Rabies Virus Infection: Report of an Autopsy Case with Comprehensive Pathologic, Immunofluorescent, Immunohistochemical and Molecular Studies

Abstract

Objective: Taiwan has been rabies-free since 1958. We report a fatal case of rabies virus infection in a 45-year-old woman from flu-Nan Province of mainland China which occurred in June 2002. Since knowledge of rabies virus distribution in body organs is limited, the present case study attempted to explore the pathogenesis of infection of this virus. Materials and Methods: We performed a detailed pathologic examination, immunofluorescence, immunohistochemistry and molecular studies in this case. Results: Acute rabies encephalitis with characteristic Negri inclusion bodies was noted. The brain stem and thalamus were most severely involved. There was mild involvement of the hippocampus and cerebellum. The inflammatory infiltrates consisted of lymphocytes involving primarily the gray matter with perivascular lymphocytic cuffing and neuronophagia. Rabies virus was isolated from fresh brain tissues and identified in neurons by immunofluoresence stain with specific rabies monoclonal antibody, and confirmed by reverse-transcriptase polymerase chain reaction with sequence analysis. In addition to encephalitis, the following pathologic changes in the peripheral organs were also noted: ganglioneuritis involving the sympathetic and submucosal ganglion of the esophagus; mild focal myocarditis; interstitial pneumonitis with diffuse alveolar damage and granulation tissue formation in the alveolar space; mild interstitial nephritis and lymphocyte infiltration in the pituitary, adrenal, and submandibular glands. Rabies virus antigen was shown with immunohistochemical stain in the brain stem, cerebellum, thalamus, hippocampus, sympathetic ganglion, submucosal ganglion of the esophagus and tubular epithelium of the kidney. Conclusions: These findings demonstrate that in addition to neurotropism, the rabies virus may disseminate into peripheral organs resulting in the development of fatal complications.