Rabies is an ancient, much-feared, and neglected infectious disease. Caused by pathogens in the family Rhabdoviridae, genus Lyssavirus, and distributed globally, this viral zoonosis results in tens of thousands of human fatalities and millions of exposures annually. All mammals are believed susceptible, but only certain taxa act as reservoirs. Dependence upon direct routing to, replication within, and passage from the central nervous system serves as a basic viral strategy for perpetuation. By a combination of stealth and subversion, lyssaviruses are quintessential neurotropic agents and cause an acute, progressive encephalitis. No treatment exists, so prevention is the key. Although not a disease considered for eradication, something of a modern rebirth has been occurring within the field as of late with regard to detection, prevention, and management as well as applied research. For example, within the past decade, new lyssaviruses have been characterized; sensitive and specific diagnostics have been optimized; pure, potent, safe, and efficacious human biologics have improved human prophylaxis; regional efforts have controlled canine rabies by mass immunization; wildlife rabies has been controlled by oral rabies vaccination over large geographic areas in Europe and North America; and debate has resumed over the controversial topic of therapy. Based upon such progress to date, there are certain expectations for the next 10 years. These include pathogen discovery, to uncover additional lyssaviruses in the Old World; laboratory-based surveillance enhancement by simplified, rapid testing; anti-viral drug appearance, based upon an improved appreciation of viral pathobiology and host response; and improvements to canine rabies elimination regionally throughout Africa, Asia, and the Americas by application of the best technical, organizational, economic, and socio-political practices. Significantly, anticipated Gavi support will enable improved access of human rabies vaccines in lesser developed countries at a national level, with integrated bite management, dose-sparing regimens, and a 1 week vaccination schedule.

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Update on lyssaviruses and rabies: will past progress play as prologue in the near term towards future elimination?

Rabies is an ancient yet still neglected tropical disease (NTD). This review focuses upon highlights of recent research and peer-reviewed communications on the underestimated tropical burden of disease and its management due to the complicated dynamics of virulent viral species, diverse mammalian reservoirs, and tens of millions of exposed humans and animals – and how laboratory-based surveillance at each level informs upon pathogen spread and risks of transmission, for targeted prevention and control. While both human and rabies animal cases in enzootic areas over the past 5 years were reported to PAHO/WHO and OIE by member countries, still there is a huge gap between these “official” data and the need for enhanced surveillance efforts to meet global program goals. A review of the complex aspects of rabies perpetuation in human, domestic animal, and wildlife communities, coupled with a high fatality rate despite the existence of efficacious biologics (but no therapeutics), warrants the need for a One Health approach toward detection via improved laboratory-based surveillance, with focal management at the viral source. More effective methods to prevent the spread of rabies from enzootic to free zones are needed. 

Rabies in the Tropics

Global burden of Rabies in 204 countries and territories, from 1990 to 2019: results from the Global Burden of Disease Study 2019.

Background Rabies is a fatal yet vaccine-preventable disease. In the last two decades, domestic dog populations have been shown to constitute the predominant reservoir of rabies in developing countries, causing 99% of human rabies cases. Despite substantial control efforts, dog rabies is still widely endemic and is spreading across previously rabies-free areas. Developing a detailed understanding of dog rabies dynamics and the impact of vaccination is essential to optimize existing control strategies and developing new ones. In this scoping review, we aimed at disentangling the respective contributions of mathematical models and phylodynamic approaches to advancing the understanding of rabies dynamics and control in domestic dog populations. We also addressed the methodological limitations of both approaches and the remaining issues related to studying rabies spread and how this could be applied to rabies control. Methodology/principal findings We reviewed how mathematical modelling of disease dynamics and phylodynamics have been developed and used to characterize dog rabies dynamics and control. Through a detailed search of the PubMed, Web of Science, and Scopus databases, we identified a total of n = 59 relevant studies using mathematical models (n = 30), phylodynamic inference (n = 22) and interdisciplinary approaches (n = 7). We found that despite often relying on scarce rabies epidemiological data, mathematical models investigated multiple aspects of rabies dynamics and control. These models confirmed the overwhelming efficacy of massive dog vaccination campaigns in all settings and unraveled the role of dog population structure and frequent introductions in dog rabies maintenance. Phylodynamic approaches successfully disentangled the evolutionary and environmental determinants of rabies dispersal and consistently reported support for the role of reintroduction events and human-mediated transportation over long distances in the maintenance of rabies in endemic areas. Potential biases in data collection still need to be properly accounted for in most of these analyses. Finally, interdisciplinary studies were determined to provide the most comprehensive assessments through hypothesis generation and testing. They also represent new avenues, especially concerning the reconstruction of local transmission chains or clusters through data integration. Conclusions/significance Despite advances in rabies knowledge, substantial uncertainty remains regarding the mechanisms of local spread, the role of wildlife in dog rabies maintenance, and the impact of community behavior on the efficacy of control strategies including vaccination of dogs. Future integrative approaches that use phylodynamic analyses and mechanistic models within a single framework could take full advantage of not only viral sequences but also additional epidemiological information as well as dog ecology data to refine our understanding of rabies spread and control. This would represent a significant improvement on past studies and a promising opportunity for canine rabies research in the frame of the One Health concept that aims to achieve better public health outcomes through cross-sector collaboration.

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Mathematical modelling and phylodynamics for the study of dog rabies dynamics and control: A scoping review.

Objective The objective of this scoping review was to map the current situation and available evidence and gaps on rabies morbidity, mortality, integrated rabies surveillance programmes, and existing prevention and control strategies in Africa. Methods We conducted a systematic scoping review following the Joanna Briggs methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist. Medline, Embase, CINAHL (EBSCOHost), Scopus, Web of Science and rabies web conferences were used to search for peer-reviewed publications between January 1946 and May 2020. Two researchers reviewed the studies and extracted data based on author (year) and region, study design and data collection duration, participants/comparators, interventions, control conditions/exposures and outcomes (rabies mortality and morbidity) and key findings/gaps/challenges. The results were reported narratively using Arksey and O’Malley’s methodological framework. Results Electronic search yielded 2775 records, of which 43 studies were included. A total of 543 714 bite victims were censored through the included studies. Most of the victims were less than 15 years of age. The studies included rabies morbidity (21) and mortality (15) fluctuating in space and time across Africa depending on countries’ rabies prevention and control practices (16). Others were surveillance (nine studies); surveillance and prevention (five studies); management and control (seven studies); and surveillance, prevention and control (six studies). We found challenges in rabies reporting, existing dog vaccination programmes and post-exposure prophylaxis availability or compliance. Conclusion This study found challenges for dog rabies control and elimination in Africa and the need for a policy to drive the goal of zero dog-transmitted rabies to humans by 2030. This is an open-access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build on this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial (see http://creativecommons.org/licenses/by-nc/4.0/).

https://bmjopen.bmj.com/content/bmjopen/11/12/e048551.full.pdf

Rabies mortality and morbidity associated with animal bites in Africa: a case for integrated rabies disease surveillance, prevention and control: a scoping review.

Pidemnéwé Pato

Papers

Dog rabies control in West and Central Africa: A review.