Special Issue "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: 31 October 2021.

Special Issue Editors

Dr. Ryan M. Wallace
E-Mail Website
Guest Editor
National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Interests: rabies control
Prof. Dr. Charles E. Rupprecht
E-Mail Website
Guest Editor
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
Dr. Amy T. Gilbert
E-Mail Website
Guest Editor
US Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, 4101 Laporte Avenue, Fort Collins, Colorado 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

Manuscript Submission Information

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Keywords

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

Published Papers (9 papers)

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Research

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Article
Data-Driven Management—A Dynamic Occupancy Approach to Enhanced Rabies Surveillance Prioritization
Viruses 2021, 13(9), 1795; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091795 - 09 Sep 2021
Viewed by 471
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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Article
Comparative Study of Optical Markers to Assess Bait System Efficiency Concerning Vaccine Release in the Oral Cavity of Dogs
Viruses 2021, 13(7), 1382; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071382 - 15 Jul 2021
Viewed by 757
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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Communication
Oral Rabies Vaccination of Small Indian Mongooses (Urva auropunctata) with ONRAB via Ultralite Baits
Viruses 2021, 13(5), 734; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050734 - 23 Apr 2021
Viewed by 582
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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Article
Feasibility and Effectiveness Studies with Oral Vaccination of Free-Roaming Dogs against Rabies in Thailand
Viruses 2021, 13(4), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040571 - 29 Mar 2021
Cited by 2 | Viewed by 819
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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Article
Towards Development of an Anti-Vampire Bat Vaccine for Rabies Management: Inoculation of Vampire Bat Saliva Induces Immune-Mediated Resistance
Viruses 2021, 13(3), 515; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030515 - 20 Mar 2021
Viewed by 1199
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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Article
Modeling Mongoose Rabies in the Caribbean: A Model-Guided Fieldwork Approach to Identify Research Priorities
Viruses 2021, 13(2), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020323 - 20 Feb 2021
Cited by 2 | Viewed by 1033
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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Article
Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016
Viruses 2021, 13(2), 157; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020157 - 22 Jan 2021
Viewed by 654
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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Review
Challenges of Rabies Serology: Defining Context of Interpretation
Viruses 2021, 13(8), 1516; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081516 - 31 Jul 2021
Viewed by 782
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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Review
The Route of Administration of Rabies Vaccines: Comparing the Data
Viruses 2021, 13(7), 1252; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071252 - 27 Jun 2021
Viewed by 689
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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