Infectious Disease · Viral Zoonoses
The facts most likely to be tested
Rabies is a rhabdovirus transmitted via the saliva of infected mammals, most commonly bats, raccoons, skunks, and foxes.
The virus travels via retrograde axonal transport from the peripheral nerves to the central nervous system.
Negri bodies, which are eosinophilic cytoplasmic inclusions in neurons, are the pathognomonic histologic finding.
Clinical presentation often begins with prodromal symptoms of pain, paresthesia, or pruritus at the bite site.
Classic manifestations include hydrophobia (fear of water) and aerophobia (fear of drafts of air) due to painful laryngeal spasms.
Post-exposure prophylaxis consists of rabies immune globulin (RIG) and the rabies vaccine administered on days 0, 3, 7, and 14.
Rabies is almost universally fatal once clinical symptoms appear, making post-exposure prophylaxis the only effective intervention.
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A 34-year-old male presents to the emergency department with a 3-day history of agitation, fever, and severe muscle spasms. He reports that he was bitten by a stray dog while hiking in a rural area 2 months ago but did not seek medical attention. On physical exam, he exhibits involuntary laryngeal spasms when offered a cup of water. He is noted to have hypersalivation and appears extremely anxious. The patient is currently experiencing aerophobia when a fan is turned on in the room.
What is the most likely diagnosis?
Rabies
The patient's presentation of hydrophobia, aerophobia, and laryngeal spasms following an animal bite is classic for rabies, which is confirmed by the presence of pathognomonic Negri bodies.
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Etiology / Epidemiology
Zoonotic rhabdovirus transmitted via saliva from bats (most common in US), raccoons, or dogs.
Clinical Manifestations
Prodrome of paresthesia at bite site followed by hydrophobia and aerophobia; nearly 100% fatal once symptomatic.
Diagnosis
Direct fluorescent antibody (DFA) test of brain tissue (post-mortem) or nuchal skin biopsy (ante-mortem).
Treatment
Immediate rabies immune globulin (RIG) and rabies vaccine (HDCV/PCECV) for post-exposure prophylaxis.
Prognosis
Once symptoms appear, mortality is >99.9%; supportive care is palliative only.
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Epidemiology & Etiology
Transmission occurs via inoculation of infected saliva through broken skin or mucous membranes. In the United States, bats are the primary reservoir, while canine rabies remains a global threat in endemic regions. Exposure is often unrecognized, particularly with minor bat bites.
Pertinent Anatomy
The virus travels via retrograde axonal transport from the peripheral nerves to the central nervous system. It preferentially targets the limbic system and brainstem, explaining the characteristic behavioral changes and autonomic instability.
Pathophysiology
The virus replicates in muscle tissue before entering the peripheral nervous system. It migrates to the dorsal root ganglia and eventually the brain, causing encephalitis. The presence of Negri bodies—eosinophilic cytoplasmic inclusions—is the hallmark histopathologic finding.
Clinical Manifestations
Patients present with a nonspecific viral prodrome followed by the classic furious rabies (agitation, hydrophobia, aerophobia) or paralytic rabies. Red flags include unexplained dysphagia, hypersalivation, and autonomic instability. Once clinical symptoms manifest, the disease is almost universally fatal.
Diagnosis
Diagnosis is rarely made ante-mortem; the direct fluorescent antibody (DFA) test on a nuchal skin biopsy is the gold standard. In suspected cases, PCR of saliva or CSF can be utilized. Post-mortem examination of brain tissue remains the definitive diagnostic method.
Treatment
Post-exposure prophylaxis (PEP) requires immediate wound cleansing and administration of rabies immune globulin (RIG) infiltrated around the wound. The rabies vaccine (HDCV or PCECV) is administered on days 0, 3, 7, and 14. Do not delay PEP while awaiting animal testing if the animal is unavailable or high-risk.
Prognosis
Survival is extremely rare once symptoms develop, with only a handful of documented cases globally. Management is strictly palliative and focused on sedation and comfort. Prevention via pre-exposure vaccination is recommended for high-risk occupations.
Differential Diagnosis
Tetanus: muscle rigidity and trismus without hydrophobia
Viral encephalitis: usually lacks the specific hydrophobia and bite history
Delirium tremens: history of alcohol withdrawal and autonomic hyperactivity
Guillain-Barré syndrome: ascending paralysis without the prodromal bite or encephalopathy
Botulism: descending flaccid paralysis without fever or sensory changes