Neurofilament Light Chain: A Potential Diagnostic Biomarker for Rabies

Rabies is a fatal, acute progressive encephalomyelitis caused by the rabies virus and other Lyssaviruses. Several other clinical conditions can mimic rabies. Antemortem laboratory diagnosis remains challenging and requires multiple or serial sampling for confirmation. Measurement of host-based biomarkers is an emerging area of research in infectious diseases; however, a reliable biomarker for rabies remains elusive. In this study, neurofilament light chain (NfL), an established marker of neuronal injury, has been investigated as a potential diagnostic marker for rabies. NfL levels were measured using the Simoa NfL v2 kit in serum and cerebrospinal fluid (CSF) samples received for routine diagnostic testing from encephalitis cases (rabies, n = 31; other encephalitides, n = 30) and controls (n = 24). The median serum NfL level in the rabies group was significantly higher than that in the control group (adjusted p  < 0.001), as well as the other encephalitides group (adjusted p = 0.024). Furthermore, the median CSF NfL level in the rabies group was significantly higher than that in the other encephalitides group (p < 0.001). There were no significant differences in serum or CSF NfL levels in rabies cases with different clinical presentations, prior vaccination status, or incubation period. These findings demonstrate for the first time that rabies can be differentiated from other causes of encephalitis by extremely high NfL levels.