What are the symptoms of rabies and what is the treatment protocol after exposure to the rabies virus?

Rabies Symptoms and Post-Exposure Treatment

Rabies causes acute, progressive encephalitis with clinical signs including inappetance, dysphagia, cranial nerve deficits, abnormal behavior, ataxia, paralysis, altered vocalization, and seizures, followed by rapid progression to death—but once symptoms appear, no effective treatment exists, making immediate post-exposure prophylaxis after any potential exposure the only life-saving intervention. 1

Clinical Symptoms of Rabies

Incubation Period

• The incubation period typically ranges from 1-3 months after exposure, but can vary from several days to years 1, 2
• In domestic animals, incubation is generally 3-12 weeks but rarely exceeds 6 months 1
• Median time from exposure to symptom onset in breakthrough infections is 20 days (IQR 16-24) 3

Neurological Manifestations

• Acute encephalomyelitis with progressive neurological deterioration 1
• Hydrophobia (fear of water) and aerophobia (fear of air currents) are highly characteristic—their presence significantly increases likelihood of antemortem diagnosis (odds ratio 11.0) 4
• Extreme agitation triggered by stimuli including loud noises, air currents, and the sight or sound of running water 5
• Cranial nerve deficits and dysphagia (difficulty swallowing) 1
• Ataxia and paralysis 1
• Seizures 1
• Altered vocalization 1

Behavioral Changes

• Abnormal behavior and inappetance 1
• Periods of lucidity alternating with severe agitation, causing psychological trauma from awareness of the disease 5

Disease Progression

• Rabies is nearly 100% fatal once clinical symptoms develop 1, 6
• Progression to death is rapid after symptom onset 1
• No proven effective medical treatment exists after clinical signs appear 5

Post-Exposure Prophylaxis (PEP) Protocol

Immediate Wound Care (Critical First Step)

• Thoroughly wash and flush all bite wounds and scratches immediately for approximately 15 minutes with soap or cleansing agent and copious amounts of water 7, 2
• Apply iodine-containing or similarly viricidal topical preparation to the wound where available 2
• Administer tetanus prophylaxis and bacterial infection control measures as indicated 2

For Previously Unvaccinated Persons

Administer a 4-dose vaccine regimen combined with rabies immune globulin (RIG): 1, 7

• Rabies vaccine: 4 doses of 1.0 mL intramuscularly (deltoid area in adults) on days 0,3,7, and 14 1, 7
• Rabies immune globulin (RIG): Single dose of 20 IU/kg administered on day 0 7, 2
  • Infiltrate the full dose around and into the wound(s) if anatomically feasible 7
  • Administer any remaining volume intramuscularly at a site distant from vaccine administration 7
  • Never administer RIG in the same site or same syringe as vaccine 1
  • RIG can be given up to the eighth day after the first vaccine dose 1

For Previously Vaccinated Persons

• Only 2 doses of vaccine on days 0 and 3 7
• No RIG administration—it can inhibit the anamnestic antibody response 7
• This applies to persons who previously received complete pre-exposure or post-exposure prophylaxis with cell-culture vaccine 1

For Immunocompromised Persons

• 5-dose vaccine regimen on days 0,3,7,14, and 28 7
• Plus RIG at 20 IU/kg, even if previously vaccinated 7

Timing Considerations

• Initiate PEP as soon as possible after exposure, ideally within 24 hours 7
• PEP is a medical urgency, not a medical emergency—but delays of even hours matter significantly 1, 7
• There is no absolute cutoff beyond which PEP should be withheld 7
• Most patients who develop rabies despite PEP received treatment within 2 days of exposure (77% of breakthrough cases), highlighting the importance of proper administration over speed alone 3

Exposure Risk Assessment

High-Risk Exposures Requiring PEP

• Any penetration of skin by teeth (bite exposure) from potentially rabid animals 1, 2
• Severe wounds: multiple wound sites or bites to the head, face, or neck carry higher risk (present in 69% of breakthrough infections) 3
• Nonbite exposures: scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or brain tissue from rabid animals 1, 2
• Bat exposures deserve special assessment: even when a bat is physically present in a room with a sleeping person or unattended child, PEP should be considered, as bat bites can cause insignificant wounds that go unrecognized 4

Exposures NOT Requiring PEP

• Petting or handling an animal 1
• Contact with blood, urine, or feces 1
• Contact of saliva with intact skin 1
• Bites from squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require PEP 2

Animal-Specific Considerations

• Wild carnivores (skunks, raccoons, foxes) and bats: regard as rabid unless proven negative by laboratory testing—consider immediate prophylaxis 2
• Domestic dogs, cats, ferrets: if healthy and available for 10-day observation, do not begin prophylaxis unless animal develops clinical signs; if rabid or suspected rabid, immediately begin prophylaxis 2
• Unprovoked attacks are more likely to indicate rabid animal than provoked attacks 1, 2

Efficacy and Outcomes

PEP Effectiveness

• When administered promptly and appropriately, PEP is nearly 100% effective in preventing human rabies 7, 6
• Post-vaccination serologic testing is not necessary in immunocompetent individuals 7

Breakthrough Infections

• Deviations from core practices (wound cleaning and proper vaccine administration) were reported in 56% of breakthrough cases 3
• Most breakthrough infections involved severe wounds (69%) and occurred despite timely PEP initiation 3
• Cold-chain integrity and potency testing of biologics were rarely assessed but were not found to be causes of breakthrough infections when evaluated 3

Treatment of Clinical Rabies

Standard Approach

• No proven effective treatment exists once clinical signs develop 5
• Primary focus should be on comfort care and adequate sedation in an appropriate medical facility 5
• Heavy sedation is necessary due to extreme agitation from stimuli 5, 6

Experimental Therapies

• Medical staff at specialized tertiary care hospitals might consider aggressive experimental therapies only in confirmed cases in young healthy persons at early disease stage, after in-depth discussions and informed consent 5
• Families must understand the high probability of treatment failure and that rare survivors may have serious neurological sequelae requiring lengthy rehabilitation 5
• Only 6 patients total have survived rabies, and 5 of these 6 had received rabies vaccination before disease onset 5
• Only one patient has recovered from rabies without prior vaccination 5

Critical Pitfalls to Avoid

• Underdiagnosis: Rabies should be included in the differential diagnosis of any acute, rapidly progressing encephalitis, even without recalled animal bite—in 78% of US cases from 1980-1996, patients had no definite history of animal bite 4
• Inadequate wound care: Deviations from proper wound cleaning contributed to over half of breakthrough infections 3
• Improper RIG administration: Must infiltrate wound site and never give in same location as vaccine 7, 2
• Delaying PEP for observation: For wild carnivores and bats, begin PEP immediately unless animal is available for expeditious laboratory testing 2
• Assuming small rodent bites require PEP: They almost never do, except for woodchucks which account for 70% of rabies cases among rodents 1