Negri bodies are distinctive features observed within the nerve cells of individuals infected with the rabies virus. Their discovery in 1903 by Adelchi Negri, an Italian pathologist, marked a significant advancement in understanding and diagnosing this severe disease. Despite Negri’s initial incorrect hypothesis that these inclusions were a parasitic protozoon causing rabies, their consistent presence in infected animals quickly established their value in diagnostic pathology. For decades, the detection of Negri bodies was the primary method for confirming a rabies diagnosis, highlighting their historical importance in public health.
Characteristics of Negri Bodies
Negri bodies are eosinophilic, sharply outlined inclusion bodies found within the cytoplasm of specific nerve cells. They appear as round or oval structures, varying in size from approximately 2 to 10 micrometers in diameter. Under microscopic examination, they exhibit a magenta color with Seller’s stain and contain small, dark-blue internal basophilic granules, sometimes arranged in a rosette pattern.
These distinctive inclusions are primarily composed of viral ribonucleoproteins and some host cell components. Negri bodies are most frequently observed in the pyramidal cells of Ammon’s horn in the hippocampus, the Purkinje cells of the cerebellar cortex, and neurons within the brainstem and various ganglia. Their location within these specific neuronal populations, combined with their unique appearance, provides a pathological signature strongly associated with rabies infection.
How Negri Bodies Form and Their Significance in Rabies
Negri bodies develop within infected neurons as a direct consequence of rabies virus replication. The rabies virus replicates in the cytoplasm of cells, leading to the accumulation of viral nucleocapsids and other viral proteins. These accumulations form the granular and filamentous material that constitutes the Negri body.
The presence of Negri bodies is considered pathognomonic for rabies infection, meaning their detection is highly indicative of the disease. They serve as a definitive post-mortem diagnostic marker. While they may not be present in every case of rabies, their identification provides strong evidence of the infection. The formation of Negri bodies may also serve as sites for viral transcription and replication, functioning as viral “factories” within the host cell.
Laboratory Detection of Negri Bodies
Laboratory identification of Negri bodies primarily relies on histopathological examination of brain tissue obtained post-mortem. Brain samples are processed and then thinly sectioned. These sections are then stained using specific histological methods to make the Negri bodies visible under a light microscope.
Common staining techniques include Seller’s stain and hematoxylin and eosin (H&E) staining. A trained microscopist can recognize these eosinophilic inclusions within the neuronal cytoplasm. While the direct fluorescent antibody test (dFA) is now the gold standard for rabies diagnosis due to its higher sensitivity, detecting rabies virus antigens in nearly all samples, Negri body detection remains a traditional and recognized approach for post-mortem confirmation.