Centrifugal spread after CNS infection to salivary glands, skin, cornea
Neuropathology: Negri bodies (intracytoplasmic inclusions) in Purkinje and hippocampal neurons
Pathognomonic on histology
Therapeutic Considerations
PEP efficacy
PEP is virtually 100% effective when administered correctly
Every documented US PEP failure involved protocol deviation
Wounds not adequately cleansed
HRIG not administered
Vaccine given in gluteal area
ACIP reduced 4-dose schedule (2010) equivalent to original 5-dose schedule
ACIP Class I recommendation based on immunogenicity data
Milwaukee Protocol
Experimental protocol for clinical rabies (induced coma plus antiviral therapy)
Rare documented survivors exist; overall survival under 1%
Not established as standard of care
Considered only in specialized centers
Pre-exposure prophylaxis (PrEP)
2022 ACIP updated 2-dose schedule (Days 0 and 7)
Replaces previous 3-dose schedule for PrEP
Followed by booster based on serology
Indications: veterinarians, spelunkers, laboratory workers, travelers to endemic regions
PrEP simplifies PEP: 2 doses, no HRIG needed
Emerging therapies
Rabies monoclonal antibody (SYN023 or NM57)
Phase 4 trial (Lancet 2025): non-inferior to HRIG for Category III exposures
Potential alternative to HRIG in resource-limited settings
Antiviral agents: no proven efficacy in established disease
Patient Discharge Instructions
copy discharge instructions
What happened today
You were treated for a potential rabies exposure
You received wound cleaning and your first rabies vaccine shot
You received rabies immune globulin (HRIG) to provide immediate protection
Rabies is almost always preventable if the complete vaccine series is given
It is nearly always fatal once symptoms appear
Completing all vaccine doses is essential
Your vaccine schedule
Return for your remaining rabies vaccine doses
Day 3 after today's visit
Day 7 after today's visit
Day 14 after today's visit
These doses can be given at your family doctor, an urgent care clinic, or the emergency department
Even a few days of delay is okay; contact public health if you miss a dose by more than a week
Animal monitoring
If a dog, cat, or ferret bit you, it must be watched for 10 days
If the animal stays healthy for 10 days, your remaining vaccine doses may not be needed
Your doctor or public health authority will let you know
Wound care at home
Wash the wound gently with soap and water twice daily
Watch for signs of infection: increasing redness, swelling, warmth, pus, or red streaks
Keep wound covered with clean bandage until healing
Return to the emergency department immediately if you develop
Fever or shaking chills
Numbness, tingling, or pain at or near the bite site
Difficulty swallowing or drinking water
Fear of water or air currents
Unusual anxiety, agitation, or confusion
Muscle weakness in your arms or legs
Headache that is severe or worsening
Tetanus and antibiotics
If a tetanus shot was given today, your arm may be sore for a few days
If antibiotics were prescribed, complete the full course even if wound looks better
Questions or concerns
Contact your local public health department for questions about rabies risk in the area
CDC Rabies information: www.cdc.gov/rabies
References
Guidelines and key sources
ACIP 2010 reduced PEP schedule
Rupprecht CE, Briggs D, Brown CM, et al. Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies. MMWR Recomm Rep. 2010
Established 4-dose PEP regimen (Days 0, 3, 7, 14) as standard of care
Annals of Emergency Medicine endorsement 2010
ACIP 2022 pre-exposure prophylaxis update
Rao AK, Briggs D, Moore SM, et al. Use of a Modified Preexposure Prophylaxis Vaccination Schedule. MMWR. 2022
Updated 2-dose PrEP schedule on Days 0 and 7
CDC Yellow Book 2025
Wallace RM and Shlim DR. Rabies. CDC Yellow Book 2025
Comprehensive travel and exposure guidance
JAMA Network Open 2022
Yuan F, Iso T, Rizk E, et al. Implementation of Clinical Decision Support on ED Delivery of HRIG. JAMA Netw Open. 2022
Clinical decision support tool to improve HRIG delivery
JAMA Network Open 2023
Charniga K, Nakazawa Y, Brown J, Jeon S, Wallace RM. Risk of Rabies and Implications for PEP Administration in the US. JAMA Netw Open. 2023
Landmark studies and reviews
Lancet Neurology 2013
Hemachudha T, Ugolini G, Wacharapluesadee S, et al. Human Rabies: Neuropathogenesis, Diagnosis, and Management. Lancet Neurol. 2013
Comprehensive review of pathophysiology and clinical management
Lancet 2014
Fooks AR, Banyard AC, Horton DL, et al. Current Status of Rabies and Prospects for Elimination. Lancet. 2014
Lancet Infectious Diseases 2023
Whitehouse ER, Mandra A, Bonwitt J, et al. Human Rabies Despite PEP: Systematic Review of Fatal Breakthrough Infections. Lancet Infect Dis. 2023
Confirmed every failure involved protocol deviation
Lancet 2025
Kulkarni PS, Potey AV, Kapse D, et al. PEP Regimen of Rabies Monoclonal Antibody and Vaccine in Category III Exposures. Phase 4 Trial. Lancet. 2025
Monoclonal antibody non-inferior to HRIG
Academic Emergency Medicine 2023
Gibbons K, Dvoracek K. Rabies PEP: What the US Emergency Medicine Provider Needs to Know. Acad Emerg Med. 2023
NEJM 1993
Fishbein DB, Robinson LE. Rabies. N Engl J Med. 1993; 329:1687-1695
NEJM 2004
Rupprecht CE, Gibbons RV. Prophylaxis against Rabies. N Engl J Med. 2004
IDSA/ASM 2024 Microbiology Lab Guide
Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update. Clin Infect Dis. 2024
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.