Negri body

**Definition:** Negri bodies are sharply demarcated, round to oval, eosinophilic intracytoplasmic inclusions (2-10 µm) in neurons. They are sites of rabies virus replication and consist of viral ribonucleoprotein (nucleoprotein N, phosphoprotein P, and L polymerase) forming liquid-like replication factories.

**Location:** Most characteristic in hippocampal pyramidal neurons (Ammon's horn) and cerebellar Purkinje cells. They can also appear in the cortex, brainstem, and ganglia.

**Pathogen:** Rabies virus is a single-stranded, negative-sense, enveloped, bullet-shaped RNA virus in the Rhabdoviridae family (genus Lyssavirus). It carries its own RNA-dependent RNA polymerase in the virion.

**Pathophysiology and transmission:** - Transmitted by the bite of an infected animal (bats, raccoons, skunks, foxes, dogs). In the US, bats are the most common source. Aerosolized bat-cave exposure and organ transplantation are rare routes. - The virus replicates locally in muscle, then binds nicotinic acetylcholine receptors (and NCAM, p75 neurotrophin receptor) at the neuromuscular junction. - It travels by retrograde axonal transport to the CNS, then spreads centrifugally to the salivary glands. - Incubation is typically 1-3 months, but varies with the distance of the bite from the CNS.

**Clinical features:** - Prodrome: fever, malaise, paresthesia or pain at the bite site. - Encephalitic ("furious") form: agitation, hydrophobia (painful laryngopharyngeal spasms), aerophobia, hypersalivation, autonomic instability. - Paralytic ("dumb") form: ascending flaccid paralysis. - Progresses to coma and death. Once symptoms begin, it is nearly 100% fatal.

**Diagnosis:** - Negri bodies on histology (brain autopsy) are classic, but their absence does not exclude rabies, so sensitivity is limited. - Modern diagnosis uses direct fluorescent antibody (DFA) testing of a nuchal skin biopsy (hair follicle nerves) or brain tissue, and RT-PCR of saliva, CSF, or skin. - Antibodies in serum and CSF (in unvaccinated patients) also support the diagnosis.

**Prevention and treatment:** - Wound washing with soap and water immediately. - Post-exposure prophylaxis (PEP): human rabies immune globulin (HRIG), infiltrated around the wound, plus rabies vaccine (inactivated, given on days 0, 3, 7, 14). Give both since the incubation period is long enough for vaccine-induced immunity to develop. - Pre-exposure vaccination for high-risk groups (veterinarians, lab workers, travelers). - Observe or test the animal if it is a domestic dog, cat, or ferret. Wild animals are typically euthanized and tested.

**High-yield board associations:** - "Eosinophilic cytoplasmic inclusion in Purkinje cells or hippocampus + animal bite + hydrophobia" = rabies. - Negative-sense, bullet-shaped RNA virus. - Retrograde axonal transport. - Other viral inclusions to differentiate: Cowdry A bodies (HSV, intranuclear), "owl's eye" (CMV, intranuclear), Guarnieri bodies (smallpox/vaccinia, cytoplasmic), Henderson-Paterson bodies (molluscum contagiosum, cytoplasmic). - Named after Adelchi Negri (1903).