Antemortem diagnosis of new york human rabies case and review of u.s. Cases

Abstract

To help elucidate rabies disease patterns and control issues, a full assessment of a human case of dog-variant rabies was undertaken. In 2000, a 54-year-old man presented to a New York hospital with lower back discomfort four days after arrival from Africa. Rabies was first suspected 8 days after hospitalization based on clinical signs, specimens were collected on the same day, and rabies infection was confirmed the following day (fluorescence antibody testing on nuchal skin biopsy specimen). By the 12(th) day after illness onset, he was unresponsive, and life support was removed on day 15. Subsequently, an African dog variant was confirmed by nucleic acid sequence analysis of rabies viral RNA extracted and amplified from the patient's saliva. Management of human concerns about exposure to the patient kept the number of persons receiving postexposure prophylaxis to 26. With less than half of the U.S. human rabies cases being diagnosed antemortem, this case emphasizes the need to routinely include rabies in the differential diagnosis of any unexplained encephalitis to ensure early confirmation and triage of human contacts to reduce associated healthcare costs.

Keywords: dog diseases; fluorescent antibody technique; inclusion bodies; rabies; reverse transcriptase polymerase chain reaction; virus disease.

Figure 1

Timeline of the year 2000 NY imported dog-variant rabies case in relation to onset of symptoms.

Figure 2

(A) Immunofluorescence evidence of rabies viral protein in antemortem skin biopsy sample. Inclusions of rabies virus antigen are disclosed in cytoplasm of sensory nerves surrounding hair follicle. Specific staining with FITC-labeled, rabies nucleocapsid antigen-specific monoclonal antibodies appears as characteristic apple-green fluorescence (arrow). With Evans blue counterstain, ×250 magnification; (B) Immunofluorescence evidence of rabies viral protein in antemortem corneal impression. Specific staining with FITC-labeled, rabies antigen-specific monoclonal antibodies appears as yellow-green fluorescence of inclusions in cytoplasm of corneal epithelial cells (arrow). With Evans blue counterstain, ×250 original magnification; (C) Immunofluorescence evidence of rabies viral protein in frozen section of unfixed postmortem cerebellum specimen. Specific staining with FITC-labeled rabies viral nucleocapsid protein-specific monoclonal antibodies, appearing as characteristic apple-green fluorescence of numerous intra-cytoplasmic inclusions in the large Purkinje cell body (arrow). With Evans blue counterstain, ×250 original magnification.

Figure 3

Photomicrographs of rabies infection involving the nervous system. (A) Cerebellar Purkinje cells infected by rabies virus containing intracytoplasmic eosinophilic Negri bodies (arrows). (B) Electron micrograph showing characteristic bullet-shaped intranuclear and cytoplasmic viral particles (arrows) in cross and longitudinal profiles (N = nucleus). (C) Perivascular lymphocytic cuffing in substantia nigra (BV = lumen of blood vessel). (D) Lymphohistiocytic ganglionitis in the paravertebral sympathetic ganglion. Original magnifications: ×400 (A, C, D), and ×40,000 (B).