Question
Negri bodies.
Answer
Negri bodies are characteristic eosinophilic, round-to-oval intracytoplasmic inclusion bodies found within the neurons of animals and humans infected with rabies virus, representing sites of active viral replication (aggregates of viral nucleocapsid protein and matrix material) — historically the classical, defining histopathological finding used to confirm rabies diagnosis.
Location: most characteristically and consistently demonstrated in the large pyramidal neurons of the hippocampus (Ammon’s horn) and in Purkinje cells of the cerebellum, though they can be found in neurons throughout the CNS.
Demonstration: classically identified on haematoxylin and eosin (H&E) staining of brain tissue (obtained post-mortem, or historically via biopsy), appearing as sharply demarcated, eosinophilic, cytoplasmic inclusions, sometimes containing small basophilic granules (“inner bodies”) within the larger inclusion; Seller’s stain was a specific historical staining method used to enhance their visualization.
Diagnostic significance and limitations: Negri bodies were historically the standard post-mortem confirmatory test for rabies, but their sensitivity is imperfect — absence of Negri bodies does NOT exclude rabies (they may be absent in a proportion of genuinely rabid animals/humans, particularly with certain virus variants or early in the disease course), an important diagnostic limitation. Modern rabies diagnosis has largely superseded histopathological Negri body identification with more sensitive and specific methods:
- Direct Fluorescent Antibody (DFA) test on brain tissue — now the gold-standard confirmatory test, detecting viral antigen directly with fluorescently labelled antibody.
- RT-PCR — highly sensitive molecular detection of viral RNA.
- Antemortem diagnosis (in a still-living suspected case) can utilize saliva, corneal impression smears, or nuchal skin biopsy (hair follicle-associated nerve tissue) for antigen/RNA detection, though a negative antemortem test cannot definitively exclude rabies given variable/intermittent viral shedding.