An infectious disease known as rabies (family Rhabdoviridae, genus Lyssavirus) causes severe damage to mammals\' central nervous systems (CNS). This illness has been around for a very long time. The majority of human cases of rabies take place in underdeveloped regions of Africa and Asia. Following viral transmission, the Rhabdovirus enters the peripheral nervous system and proceeds to the CNS, where it targets the encephalon and produces encephalomyelitis. Postbite prophylaxis requires laboratory confirmation of rabies in both people and animals. All warm-blooded animals can transmit the Lyssavirus infection, while the virus can also develop in the cells of cold-blooded animals. In the 21st century, more than 3 billion people are in danger of contracting the rabies virus in more than 100 different nations, resulting in an annual death toll of 50,000-59,000. There are three important elements in handling rabies disease in post exposure prophylaxis (PEP), namely wound care, administration of anti-rabies serum, and anti-rabies vaccine. Social costs include death, lost productivity as a result of early death, illness as a result of vaccination side effects, and the psychological toll that exposure to these deadly diseases has on people. Humans are most frequently exposed to canine rabies, especially youngsters and the poor, and there are few resources available to treat or prevent exposure, making prevention of human rabies challenging.

Dog-maintained rabies virus variant (DMRVV) was eliminated in the United States in 2007. During 2015–2019, three dogs with rabies were imported into the United States from Egypt, where DMRVV is endemic. CDC developed a risk mitigation strategy, in consultation with a diverse group of subject matter experts, that permitted 296 dogs to be imported from Egypt during May 10, 2019–December 31, 2020, minimizing the risk for future rabid dog importations. The broadly vetted risk mitigation strategy, which included serologic testing for rabies antibody titer, improved CDC’s ability to ensure that imported dogs from Egypt posed no public health risk in the United States. This strategy could be used to guide future policy decisions regarding dog importations.

This study comprehensively evaluated and compared three human rabies vaccines. Seven electronic databases were systematically searched. The Cochrane Handbook v5.1.0 was used to assess the risk of bias. A random-effects model was used to combine individual rates, and network meta-analysis was used for pairwise comparisons. Twenty-seven articles were included, with a total of 18,630 participants. The pooled incidence of the total adverse reaction to HDCV was significantly lower than that of PCECV. HDCV administration resulted in a lower incidence of local pain, fever, and weakness than purified Vero cell vaccine. HDCV caused a lower incidence of local pain and fever than PCECV. No significant difference was observed in terms of the seroconversion rate on day 7 or the rabies virus-neutralizing antibody titer on day 14. HDCV demonstrated superiority in terms of safety compared with the other two rabies vaccines, while the same was not observed in terms of immunogenicity.

Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state.

Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys.
Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs.
Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies.
There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies.

Rabies is a major public health problem with a fatality rate close to 100%, caused by a virus of the Lyssavirus genus, of which rabies virus (RABV) is the prototype. Nonetheless, the complete prevention can be achieved by the induction of neutralizing antibodies by pre- or post-exposure prophylaxis. According to the world health organization (WHO) and World Organization for animal health (OIE), serum titers of rabies virus neutralizing antibodies (RVNA) that are higher or equal to 0.5 international units (IU)/ml indicate adequate immune response after vaccination against rabies. Currently, RFFIT and FAVN are the gold standard tests recommended by both WHO and OIE for detecting and quantitating RVNA in biological samples from individuals or animals previously vaccinated and/or subjects suspected of having been infected by RABV. Although the tests RFFIT and FAVN are efficient, they are time-consuming, labor-intensive manual tests and not cost-effective for routine use. Following the previously mentioned, approaches with alternative methods have been developed to detect RVNA or rabies-specific antibodies in human or animal serum, but with variable success. This work summarizes the advances in the serological assays for the detection of neutralizing antibodies or rabies antibodies and assesses the individual immune status after vaccination against rabies, as well as the mechanisms of RABV neutralization mediated by antibodies. Therefore, the main alternative methods for the determination of RABV or rabies-specific antibodies are exposed, with promising results, besides being easy to execute, of low cost, and representing a possibility of being applied, according to the proposal of each test to the network of Rabies Surveillance Laboratories.

Rabies is transmitted to humans mainly by dogs but also by other animal species. Reliable data on the incidence of Rabies virus (RABV) in humans, dogs, and other animal species in Africa, could be essential in the implementation of a global strategic plan to eliminate the RABV by 2030 as adopted by the WHO, OIE, and FAO. We searched the Pubmed, Embase, Scopus, African Journal Online, and African Index Medicus databases for relevant studies that report data on the incidence of RABV in Africa up to February 17, 2020. Information on active and past RABV exposures in various categories of dogs, humans and other animal species were extracted. Incidence and seroprevalence estimates were pooled using a random-effect meta-analysis. We included 73 articles which provided 142 RABV incidence and seroprevalence records in 21 African countries. The estimated incidence of RABV in 222 humans, 15,600 dogs, and 12,865 other animal species was 83.4% (95% CI = 64.6-96.5), 44.1% (95% CI = 35.1-53.4), and 41.4% (95% CI = 29.6-53.8), respectively. The estimated seroprevalence of RABV in 420 humans, 3577 dogs, and 8,55 other animal species was 33.8% (95% CI = 21.9-46.8), 19.8% (95% CI = 13.3-27.3), and 3.6% (95% CI = 0.3-9.2), respectively. The incidence of RABV in general was higher in suspected rabid dogs, other animal species of the Orders Perissodactyla, Artiodactyla and Carnivora. The incidence of RABV was higher for humans in regions of West and East Africa, for dogs in urban areas and in regions of Central and South Africa, and for animals of the order Perissodactyla in urban areas. This meta-analysis demonstrated a high incidence of RABV in Africa. Itis necessary to improve surveillance system to provide reliable data on RABV in Africa, essential for the implementation of an effective control strategy.

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.
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.
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.

Porcine rabies is exceedingly rare worldwide. We describe herein the neuropathology and the diagnostic features of an outbreak of rabies in a litter of piglets attacked by a skunk in Georgia, United States. Rabies viral infection was confirmed in 2 of 3 piglets submitted for testing. Inflammatory and degenerative changes were more prominent in the brainstem and consisted of lymphoplasmacytic meningoencephalitis with glial nodules, neuronal necrosis, and neuronophagia. No viral inclusions (Negri bodies) were observed in multiple sections of brain. A fluorescent antibody test on fresh samples of brainstem and cerebellum was confirmatory for the eastern United States raccoon rabies virus variant. Immunoreactivity for rabies virus was detected across all brain sections in both cases but was more prominent in the thalamic and brainstem nuclei, as well as in the medial lemniscus. Rabies is an important differential diagnosis in pigs with neurologic disease.

Despite successful control in many parts of the world, rabies virus continues to result in tens of thousands of deaths each year. Death from rabies can be prevented by timely and appropriate post exposure prophylaxis including wound cleaning and administration of vaccine and rabies immunoglobulin. Currently, rabies immunoglobulin is derived from the blood plasma of horses or humans and has several limitations relating to supply, cost and quality. Monoclonal antibodies produced through recombinant DNA technologies could potentially overcome these limitations. The first anti-rabies monoclonal antibody has recently gained regulatory approval in India and there are several other candidates being evaluated in clinical trials. Given the advances in the field, rabies monoclonal antibodies have been recently considered by the World Health Organization\'s Strategic Advisory Group of Experts on Immunization and included in updated WHO immunization policy recommendations for rabies published in April 2018. This article reviews the current landscape of the clinical trial development of anti-rabies monoclonal antibodies and the historical clinical trial pathways followed for blood-derived rabies immunoglobulin before discussing challenges in the clinical evaluation, regulatory approval, uptake and monitoring of these products.