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

Abstract

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics—and an understanding of pathobiology and epizootiology of rabies in testament to One Health—before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable—occasional treatment—of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral–essentially ‘one and done’. Exploiting mammalian social behaviors, future ‘spreadable vaccines’ might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

Human Rabies during the COVID-19 Pandemic: Insights into Rabies Worldwide and Brazil

“…Specifically for rabies, the cancellation or disruption of dog vaccination campaigns, vaccine shortages, reduced animal testing, an increase in the stray dog population, and a rise in animal bites have all contributed to its resurgence. The interruption of dog mass vaccination campaigns between 2020 and 2021 may have played a role in the post-pandemic resurgence of HR 39 . Furthermore, the costs and concerns about COVID-19 transmission led to many dogs being abandoned and left without food, exacerbating the increase in strays and, consequently, the transmission of rabies 39 .…”

“…The interruption of dog mass vaccination campaigns between 2020 and 2021 may have played a role in the post-pandemic resurgence of HR 39 . Furthermore, the costs and concerns about COVID-19 transmission led to many dogs being abandoned and left without food, exacerbating the increase in strays and, consequently, the transmission of rabies 39 . Indeed, the pandemic underscored the need for ongoing rabies surveillance in dogs and the importance of maintaining continuous strategies that should not be interrupted worldwide.…”

A pilot study on the impact of parenteral vaccination of free-roaming dogs within the rabies control framework in Ukraine

“…The disease claims an estimated 59,000 lives annually, mainly in Asia and Africa, with children under 15 years accounting for 40% of the victims (WHO, TRS, 2018;Rupprecht et al, 2020;Mbilo et al, 2021). Dog bites cause over 99% of these deaths, leading to 3.7 million lost disa-bility-adjusted life years (DALY) and $8.6 billion in annual economic losses (Hampson et al, 2015;Rupprecht et al, 2023;Taylor et al, 2023). With a WOAH estimated population of 700 million domestic dogs worldwide, 75% of which are free-roaming (unowned dog that is without direct human supervision or control), reaching all these animals is posing a huge challenge (Fahrion et al, 2017;.…”

TRIM72 restricts lyssavirus infection by inducing K48-linked ubiquitination and proteasome degradation of the matrix protein

“…Lyssavirus, a genus of the family Rhabdoviridae , is a single-stranded negative-sense RNA virus that encodes five viral proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and large RNA polymerase protein (L). The lyssavirus genus is currently composed of 17 viral species [ 1 ], typical lyssavirus species include Rabies lyssavirus (RABV), Australian bat lyssavirus (ABLV), Duvenhage lyssavirus (DUVV), European bat lyssavirus (EBLV), Lagos bat lyssavirus (LBV) and Mokola lyssavirus (MOKV), etc [ 2 , 3 ]. Among those lyssaviruses, RABV is the most well-known lyssavirus and is responsible for causing rabies, resulting in approximately 59000 human deaths globally each year [ 4 – 6 ].…”