Special Issue "Rabies Symptoms, Diagnosis, Prophylaxis and Treatment"

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366).

Deadline for manuscript submissions: closed (30 June 2017).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Guest Editor
Dr. Charles E. Rupprecht

1. Adjunct Professor, The Wistar Institute, Philadelphia, United States
2.CEO, LYSSA LLC, Lawrenceville, GA 30044, United States
Website | E-Mail
Interests: lyssaviruses; zoonoses; One Health; epidemiology; conservation biology
Guest Editor
Prof. Dr. Bernhard Dietzschold

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, United States
Website | E-Mail
Interests: molecular parthenogenesis of rabies; protective immune responses against rabies; development of live-attenuated rabies virus recombinant vaccines; development of monoclonal antibodies for post-exposure treatment of human rabies

Special Issue Information

Dear Colleagues,

Rabies is an acute progressive encephalitis, caused by highly neurotropic lyssaviruses, with the highest case fatality of any infectious disease, yet remains neglected at a global scale, particularly in poor rural areas of Asia, Africa and the Americas.

Recently, staff from FAO (Food and Agriculture Organization of the United Nations), OIE (World Organisation for Animal Health), WHO (World Health Organization) and global opinion leaders met to discuss a path forward for the elimination of human rabies mediated by dogs by 2030, employing a coordinated mass canine vaccination program. In a true One Health context, a transdisciplinary approach is necessary to fulfill such a goal. Not only will success be measured in the proportions of dog populations vaccinated, but also parameters to herald progress by a substantive decrease in human rabies cases.

Therefore, understanding how to better measure and monitor the human rabies burden, make salient progress with existing biologics in medical portfolio, ensure the health economics data remain positive and balance the prevention approach with the expectations and ethics of individual case intervention, are concomitant public health issue, as plans for canine rabies elimination unfold.

Despite being one of the oldest known diseases, questions about rabies abound in the 21st century. For example: Are we missing human rabies fatalities due to changes in clinical manifestations or is there another explanation for the paucity of confirmed cases? Why do people still die of rabies? Do diagnosticians in developed countries expect too much from laboratory workers in GAVI-eligible countries (GAVI: Global Alliance for Vaccines and Immunization)? How can pathogen detection be improved realistically in the field? Is the apparent virulence and pathogenesis of various lyssaviruses different? Can rabies prophylaxis be administered safely without the necessity of rabies-immune globulin? What is being missed in a more holistic approach to rabies treatment? Will the focus upon human rabies alter the prioritization and timetable of canine rabies elimination? Who are the new collective advocates and supporters to move the agenda forward by over the next decade?

In this Special Issue, we will focus upon basic research, clinical studies and case reports that contribute to translational improvements in laboratory-based surveillance, diagnostics, pathobiology, prophylaxis and experimental therapy of human rabies.

We look forward to your provocative contributions on this inter-related topic.

Dr. Charles Rupprecht
Prof. Dr. Bernhard Dietzschold
Guest Editors

Manuscript Submission Information

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Keywords

  • Diagnosis
  • Encephalitis
  • Lyssavirus
  • Neglected diseases
  • Prophylaxis
  • Rabies
  • Surveillance
  • Therapeutics
  • Viral infections
  • Zoonosis

Published Papers (26 papers)

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Editorial

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Open AccessEditorial
Special Issue: Rabies Symptoms, Diagnosis, Prophylaxis, and Treatment
Trop. Med. Infect. Dis. 2017, 2(4), 59; https://doi.org/10.3390/tropicalmed2040059
Received: 6 November 2017 / Accepted: 8 November 2017 / Published: 14 November 2017
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Abstract
Rabies is an acute, progressive, incurable viral encephalitis found throughout the world. Despite being one of the oldest recognized pathogens, its impact remains substantial in public health, veterinary medicine, and conservation biology.[...] Full article

Research

Jump to: Editorial, Review, Other

Open AccessArticle
In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants
Trop. Med. Infect. Dis. 2017, 2(3), 48; https://doi.org/10.3390/tropicalmed2030048
Received: 3 July 2017 / Revised: 8 September 2017 / Accepted: 12 September 2017 / Published: 20 September 2017
Cited by 1 | PDF Full-text (887 KB) | HTML Full-text | XML Full-text
Abstract
Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG [...] Read more.
Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally. Full article
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Open AccessArticle
Public Preference for Pet-Rabies Prophylaxis: Opportunities and Information Dissemination
Trop. Med. Infect. Dis. 2017, 2(3), 46; https://doi.org/10.3390/tropicalmed2030046
Received: 20 June 2017 / Revised: 25 August 2017 / Accepted: 7 September 2017 / Published: 13 September 2017
Cited by 1 | PDF Full-text (214 KB) | HTML Full-text | XML Full-text
Abstract
Risky human behavior and high density of rabies vectors in urban environments combine to increase the risk of rabies. Pet vaccination, wildlife vector management, and public health education may be the most efficient ways to prevent urban rabies epidemics. Racial, ethnic, and socio-economic [...] Read more.
Risky human behavior and high density of rabies vectors in urban environments combine to increase the risk of rabies. Pet vaccination, wildlife vector management, and public health education may be the most efficient ways to prevent urban rabies epidemics. Racial, ethnic, and socio-economic factors influence the use of low-cost rabies vaccination clinics, understanding rabies reporting requirements, and learning preferences. In collaboration with the City of Greensboro and Animal Control in Guilford County, NC, we conducted a survey of rabies prevention and transmission across socio-economic strata representing Latinos, African Americans, and Whites, and different income and education levels. Compliance with vaccination was low among Latinos; African Americans and Latinos were not aware of low-cost rabies vaccination clinics; and most respondents were willing to report rabid animals but did not know whom to call. White respondents preferred online information delivery, whereas Latinos and African Americans preferred postal mail. Communication targeting the public requires the consideration of different message decoding and interpretation based on the ethnicity, income, and educational level, and other barriers such as language. Differing message delivery methods may be required to achieve full dissemination. Full article
Open AccessArticle
Modeling Raccoon (Procyon lotor) Habitat Connectivity to Identify Potential Corridors for Rabies Spread
Trop. Med. Infect. Dis. 2017, 2(3), 44; https://doi.org/10.3390/tropicalmed2030044
Received: 31 May 2017 / Revised: 7 August 2017 / Accepted: 10 August 2017 / Published: 28 August 2017
Cited by 3 | PDF Full-text (1290 KB) | HTML Full-text | XML Full-text
Abstract
The United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Wildlife Services National Rabies Management Program has conducted cooperative oral rabies vaccination (ORV) programs since 1997. Understanding the eco-epidemiology of raccoon (Procyon lotor) variant rabies (raccoon rabies) [...] Read more.
The United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Wildlife Services National Rabies Management Program has conducted cooperative oral rabies vaccination (ORV) programs since 1997. Understanding the eco-epidemiology of raccoon (Procyon lotor) variant rabies (raccoon rabies) is critical to successful management. Pine (Pinus spp.)-dominated landscapes generally support low relative raccoon densities that may inhibit rabies spread. However, confounding landscape features, such as wetlands and human development, represent potentially elevated risk corridors for rabies spread, possibly imperiling enhanced rabies surveillance and ORV planning. Raccoon habitat suitability in pine-dominated landscapes in Massachusetts, Florida, and Alabama was modeled by the maximum entropy (Maxent) procedure using raccoon presence, and landscape and environmental data. Replicated (n = 100/state) bootstrapped Maxent models based on raccoon sampling locations from 2012–2014 indicated that soil type was the most influential variable in Alabama (permutation importance PI = 38.3), which, based on its relation to landcover type and resource distribution and abundance, was unsurprising. Precipitation (PI = 46.9) and temperature (PI = 52.1) were the most important variables in Massachusetts and Florida, but these possibly spurious results require further investigation. The Alabama Maxent probability surface map was ingested into Circuitscape for conductance visualizations of potential areas of habitat connectivity. Incorporating these and future results into raccoon rabies containment and elimination strategies could result in significant cost-savings for rabies management here and elsewhere. Full article
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Open AccessArticle
The Importance of a Participatory and Integrated One Health Approach for Rabies Control: The Case of N’Djaména, Chad
Trop. Med. Infect. Dis. 2017, 2(3), 43; https://doi.org/10.3390/tropicalmed2030043
Received: 31 May 2017 / Revised: 27 July 2017 / Accepted: 3 August 2017 / Published: 23 August 2017
Cited by 5 | PDF Full-text (1907 KB) | HTML Full-text | XML Full-text
Abstract
This study compares data on animal rabies cases from the Chadian national rabies laboratory, hosted at the Insitut de Recherche en Elevage pour le Developpement (IRED), with bite case reporting from health facilities. The data collection accompanied a mass dog vaccination intervention over [...] Read more.
This study compares data on animal rabies cases from the Chadian national rabies laboratory, hosted at the Insitut de Recherche en Elevage pour le Developpement (IRED), with bite case reporting from health facilities. The data collection accompanied a mass dog vaccination intervention over two years in N’Djaména, Chad. This allowed for a comparison of the dynamics of the incidence of animal rabies cases, human bite exposure incidence and post-exposure prophylaxis (PEP) demand during a dog rabies elimination attempt. Following the mass vaccination, the monthly animal rabies incidence dropped from 1.1/10,000 dogs, as observed prior to the campaign in 2012, to 0.061/10,000 dogs in 2014. However, the PEP demand was found to be largely unaffected. The suspicion of the rabies exposure as reported by health personnel in most cases did not reflect the status of the biting animal but rather the severity of the bite wound, resulting in inappropriate PEP recommendations. In addition, the levels of reporting dead or killed animals to the rabies laboratory was found to be very low. These results reveal a profound lack of communication between health facilities and veterinary structures and the absence of an integrated bite case management (IBCM) approach. Improved communication between human health and veterinary workers is imperative to prevent human rabies deaths through the appropriate use of PEP and to further translate success in animal rabies control into cost savings for the public health sector through a lower PEP demand. Improved training of health and veterinary personnel and the sensitisation of the public are needed to achieve good IBCM practice, to increase the rate of diagnostic testing, to provide adequate and timely PEP, and to reduce the wastage of scarce vaccine resources. Full article
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Open AccessArticle
Evaluation of Bait Station Density for Oral Rabies Vaccination of Raccoons in Urban and Rural Habitats in Florida
Trop. Med. Infect. Dis. 2017, 2(3), 41; https://doi.org/10.3390/tropicalmed2030041
Received: 7 July 2017 / Revised: 15 August 2017 / Accepted: 18 August 2017 / Published: 22 August 2017
Cited by 2 | PDF Full-text (1374 KB) | HTML Full-text | XML Full-text
Abstract
Efforts to eliminate the raccoon variant of the rabies virus (raccoon rabies) in the eastern United States by USDA, APHIS, Wildlife Services and cooperators have included the distribution of oral rabies vaccine baits from polyvinyl chloride (PVC) bait stations in west-central Florida from [...] Read more.
Efforts to eliminate the raccoon variant of the rabies virus (raccoon rabies) in the eastern United States by USDA, APHIS, Wildlife Services and cooperators have included the distribution of oral rabies vaccine baits from polyvinyl chloride (PVC) bait stations in west-central Florida from 2009 to 2015. Achieving sufficient vaccine bait uptake among urban raccoons is problematic, given limitations on aerial and vehicle-based bait distribution for safety and other reasons. One or three bait stations/km2 were deployed across four 9-km2 sites within rural and urban sites in Pasco and Pinellas Counties, Florida. Based on tetracycline biomarker analysis, bait uptake was only significantly different among the urban (Pinellas County) high and low bait station densities in 2012 (p = 0.0133). Significant differences in RVNA were found between the two bait station densities for both urban 2011 and 2012 samples (p = 0.0054 and p = 0.0031). Landscape differences in terms of urban structure and human population density may modify raccoon travel routes and behavior enough for these differences to emerge in highly urbanized Pinellas County, but not in rural Pasco County. The results suggest that, in urban settings, bait stations deployed at densities of >1/km2 are likely to achieve higher seroprevalence as an index of population immunity critical to successful raccoon rabies control. Full article
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Open AccessArticle
Progress towards Bait Station Integration into Oral Rabies Vaccination Programs in the United States: Field Trials in Massachusetts and Florida
Trop. Med. Infect. Dis. 2017, 2(3), 40; https://doi.org/10.3390/tropicalmed2030040
Received: 14 July 2017 / Revised: 10 August 2017 / Accepted: 11 August 2017 / Published: 21 August 2017
Cited by 1 | PDF Full-text (2577 KB) | HTML Full-text | XML Full-text
Abstract
Bait stations for distribution of oral rabies vaccine baits are designed for rabies management in highly-developed areas where traditional distribution of oral rabies vaccine baits may be difficult. As part of national efforts to contain and eliminate the raccoon (Procyon lotor) [...] Read more.
Bait stations for distribution of oral rabies vaccine baits are designed for rabies management in highly-developed areas where traditional distribution of oral rabies vaccine baits may be difficult. As part of national efforts to contain and eliminate the raccoon (Procyon lotor) variant of the rabies virus (raccoon rabies) in the eastern United States, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services program, distributed vaccine baits by bait stations experimentally and operationally in Massachusetts during 2006-present, and in Florida during 2009–2015. In Massachusetts, a rabies virus-neutralizing antibody (RVNA) response of 42.1% for raccoons captured in areas baited with high density bait stations during 2011–2015 was achieved, compared with 46.2% in areas baited by hand, suggesting the continuation of this as a strategy for the oral rabies vaccination (ORV) program there, and for similar locations. Non-target competition for vaccine baits is problematic, regardless of distribution method. In Massachusetts, bait station visitation rates for targeted raccoons and non-target opossums (Didelphis virginiana) were similar (1.18:1) during 2006–2009 (p > 0.05). Bait station modifications for reducing non-target uptake were tested, and in Massachusetts, reduced non-target bait access was achieved with two design alternatives (p < 0.001). However, no difference was noted between the control and these two alternative designs in Florida. Due to ongoing trials of new vaccines and baits, the bait station performance of an adenovirus rabies glycoprotein recombinant vaccine bait, ONRAB® bait (Artemis Technologies, Guelph, ON, Canada) and a vaccinia-rabies glycoprotein recombinant vaccine bait, RABORAL V-RG®bait (Merial Limited, Athens, GA, USA), was compared. While uptake of the ONRAB bait was greater in Massachusetts (p < 0.001) in this limited trial, both types performed equally well in Florida. Since bait station tampering or theft as well as potential human bait contacts has been problematic, performance of camouflaged versus unpainted white bait stations was analyzed in terms of internal temperatures and maintaining a stable bait storage environment. In Massachusetts, camouflaged bait station interiors did not reach higher average temperatures than plain white bait stations in partially- or fully-shaded locations, while in Florida, camouflaged bait stations were significantly warmer in light exposure categories (p < 0.05). As ORV operations expand into more heavily-urbanized areas, bait stations will be increasingly important for vaccine bait distribution, and continued refinements in the strategy will be key to that success. Full article
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Open AccessArticle
Spatial Association of Canine Rabies Outbreak and Ecological Urban Corridors, Arequipa, Peru
Trop. Med. Infect. Dis. 2017, 2(3), 38; https://doi.org/10.3390/tropicalmed2030038
Received: 1 July 2017 / Revised: 8 August 2017 / Accepted: 9 August 2017 / Published: 13 August 2017
Cited by 1 | PDF Full-text (4029 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the city of Arequipa, Peru, a rabid dog was detected in March 2015, marking the reintroduction of the rabies virus in the area; more rabid dogs have been detected since then. The presence of free-roaming dogs in Arequipa seems to be higher [...] Read more.
In the city of Arequipa, Peru, a rabid dog was detected in March 2015, marking the reintroduction of the rabies virus in the area; more rabid dogs have been detected since then. The presence of free-roaming dogs in Arequipa seems to be higher in dry water channels, which are widespread in the city. We created a geographic information system (GIS) with surveillance data on the location of rabid dogs detected during the first year of the outbreak, as well as the water channels. We conducted a spatial analysis using Monte Carlo simulations to determine if detected rabid dogs were closer to the water channels than expected. Thirty rabid dogs were detected during the first year of the outbreak, and they were statistically associated with the water channels (average distance to closest water channel = 334 m; p-value = 0.027). Water channels might play a role in the ecology of free-roaming dog populations, functioning as ecological corridors. Landscape ecology could assist in understanding the impact of these urban structures on control activities and the persistence of transmission. Full article
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Open AccessArticle
Pathogenicity and Immunogenicity of Recombinant Rabies Viruses Expressing the Lagos Bat Virus Matrix and Glycoprotein: Perspectives for a Pan-Lyssavirus Vaccine
Trop. Med. Infect. Dis. 2017, 2(3), 37; https://doi.org/10.3390/tropicalmed2030037
Received: 30 June 2017 / Revised: 31 July 2017 / Accepted: 4 August 2017 / Published: 9 August 2017
Cited by 1 | PDF Full-text (997 KB) | HTML Full-text | XML Full-text
Abstract
Lagos bat virus (LBV) is a phylogroup II lyssavirus exclusively found in Africa. Previous studies indicated that this virus is lethal to mice after intracranial and intramuscular inoculation. The antigenic composition of LBV differs substantially from that of rabies virus (RABV) and current [...] Read more.
Lagos bat virus (LBV) is a phylogroup II lyssavirus exclusively found in Africa. Previous studies indicated that this virus is lethal to mice after intracranial and intramuscular inoculation. The antigenic composition of LBV differs substantially from that of rabies virus (RABV) and current rabies vaccines do not provide cross protection against phylogroup II lyssaviruses. To investigate the potential role of the LBV matrix protein (M) and glycoprotein (G) in pathogenesis, reverse genetics technology was used to construct recombinant viruses. The genes encoding the glycoprotein, or the matrix and glycoprotein of the attenuated RABV strain SPBN, were replaced with those of LBV resulting in SPBN-LBVG and SPBN-LBVM-LBVG, respectively. To evaluate the immunogenicity of the LBV G, the recombinant RABV SPBNGAS-LBVG-GAS was constructed with the LBV G inserted between two mutated RABV G genes (termed GAS). All the recombinant viruses were lethal to mice after intracranial (i.c.) inoculation although the pathogenicity of SPBNGAS-LBVG-GAS was lower compared to the other recombinant viruses. Following intramuscular (i.m.) inoculation, only SPBN-LBVM-LBVG was lethal to mice, indicating that both the M and G of LBV play a role in the pathogenesis. Most interestingly, serum collected from mice that were inoculated i.m. with SPBNGAS-LBVG-GAS neutralized phylogroup I and II lyssaviruses including RABV, Duvenhage virus (DUVV), LBV, and Mokola virus (MOKV), indicating that this recombinant virus has potential to be developed as a pan-lyssavirus vaccine. Full article
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Open AccessArticle
Enhanced Rabies Surveillance to Support Effective Oral Rabies Vaccination of Raccoons in the Eastern United States
Trop. Med. Infect. Dis. 2017, 2(3), 34; https://doi.org/10.3390/tropicalmed2030034
Received: 31 May 2017 / Revised: 14 July 2017 / Accepted: 24 July 2017 / Published: 28 July 2017
Cited by 3 | PDF Full-text (820 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Enhanced rabies surveillance (ERS) is essential for sound oral rabies vaccination (ORV) decisions to prevent the spread of specific rabies virus variants in meso-carnivores and to achieve disease elimination. Use of a direct rapid immunohistochemistry test (dRIT) in North America for timely, accurate [...] Read more.
Enhanced rabies surveillance (ERS) is essential for sound oral rabies vaccination (ORV) decisions to prevent the spread of specific rabies virus variants in meso-carnivores and to achieve disease elimination. Use of a direct rapid immunohistochemistry test (dRIT) in North America for timely, accurate rabies diagnosis in the field has facilitated greater ERS emphasis since 2005. ERS used in tandem with exposure-based public health surveillance provides a comprehensive understanding of the geographic distribution of rabies as an aid to formulate effective management strategies for raccoons and other meso-carnivores. In 2015, best management practices were implemented for improving, reinvigorating, and standardizing ERS. A point system for weighing ERS sample categories was evaluated, to determine whether sampling emphasis should be focused upon ill or strange-acting animals, the highest quality category. During 2016, 70.7% of rabid animals detected through ERS in raccoon rabies management states were obtained from strange-acting animals, followed by animals found dead (14.1%), road kills (9.1%), and nuisance-collected specimens (6.1%). Sample category weights may be adjusted based on additional evaluation to ensure continued emphasis on the highest value samples. High quality ERS, in conjunction with serologic evidence of population-based immunity, form the backbone for ORV decisions in the elimination of raccoon rabies. Full article
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Open AccessArticle
Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife
Trop. Med. Infect. Dis. 2017, 2(3), 31; https://doi.org/10.3390/tropicalmed2030031
Received: 2 June 2017 / Revised: 6 July 2017 / Accepted: 8 July 2017 / Published: 21 July 2017
Cited by 11 | PDF Full-text (2616 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV) of wildlife reservoir populations for decades [...] Read more.
Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV) of wildlife reservoir populations for decades to control circulation of rabies virus in free-ranging hosts. There remains much debate about the levels of rabies antibodies (and the assays to measure them) that confer resistance to rabies virus. In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, are examined as correlates of protection against lethal rabies infection in captive challenge settings. Analysis of our studies suggests that, though serum neutralization test results are expected to reflect in vivo protection, the blocking enzyme linked immunosorbent assay (ELISA) result at Day 28 was a better predictor of survival. ELISA kits may have an advantage of greater precision and ability to compare results among different studies and laboratories based on the inherent standardization of the kit format. This paper examines current knowledge and study findings to guide meaningful interpretation of serology results in oral baiting monitoring. Full article
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Open AccessArticle
Epidemiology of Rabies in Lesotho: The Importance of Routine Surveillance and Virus Characterization
Trop. Med. Infect. Dis. 2017, 2(3), 30; https://doi.org/10.3390/tropicalmed2030030
Received: 27 June 2017 / Revised: 14 July 2017 / Accepted: 16 July 2017 / Published: 19 July 2017
Cited by 2 | PDF Full-text (1367 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rabies is widespread throughout Africa and Asia, despite the fact that the control and elimination of this disease has been proven to be feasible. Lesotho, a small landlocked country surrounded by South Africa, has been known to be endemic for rabies since the [...] Read more.
Rabies is widespread throughout Africa and Asia, despite the fact that the control and elimination of this disease has been proven to be feasible. Lesotho, a small landlocked country surrounded by South Africa, has been known to be endemic for rabies since the 1980s but the epidemiology of the disease remains poorly understood due to limited sample submission, constrained diagnostic capabilities, and a lack of molecular epidemiological data. Considering the existing challenges experienced in Lesotho, we aimed to evaluate the direct, rapid immunohistochemical test (DRIT) as an alternative to the direct fluorescent antibody (DFA) test for rabies diagnosis in Lesotho. Towards this aim, extensive training on the implementation and interpretation of the DRIT was hosted in Lesotho in April 2016 before both tests were applied to all samples subjected to routine rabies diagnosis at the Central Veterinary Laboratory (CVL). We found agreement between the DFA and DRIT assays in 90/96 samples (93.75%). The samples that produced inconsistent results (n = 6) were re-tested a further two times with both assays before being subjected to a real-time qPCR to confirm the diagnosis. Additionally, a statistically significant three-fold increase in the average number of samples submitted per month was observed after the DRIT implementation started, following continuous rabies awareness initiatives amongst the animal health professionals in the country over a 12-month period (p = 0.0279). Partial G-L intergenic regions of selected rabies-positive samples (n = 21) were amplified, sequenced, and subjected to phylogenetic analyses. Molecular epidemiological analyses, that included viruses from neighbouring provinces in South Africa, suggested that at least three independent rabies cycles within Lesotho were implicated in instances of cross-border transmission. This study has evaluated alternative methods for diagnosing and improving rabies surveillance in Lesotho, as well as providing new information that would be of importance in the planning of future disease intervention campaigns, not only in Lesotho, but also in neighbouring South Africa. Full article
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Open AccessCommunication
The Formation of the Eastern Africa Rabies Network: A Sub-Regional Approach to Rabies Elimination
Trop. Med. Infect. Dis. 2017, 2(3), 29; https://doi.org/10.3390/tropicalmed2030029
Received: 30 June 2017 / Revised: 11 July 2017 / Accepted: 13 July 2017 / Published: 18 July 2017
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Abstract
Abstract: International rabies networks have been formed in many of the canine-rabies endemic regions around the world to create unified and directed regional approaches towards elimination. The aim of the first sub-regional Eastern Africa rabies network meeting, which included Kenya, Ethiopia, Tanzania, [...] Read more.
Abstract: International rabies networks have been formed in many of the canine-rabies endemic regions around the world to create unified and directed regional approaches towards elimination. The aim of the first sub-regional Eastern Africa rabies network meeting, which included Kenya, Ethiopia, Tanzania, Rwanda, and Uganda, was to discuss how individual country strategies could be coordinated to address the unique challenges that are faced within the network. The Stepwise Approach towards Rabies Elimination and the Global Dog Rabies Elimination Pathway tool were used to stimulate discussion and planning to achieve the elimination of canine-mediated human rabies by 2030. Our analysis estimated a total dog population of 18.3 million dogs in the Eastern Africa region. The current dog vaccination coverage was estimated to be approximately 5% (915,000 dogs), with an estimated 4910 vaccinators available. Assuming that every vaccinator performs rabies vaccination, this equated to each vaccinator currently vaccinating 186 dogs per year, whilst the target would be to vaccinate 2609 dogs every year for the community to reach 70% coverage. In order to achieve the World Health Organization-recommended 70% vaccination coverage, an additional 11 million dogs need to be vaccinated each year, pointing to an average annual shortfall of $ 23 million USD in current spending to achieve elimination by 2030 across the region. Improved vaccination efficiency within the region could be achieved by improving logistics and/or incorporating multiple vaccination methods to increase vaccinator efficiency, and could serve to reduce the financial burden associated with rabies elimination. Regional approaches to rabies control are of value, as neighboring countries can share their unique challenges while, at the same time, common approaches can be developed and resource-saving strategies can be implemented. Full article
Open AccessArticle
Sero-Surveillance of Lyssavirus Specific Antibodies in Nigerian Fruit Bats (Eidolon helvum)
Trop. Med. Infect. Dis. 2017, 2(3), 26; https://doi.org/10.3390/tropicalmed2030026
Received: 30 May 2017 / Revised: 4 June 2017 / Accepted: 4 June 2017 / Published: 9 July 2017
Cited by 4 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
The aetiological agent of rabies is a member of the Lyssavirus genus (Rhabdoviridae family, order Mononegavirales). The disease (rabies) is endemic in many parts of Asia and Africa and still remains an important public and veterinary health threat. In Nigeria, there [...] Read more.
The aetiological agent of rabies is a member of the Lyssavirus genus (Rhabdoviridae family, order Mononegavirales). The disease (rabies) is endemic in many parts of Asia and Africa and still remains an important public and veterinary health threat. In Nigeria, there is a dearth of information on the natural infection and/or exposure of bat species to lyssaviruses. Therefore, this study was undertaken to assess the prevalence of rabies virus (RABV) neutralizing antibodies in sera obtained from bats from the central Plateau and North-East Bauchi States in Nigeria. Two hundred serum samples were collected from Nigerian fruit bats from six different locations and tested for anti-RABV antibodies using a commercial blocking ELISA. Of the 200 bat serum samples collected, one batch consisting of 111 samples did not meet the validation criteria and hence was not included in the final analysis. Of the remaining 89, only three (3.4%) contained anti-lyssavirus antibodies, demonstrating a low prevalence of lyssavirus antibodies in the study population. In order to further understand the exposure of bat species to phylogroup II lyssaviruses (Lagos bat virus and Mokola virus), the same panel of samples will be tested for neutralizing antibodies to phylogroup II members, viruses that do not cross-neutralize with members of phylogroup I. Full article
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Open AccessArticle
Lagos Bat Virus Infection Dynamics in Free-Ranging Straw-Colored Fruit Bats (Eidolon helvum)
Trop. Med. Infect. Dis. 2017, 2(3), 25; https://doi.org/10.3390/tropicalmed2030025
Received: 20 May 2017 / Revised: 30 June 2017 / Accepted: 4 July 2017 / Published: 8 July 2017
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Abstract
Bats are key species for ecological function, but they are also reservoirs of zoonotic agents, such as lyssaviruses that cause rabies. Little is known about the maintenance and transmission of lyssaviruses in bats, although the observation of clinically sick bats, both in experimental [...] Read more.
Bats are key species for ecological function, but they are also reservoirs of zoonotic agents, such as lyssaviruses that cause rabies. Little is known about the maintenance and transmission of lyssaviruses in bats, although the observation of clinically sick bats, both in experimental studies and wild bats, has at least demonstrated that lyssaviruses are capable of causing clinical disease in bat species. Despite this, extensive surveillance for diseased bats has not yielded lyssaviruses, whilst serological surveys demonstrate that bats must be exposed to lyssavirus without developing clinical disease. We hypothesize that there is endemic circulation of Lagos bat virus (LBV) in the straw-coloured fruit bat (Eidolon helvum) in Ghana, West Africa. To investigate this further, longitudinal blood sampling was undertaken quarterly between 2012 and 2014 on wild E. helvum at two sites in Ghana. Serum samples were collected and tested for LBV-neutralizing antibodies using a modified flourescent antibody virus neutralisation (FAVN) assay (n = 294) and brains from moribund or dead bats were tested for antigen and viral RNA (n = 55). Overall, 44.7% of the 304 bats sampled had LBV-neutralising antibodies. None of the brain samples from bats contained lyssavirus antigen or RNA. Together with the results of an earlier serological study, our findings demonstrate that LBV is endemic and circulates within E. helvum in Ghana even though the detection of viral infection in dead bats was unsuccessful. Confirmation that LBV infection is endemic in E. helvum in Ghana is an important finding and indicates that the potential public health threats from LBV warrant further investigation. Full article
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Open AccessArticle
Comparison of a Micro-Neutralization Test with the Rapid Fluorescent Focus Inhibition Test for Measuring Rabies Virus Neutralizing Antibodies
Trop. Med. Infect. Dis. 2017, 2(3), 24; https://doi.org/10.3390/tropicalmed2030024
Received: 19 May 2017 / Revised: 26 June 2017 / Accepted: 30 June 2017 / Published: 7 July 2017
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Abstract
The rapid fluorescent focus inhibition test (RFFIT) is routinely used in the United States to measure rabies virus neutralizing antibodies (rVNA). RFFIT has a long history of reproducible and reliable results. The test has been modified over the years to use smaller volumes [...] Read more.
The rapid fluorescent focus inhibition test (RFFIT) is routinely used in the United States to measure rabies virus neutralizing antibodies (rVNA). RFFIT has a long history of reproducible and reliable results. The test has been modified over the years to use smaller volumes of reagents and samples, but requires a 50 μL minimum volume of test serum. To conduct pathogenesis studies, small laboratory animals such as mice are regularly tested for rVNA, but the minimum volume for a standard RFFIT may be impossible to obtain, particularly in scenarios of repeated sampling. To address this problem, a micro-neutralization test was developed previously. In the current study, the micro-neutralization test was compared to the RFFIT using 129 mouse serum samples from rabies vaccine studies. Using a cut-off value of 0.1 IU/mL, the sensitivity, specificity, and concordance of the micro-neutralization test were 100%, 97.5%, and 98%, respectively. The geometric mean titer of all samples above the cut-off was 2.0 IU/mL using RFFIT and 3.4 IU/mL using the micro-neutralization test, indicating that titers determined using the micro-neutralization test are not equivalent to RFFIT titers. Based on four rVNA-positive hamster serum samples, the intra-assay coefficient of variability was 24% and inter-assay coefficient of variability was 30.4%. These results support continued use of the micro-neutralization test to determine rabies virus neutralizing antibody titers for low-volume serum samples. Full article
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Open AccessArticle
Protection Against CNS-Targeted Rabies Virus Infection is Dependent upon Type-1 Immune Mechanisms Induced by Live-Attenuated Rabies Vaccines
Trop. Med. Infect. Dis. 2017, 2(3), 22; https://doi.org/10.3390/tropicalmed2030022
Received: 17 May 2017 / Revised: 28 June 2017 / Accepted: 29 June 2017 / Published: 4 July 2017
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Abstract
Rabies remains a major public health issue worldwide, especially in developing countries where access to medical care can represent a real challenge. While there is still no cure for rabies, it is a vaccine-preventable disease with pre- and post-exposure prophylaxis regimens approved by [...] Read more.
Rabies remains a major public health issue worldwide, especially in developing countries where access to medical care can represent a real challenge. While there is still no cure for rabies, it is a vaccine-preventable disease with pre- and post-exposure prophylaxis regimens approved by the World Health Organization (WHO). However, many rabies-exposed individuals have limited access to vaccines and virus-neutralizing antibodies approved for post-exposure prophylaxis. Unfortunately, any delay in the administration of these reagents can have lethal consequences. This highlights the need to develop cost-effective immunological reagents with a greater window of efficacy. Live-attenuated vaccine strains of rabies virus presents a potential treatment in filling this gap. We show here that immunization with live-attenuated vaccines provide long-lasting rabies immunity, superior to the protection induced by inactivated vaccines. In the absence of an immunostimulatory adjuvant, vaccination with multiple doses of inactivated rabies virus induces a type-2 immune response. This type of immunity is highly effective at inducing neutralizing antibody but has limited efficacy in clearing the virus from central nervous system (CNS) tissues. In contrast, a single infection with live-attenuated rabies vaccine safely drives a type-1 immune response, associated with both the production of a neutralizing antibody and the clearance of wild-type rabies virus from CNS tissues. These results indicate that live-attenuated rabies strains have the potential to be more effective in post-exposure prophylaxis than conventional inactivated vaccines. Full article
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Open AccessArticle
Incorporating Direct Rapid Immunohistochemical Testing into Large-Scale Wildlife Rabies Surveillance
Trop. Med. Infect. Dis. 2017, 2(3), 21; https://doi.org/10.3390/tropicalmed2030021
Received: 31 May 2017 / Revised: 23 June 2017 / Accepted: 25 June 2017 / Published: 30 June 2017
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Abstract
Following an incursion of the mid-Atlantic raccoon variant of the rabies virus into southern Ontario, Canada, in late 2015, the direct rapid immunohistochemical test for rabies (dRIT) was employed on a large scale to establish the outbreak perimeter and to diagnose specific cases [...] Read more.
Following an incursion of the mid-Atlantic raccoon variant of the rabies virus into southern Ontario, Canada, in late 2015, the direct rapid immunohistochemical test for rabies (dRIT) was employed on a large scale to establish the outbreak perimeter and to diagnose specific cases to inform rabies control management actions. In a 17-month period, 5800 wildlife carcasses were tested using the dRIT, of which 307 were identified as rabid. When compared with the gold standard fluorescent antibody test (FAT), the dRIT was found to have a sensitivity of 100% and a specificity of 98.2%. Positive and negative test agreement was shown to be 98.3% and 99.1%, respectively, with an overall test agreement of 98.8%. The average cost to test a sample was $3.13 CAD for materials, and hands-on technical time to complete the test is estimated at 0.55 h. The dRIT procedure was found to be accurate, fast, inexpensive, easy to learn and perform, and an excellent tool for monitoring the progression of a wildlife rabies incursion. Full article
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Open AccessArticle
Field Studies Evaluating Bait Acceptance and Handling by Dogs in Navajo Nation, USA
Trop. Med. Infect. Dis. 2017, 2(2), 17; https://doi.org/10.3390/tropicalmed2020017
Received: 26 April 2017 / Revised: 9 June 2017 / Accepted: 12 June 2017 / Published: 15 June 2017
Cited by 4 | PDF Full-text (1777 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mass parenteral vaccination remains the cornerstone of dog rabies control. Oral rabies vaccination (ORV) could increase vaccination coverage where free-roaming dogs represent a sizeable segment of the population at risk. ORV’s success is dependent on the acceptance of baits that release an efficacious [...] Read more.
Mass parenteral vaccination remains the cornerstone of dog rabies control. Oral rabies vaccination (ORV) could increase vaccination coverage where free-roaming dogs represent a sizeable segment of the population at risk. ORV’s success is dependent on the acceptance of baits that release an efficacious vaccine into the oral cavity. A new egg-flavored bait was tested alongside boiled bovine intestine and a commercially available fishmeal bait using a hand-out model on the Navajo Nation, United States, during June 2016. A PVC capsule and biodegradable sachet were tested, and had no effect on bait acceptance. The intestine baits had the highest acceptance (91.9%; 95% confidence interval (CI), 83.9%–96.7%), but the fishmeal (81.1%; 95% CI, 71.5%–88.6%) and the egg-flavored baits (77.4%; 95% CI, 72.4%–81.8%) were also well accepted, suggesting that local bait preference studies may be warranted to enhance ORV’s success in other areas where canine rabies is being managed. Based on a dyed water marker, the delivery of a placebo vaccine was best in the intestine baits (75.4%; 95% CI, 63.5%–84.9%), followed by the egg-flavored (68.0%; 95% CI, 62.4%–73.2%) and fishmeal (54.3%; 95% CI, 42.9%–65.4%) baits. Acceptance was not influenced by the supervision or ownership, or sex, age, and body condition of the dogs. This study illustrates that a portion of a dog population may be orally vaccinated as a complement to parenteral vaccination to achieve the immune thresholds required to eliminate dog rabies. Full article
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Open AccessArticle
Retrospective Cohort Study to Assess the Risk of Rabies in Biting Dogs, 2013–2015, Republic of Haiti
Trop. Med. Infect. Dis. 2017, 2(2), 14; https://doi.org/10.3390/tropicalmed2020014
Received: 29 April 2017 / Revised: 29 May 2017 / Accepted: 6 June 2017 / Published: 12 June 2017
Cited by 2 | PDF Full-text (836 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: In canine rabies endemic countries the World Health Organization recommends post-exposure prophylaxis (PEP) be initiated immediately after exposure to an animal suspected to have rabies. Limited capacity in low and middle income countries to assess biting animals for rabies may result in [...] Read more.
Background: In canine rabies endemic countries the World Health Organization recommends post-exposure prophylaxis (PEP) be initiated immediately after exposure to an animal suspected to have rabies. Limited capacity in low and middle income countries to assess biting animals for rabies may result in the over prescription of rabies biologics. Few guidelines exist to determine the risk of whether a dog that has bitten someone is rabid. Given PEP cost and access limitations in many countries, accurate and timely assessment of dogs that have bitten people may reduce unwarranted PEP use and improve healthcare seeking behaviors. Methods: Haiti’s animal rabies surveillance program utilizes veterinary professionals to conduct rabies assessments on reported biting dogs and records characteristics of the dog, health outcomes, and laboratory results in a national database. Characteristics of rabid dogs were assessed through a retrospective cohort study of biting dogs investigated during the period from January 2013–December 2015. 1409 biting dogs were analyzed; 1361 dogs that were determined to not have rabies were compared to 48 laboratory-confirmed rabid dogs. Rate ratios, sensitivity, specificity, positive predictive values, negative predictive values, likelihood ratios, quarantine survival of biting dogs, and a risk matrix were developed. Findings: The assessor’s determination that the animal likely had rabies was the most significant predictive factor for a rabid dog (RR = 413.4, 95% CI 57.33–2985, Sn = 79.17, Sp = 91.92). Clinical factors significantly associated with rabid dogs included hypersalivation, paralysis, and lethargy (RR = 31.2, 19.7, 15.4, respectively). Rabid dogs were 23.2 times more likely to be found dead at the time of the investigation compared to case negative dogs (95% CI 14.0–38.6). Rabid dogs were also significantly more likely to lack a history of rabies vaccination or be unowned (RR = 10.3 95% CI 2.5–42.3 and RR = 4.5 95% CI 2.0–10.1, respectively). Rabid dogs were four times more likely to have bitten multiple people (RR = 4.0 95% CI 1.9–8.3). Most rabid dogs died or were killed before quarantine (75%) and all died by day 3 of quarantine, compared to <1% of quarantined case-negatives. The greatest risk of death was predicted to be for persons bitten on the head or neck from symptomatic dogs. Bites from dogs deemed healthy by veterinary assessors and which were available for quarantine presented less than a 0.05% risk of rabies death to the victim. Conclusions: Vaccination of all persons exposed to a suspected rabid dog is a highly effective approach to minimize human rabies deaths. However, this may place undue financial burden on bite victims that have had a low-risk exposure and over-prescription may contribute to regional supply shortages. The results here indicate that in a low-resource country such as Haiti, a well-trained veterinary assessor can provide an accurate risk assessment of biting dogs based on a standard case investigation protocol. In canine rabies endemic countries with limited access to PEP, or where PEP costs may cause undue burden on bite victims, structured risk assessments by trained professionals may be a reliable method of triaging PEP for bite victims. Evaluating rabies risk through a matrix of bite location and risk factor in the dog presents a clear delineation of high and low risk encounters and should be used to develop data-derived PEP recommendations. Full article
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Open AccessArticle
Cost and Relative Value of Road Kill Surveys for Enhanced Rabies Surveillance in Raccoon Rabies Management
Trop. Med. Infect. Dis. 2017, 2(2), 13; https://doi.org/10.3390/tropicalmed2020013
Received: 7 March 2017 / Revised: 8 May 2017 / Accepted: 10 May 2017 / Published: 23 May 2017
Cited by 1 | PDF Full-text (4205 KB) | HTML Full-text | XML Full-text
Abstract
Oral rabies vaccination (ORV) requires knowledge of the spatial-temporal distribution of rabies virus variants targeted for control. Rabies-exposure based public health surveillance alone may not provide a sound basis for ORV decisions. The value and cost of road kill surveys was evaluated for [...] Read more.
Oral rabies vaccination (ORV) requires knowledge of the spatial-temporal distribution of rabies virus variants targeted for control. Rabies-exposure based public health surveillance alone may not provide a sound basis for ORV decisions. The value and cost of road kill surveys was evaluated for the late spring–early fall 2005–2007 as a part of enhanced rabies surveillance in northern New York, where raccoon rabies is enzootic and ORV has occurred since the late 1990s. Structured surveys were conducted to collect raccoons and other meso-carnivores for rabies testing at the New York State Rabies Laboratory. Of the 209 meso-carnivore heads collected and submitted for testing, 175 were testable by direct fluorescent antibody; none was rabid. Rabies was also not reported through public health surveillance in survey zones during 2005–2007. Overall, survey costs were $37,118 (2016 USD). Salaries and benefits accounted for 61% of costs, followed by fuel (22%), vehicle depreciation (14%), and sample shipping (3%). Mean daily distance driven was 303 ± 37 km and 381 ± 28 km for total road kills and raccoons, respectively. Costs/road kill collected and submitted was $176/all species and $224/raccoon. This study provides costs for planning road kill surveys and underscores the need to continually improve enhanced rabies surveillance approaches to support ORV decision making. Full article
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Review

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Open AccessReview
The Imperative of Palliation in the Management of Rabies Encephalomyelitis
Trop. Med. Infect. Dis. 2017, 2(4), 52; https://doi.org/10.3390/tropicalmed2040052
Received: 8 September 2017 / Revised: 18 September 2017 / Accepted: 28 September 2017 / Published: 4 October 2017
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Abstract
The aim of this review is to guide clinicians in the practical management of patients suffering from rabies encephalomyelitis. This condition is eminently preventable by modern post-exposure vaccination, but is virtually always fatal in unvaccinated people. In the absence of any proven effective [...] Read more.
The aim of this review is to guide clinicians in the practical management of patients suffering from rabies encephalomyelitis. This condition is eminently preventable by modern post-exposure vaccination, but is virtually always fatal in unvaccinated people. In the absence of any proven effective antiviral or other treatment, palliative care is an imperative to minimise suffering. Suspicion of rabies encephalomyelitis depends on recognising the classic symptomatology and eliciting a history of exposure to a possibly rabid mammal. Potentially treatable differential diagnoses must be eliminated, notably other infective encephalopathies. Laboratory confirmation of suspected rabies is not usually possible in many endemic areas, but is essential for public health surveillance. In a disease as agonising and terrifying as rabies encephalomyelitis, alleviation of distressing symptoms is the primary concern and overriding responsibility of medical staff. Calm, quiet conditions should be created, allowing relatives to communicate with the dying patient in safety and privacy. Palliative management must address thirst and dehydration, fever, anxiety, fear, restlessness, agitation, seizures, hypersecretion, and pain. As the infection progresses, coma and respiratory, cardiovascular, neurological, endocrine, or gastrointestinal complications will eventually ensue. When the facilities exist, the possibility of intensive care may arise, but although some patients may survive, they will be left with severe neurological sequelae. Recovery from rabies is extremely rare, and heroic measures with intensive care should be considered only in patients who have been previously vaccinated, develop rabies antibody within the first week of illness, or were infected by an American bat rabies virus. However, in most cases, clinicians must have the courage to offer compassionate palliation whenever the diagnosis of rabies encephalomyelitis is inescapable. Full article
Open AccessReview
The History of Rabies in Trinidad: Epidemiology and Control Measures
Trop. Med. Infect. Dis. 2017, 2(3), 27; https://doi.org/10.3390/tropicalmed2030027
Received: 19 May 2017 / Revised: 26 June 2017 / Accepted: 3 July 2017 / Published: 11 July 2017
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Abstract
Vampire bat-transmitted rabies was first recognized in Trinidad during a major outbreak reported in 1925. Trinidad is the only Caribbean island with vampire bat-transmitted rabies. We conducted a literature review to describe the changing epidemiology of rabies in Trinidad and give a historical [...] Read more.
Vampire bat-transmitted rabies was first recognized in Trinidad during a major outbreak reported in 1925. Trinidad is the only Caribbean island with vampire bat-transmitted rabies. We conducted a literature review to describe the changing epidemiology of rabies in Trinidad and give a historical perspective to rabies prevention and control measures on the island. The last human case of rabies occurred in 1937 and although no case of canine-transmitted rabies was reported since 1914, sporadic outbreaks of bat-transmitted rabies still occur in livestock to date. Over the last century, seven notable epidemics were recorded in Trinidad with the loss of over 3000 animals. During the 1950s, several measures were effectively adopted for the prevention and control of the disease which led to a significant reduction in the number of cases. These measures include: vampire bat population control, livestock vaccination, and animal surveillance. However, due to lapses in these measures over the years (e.g., periods of limited vampire control and incomplete herd vaccination), epidemics have occurred. In light of the significant negative impact of rabies on animal production and human health, rabies surveillance in Trinidad should be enhanced and cases evaluated towards the design and implementation of more evidence-based prevention and control programs. Full article
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Open AccessReview
Heterogeneity of Rabies Vaccination Recommendations across Asia
Trop. Med. Infect. Dis. 2017, 2(3), 23; https://doi.org/10.3390/tropicalmed2030023
Received: 30 May 2017 / Revised: 27 June 2017 / Accepted: 29 June 2017 / Published: 6 July 2017
Cited by 3 | PDF Full-text (559 KB) | HTML Full-text | XML Full-text
Abstract
Asian countries bear the greatest burden of the disease, with a majority (59%) of rabies-related deaths occurring in Asia. In order to promote best practices, we summarized national human vaccination guidelines across this region, to highlight differences and similarities and to discuss the [...] Read more.
Asian countries bear the greatest burden of the disease, with a majority (59%) of rabies-related deaths occurring in Asia. In order to promote best practices, we summarized national human vaccination guidelines across this region, to highlight differences and similarities and to discuss the aspects that would benefit from updates. National management guidelines for rabies were retrieved from various sources to extract information on rabies pre- and post-exposure prophylaxis (PrEP, and PEP), booster vaccination, and route of administration. Rabies guidelines recommendations for wound management and PrEP across Asia are broadly aligned to the World Health Organization (WHO) guidelines. For PEP, the 5-dose Essen, and the 4-dose Zagreb are the regimens of choice for intramuscular (IM), and the Thai Red Cross regimen for intradermal (ID), administration. Several national guidelines have yet to endorse ID vaccine administration. Most guidelines recommend rabies immunoglobulin in category III exposures. Booster recommendations are not included in all guidelines, with limited clarity on booster requirement across the spectrum of risk of rabies exposure. In conclusion, national recommendations across Asian countries differ and while some guidelines are closely aligned to the WHO recommendations, resource-saving ID administration and use of rational abbreviated schedules have yet to be endorsed. Full article
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Open AccessReview
Four Thousand Years of Concepts Relating to Rabies in Animals and Humans, Its Prevention and Its Cure
Trop. Med. Infect. Dis. 2017, 2(2), 5; https://doi.org/10.3390/tropicalmed2020005
Received: 20 February 2017 / Revised: 16 March 2017 / Accepted: 17 March 2017 / Published: 24 March 2017
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Abstract
The epitome of the One Health paradigm—and of its shortcomings—rabies has been known to humankind for at least 4000 years. We review the evolution through history of concepts leading to our current understanding of rabies in dogs and humans and its prevention, as [...] Read more.
The epitome of the One Health paradigm—and of its shortcomings—rabies has been known to humankind for at least 4000 years. We review the evolution through history of concepts leading to our current understanding of rabies in dogs and humans and its prevention, as transmitted by accessible and surviving written texts. The tools and concepts currently available to control rabies were developed at the end of the 19th Century, including the first live, attenuated vaccine ever developed for humans and the first post-exposure prophylaxis (PEP) regimen. No progress, however, has been made in etiological treatment, leaving clinicians who provide care to animals or patients with symptomatic rabies as powerless today as their colleagues in Mesopotamia, 40 centuries ago. Rabies remains to date the most lethal infectious disease known to humans. Widespread access to timely, effective, and affordable PEP in rural areas of developing countries is urgently needed. Full article
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Other

Open AccessPerspective
Childhood Rabies Deaths and the Rule of Rescue
Trop. Med. Infect. Dis. 2017, 2(2), 9; https://doi.org/10.3390/tropicalmed2020009
Received: 6 January 2017 / Revised: 7 April 2017 / Accepted: 11 April 2017 / Published: 17 April 2017
Cited by 1 | PDF Full-text (160 KB) | HTML Full-text | XML Full-text
Abstract
Every childhood rabies death is potentially preventable. The vaccine that prevents rabies disease has a formidable safety and efficacy track record. Rabies vaccination of dogs and timely pre-and post-exposure vaccine administration are life-saving and cost-effective, and yet nearly 60,000 people, mainly children, die [...] Read more.
Every childhood rabies death is potentially preventable. The vaccine that prevents rabies disease has a formidable safety and efficacy track record. Rabies vaccination of dogs and timely pre-and post-exposure vaccine administration are life-saving and cost-effective, and yet nearly 60,000 people, mainly children, die unnecessarily each year. Poor performance by many veterinary and public health systems, and neglect by complicit authorities is in stark contravention of the Convention on the Rights of the Child. The ethical principle of beneficence and the rule of rescue demand re-energised commitment to eradicating childhood rabies deaths. Full article
Trop. Med. Infect. Dis. EISSN 2414-6366 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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