Innovative Techniques and Approaches in the Control and Prevention of Rabies Virus

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 52543

Special Issue Editors

National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Interests: rabies control
LYSSA LLC, 647 MICHELLE CT, Lawrenceville, GA 30044, USA
Interests: lyssavirus diagnostics and pathobiology; rabies prevention and control; epizootiology of viral zoonoses
Special Issues, Collections and Topics in MDPI journals
US Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, 4101 Laporte Avenue, Fort Collins, CO 80521, USA
Interests: virus spillover, disease ecology, wildlife diseases, zoonoses, wildlife rabies control

Special Issue Information

Dear Colleagues,

Rabies is one of the oldest documented and most fatal zoonoses known to man. Annually, tens of thousands of human rabies fatalities result from the bite of a rabid dog. Uniquely, rabies is the only zoonosis in which routine laboratory examination of a suspect animal directly determines the need for immediate biomedical care to an exposed person with life-saving prophylaxis. Vaccination against rabies includes both post-exposure prophylaxis (PEP) if a bite occurs and preexposure (Pre-P) for individuals determined to be at risk of exposure, such as veterinarians, animal handlers, laboratory workers, cavers, and certain travelers. During 2015, the FAO (Food and Agriculture Organization of the United Nations), the OIE (World Organization for Animal Health), and the WHO (World Health Organization) described a plan for the global elimination of human rabies from dogs (GEHRD) by 2030, through the application of mass canine vaccination and human prophylaxis. Substantial progress on canine rabies elimination in the Americas provided a regional proof of concept for this plan. In 2016, WHO established a Strategic Advisory Group of Experts (SAGE) to consider new recommendations on human rabies vaccines and immune globulins, in support of the GEHRD. Throughout the 20th century, sensitive and specific diagnostic methods were developed for viral detection, and safe and effective vaccines were constructed for humans, domestic animals, and free-ranging wildlife. Will such methods still be applicable today or do we need newer tools in diagnosis and immunization to better support the SAGE recommendations and the GEHRD specifically and to better appreciate aspects of rabies holistically in conservation biology, public health, and veterinary medicine?

Dr. Ryan M. Wallace
Prof. Dr. Charles E. Rupprecht
Dr. Amy T. Gilbert
Guest Editors

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Keywords

  • Encephalitis
  • lyssavirus
  • prophylaxis
  • rabies
  • rhabdovirus
  • vaccination
  • wildlife
  • zoonosis
  • canine
  • technology
  • innovation
  • oral vaccination

Published Papers (18 papers)

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Editorial

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2 pages, 180 KiB  
Editorial
Special Issue “Innovative Techniques and Approaches in the Control and Prevention of Rabies Virus”
by Amy T. Gilbert, Ryan M. Wallace and Charles E. Rupprecht
Viruses 2022, 14(5), 845; https://0-doi-org.brum.beds.ac.uk/10.3390/v14050845 - 19 Apr 2022
Viewed by 1768
Abstract
Rabies is an ancient lethal scourge that has plagued humankind for centuries [...] Full article

Research

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17 pages, 1041 KiB  
Article
Development of Dog Vaccination Strategies to Maintain Herd Immunity against Rabies
by Ahmed Lugelo, Katie Hampson, Elaine A. Ferguson, Anna Czupryna, Machunde Bigambo, Christian Tetteh Duamor, Rudovick Kazwala, Paul C. D. Johnson and Felix Lankester
Viruses 2022, 14(4), 830; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040830 - 16 Apr 2022
Cited by 7 | Viewed by 2731
Abstract
Human rabies can be prevented through mass dog vaccination campaigns; however, in rabies endemic countries, pulsed central point campaigns do not always achieve the recommended coverage of 70%. This study describes the development of a novel approach to sustain high coverage based on [...] Read more.
Human rabies can be prevented through mass dog vaccination campaigns; however, in rabies endemic countries, pulsed central point campaigns do not always achieve the recommended coverage of 70%. This study describes the development of a novel approach to sustain high coverage based on decentralized and continuous vaccination delivery. A rabies vaccination campaign was conducted across 12 wards in the Mara region, Tanzania to test this approach. Household surveys were used to obtain data on vaccination coverage as well as factors influencing dog vaccination. A total 17,571 dogs were vaccinated, 2654 using routine central point delivery and 14,917 dogs using one of three strategies of decentralized continuous vaccination. One month after the first vaccination campaign, coverage in areas receiving decentralized vaccinations was higher (64.1, 95% Confidence Intervals (CIs) 62.1–66%) than in areas receiving pulsed vaccinations (35.9%, 95% CIs 32.6–39.5%). Follow-up surveys 10 months later showed that vaccination coverage in areas receiving decentralized vaccinations remained on average over 60% (60.7%, 95% CIs 58.5–62.8%) and much higher than in villages receiving pulsed vaccinations where coverage was on average 32.1% (95% CIs 28.8–35.6%). We conclude that decentralized continuous dog vaccination strategies have the potential to improve vaccination coverage and maintain herd immunity against rabies. Full article
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10 pages, 267 KiB  
Article
Filter Papers to Collect Blood Samples from Dogs: An Easier Way to Monitor the Mass Vaccination Campaigns against Rabies?
by Marine Wasniewski, Jacques Barrat, Samia Ben Maiez, Habib Kharmachi, Mariem Handous and Florence Cliquet
Viruses 2022, 14(4), 711; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040711 - 29 Mar 2022
Cited by 1 | Viewed by 1722
Abstract
Rabies is a deadly viral disease present mainly in low-income countries of Africa and Asia. Dogs are the main reservoir and the source of human deaths. Mass vaccination campaigns of dogs are pivotal to achieve rabies elimination. The monitoring of the immune response [...] Read more.
Rabies is a deadly viral disease present mainly in low-income countries of Africa and Asia. Dogs are the main reservoir and the source of human deaths. Mass vaccination campaigns of dogs are pivotal to achieve rabies elimination. The monitoring of the immune response of the dog population is necessary to evaluate the effectiveness of these campaigns, taking into account field conditions. This study explores the feasibility and the performance of a new tool using filter papers (FPs) to collect blood samples associated with an Enzyme-Linked ImmunoSorbent Assay (ELISA) titration of rabies antibodies in dogs. A total of 216 eluates from FP samples were collected from 111 dogs kept in experimental facilities in France and 29 dogs from the field in Tunisia. Sera were also analyzed using both the Fluorescence Antibody Virus Neutralization test (FAVNt) and ELISA. A high specificity (98.0%) was obtained by testing FP blood eluates from 51 unvaccinated dogs, with the results compared with those of FAVNt and ELISA on serum samples. The coefficients of concordance between FP eluates and tested sera were 88.9% for FAVNt and 88.0% for ELISA. Blood filter papers coupled with the titration of rabies antibodies by ELISA provide a reliable, simple, and effective solution to overcome the issues of the logistics and transport of samples, especially in low-income countries. Full article
11 pages, 908 KiB  
Article
Gene Expression Profile Induced by Two Different Variants of Street Rabies Virus in Mice
by Camila M. Appolinário, Janet M. Daly, Richard D. Emes, Fabio Albuquerque Marchi, Bruna Leticia Devidé Ribeiro and Jane Megid
Viruses 2022, 14(4), 692; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040692 - 27 Mar 2022
Cited by 1 | Viewed by 1916
Abstract
Pathogenicity and pathology of rabies virus (RABV) varies according to the variant, but the mechanisms are not completely known. In this study, gene expression profile in brains of mice experimentally infected with RABV isolated from a human case of dog rabies (V2) or [...] Read more.
Pathogenicity and pathology of rabies virus (RABV) varies according to the variant, but the mechanisms are not completely known. In this study, gene expression profile in brains of mice experimentally infected with RABV isolated from a human case of dog rabies (V2) or vampire bat-acquired rabies (V3) were analyzed. In total, 138 array probes associated with 120 genes were expressed differentially between mice inoculated with V2 and sham-inoculated control mice at day 10 post-inoculation. A single probe corresponding to an unannotated gene was identified in V3 versus control mice. Gene ontology (GO) analysis revealed that all of the genes upregulated in mice inoculated with V2 RABV were involved in the biological process of immune defense against pathogens. Although both variants are considered pathogenic, inoculation by the same conditions generated different gene expression results, which is likely due to differences in pathogenesis between the dog and bat RABV variants. This study demonstrated the global gene expression in experimental infection due to V3 wild-type RABV, from the vampire bat Desmodus rotundus, an important source of infection for humans, domestic animals and wildlife in Latin America. Full article
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9 pages, 1663 KiB  
Communication
Whole Genome Sequencing and Phylogenetic Analysis of Rabies Viruses from Bats in Connecticut, USA, 2018–2019
by Ji-Yeon Hyeon, Guillermo R. Risatti, Zeinab H. Helal, Holly McGinnis, Maureen Sims, Amelia Hunt, David H. Chung, Junwon Kim, Julia Desiato and Dong-Hun Lee
Viruses 2021, 13(12), 2500; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122500 - 13 Dec 2021
Cited by 1 | Viewed by 3238
Abstract
We performed whole genome sequencing and genetic characterization of rabies viruses (RABV) detected in bats submitted to the Connecticut Veterinary Medical Diagnostic Laboratory (CVMDL) during 2018–2019. Among 88 bats submitted to CVMDL, six brain samples (6.8%, 95% confidence interval: 1.6% to 12.1%) tested [...] Read more.
We performed whole genome sequencing and genetic characterization of rabies viruses (RABV) detected in bats submitted to the Connecticut Veterinary Medical Diagnostic Laboratory (CVMDL) during 2018–2019. Among 88 bats submitted to CVMDL, six brain samples (6.8%, 95% confidence interval: 1.6% to 12.1%) tested positive by direct fluorescent antibody test. RABVs were detected in big brown bats (Eptesicus fuscus, n = 4), a hoary bat (Lasiurus cinereus, n = 1), and an unidentified bat species (n = 1). Complete coding sequences of four out of six detected RABVs were obtained. In phylogenetic analysis, the RABVs (18-62, 18-4347, and 19-2274) from big brown bats belong to the bats EF-E1 clade, clustering with RABVs detected from the same bat species in Pennsylvania and New Jersey. The bat RABV (19-2898) detected from the migratory hoary bat belongs to the bats LC clade, clustering with the eleven viruses detected from the same species in Arizona, Washington, Idaho, and Tennessee. The approach used in this study generated novel data regarding genetic relationships of RABV variants, including their reservoirs, and their spatial origin and it would be useful as reference data for future investigations on RABV in North America. Continued surveillance and genome sequencing of bat RABV would be needed to monitor virus evolution and transmission, and to assess the emergence of genetic mutations that may be relevant for public health. Full article
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11 pages, 1303 KiB  
Article
Characterization of Single-Chain Fv Fragments of Neutralizing Antibodies to Rabies Virus Glycoprotein
by Kohei Yumoto, Tomoaki Arisaka, Kazuma Okada, Kyosuke Aoki, Toyoyuki Ose, Tatsunori Masatani, Makoto Sugiyama, Naoto Ito, Hideo Fukuhara and Katsumi Maenaka
Viruses 2021, 13(11), 2311; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112311 - 19 Nov 2021
Cited by 2 | Viewed by 2279
Abstract
Rabies has almost a 100% case-fatality rate and kills more than 59,000 people annually around the world. There is no established treatment for rabies. The rabies virus (RABV) expresses only the glycoprotein (RABVG) at the viral surface, and it is the target for [...] Read more.
Rabies has almost a 100% case-fatality rate and kills more than 59,000 people annually around the world. There is no established treatment for rabies. The rabies virus (RABV) expresses only the glycoprotein (RABVG) at the viral surface, and it is the target for the neutralizing antibodies. We previously established mouse monoclonal antibodies, 15–13 and 12–22, which showed neutralizing activity against the RABV, targeting the sequential and conformational epitopes on the RABVG, respectively. However, the molecular basis for the neutralizing activity of these antibodies is not yet fully understood. In this study, we evaluated the binding characteristics of the Fab fragments of the 15–13 and 12–22 antibodies. The recombinant RABVG protein, in prefusion form for the binding analysis, was prepared by the silkworm–baculovirus expression system. Biolayer interferometry (BLI) analysis indicated that the 15–13 Fab interacts with the RABVG, with a KD value at the nM level, and that the 12–22 Fab has a weaker binding affinity (KD ~ μM) with the RABVG compared to the 15–13 Fab. Furthermore, we determined the amino acid sequences of both the antibodies and the designed single-chain Fv fragments (scFvs) of the 15–13 and 12–22 antibodies as another potential biopharmaceutical for targeting rabies. The 15–13 and 12–22 scFvs were successfully prepared by the refolding method and were shown to interact with the RABVG at the nM level and the μM level of the KD, respectively. These binding characteristics were similar to that of each Fab. On the other hand, differential scanning fluorometry (DSF) revealed that the thermal stability of these scFvs decreases compared to their Fabs. While the improvement of the stability of scFvs will still be required, these results provide insights into the neutralizing activity and the potential therapeutic use of antibody fragments for RABV infection. Full article
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11 pages, 1171 KiB  
Article
Data-Driven Management—A Dynamic Occupancy Approach to Enhanced Rabies Surveillance Prioritization
by Amy J. Davis, Jordona D. Kirby, Richard B. Chipman, Kathleen M. Nelson and Amy T. Gilbert
Viruses 2021, 13(9), 1795; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091795 - 09 Sep 2021
Cited by 8 | Viewed by 2012
Abstract
Rabies lyssavirus (RABV) is enzootic in raccoons across the eastern United States. Intensive management of RABV by oral rabies vaccination (ORV) has prevented its spread westward and shown evidence of local elimination in raccoon populations of the northeastern US. The USDA, Wildlife Services, [...] Read more.
Rabies lyssavirus (RABV) is enzootic in raccoons across the eastern United States. Intensive management of RABV by oral rabies vaccination (ORV) has prevented its spread westward and shown evidence of local elimination in raccoon populations of the northeastern US. The USDA, Wildlife Services, National Rabies Management Program (NRMP) collaborates with other agencies to implement broad-scale ORV and conducts extensive monitoring to measure the effectiveness of the management. Enhanced Rabies Surveillance (ERS) was initiated during 2005 and updated in 2016 to direct surveillance efforts toward higher-value specimens by assigning points to different methods of encountering specimens for collection (strange-acting, roadkill, surveillance-trapped, etc.; specimen point values ranged from 1 to 15). We used the 2016–2019 data to re-evaluate the point values using a dynamic occupancy model. Additionally, we used ERS data from 2012–2015 and 2016–2019 to examine the impact that the point system had on surveillance data. Implementation of a point system increased positivity rates among specimens by 64%, indicating a substantial increase in the efficiency of the ERS to detect wildlife rabies. Our re-evaluation found that most points accurately reflect the value of the surveillance specimens. The notable exception was that samples from animals found dead were considerably more valuable for rabies detection than originally considered (original points = 5, new points = 20). This work demonstrates how specimen prioritization strategies can be used to refine and improve ERS in support of wildlife rabies management. Full article
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16 pages, 2292 KiB  
Article
Comparative Study of Optical Markers to Assess Bait System Efficiency Concerning Vaccine Release in the Oral Cavity of Dogs
by Anna Langguth, Kansuda Leelahapongsathon, Napasaporn Wannapong, Suwicha Kasemsuwan, Steffen Ortmann, Ad Vos and Michael Böer
Viruses 2021, 13(7), 1382; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071382 - 15 Jul 2021
Cited by 4 | Viewed by 2562
Abstract
Oral vaccination of dogs against rabies has the potential to achieve mass coverage and thus deplete the virus of its most important reservoir host species. There is, however, no established non-invasive method to evaluate vaccine release in the oral cavity, following bait ingestion. [...] Read more.
Oral vaccination of dogs against rabies has the potential to achieve mass coverage and thus deplete the virus of its most important reservoir host species. There is, however, no established non-invasive method to evaluate vaccine release in the oral cavity, following bait ingestion. In this study, two pre-selected marker methods in conjunction with their acceptance were assessed in local Thai dogs. Shelter dogs (n = 47) were offered one of four randomized bait formulations; bait type A-, containing Green S (E142) in a fructose solution; type B-, containing Patent Blue V (E131) in a fructose solution; type C-, containing the medium used for delivery of oral rabies vaccine in baits commercially produced; and type D-, containing denatonium benzoate, which was to serve as the negative control, due to its perceived bitterness. Patent Blue V was found to possess overall stronger dyeing capacities compared to Green S. Furthermore, there was no significant difference in the acceptance or bait handling of Patent Blue V baits compared to those containing the oral rabies vaccine medium alone, suggesting the potential use of this dye as a surrogate for rabies vaccine when testing newly developed bait formats. Full article
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6 pages, 627 KiB  
Communication
Oral Rabies Vaccination of Small Indian Mongooses (Urva auropunctata) with ONRAB via Ultralite Baits
by Are R. Berentsen, Israel L. Leinbach, Mel J. Rivera-Rodriguez and Amy T. Gilbert
Viruses 2021, 13(5), 734; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050734 - 23 Apr 2021
Cited by 2 | Viewed by 1793
Abstract
The Ontario Rabies Vaccine (ONRAB) is a human adenovirus rabies glycoprotein recombinant oral vaccine immunogenic for small Indian mongooses when delivered by direct instillation into the oral cavity. We offered Ultralite baits containing ~1.8 mL 109.5 TCID50 ONRAB oral rabies vaccine [...] Read more.
The Ontario Rabies Vaccine (ONRAB) is a human adenovirus rabies glycoprotein recombinant oral vaccine immunogenic for small Indian mongooses when delivered by direct instillation into the oral cavity. We offered Ultralite baits containing ~1.8 mL 109.5 TCID50 ONRAB oral rabies vaccine to 18 mongooses, while 6 mongooses were offered identical baits in placebo form. We collected sera from individual mongooses at days 0, 14 and 30 post vaccination (pv) and quantified rabies virus neutralizing antibodies (RVNA) using the rapid fluorescent focus inhibition test, with titers greater than or equal to 0.1 IU/mL considered positive. All study subjects were RVNA negative prior to bait offering. Bait consumption was variable: all 6 sham and 13 of 18 (72%) treatment animals consumed/punctured the baits offered. By day 30 pv, RVNA were detected among 11 of 13 (84.6%) of treatment mongooses that consumed/punctured baits, whereas sham-vaccinated mongooses remained RVNA negative throughout the study. We conclude ONRAB is immunogenic for mongooses by Ultralite bait delivery, although the bait design may need further optimization. Full article
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12 pages, 825 KiB  
Article
Feasibility and Effectiveness Studies with Oral Vaccination of Free-Roaming Dogs against Rabies in Thailand
by Karoon Chanachai, Vilaiporn Wongphruksasoong, Ad Vos, Kansuda Leelahapongsathon, Ratanaporn Tangwangvivat, Onpawee Sagarasaeranee, Paisin Lekcharoen, Porathip Trinuson and Suwicha Kasemsuwan
Viruses 2021, 13(4), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040571 - 29 Mar 2021
Cited by 22 | Viewed by 4386
Abstract
(1) Background: Thailand has made significant progress in reducing the number of human and animal rabies cases. However, control and elimination of the last remaining pockets of dog-mediated rabies have shown to be burdensome, predominantly as a result of the large numbers of [...] Read more.
(1) Background: Thailand has made significant progress in reducing the number of human and animal rabies cases. However, control and elimination of the last remaining pockets of dog-mediated rabies have shown to be burdensome, predominantly as a result of the large numbers of free-roaming dogs without an owner that cannot be restrained without special efforts and therefore remain unvaccinated. To reach these dogs, the feasibility, and benefits of oral rabies vaccination (ORV) as a complementary tool has been examined under field conditions. (2) Methods: ORV of dogs was tested in five study areas of four provinces in Thailand. In these areas, sites with free-roaming dogs were identified with the support of local municipal workers and dog caretakers. ORV teams visited each of five study areas and distributed rabies vaccine (SPBN GASGAS) in three bait formats that were offered to the dogs using a hand-out and retrieval model. The three bait types tested included: egg-flavored baits, egg-flavored baits pasted with commercially available cat liquid snack, and boiled-intestine baits. A dog offered a vaccine bait was considered vaccinated when the discarded sachet was perforated or if a dog chewed vaccine bait at least 5 times before it swallowed the bait, including the sachet. (3) Results: A total of 2444 free-roaming dogs considered inaccessible for parenteral vaccination were identified at 338 sites. As not all dogs were approachable, 79.0% were offered a bait; of these dogs, 91.6% accepted the bait and subsequently 83.0% were considered successfully vaccinated. (4) Conclusion: Overall, 65.6% of the free-roaming dogs at these sites were successfully vaccinated by the oral route. Such a significant increase of the vaccination coverage of the free-roaming dog population could interrupt the rabies transmission cycle and offers a unique opportunity to reach the goal to eliminate dog-mediated human rabies in Thailand by 2030. Full article
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11 pages, 2008 KiB  
Article
Towards Development of an Anti-Vampire Bat Vaccine for Rabies Management: Inoculation of Vampire Bat Saliva Induces Immune-Mediated Resistance
by Horacio A. Delpietro, Roberto G. Russo, Charles E. Rupprecht and Gabriela L. Delpietro
Viruses 2021, 13(3), 515; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030515 - 20 Mar 2021
Cited by 4 | Viewed by 3795
Abstract
The common vampire bat (Desmodus rotundus) is a hematophagous species responsible for paralytic rabies and bite damage that affects livestock, humans and wildlife from Mexico to Argentina. Current measures to control vampires, based upon coumarin-derived poisons, are not used extensively due [...] Read more.
The common vampire bat (Desmodus rotundus) is a hematophagous species responsible for paralytic rabies and bite damage that affects livestock, humans and wildlife from Mexico to Argentina. Current measures to control vampires, based upon coumarin-derived poisons, are not used extensively due in part to the high cost of application, risks for bats that share roosts with vampires and residual environmental contamination. Observations that vampire bat bites may induce resistance in livestock against vampire bat salivary anticoagulants encourage research into novel vaccine-based alternatives particularly focused upon increasing livestock resistance to vampire salivary components. We evaluated the action of vampire bat saliva-Freund’s incomplete adjuvant administered to sheep with anticoagulant responses induced by repeated vampire bites in a control group and examined characteristics of vampire bat salivary secretion. We observed that injections induced a response against vampire bat salivary anticoagulants stronger than by repeated vampire bat bites. Based upon these preliminary findings, we hypothesize the utility of developing a control technique based on induction of an immunologically mediated resistance against vampire bat anticoagulants and rabies virus via dual delivery of appropriate host and pathogen antigens. Fundamental characteristics of host biology favor alternative strategies than simple culling by poisons for practical, economical, and ecologically relevant management of vampire populations within a One Health context. Full article
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27 pages, 4098 KiB  
Article
Modeling Mongoose Rabies in the Caribbean: A Model-Guided Fieldwork Approach to Identify Research Priorities
by Caroline C. Sauvé, Erin E. Rees, Amy T. Gilbert, Are R. Berentsen, Agathe Allibert and Patrick A. Leighton
Viruses 2021, 13(2), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020323 - 20 Feb 2021
Cited by 9 | Viewed by 3102
Abstract
We applied the model-guided fieldwork framework to the Caribbean mongoose rabies system by parametrizing a spatially-explicit, individual-based model, and by performing an uncertainty analysis designed to identify parameters for which additional empirical data are most needed. Our analysis revealed important variation in output [...] Read more.
We applied the model-guided fieldwork framework to the Caribbean mongoose rabies system by parametrizing a spatially-explicit, individual-based model, and by performing an uncertainty analysis designed to identify parameters for which additional empirical data are most needed. Our analysis revealed important variation in output variables characterizing rabies dynamics, namely rabies persistence, exposure level, spatiotemporal distribution, and prevalence. Among epidemiological parameters, rabies transmission rate was the most influential, followed by rabies mortality and location, and size of the initial infection. The most influential landscape parameters included habitat-specific carrying capacities, landscape heterogeneity, and the level of resistance to dispersal associated with topography. Movement variables, including juvenile dispersal, adult fine-scale movement distances, and home range size, as well as life history traits such as age of independence, birth seasonality, and age- and sex-specific mortality were other important drivers of rabies dynamics. We discuss results in the context of mongoose ecology and its influence on disease transmission dynamics. Finally, we suggest empirical approaches and study design specificities that would provide optimal contributing data addressing the knowledge gaps identified by our approach, and would increase our potential to use epidemiological models to guide mongoose rabies control and management in the Caribbean. Full article
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18 pages, 1344 KiB  
Article
Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016
by Shylo R. Johnson, Dennis Slate, Kathleen M. Nelson, Amy J. Davis, Samual A. Mills, John T. Forbes, Kurt C. VerCauteren, Amy T. Gilbert and Richard B. Chipman
Viruses 2021, 13(2), 157; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020157 - 22 Jan 2021
Cited by 8 | Viewed by 1956
Abstract
Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon ( [...] Read more.
Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km2 followed by three years (2014–2016) of evaluation at 300 baits/km2. We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km2 to 300/km2 corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA. Full article
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Review

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19 pages, 1213 KiB  
Review
Review of Oral Rabies Vaccination of Dogs and Its Application in India
by Gowri Yale, Marwin Lopes, Shrikrishna Isloor, Jennifer R. Head, Stella Mazeri, Luke Gamble, Kinzang Dukpa, Gyanendra Gongal and Andrew D. Gibson
Viruses 2022, 14(1), 155; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010155 - 14 Jan 2022
Cited by 13 | Viewed by 5915
Abstract
Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. [...] Read more.
Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state. Full article
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10 pages, 558 KiB  
Review
Challenges of Rabies Serology: Defining Context of Interpretation
by Susan M. Moore
Viruses 2021, 13(8), 1516; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081516 - 31 Jul 2021
Cited by 10 | Viewed by 4074
Abstract
The case fatality rate of rabies, nearly 100%, is one of the most unique characteristic of this ancient virus infection. The crucial role rabies virus neutralizing antibody plays in protection is both well established and explanation of why rabies serology is important. Various [...] Read more.
The case fatality rate of rabies, nearly 100%, is one of the most unique characteristic of this ancient virus infection. The crucial role rabies virus neutralizing antibody plays in protection is both well established and explanation of why rabies serology is important. Various laboratory methods can and have been used but serum neutralization methods have long been the gold standard due to the ability to measure function (neutralization), however these methods can be difficult to perform for several reasons. Assays such as enzyme linked absorbance assays (ELISA), indirect fluorescence antibody (IFA) and more recently lateral flow methods are in use. Interpretation of results can be problematic, not only between methods but also due to modifications of the same method that can lead to misinterpretations. A common assumption in review of laboratory test results is that different methods for the same component produce comparable results under all conditions or circumstances. Assumptions and misinterpretations provide the potential for detrimental decisions, ranging from regulatory to clinically related, and most importantly what ‘level’ is protective. Review of the common challenges in performance and interpretation of rabies serology and specific examples illuminate critical issues to consider when reviewing and applying results of rabies serological testing. Full article
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7 pages, 193 KiB  
Review
The Route of Administration of Rabies Vaccines: Comparing the Data
by Deborah J. Briggs and Susan M. Moore
Viruses 2021, 13(7), 1252; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071252 - 27 Jun 2021
Cited by 10 | Viewed by 2901 | Correction
Abstract
Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts [...] Read more.
Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts to reduce the cost of PEP without impinging on safety, additional research on two strategies was encouraged by the WHO including the development of less expensive production methods for CCVs and the administration of reduced volumes of CCVs via the intradermal (ID) route. Numerous clinical trials have provided sufficient data to support a reduction in the number of doses, a shorter timeline required for PEP, and the approval of the intradermal route of administration for PEP and pre-exposure prophylaxis (PreP). However, the plethora of data that have been published since the development of CCVs can be overwhelming for public health officials wishing to review and make a decision as to the most appropriate PEP and PreP regimen for their region. In this review, we examine three critical benchmarks that can serve as guidance for health officials when reviewing data to implement new PEP and PreP regimens for their region including: evidence of immunogenicity after vaccination; proof of efficacy against development of disease; and confirmation that the regimen being considered elicits a rapid anamnestic response after booster vaccination. Full article

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1 pages, 153 KiB  
Correction
Correction: Briggs, D.J.; Moore, S.M. The Route of Administration of Rabies Vaccines: Comparing the Data. Viruses 2021, 13, 1252
by Deborah J. Briggs and Susan M. Moore
Viruses 2022, 14(7), 1368; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071368 - 23 Jun 2022
Viewed by 896
Abstract
The authors wish to make the following corrections to this paper [...] Full article
8 pages, 872 KiB  
Brief Report
A Comparative Evaluation of the Estimation of Rabies Virus Antibodies among Free-Roaming, Vaccinated Dogs in Bengaluru, India
by Lekshmi J. Das, Shrikrishna Isloor, Alur Kotrappa Santosh, Avinash Bhat, Ramakrishnaiah Sharada, Doddamane Rathnamma, Belamaranahally Muniveerappa Veeregowda, Konanduru Lingappa Phaniraj, Nageshkumar Abhijit Kumar and Abi T. Vanak
Viruses 2022, 14(3), 484; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030484 - 26 Feb 2022
Cited by 2 | Viewed by 2287
Abstract
Vaccination is the practical solution for the prevention of rabies in dogs. Assessment of the immunogenicity of vaccination includes estimation of specific rabies virus neutralizing antibodies (VNA) in the target species. We undertook a study to estimate the levels of VNA in free-roaming [...] Read more.
Vaccination is the practical solution for the prevention of rabies in dogs. Assessment of the immunogenicity of vaccination includes estimation of specific rabies virus neutralizing antibodies (VNA) in the target species. We undertook a study to estimate the levels of VNA in free-roaming dogs with a history of rabies vaccination in Bengaluru city, India. We compared the rapid fluorescent focus inhibition test (RFFIT) and an in-house quantitative indirect ELISA (iELISA). The study area comprised the jurisdiction of Bruhat Bengaluru Mahanagara Palike (BBMP), the Bengaluru civic body. The BBMP, along with several non-government organizations (NGO), were conducting a trap- neuter- vaccinate- release program for the prevention of dog rabies. Serum samples were collected from 250 free-roaming dogs from representative regions of BBMP, of which 125 had a VNA titre of 0.5 IU or more by the RFFIT. Furthermore, 126 dogs showed percent positivity values (PP values) more than the cut off PP value of 57.1 by the iELISA, accounting for 50.4% of satisfactory post-vaccinal serum conversion. The sensitivity and specificity of the iELISA was 94.4% and 95.2%, respectively. Based on these data, a quantitative iELISA may be a complementary tool for sero-monitoring immune responses of free-ranging animals after rabies vaccination. Full article
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