Lyssavirus zoonosis transmitted via mammalian bites; near-100% fatal once symptomatic — post-exposure prophylaxis with vaccine and HRIG is highly effective.
Also known as: rabies, rabies PEP, post-exposure prophylaxis, hydrophobia, lyssavirus
Overview
Acute viral encephalomyelitis caused by Lyssavirus (Rabies virus), an enveloped negative-sense RNA virus of the Rhabdoviridae family, transmitted by infected mammalian saliva (bite, less often mucous membrane exposure). Once symptomatic, mortality is virtually 100%.
Epidemiology
US: 1-3 human cases annually, mostly bat-related. Worldwide ~59,000 deaths/year, predominantly dog bites in Asia and Africa. In the US, wildlife reservoirs are bats, raccoons, skunks, foxes; small rodents (squirrels, mice) are virtually never infected.
Try two board-style Rabies Post-Exposure Prophylaxis questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1Infectious DiseaseMedium
A 42-year-old man presents with a 3-day history of fever, malaise, paresthesias at a healed wound on his right hand, anxiety, and hydrophobia triggered by attempts to drink water. Two months ago he was bitten by a stray dog while traveling in rural India and did not receive postexposure prophylaxis. On exam he is agitated with hypersalivation and pharyngeal spasms when offered fluids. Which test is most likely to confirm the diagnosis?
ALumbar puncture with viral culture of CSF
BSerum IgM enzyme immunoassay for rabies
CBrain MRI with gadolinium enhancement
DRT-PCR of saliva plus nuchal skin biopsy
Reveal answer & full explanation
Correct answer: D — RT-PCR of saliva plus nuchal skin biopsy
ALumbar puncture with viral culture of CSF
BSerum IgM enzyme immunoassay for rabies
CBrain MRI with gadolinium enhancement
DRT-PCR of saliva plus nuchal skin biopsy✓
Why RT-PCR of saliva plus nuchal skin biopsy is correct
This patient has encephalitic rabies after an untreated dog bite (no postexposure prophylaxis received), with the classic prodrome: paresthesias at the bite site, followed by hydrophobia, hypersalivation, pharyngeal spasms, and agitation
Antemortem diagnosis is best achieved with a combination of RT-PCR on saliva and a full-thickness skin biopsy from the nape of the neck (which samples hair follicle nerve endings); together these have high sensitivity
Why the others are wrong
B) Serum IgM enzyme immunoassay for rabies — unreliable because antibodies often do not appear until late in the illness, particularly in unvaccinated patients
A) Lumbar puncture with viral culture of CSF — rabies virus is rarely recovered from CSF; lumbar puncture findings are nonspecific; viral culture is insensitive and slow
C) Brain MRI with gadolinium enhancement — may show nonspecific signal changes in the brainstem and limbic system but cannot establish the diagnosis
Additional high-yield points
Once clinical disease develops, rabies is almost universally fatal
This underscores the importance of timely postexposure prophylaxis with rabies immune globulin plus vaccine
Question 2Infectious DiseaseMedium
A 41-year-old missionary develops fever, agitation, and painful pharyngeal spasms when attempting to drink. He recalls being bitten on the right calf by a stray dog while abroad roughly 10 weeks earlier; the small wound healed and he never sought care. On exam he is hypersalivating and intermittently lucid. Skin biopsy with direct fluorescent antibody confirms rabies. Which of the following best explains the prolonged interval between his bite and the onset of symptoms?
ARetrograde axonal transport of the virus along peripheral nerves to the CNS
BIntegration of viral DNA into host neurons with subsequent delayed reactivation
CAutoantibody-mediated slow demyelination of the peripheral motor nerves
DHematogenous spread of the virus following latency within regional lymph nodes
Reveal answer & full explanation
Correct answer: A — Retrograde axonal transport of the virus along peripheral nerves to the CNS
ARetrograde axonal transport of the virus along peripheral nerves to the CNS✓
BIntegration of viral DNA into host neurons with subsequent delayed reactivation
CAutoantibody-mediated slow demyelination of the peripheral motor nerves
DHematogenous spread of the virus following latency within regional lymph nodes
Why Retrograde axonal transport of the virus along peripheral nerves to the CNS is correct
After local replication in muscle, rabies virus enters peripheral nerves at the neuromuscular junction and travels retrograde along axons toward the CNS at only ~12-100 mm/day.
The long, variable incubation (typically 1-3 months, occasionally years) directly reflects the time needed for this slow axonal transport from the bite site; distal bites and larger inocula tend to shorten it.
Once it reaches the CNS, the virus replicates massively in neurons (Negri bodies) and spreads centrifugally to the salivary glands and skin, producing the hydrophobia and hypersalivation seen here.
Why the others are wrong
Hematogenous spread of the virus following latency within regional lymph nodes: rabies spreads neurally rather than through blood or lymph; meaningful viremia is not part of its pathophysiology.
Autoantibody-mediated slow demyelination of the peripheral motor nerves: this describes an immune-mediated, Guillain-Barre-like process; paralytic rabies can mimic GBS, but the incubation delay comes from axonal transport, not autoantibody-driven demyelination.
Integration of viral DNA into host neurons with subsequent delayed reactivation: rabies is a negative-sense RNA virus (Rhabdoviridae) with no DNA stage and no genomic integration or latency-reactivation; that pattern describes herpesviruses.
🔒 Free preview limit reached
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Rabies Post-Exposure Prophylaxis outline — plus all 514 diagnoses, 6,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Bite from bat, raccoon, skunk, fox, coyote, or unvaccinated dog/cat (especially abroad)
Sleeping in a room where a bat is found (potential unrecognized exposure)
Travel to dog-rabies endemic areas (India, China, Africa)
Spelunking, wildlife handling, veterinary work
Failure to seek timely PEP after exposure
Pathophysiology
Virus replicates locally in muscle, then enters peripheral nerves at neuromuscular junctions and travels retrograde axonally to the CNS at ~12-100 mm/day. Replicates massively in CNS neurons (Negri bodies on histology) → encephalitis. Then spreads centrifugally to salivary glands, skin, cornea, and other organs. Long incubation (typically 1-3 months, range days to years) reflects time required for axonal transport from the bite site.
Clinical presentation
Symptoms
Prodrome (1-7 days): fever, malaise, headache, anorexia; pain or paresthesias at bite site (pathognomonic)
Furious form (~80%): hydrophobia (painful pharyngeal spasms triggered by attempts to drink), aerophobia, agitation, hyperactivity, hallucinations, autonomic instability (hypersalivation, sweating, lacrimation), seizures
Paralytic form (~20%): ascending flaccid paralysis resembling Guillain-Barre
Coma, multi-organ failure, death within 1-2 weeks of symptom onset
Signs / physical exam
Hypersalivation, lacrimation, sweating
Pharyngeal/laryngeal spasm with drinking
Hyperactivity alternating with lucid intervals
Cranial nerve palsies
Negri bodies (eosinophilic cytoplasmic inclusions in neurons) on autopsy — historical hallmark
Classic findings
Hydrophobia and aerophobia in an encephalopathic patient with a remote animal bite — virtually pathognomonic for clinical rabies.
Tetanus — Rigidity with preserved consciousness; unattended wound; differs from rabies encephalitis
Acute psychosis or substance intoxication — May mimic furious rabies; toxicology screen, history
Other encephalitides (autoimmune, anti-NMDA) — Autoantibodies, immunotherapy response
Diagnostic workup
Diagnostic criteria
Clinical syndrome with exposure history and laboratory confirmation. Diagnosis is most often confirmed in the animal source.
Labs
Pre-mortem diagnosis difficult: skin biopsy (nuchal area) with direct fluorescent antibody for viral antigen, CSF/saliva PCR, serum/CSF antibody (after 7-10 days of illness)
Animal testing: brain tissue with direct fluorescent antibody is gold standard (requires euthanasia)
Post-mortem: brain biopsy with Negri bodies and direct fluorescent antibody
Imaging
MRI may show abnormal signal in brainstem, hippocampus, hypothalamus — non-specific
Diagnostic algorithm
flowchart TD
A[Potential rabies exposure<br/>bite or saliva to wound/mucosa] --> B{Animal type}
B -->|Small rodent / rabbit| C[PEP rarely indicated]
B -->|Healthy dog/cat available| D[Quarantine animal 10 days]
D -->|Healthy at 10 d| E[No PEP]
D -->|Develops illness| F[Initiate PEP]
B -->|Wild reservoir<br/>bat, raccoon, skunk, fox| G[Initiate PEP immediately<br/>test animal if available]
G --> H[Step 1: Wash wound<br/>15 min soap and water]
H --> I[Step 2: HRIG 20 IU/kg<br/>infiltrate around wound]
I --> J[Step 3: Vaccine days 0, 3, 7, 14<br/>5 doses if immunocompromised]
Post-exposure prophylaxis (PEP) is highly effective if started promptly:
1. Wound care: thorough washing with soap and water for 15 minutes, then povidone-iodine or virucidal agent — reduces local viral load and is the single most important step
2. Human rabies immune globulin (HRIG) 20 IU/kg — infiltrate as much as possible AROUND the wound; remainder IM at a distant site. Given only ONCE, ideally on day 0
3. Rabies vaccine series (HDCV or PCECV) IM in the deltoid (or anterolateral thigh in young children) on days 0, 3, 7, and 14 (4 doses for immunocompetent — ACIP 2010)
4. Immunocompromised patients: 5-dose series on days 0, 3, 7, 14, and 28 PLUS HRIG
5. Pre-existing immunization (pre-exposure prophylaxis received): 2 booster doses on days 0 and 3; do NOT give HRIG
Second-line / adjunct
Pre-exposure prophylaxis (PrEP): vaccine series for high-risk workers (veterinarians, lab workers, spelunkers, travelers to endemic areas) — 2-dose series on days 0 and 7 per ACIP 2022 update
Milwaukee protocol (induced coma, antivirals) — experimental, virtually no proven survival benefit; not standard
Once symptomatic, treatment is supportive comfort care; survival reports remain anecdotal
Complications
Death from rabies encephalitis (virtually 100% once symptomatic)
PEP side effects: mild local reactions, low-grade fever; serum sickness rare with modern HDCV/PCECV (vs. older nerve tissue vaccines)
PANCE pearls
Bat exposures: any potential contact with a bat (e.g., waking with bat in room, child sleeping in room with bat) is grounds for PEP unless the bat tests negative — bites can be too small to detect.
Small rodents (squirrels, hamsters, mice, rats) and rabbits virtually never transmit rabies in the US — PEP rarely indicated.
Healthy dog/cat that bit a human can be quarantined and observed for 10 days; if remains healthy, PEP can be deferred.
Always wash the wound first — physical removal of virus from the wound is a critical part of PEP.
Do NOT give HRIG in the same syringe or site as the vaccine — antibody can neutralize antigen and blunt response.
References
ACIP 2010 — Rupprecht et al., Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies (MMWR Recommendations and Reports)
ACIP 2022 — Updated recommendations for pre-exposure prophylaxis against rabies (MMWR)
WHO 2018 — WHO Expert Consultation on Rabies, third report (Technical Report Series 1012)
Practice Infectious Disease questions on FirstPassPA
Turn this outline into retention. 6,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.