Table 3.

Paradigm shifts in rabies detection, prevention, control & treatment in the 21^st century

Topic	Change	Reference
Etiology	Classical rabies virus recognized as the most important member of the genus, but > 17 putative or recognized lyssaviruses, including highly divergent viral spp.	Fooks et al. 2021
Diagnosis	Since the early twentieth century, microscopic recognition of intracytoplasmic ‘viral factories’ within neurons, now supplemented by highly sensitive, specific, and economical tests for rapid ante- and postmortem laboratory confirmation and enhanced point-of-care field surveillance development	World Health Organization (WHO), 2018
Pathobiology	In addition to exposure via transdermal, mucosal and aerosol routes, transmission via solid organ and tissue transplantation	Srinivasan et al. 2005
Treatment	Survivors, without a history of prior vaccination	Willoughby et al. 2005
Safety	Abandonment of nerve tissue-based vaccines by safer alternatives	Gongal & Sampath 2019
Vaccine potency	In vitro alternates to the use of animal testing in the NIH test	Stokes et al. 2012
Passive immunity	Monoclonal antibodies used increasingly in humans	Sparrow et al. 2019
Improvement in biologics	Multiple novel biologics licensed or in human clinical trials	Ertl 2019
Prophylaxis	Efficacious and economical dose-sparing and 1-week strategies	WHO Rabies Modeling Consortium 2019
Wildlife rabies vaccination	Elimination of rabies in red foxes in western Europe, and Texas gray fox and coyote rabies virus variants in USA	Mähl et al. 2014; Maki et al. 2017; Vos et al. 1999
One Health	Global program for elimination of human rabies caused via dogs by 2030	Abela-Ridder et al. 2016
Advocacy	Inauguration of World Rabies Day	Centers for Disease Control Prevention (CDC), 2007