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

Abstract

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.

Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism

“…Considering the taxonomic breadth of extant warm-blooded vertebrates, more than 16,000 potential species are considered susceptible to lyssavirus infection (Paarmann 1955 ; Baby et al 2015 ; Gilbert 2018 ; Rohde and Rupprecht 2020 ). This wide span reflects in part both viral plasticity and various host conserved factors over evolutionary time, including structural and biochemical features of receptors, replication dynamics, excretion mechanisms, and host innate/adaptive immunity (Conselheiro et al 2022 ; Gérard et al 2022 ; Lian et al 2022 ).…”

“…This wide span reflects in part both viral plasticity and various host conserved factors over evolutionary time, including structural and biochemical features of receptors, replication dynamics, excretion mechanisms, and host innate/adaptive immunity (Conselheiro et al 2022 ; Gérard et al 2022 ; Lian et al 2022 ). The capability of infection for all hosts is dissimilar from perpetuation, as birds have been toothless for millions of years, removing one major anatomical assist for viral entry, notwithstanding the potential capabilities of beaks to create lesions from modern avianized dinosaurs (Rohde and Rupprecht 2020 ). Any resulting productive infection is impacted at the outset by a time-space continuum overlap, requiring simultaneous engagement of host and pathogen (Jacquot et al 2022 ).…”

Demographic, temporal, and spatial analysis of human rabid animal bite cases in Mymensingh District, Bangladesh

“…Rabies underreporting often occurs due to poor surveillance and diagnostic challenges, resulting in an underestimated disease burden (13). Depending exclusively on clinical diagnoses undermines the reliability of rabies surveillance systems (7). Therefore, the number of recorded animal bite cases in routine surveillance within the Mymensingh district might represent only a portion of the disease burden.…”

“…In humans, transmission mainly occurs from canines, as well as from cats, mongoose, bats, and in rare cases, farm animals (6). Globally, > over 1.4 billion people are at risk of rabies, and approximately 45% of rabies-related deaths occur in Asia (7). Human rabies cases that result from dog bites constitute 97% of all cases (8).…”

An Overview of Anthropogenic Actions as Drivers for Emerging and Re-Emerging Zoonotic Diseases

“…Rabies is an ancient, underreported, and progressive neurological zoonotic disease with nearly a 100% mortality rate [119]. It is caused by a single-stranded RNA virus that belongs to the Lyssavirus genus of the Rhabdoviridae family [120]. Although rabies can be prevented by vaccines, about 59,000 people die from rabies each year, globally [119].…”