Biosafety of rabies virus and related lyssaviruses: Risks, precautions, and knowledge gaps in diagnostic and research laboratories

Lyssaviruses cause rabies in mammals, a viral encephalomyelitis that is almost always fatal once clinical symptoms develop and can be transmitted to humans. Given this high fatality rate, strict biosafety measures are essential during laboratory handling of potentially infectious materials. This review critically assesses current biosafety practices in rabies diagnostic and research laboratories by examining principal risk factors, transmission pathways, and the effectiveness of existing preventive measures. We conducted a comprehensive review of the literature on biosafety risks associated with handling rabies virus and related lyssaviruses, including the use of personal protective equipment, sample handling procedures, and chemical and physical methods for virus inactivation. Particular attention was given to documented cases of laboratory-acquired rabies and their implications for laboratory safety. Although laboratory-acquired infections remain rare, their occurrence highlights important gaps in current biosafety practices. The effectiveness of disinfection and inactivation methods varies widely, especially in resource-limited settings, and key diagnostic procedures, such as the direct fluorescent antibody test, require validation under biosafety constraints. Significant knowledge gaps remain regarding infectious dose, the effectiveness of decontamination methods, and diagnostic standardisation. Strengthening evidence-based biosafety protocols and validating inactivation methods are essential to ensure safer rabies diagnostics and to support effective rabies control, particularly in low-resource settings.