Alternative Methods to Current In Vivo Procedures to Address the 3Rs Tenet in Rabies Proficiency Testing

Abstract

Canine rabies is responsible for an estimated 59,000 human deaths every year. In an attempt to reach the ZeroBy30 goal, robust disease surveillance coupled with improved diagnostics play a paramount role in ensuring reliable data and gradually attesting rabies control advancements. In this context, proficiency testing is organized to harmonize rabies diagnostic capacities. In most exercises, rabies-positive samples consist of brains collected from intracerebrally inoculated mice. This procedure causes distress and severe suffering to animals, raising important ethical concerns that can no longer be ignored. In the last decades, the 3Rs tenet (Replace, Reduce, Refine) has been successfully implemented in several scientific areas, and we strongly support its application in the framework of rabies proficiency testing. Here, we discuss cell-based technologies as innovative sustainable in vitro candidate systems to replace in vivo experiments for the production of proficiency testing samples. The application of these alternative methods can allow completely in vitro or ex vivo production of rabies proficiency testing panels, which would represent an important replacement or reduction/refinement for current in vivo procedures.

Special Issue “Advances in Rabies Research”

“…Generation of PT panels for use in the RABV DFA test requires significant quantities of well-standardized rabies-positive tissues, which are usually generated via viral propagation in large numbers of intracerebrally inoculated mice. To address resulting animal welfare concerns, an opinion piece describes alternative methods used to compile PT panels for use in both DFA and RT-PCR testing, which apply the 3Rs (Replace, Reduce, Refine) [ 4 ].…”