Lyssaviruses and Rabies: Prevention, Control and Elimination

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Vector-Borne Diseases".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 66871

Special Issue Editor


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Guest Editor
1. Adjunct Professor, The Wistar Institute, Philadelphia, PA, USA
2.CEO, LYSSA LLC, Lawrenceville, GA 30044, USA
Interests: lyssaviruses; zoonoses; One Health; epidemiology; conservation biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Rabies is one of the oldest documented zoonoses, but it remains a neglected infectious disease with a pressing need for resolution of many unanswered questions. Prior to the 1950s, rabies was believed to be caused only by rabies virus. Since that time, more than 17 different lyssaviruses have been described, due, in part, to improvements in laboratory-based surveillance and viral characterization. Yet, if our current approach to such pathogen discovery and biosecurity is to be considered adequate, how are new lyssaviruses being reported from Western Europe, and what does this finding say about the undiscovered lyssavirus diversity within Africa and Asia?

Annually, most of the tens of thousands of human rabies fatalities result from the bite of a rabid dog. During 2015, the FAO (Food and Agriculture Organization of the United Nations), the OIE (World Organisation 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. This is an ambitious but achievable goal. However, especially considering the poorly defined burden of human rabies in lesser developed countries, are we on track to declare zero human fatalities caused by dogs over the ensuing decade?

As an acute, progressive, incurable viral encephalitis, elimination of exposure to lyssaviruses is a fundamental feature of any agricultural, environmental, or public health plan. The GEHRD is no exception. Education of professionals and the public is a priority, especially children, who remain a highly vulnerable population at risk. While many education programs on bite prevention have been created, and multiple community knowledge, attitudes and practice surveys have been conducted, how do we evaluate their utility objectively to demonstrably affect positive change?

Somewhat unique for viral zoonoses, vaccination against rabies includes both postexposure 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 2017, while on tour in India, a woman from Virginia was bitten by a puppy; she returned home and became the ninth person exposed to rabies virus abroad who has died from rabies in the USA since 2008. Given such incidents in highly developed countries with adequate health care resources, do we believe our discussions with travelers on bite avoidance, Pre-P considerations and PEP-seeking behavior as well as such obvious deliberations for residents within highly enzootic regions are still relevant?

At its root cause, rabies is a disease of nature. All warm-blooded vertebrates are believed to be susceptible. 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. 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?

Historically, lethal control of animal populations was employed widely in an attempt to curb rabies incidents at local, national, and regional levels. Over the years, substantial evidence has mounted that seriously questions the basis for the killing of healthy animals in response to rabies concerns on firm ethical, ecological, and economic grounds. Clearly, the rationale for the GEHRD lies in the resulting herd immunity from vaccinated dogs en masse and the prophylaxis of exposed persons. Unfortunately, reports of inhumane and ineffective culling continue to surface. What needs to occur to reverse such incidents and promote more modern economical and efficacious means of rabies prevention and control?

In this Special Issue, we will focus upon applied research, clinical studies, and case reports that contribute to relevant improvements in the laboratory-based surveillance, epidemiology, pathogen discovery, prophylaxis, and related aspects of the GEHRD towards the realization of broader disease prevention, control, and elimination actions.

Much remains to be accomplished; we value your involvement to date and look forward to your additional provocative scientific contributions towards this trans-disciplinary subject.

Dr. Charles E. Rupprecht
Guest Editor

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Keywords

  • diagnosis
  • epidemiology
  • lyssavirus
  • neglected diseases
  • prophylaxis
  • rabies
  • surveillance
  • vaccine
  • viral infections
  • zoonosis

Published Papers (14 papers)

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Editorial

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3 pages, 174 KiB  
Editorial
The Rabies Concert: Rising towards the Last Waltz?
by Charles E. Rupprecht
Trop. Med. Infect. Dis. 2021, 6(3), 124; https://doi.org/10.3390/tropicalmed6030124 - 8 Jul 2021
Cited by 1 | Viewed by 3903
Abstract
Apologies for the brief intermission imposed by the pandemic, between the opening piece of our Special Issue “Lyssaviruses and Rabies: Prevention, Control and Elimination” and this closing act of commentary [...] Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)

Research

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12 pages, 2846 KiB  
Article
Controlling Human Rabies: The Development of an Effective, Inexpensive and Locally Made Passive Cooling Device for Storing Thermotolerant Animal Rabies Vaccines
by Ahmed Lugelo, Katie Hampson, Machunde Bigambo, Rudovick Kazwala and Felix Lankester
Trop. Med. Infect. Dis. 2020, 5(3), 130; https://doi.org/10.3390/tropicalmed5030130 - 11 Aug 2020
Cited by 13 | Viewed by 4093
Abstract
Thermotolerant vaccines greatly improved the reach and impact of large-scale vaccination programs to eliminate diseases such as smallpox, polio and rinderpest. A recent study demonstrated that the potency of the Nobivac® Canine Rabies vaccine was not impacted following experimental storage at 30 [...] Read more.
Thermotolerant vaccines greatly improved the reach and impact of large-scale vaccination programs to eliminate diseases such as smallpox, polio and rinderpest. A recent study demonstrated that the potency of the Nobivac® Canine Rabies vaccine was not impacted following experimental storage at 30 °C for three months. We conducted a study to develop a passive cooling device (PCD) that could store thermotolerant vaccines under fluctuating subambient temperatures. Through a participatory process with local communities in Northern Tanzania, we developed innovative PCD designs for local manufacture. A series of field experiments were then carried out to evaluate the effectiveness of five PCDs for vaccine storage under varying climatic conditions. Following iterative improvement, a final prototype “Zeepot Clay” was developed at the cost of US$11 per unit. During a further field-testing phase over a 12-month period, the internal temperature of the device remained below 26 °C, despite ambient temperatures exceeding 42 °C. Our study thus demonstrated that locally designed PCDs have utility for storing thermotolerant rabies vaccines at subambient temperatures. These results have application for the scaling up of mass dog vaccination programs in low-and-middle income countries, particularly for hard-to-reach populations with limited access to power and cold-chain vaccine storage. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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14 pages, 1445 KiB  
Article
Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
by Sintayehu Arega, Anne Conan, Claude T. Sabeta, Jan E. Crafford, Jeanette Wentzel, Bjorn Reininghaus, Louise Biggs, Andrew L. Leisewitz, Melvyn Quan, Felix Toka and Darryn L. Knobel
Trop. Med. Infect. Dis. 2020, 5(1), 45; https://doi.org/10.3390/tropicalmed5010045 - 12 Mar 2020
Cited by 13 | Viewed by 6244
Abstract
To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by [...] Read more.
To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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17 pages, 2165 KiB  
Article
Risk Modeling of Bat Rabies in the Caribbean Islands
by Clint N. Morgan, Ryan M. Wallace, Alexandra Vokaty, Janine F.R. Seetahal and Yoshinori J. Nakazawa
Trop. Med. Infect. Dis. 2020, 5(1), 35; https://doi.org/10.3390/tropicalmed5010035 - 1 Mar 2020
Cited by 7 | Viewed by 3603
Abstract
Rabies surveillance and control measures vary significantly between Caribbean islands. The Centers for Disease Control and Prevention currently recommends certain groups of U.S. travelers to any Caribbean island receive pre-exposure rabies immunization. However, most islands self-declare as “rabies free”, and have never publicly [...] Read more.
Rabies surveillance and control measures vary significantly between Caribbean islands. The Centers for Disease Control and Prevention currently recommends certain groups of U.S. travelers to any Caribbean island receive pre-exposure rabies immunization. However, most islands self-declare as “rabies free”, and have never publicly released data to support rabies-free claims. We used the Analytic Hierarchy Process to create pairwise comparison values among five risk factors determined by subject matter experts. Risk factor weights were calculated and used in a geospatial analysis to calculate a risk value for each island nation (higher values indicate higher risk). Risk values ranged from 8.73 (Trinidad) to 1.57 (The Bahamas, Turks and Caicos Islands). All four countries that have documented occurrences of laboratory confirmed rabid bats were ranked highest (Trinidad and Tobago, Grenada, Cuba, Dominican Republic), as well as Haiti. The top five highest risk countries that currently have no reports of bat rabies include St. Vincent and the Grenadines, Jamaica, Puerto Rico, the Cayman Islands, and Dominica. This study reviews the inter-island movement potential of bats, designates areas of high risk for bat-associated rabies within the Caribbean islands, and demonstrates a need for further surveillance efforts in bat populations within islands that self-declare as rabies free. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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12 pages, 1599 KiB  
Article
Wildlife and Bait Density Monitoring to Describe the Effectiveness of a Rabies Vaccination Program in Foxes
by Paolo Tizzani, Angela Fanelli, Carsten Potzsch, Joerg Henning, Srdjan Šašić, Paolo Viviani and Mevlida Hrapović
Trop. Med. Infect. Dis. 2020, 5(1), 32; https://doi.org/10.3390/tropicalmed5010032 - 21 Feb 2020
Cited by 2 | Viewed by 2595
Abstract
Fox rabies has been eliminated from vast areas of West and Central Europe, but cases still occur in the Balkans. Oral vaccination is an effective method for reducing the incidence of the disease in wildlife, but it requires monitoring if bait density is [...] Read more.
Fox rabies has been eliminated from vast areas of West and Central Europe, but cases still occur in the Balkans. Oral vaccination is an effective method for reducing the incidence of the disease in wildlife, but it requires monitoring if bait density is adequate for the density of the wildlife reservoir. We developed a methodology to evaluate the effectiveness of aerial vaccination campaigns conducted in Montenegro during autumn 2011 and spring 2012. The effectiveness of the vaccination campaign was assessed by (i) estimating the density of baits, (ii) estimating the distribution of the red fox, (iii) identifying critical areas of insufficient bait density by combining both variables. Although the two vaccination campaigns resulted in 45% and 47% of the country’s total area not reaching recommended density of 20 baits/km2, the consecutive delivery of both campaigns reduced these “gaps” to 6%. By combining bait and reservoir density data, we were able to show that bait density was lower than fox density in only 5% of Montenegro’s territory. The methodology described can be used for real-time evaluation of aerial vaccine delivery campaigns, to identify areas with insufficient bait densities. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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9 pages, 1011 KiB  
Article
In Vivo Efficacy of SYN023, an Anti-Rabies Monoclonal Antibody Cocktail, in Post-Exposure Prophylaxis Animal Models
by Tzu-Yuan Chao, Shou-feng Zhang, Li Chen, Eric Tsao and Charles E. Rupprecht
Trop. Med. Infect. Dis. 2020, 5(1), 31; https://doi.org/10.3390/tropicalmed5010031 - 21 Feb 2020
Cited by 9 | Viewed by 3716
Abstract
Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP) because it provides passive immunity to prevent this otherwise inescapably fatal disease in Category III exposed patients. Even with decades of development, RIG products are still criticized for their high [...] Read more.
Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP) because it provides passive immunity to prevent this otherwise inescapably fatal disease in Category III exposed patients. Even with decades of development, RIG products are still criticized for their high cost, lot-to-lot variation, and potential safety issues. They remain largely unattainable in most developing regions of the world, where demand is highest. In recent years, monoclonal antibodies (MAbs) have become widely accepted as safer and more cost-effective alternatives to RIG products. As an example, SYN023 is a 1:1 cocktail of two humanized anti-rabies MAbs previously shown to display extensive neutralizing capabilities. Here, we further assessed the efficacy of SYN023 in animal models of rabies, and found that SYN023 afforded protection equal to a standard dose of human RIG (HRIG) at 0.03 mg/kg in Syrian hamsters and 0.1 mg/kg in beagles. Potential interference with vaccine-induced immunity was analyzed for the MAbs at these concentrations. While individual MAbs did not interfere with vaccine response, SYN023 at dosages of 0.1 mg/kg and above resulted in reduced neutralizing antibody titers similar to HRIG. Thus, the in vivo characterization of SYN023 supports its utility in human rabies PEP as an efficacious alternative to RIG products. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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11 pages, 623 KiB  
Communication
Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies
by Antonia Klein, Anna Fahrion, Stefan Finke, Marina Eyngor, Shiri Novak, Boris Yakobson, Ernest Ngoepe, Baby Phahladira, Claude Sabeta, Paola De Benedictis, Morgane Gourlaouen, Lillian A. Orciari, Pamela A. Yager, Crystal M. Gigante, M. Kimberly Knowles, Christine Fehlner-Gardiner, Alexandre Servat, Florence Cliquet, Denise Marston, Lorraine M. McElhinney, Trudy Johnson, Anthony R. Fooks, Thomas Müller and Conrad M. Freulingadd Show full author list remove Hide full author list
Trop. Med. Infect. Dis. 2020, 5(1), 13; https://doi.org/10.3390/tropicalmed5010013 - 18 Jan 2020
Cited by 11 | Viewed by 3454
Abstract
As a neglected zoonotic disease, rabies causes approximately 5.9 × 104 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. [...] Read more.
As a neglected zoonotic disease, rabies causes approximately 5.9 × 104 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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13 pages, 2061 KiB  
Article
Fighting Dog-Mediated Rabies in Namibia—Implementation of a Rabies Elimination Program in the Northern Communal Areas
by Rauna Athingo, Tenzin Tenzin, Albertina Shilongo, Emmanuel Hikufe, Kenneth K. Shoombe, Siegfried Khaiseb, Jolandie van der Westhuizen, Moetapele Letshwenyo, Gregorio Torres, Thomas C. Mettenleiter, Conrad M. Freuling and Thomas Müller
Trop. Med. Infect. Dis. 2020, 5(1), 12; https://doi.org/10.3390/tropicalmed5010012 - 17 Jan 2020
Cited by 17 | Viewed by 4983
Abstract
The major part of the global burden of dog-mediated rabies falls on Africa and Asia, where still an estimated 60,000 people die of the disease annually. Like in many African countries, dog-mediated rabies is a major public health concern in Namibia, costing the [...] Read more.
The major part of the global burden of dog-mediated rabies falls on Africa and Asia, where still an estimated 60,000 people die of the disease annually. Like in many African countries, dog-mediated rabies is a major public health concern in Namibia, costing the country an estimated 242 human deaths during the past two decades, in particular in the Northern Communal Areas (NCAs). Consequently, under the “One Health” concept, the Namibian government adopted a National Rabies Control Strategy in 2015, which strives to contribute to the global goal of ending dog-mediated human rabies deaths by 2030. A key component of this strategy was the implementation a dog rabies elimination program in the NCAs in 2016, being designed as a stepwise regional rollout strategy by building on experience gained in a pilot project area. The area of implementation covers approximately 263,376 km2 and 64 constituencies, with around 1.2 million inhabitants and estimated 93,000 dogs. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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13 pages, 1444 KiB  
Article
Development of a Non-Meat-Based, Mass Producible and Effective Bait for Oral Vaccination of Dogs against Rabies in Goa State, India
by Andrew D. Gibson, Stella Mazeri, Gowri Yale, Santosh Desai, Vilas Naik, Julie Corfmat, Steffen Ortmann, Alasdair King, Thomas Müller, Ian Handel, Berend MdeC. Bronsvoort, Luke Gamble, Richard J. Mellanby and Ad Vos
Trop. Med. Infect. Dis. 2019, 4(3), 118; https://doi.org/10.3390/tropicalmed4030118 - 4 Sep 2019
Cited by 15 | Viewed by 5134
Abstract
Introduction: To achieve the global goal of canine-mediated human rabies elimination by 2030 there is an urgent need to scale-up mass dog vaccination activities in regions with large dog populations that are difficult to access; a common situation in much of India. Oral [...] Read more.
Introduction: To achieve the global goal of canine-mediated human rabies elimination by 2030 there is an urgent need to scale-up mass dog vaccination activities in regions with large dog populations that are difficult to access; a common situation in much of India. Oral rabies vaccination may enable the vaccination of free-roaming dogs that are inaccessible to parenteral vaccination, and is considered a promising complementary measure to parenteral mass dog vaccination campaigns. WHO and OIE have published detailed minimum requirements for rabies vaccines and baits to be used for this purpose, requiring that baits must not only be well-accepted by the target population but must also efficiently release the vaccine in the oral cavity. For oral rabies vaccination approaches to be successful, it is necessary to develop baits which have a high uptake by the target population, are culturally accepted and amenable to mass production. The aim of this study was to compare the interest and uptake rates of meat-based and an egg-based prototype bait constructs by free roaming dogs in Goa, India. Methods: Three teams randomly distributed two prototype baits; an egg-flavoured bait and a commercial meat dog food (gravy) flavoured bait. The outcomes of consumption were recorded and compared between baits and dog variables. Results: A total of 209 egg-bait and 195 gravy-bait distributions were recorded and analysed. No difference (p = 0.99) was found in the percentage of dogs interested in the baits when offered. However, significantly more dogs consumed the egg-bait than the gravy-bait; 77.5% versus 68.7% (p = 0.04). The release of the blue-dyed water inside the sachet in the oral cavity of the animals was significant higher in the dogs consuming an egg-bait compared to the gravy-bait (73.4% versus 56.7%, p = 0.001). Conclusions: The egg-based bait had a high uptake amongst free roaming dogs and also enabled efficient release of the vaccine in the oral cavity, whilst also avoiding culturally relevant materials of bovine or porcine meat products. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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13 pages, 1299 KiB  
Article
Cost Savings of Using Updated Thai Red Cross Intradermal Regimen in a High-Throughput Anti-Rabies Clinic in New Delhi, India
by Bijit Kumar Kundu, Girish Gulab Meshram, Shrinath Bhargava and Omprakash Meena
Trop. Med. Infect. Dis. 2019, 4(1), 50; https://doi.org/10.3390/tropicalmed4010050 - 22 Mar 2019
Cited by 6 | Viewed by 3971
Abstract
Replacement of the Essen intramuscular (EIM) by the updated Thai Red Cross intradermal (UTRCID) regimen for rabies post-exposure prophylaxis (PEP), in high-throughput hospitals of India, has been advocated since 2006 thanks to its cost-effectiveness. However, several anti-rabies clinics in India and other parts [...] Read more.
Replacement of the Essen intramuscular (EIM) by the updated Thai Red Cross intradermal (UTRCID) regimen for rabies post-exposure prophylaxis (PEP), in high-throughput hospitals of India, has been advocated since 2006 thanks to its cost-effectiveness. However, several anti-rabies clinics in India and other parts of the world have not initiated this switchover of regimens because of the paucity of financial literature, generated in realistic settings, regarding the same. We calculated the procurement costs of various items required for providing rabies vaccinations via the EIM regimen and UTRCID regimen, on an annual basis, a year before and after the switchover. From a healthcare provider’s perspective, the cost of vaccination per patient was calculated to be 5.60 USD for the EIM regimen and 2.40 USD for the UTRCID regimen. The switchover to the UTRCID regimen from the EIM regimen reduced the financial burden of the rabies vaccination by almost 60%. Procurement of vaccine vials contributed to the majority of the cost (>94%) in both of the regimens. Procurement of syringes with fixed needles contributed negligibly (<6%) to the financial burden in both the regimens. A policy to progressively switch over to the UTRCID regimen from the EIM in all high-throughput anti-rabies centers of India would dramatically reduce the economic burden of running a successful anti-rabies program. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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Review

Jump to: Editorial, Research, Other

21 pages, 2887 KiB  
Review
Reviewing Solutions of Scale for Canine Rabies Elimination in India
by Andrew D. Gibson, Ryan M. Wallace, Abdul Rahman, Omesh K. Bharti, Shrikrishna Isloor, Frederic Lohr, Luke Gamble, Richard J. Mellanby, Alasdair King and Michael J. Day
Trop. Med. Infect. Dis. 2020, 5(1), 47; https://doi.org/10.3390/tropicalmed5010047 - 23 Mar 2020
Cited by 12 | Viewed by 7518
Abstract
Canine rabies elimination can be achieved through mass vaccination of the dog population, as advocated by the WHO, OIE and FAO under the ‘United Against Rabies’ initiative. Many countries in which canine rabies is endemic are exploring methods to access dogs for vaccination, [...] Read more.
Canine rabies elimination can be achieved through mass vaccination of the dog population, as advocated by the WHO, OIE and FAO under the ‘United Against Rabies’ initiative. Many countries in which canine rabies is endemic are exploring methods to access dogs for vaccination, campaign structures and approaches to resource mobilization. Reviewing aspects that fostered success in rabies elimination campaigns elsewhere, as well as examples of largescale resource mobilization, such as that seen in the global initiative to eliminate poliomyelitis, may help to guide the planning of sustainable, scalable methods for mass dog vaccination. Elimination of rabies from the majority of Latin America took over 30 years, with years of operational trial and error before a particular approach gained the broad support of decision makers, governments and funders to enable widespread implementation. The endeavour to eliminate polio now enters its final stages; however, there are many transferrable lessons to adopt from the past 32 years of global scale-up. Additionally, there is a need to support operational research, which explores the practicalities of mass dog vaccination roll-out and what are likely to be feasible solutions at scale. This article reviews the processes that supported the scale-up of these interventions, discusses pragmatic considerations of campaign duration and work-force size and finally provides an examples hypothetical resource requirements for implementing mass dog vaccination at scale in Indian cities, with a view to supporting the planning of pilot campaigns from which expanded efforts can grow. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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15 pages, 1725 KiB  
Review
Purified Vero Cell Rabies Vaccine (PVRV, Verorab®): A Systematic Review of Intradermal Use Between 1985 and 2019
by Thomas Moulenat, Céline Petit, Valérie Bosch Castells and Guy Houillon
Trop. Med. Infect. Dis. 2020, 5(1), 40; https://doi.org/10.3390/tropicalmed5010040 - 7 Mar 2020
Cited by 9 | Viewed by 5996
Abstract
The purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi Pasteur) has been used in rabies prevention since 1985. Evolving rabies vaccination trends, including shorter intradermal (ID) regimens with reduced volume, along with WHO recommendation for ID administration has driven recent ID [...] Read more.
The purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi Pasteur) has been used in rabies prevention since 1985. Evolving rabies vaccination trends, including shorter intradermal (ID) regimens with reduced volume, along with WHO recommendation for ID administration has driven recent ID PVRV regimen assessments. Thus, a consolidated review comparing immunogenicity of PVRV ID regimens during pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is timely and beneficial in identifying gaps in current research. A search of seven databases for studies published from 1985 to November 2019 identified 35 studies. PrEP was assessed in 10 studies (n = 926) with 1–3-site, 1–3-visit regimens of up to 3-months duration. Seroconversion (rabies virus neutralizing antibodies [RVNA] ≥ 0.5 IU/mL) rates of 90–100% were reported within weeks, irrespective of regimen, with robust booster responses at 1 year (100% seroconversion rates by day 14 post-booster). However, data are lacking for the current WHO-recommended, 2-site, 1-week ID PrEP regimen. PEP was assessed in 25 studies (n = 2136) across regimens of 1-week to 90-day duration. All ID PEP regimens assessed induced ≥ 99% seroconversion rates (except in HIV participants) by day 14–28. This review confirms ID PVRV suitability for rabies prophylaxis and highlights the heterogeneity of use in the field. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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10 pages, 2293 KiB  
Review
Zero Endemic Cases of Wildlife Rabies (Classical Rabies Virus, RABV) in the European Union by 2020: An Achievable Goal
by Emmanuelle Robardet, Dean Bosnjak, Lena Englund, Panayiotis Demetriou, Pedro Rosado Martín and Florence Cliquet
Trop. Med. Infect. Dis. 2019, 4(4), 124; https://doi.org/10.3390/tropicalmed4040124 - 30 Sep 2019
Cited by 36 | Viewed by 5637
Abstract
The elimination of rabies transmitted by Classical Rabies Virus (RABV) in the European Union (EU) is now in sight. Scientific advances have made it possible to develop oral vaccination for wildlife by incorporating rabies vaccines in baits for foxes. At the start of [...] Read more.
The elimination of rabies transmitted by Classical Rabies Virus (RABV) in the European Union (EU) is now in sight. Scientific advances have made it possible to develop oral vaccination for wildlife by incorporating rabies vaccines in baits for foxes. At the start of the 1980s, aerial distribution of vaccine baits was tested and found to be a promising tool. The EU identified rabies elimination as a priority, and provided considerable financial and technical resources to the infected EU Member States, allowing regular and large-scale rabies eradication programs based on aerial vaccination. The EU also provides support to non-EU countries in its eastern and south eastern borders. The key elements of the rabies eradication programs are oral rabies vaccination (ORV), quality control of vaccines and control of their distribution, rabies surveillance and monitoring of the vaccination effectiveness. EU Member States and non-EU countries with EU funded eradication programs counted on the technical support of the rabies subgroup of the Task Force for monitoring disease eradication and of the EU Reference Laboratory (EURL) for rabies. In 2018, eight rabies cases induced by classical rabies virus RABV (six in wild animals and two in domestic animals) were detected in three EU Member States, representing a sharp decrease compared to the situation in 2010, where there were more than 1500 cases in nine EU Member States. The goal is to reach zero cases in wildlife and domestic animals in the EU by 2020, a target that now seems achievable. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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Case Report
Clinical Presentation and Serologic Response during a Rabies Epizootic in Captive Common Vampire Bats (Desmodus rotundus)
by Elsa M. Cárdenas-Canales, Crystal M. Gigante, Lauren Greenberg, Andres Velasco-Villa, James A. Ellison, Panayampalli S. Satheshkumar, Lex G. Medina-Magües, Richard Griesser, Elizabeth Falendysz, Ignacio Amezcua, Jorge E. Osorio and Tonie E. Rocke
Trop. Med. Infect. Dis. 2020, 5(1), 34; https://doi.org/10.3390/tropicalmed5010034 - 1 Mar 2020
Cited by 12 | Viewed by 3996
Abstract
We report mortality events in a group of 123 common vampire bats (Desmodus rotundus) captured in México and housed for a rabies vaccine efficacy study in Madison, Wisconsin. Bat mortalities occurred in México and Wisconsin, but rabies cases reported herein are [...] Read more.
We report mortality events in a group of 123 common vampire bats (Desmodus rotundus) captured in México and housed for a rabies vaccine efficacy study in Madison, Wisconsin. Bat mortalities occurred in México and Wisconsin, but rabies cases reported herein are only those that occurred after arrival in Madison (n = 15). Bats were confirmed positive for rabies virus (RABV) by the direct fluorescent antibody test. In accordance with previous reports, we observed long incubation periods (more than 100 days), variability in clinical signs prior to death, excretion of virus in saliva, and changes in rabies neutralizing antibody (rVNA) titers post-infection. We observed that the furious form of rabies (aggression, hyper-salivation, and hyper-excitability) manifested in three bats, which has not been reported in vampire bat studies since 1936. RABV was detected in saliva of 5/9 bats, 2–5 days prior to death, but was not detected in four of those bats that had been vaccinated shortly after exposure. Bats from different capture sites were involved in two separate outbreaks, and phylogenetic analysis revealed differences in the glycoprotein gene sequences of RABV isolated from each event, indicating that two different lineages were circulating separately during capture at each site. Full article
(This article belongs to the Special Issue Lyssaviruses and Rabies: Prevention, Control and Elimination)
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