What is the most effective treatment for rabies exposure?

Rabies Treatment Effectiveness

Postexposure prophylaxis combining immediate wound cleansing, rabies immune globulin, and rabies vaccine is nearly 100% effective when properly administered, but once clinical symptoms develop, rabies is essentially incurable with only one documented survivor who did not receive vaccination. 1, 2

Treatment Before Symptom Onset: Postexposure Prophylaxis (PEP)

Immediate Wound Management

• Wash all bite wounds and scratches immediately and thoroughly with soap and water for 15 minutes—this single intervention markedly reduces rabies risk and is perhaps the most effective measure for preventing infection. 1, 2, 3
• Irrigate the wound with a virucidal agent such as povidone-iodine solution if available after soap and water cleansing. 2, 4
• Administer tetanus prophylaxis and antibiotics as indicated for bacterial infection control. 2, 3

For Previously Unvaccinated Persons

Administer both human rabies immune globulin (HRIG) and a 4-dose vaccine series—this combination is uniformly effective when appropriately administered. 1, 2

HRIG Administration

• Give HRIG at exactly 20 IU/kg body weight as a single dose on day 0, ideally simultaneously with the first vaccine dose. 2, 5
• Infiltrate the full calculated dose thoroughly around and into all wounds if anatomically feasible—this provides immediate passive immunity at the wound site during the first 7-10 days before vaccine-induced antibodies develop. 2, 5, 3
• Inject any remaining volume intramuscularly at a site distant from vaccine administration. 5, 3
• Do not exceed 20 IU/kg, as higher doses suppress active antibody production. 5
• HRIG can be administered up to and including day 7 after the first vaccine dose if not given initially. 5, 3

Vaccine Administration

• Administer 1.0 mL of HDCV (human diploid cell vaccine) or PCECV (purified chick embryo cell vaccine) intramuscularly on days 0,3,7, and 14. 1, 2, 5
• Inject in the deltoid muscle for adults and older children, or the anterolateral thigh for young children—never use the gluteal area as this produces inadequate antibody response and has been associated with vaccine failures. 1, 2, 5
• Day 0 is defined as the day the first dose is given, not necessarily the day of exposure. 5

For Previously Vaccinated Persons

• Administer only 2 doses of vaccine on days 0 and 3—do NOT give HRIG as it will inhibit the rapid anamnestic antibody response. 2, 5
• This simplified regimen applies to anyone who has completed a recommended pre-exposure or post-exposure vaccination series with a cell culture vaccine. 5

For Immunocompromised Patients

• Administer a 5-dose vaccine regimen on days 0,3,7,14, and 28, plus HRIG at 20 IU/kg on day 0, even if previously vaccinated—the standard 4-dose schedule is inadequate for this population. 5
• Corticosteroids, other immunosuppressive agents, antimalarials, and immunosuppressive illnesses (including HIV, chronic lymphoproliferative leukemia) substantially reduce immune responses to rabies vaccines. 5
• Test rabies virus-neutralizing antibody by RFFIT 1-2 weeks after the final vaccine dose (day 42 for immunocompromised patients). 5
• An acceptable antibody response is defined as complete neutralization of challenge virus at a 1:5 serum dilution. 5

Timing Considerations

• Initiate PEP as soon as possible after exposure, ideally within 24 hours, but treatment should begin immediately upon recognition of exposure even if weeks or months have elapsed—there is no absolute cutoff for initiating PEP. 5, 6
• Rabies incubation periods can exceed one year, and the disease is uniformly fatal once symptoms appear. 5
• Delays of a few days for individual doses are unimportant, though the effect of longer lapses of weeks or more is unknown. 5

Evidence of Effectiveness

• Studies describing extensive field experience indicate that postexposure prophylaxis combining wound treatment, local infiltration of rabies immune globulin, and vaccination is uniformly effective when appropriately administered. 1
• No case of human rabies in the United States has been documented since current cell culture biologics were licensed when PEP was properly administered. 2
• In experimental animals, the combination of vaccine and immune globulin was 100% effective in preventing rabies after lethal challenge. 7
• Over 1,000 persons annually in the United States receive only 3 or 4 doses instead of the complete regimen, with no documented cases of rabies developing, even when >30% had confirmed exposure to rabid animals. 5

Common Causes of PEP Failure

When breakthrough infections occur despite PEP, they are almost always due to deviations from core practices rather than vaccine failure. 8

• Deviations from core practices (wound cleaning and vaccine administration) were reported in 68 (56%) of 122 breakthrough infections reviewed. 8
• Specific failures included: not cleansing wounds with soap and water, not administering HRIG around the wound site, administering vaccine in the gluteal area instead of deltoid, and delays in seeking health care. 1, 8
• Severe wounds involving multiple sites or bites to the head, face, or neck were common in breakthrough cases (69% of cases). 8
• Cold-chain integrity and potency testing of PEP biologics were rarely found to be causes of breakthrough infections. 8

Treatment After Symptom Onset: Clinical Rabies

Once clinical symptoms develop, rabies is not considered curable—only one patient has recovered from rabies without the institution of rabies vaccination before symptom onset. 1

Current Approach to Clinical Rabies

• Primary health considerations should focus, at a minimum, on comfort care and adequate sedation of the patient in an appropriate medical facility. 1
• Sedation is often necessary because patients become extremely agitated, especially in the presence of stimuli such as loud noises, air currents, and the sight or sound of running water during the acute neurologic phase. 1
• Medical staff at specialized tertiary care hospitals might consider institution of aggressive experimental therapies (such as the Milwaukee Protocol) in confirmed cases in young healthy persons at an early stage of clinical disease, after informed consent. 1
• Parties authorized to give permission for such treatment should be aware of the high probability for treatment failure, the anticipated expenses, and that in rare instances of patient survival, recovery might be associated with neurologic deficits requiring lengthy rehabilitation. 1

Experimental Approaches

• Treatment of clinical rabies consists of medical support in an intensive care unit using supportive care, heavy sedation, analgesics, anticonvulsants, and antivirals, though outcomes remain poor. 6
• The Milwaukee Protocol added induction of therapeutic coma to supportive care measures and antivirals, but its use has shown inconsistent outcomes. 6
• To date, only seven individuals have survived rabies virus infection after symptom onset. 6

Infection Control for Clinical Cases

• Human rabies patients do not pose any greater infection risk to health-care personnel than patients with more common bacterial and viral infections. 1
• Medical staff should adhere to standard precautions: wear gowns, goggles, masks, and gloves, particularly during intubation and suctioning. 1
• Postexposure prophylaxis is indicated only when the patient has bitten another person or when the patient's saliva or other potentially infectious material has contaminated an open wound or mucous membrane. 1

Critical Pitfalls to Avoid

• Never administer vaccine in the gluteal area—this produces inadequate antibody response and is associated with vaccine failures. 1, 2, 5
• Never give HRIG to previously vaccinated persons—this suppresses the memory immune response. 2, 5
• Never exceed 20 IU/kg for HRIG dose—excess HRIG suppresses active antibody production. 5, 4
• Never delay or omit thorough wound cleansing with soap and water—this is the single most effective measure for preventing rabies. 2, 5, 4
• Never fail to infiltrate HRIG around and into the wound site—this provides critical immediate passive immunity. 1, 2, 5
• Never use the standard 4-dose regimen for immunocompromised patients—they require the 5-dose regimen plus HRIG even if previously vaccinated. 5