of rabies into an as yet unaffected area met with widespread public support and approval due in large part to the use of a unique risk communication planning process. This paper will describe the risk communication planning process used to gain public support and approval for release of oral rabies raccoon vaccine while focusing on the evaluation component of the process. The seven step process includes setting goals, profiling the issue or information gathering, audience identification and assessment, message development, method selection, implementation of the strategy and evaluation and follow-up. The goal of the evaluation component was to determine the effectiveness of the public information campaign on citizen`s knowledge of the field trial nearly three years after the initial announcement. In addition, it sought to learn citizen interest in maintaining the rabies free barrier that was created by the field trial using funds from local taxes. This evaluation includes the results of a mailed survey to 280 citizens, local officials and professional organizations. Finally, this paper will discuss the implications for future outreach efforts dealing complicated technical

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

PubMed

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.

Phylogeographic analysis of rabies viruses in the Philippines.

PubMed

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

2014-04-01

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

Arctic rabies--a review.

PubMed

Mørk, Torill; Prestrud, Pål

2004-01-01

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.

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 bymore » 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.« less

Influenza-related mortality trends in Japanese and American seniors: evidence for the indirect mortality benefits of vaccinating schoolchildren.

PubMed

Charu, Vivek; Viboud, Cécile; Simonsen, Lone; Sturm-Ramirez, Katharine; Shinjoh, Masayoshi; Chowell, Gerardo; Miller, Mark; Sugaya, Norio

2011-01-01

The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US. We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978-1994) and after the program was discontinued (1995-2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control. We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17-51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400-1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population. The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors.

Population Dynamics of Owned, Free-Roaming Dogs: Implications for Rabies Control

PubMed Central

Conan, Anne; Akerele, Oluyemisi; Simpson, Greg; Reininghaus, Bjorn; van Rooyen, Jacques; Knobel, Darryn

2015-01-01

Background Rabies is a serious yet neglected public health threat in resource-limited communities in Africa, where the virus is maintained in populations of owned, free-roaming domestic dogs. Rabies elimination can be achieved through the mass vaccination of dogs, but maintaining the critical threshold of vaccination coverage for herd immunity in these populations is hampered by their rapid turnover. Knowledge of the population dynamics of free-roaming dog populations can inform effective planning and implementation of mass dog vaccination campaigns to control rabies. Methodology/Principal Findings We implemented a health and demographic surveillance system in dogs that monitored the entire owned dog population within a defined geographic area in a community in Mpumalanga Province, South Africa. We quantified demographic rates over a 24-month period, from 1st January 2012 through 1st January 2014, and assessed their implications for rabies control by simulating the decline in vaccination coverage over time. During this period, the population declined by 10%. Annual population growth rates were +18.6% in 2012 and -24.5% in 2013. Crude annual birth rates (per 1,000 dog-years of observation) were 451 in 2012 and 313 in 2013. Crude annual death rates were 406 in 2012 and 568 in 2013. Females suffered a significantly higher mortality rate in 2013 than males (mortality rate ratio [MRR] = 1.54, 95% CI = 1.28–1.85). In the age class 0–3 months, the mortality rate of dogs vaccinated against rabies was significantly lower than that of unvaccinated dogs (2012: MRR = 0.11, 95% CI = 0.05–0.21; 2013: MRR = 0.31, 95% CI = 0.11–0.69). The results of the simulation showed that achieving a 70% vaccination coverage during annual campaigns would maintain coverage above the critical threshold for at least 12 months. Conclusions and Significance Our findings provide an evidence base for the World Health Organization’s empirically-derived target of 70% vaccination coverage

Acute demyelinating encephalomyelitis due to neural antirabies vaccine.

PubMed

Shah, Ira

2008-01-01

Rabies is highly endemic in India and seen with dog bites from rabid dogs. In India, nervous tissue vaccine is commonly used as it is inexpensive and freely available despite frequent neurological complications. Neurological complications seen with traditional vaccine are morbid and the medical community should switch over to the cell culture rabies vaccine in spite of the expense to prevent these complications with rabies vaccine.

Epidemiologic trends of rabies in domestic animals in southern Thailand, 1994-2008.

PubMed

Thiptara, Anyarat; Atwill, Edward R; Kongkaew, Wandee; Chomel, Bruno B

2011-07-01

Rabies and associated risk factors in dogs, cats and cattle (n = 3,454) in southern Thailand during 1994-2008 were evaluated by using a mixed-effect logistic regression model. Overall prevalence was 48%. In dogs, odds of being rabid were 1.7 times higher in unvaccinated dogs than in vaccinated dogs and two times higher in dogs with bite history than in dogs with no known bite history. Similarly, aggressive dogs were more likely to be rabid than non-aggressive dogs. In cattle, aggression, pharyngeal paralysis, hyperactivity, and depression were clinical signs associated with being rabid. Annual fluctuations of the species-specific prevalence of rabies is suggestive of a positive correlation between canine and either feline (r = 0.60, P = 0.05) or bovine rabies (r = 0.78, P = 0.004). Insufficient vaccination coverage led to maintenance of rabies, which could be easily controlled by increased vaccine coverage and public education.

Surveillance guidelines for disease elimination: A case study of canine rabies

PubMed Central

Townsend, Sunny E.; Lembo, Tiziana; Cleaveland, Sarah; Meslin, François X.; Miranda, Mary Elizabeth; Putra, Anak Agung Gde; Haydon, Daniel T.; Hampson, Katie