Pathology of rabies: A light- and electron-microscopical study with particular reference to the changes in cases with prolonged survival

Abstract

Light- and electron-microscopical studies were conducted on necropsy material from six cases of rabies encephalitis including three with the unusual feature of surviving for over 14 days as a result of intensive medical care. This included administration of antiviral agents and interferon inducers and prevention of hypoxia by intermittent positive pressure ventilation. In all these cases, typical Negri bodies were demonstrated. Inflammatory reaction was absent or minimal. Unlike the cases with short survival where Negri bodies were infrequently seen and restricted mostly to the hippocampus, in cases with prolonged survival, they were present in large number, widely distributed throughout the grey matter of the brain. The associated inflammatory reaction in these cases, however, did not keep pace with the increase in number of inclusion bodies. Peripheral neuritis was observed in two of these cases, which also showed myelitis involving the cervical region and inflammation of dorsal root ganglia. One of them showed necrosis and severe inflammation of the lower cervical sympathetic ganglion. An electron-microscopical study conducted in four cases showed three forms of the inclusion body in the cytoplasm of neurons.

Pathology

“…Remarkably, numerous and diffusely distributed Negri bodies have been reported in two immunocompromised patients, one of whom had AIDS (Adle-Biassette et al, 1996) and the other a renal transplant recipient with prolonged survival (Mackenzie et al, 2003). More numerous and widely distributed Negri bodies have also been observed with increasing duration of survival in some human case series (Sandhyamani, Roy, Gode, & Kalla, 1981). More numerous and widely distributed Negri bodies have also been observed with increasing duration of survival in some human case series (Sandhyamani, Roy, Gode, & Kalla, 1981).…”

“…Many of the neurons were moderately swollen, with pale finely vacuolated cytoplasm, and some fragmented neurons undergoing neuronophagia by histiocytes were seen. Severe lymphocytic inflammation and necrosis has been observed in the inferior cervical sympathetic ganglion of an encephalitic rabies case with prolonged survival (Sandhyamani et al, 1981). Numerous Negri bodies have been found in the Gasserian (Garcia-Tamayo, Avila-Mayor, & Anzola-Perez, 1972) and dorsal root ganglia (Sung et al, 1976) in some cases.…”

“…The ultrastructure of Negri bodies and rabies virions has been investigated in human rabies cases (Adle-Biassette et al, 1996;de Brito, Araujo, & Tiriba, 1973;Gonzalez-Angulo, Marquez-Monter, Feria-Velasco, & Zavala, 1970;Iwasaki, Liu, Yamamoto, & Konno, 1985;Leech, 1971;Manghani, Dastur, Nanavaty, & Patel, 1986;Morecki & Zimmerman, 1969;Mrak & Young, 1993;Sandhyamani et al, 1981) and in experimentally inoculated animals (Charlton & Casey, 1979;Fekadu et al, 1982;Hottle, Morgan, Peers, & Wyckoff, 1951;Iwasaki, Ohtani, & Clark, 1975;Miyamoto & Matsumoto, 1965;Perl, Callaway, & Hicklin, 1972). In addition, many aspects of rabies virus replication and virus/ host cell interaction have been studied ultrastructurally in vitro (Davies, Englert, Sharpless, & Cabasso, 1963;Hummeler, Koprowski, & Wiktor, 1967;Iwasaki & Clark, 1977;Iwasaki & Minamoto, 1982;Iwasaki, Wiktor, & Koprowski, 1973;Lewis & Lentz, 1998;Matsumoto & Kawai, 1969;Matsumoto, Schneider, Kawai, & Yonezawa, 1974).…”

“…In "immature" inclusions, it has a filamentous appearance with visible substructural coiling of the nucleocapsid strands, but with maturation and increasing density, the individual strands become increasingly difficult to resolve, such that the matrix has a more granular and electrondense appearance (Matsumoto et al, 1974;Miyamoto & Matsumoto, 1967;. Bullet-shaped or tubular virions are typically associated with the matrix accumulations (for more detailed descriptions, see Perl & Good (1991), Iwasaki & Tobita (2002), and Chapter 2), but may be absent in some Negri bodies (Morecki & Zimmerman, 1969;Perl & Good, 1991;Sandhyamani et al, 1981). In a study of experimentally infected rhesus monkey tissue, Perl and colleagues (Perl et al, 1972;Perl & Good, 1991) described three basic ultrastructural configurations of Negri bodies.…”

Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis

“…Autopsy study of cases with prolonged survival of up to 14 days after intensive care with ventilation, IFN therapy, and ribavirin demonstrated widespread Negri bodies with minimal inflammation [168].…”