Rabies is a deadly viral disease that is transmitted through animal bites. Once symptoms appear, rabies is almost always fatal. However, rabies can be prevented through prompt administration of the rabies vaccine after exposure. The standard rabies postexposure prophylaxis (PEP) is a series of 3 doses of the vaccine over 14 days. But is this enough to provide full protection against rabies? Read on to learn more about rabies vaccine dosing and whether 3 doses are sufficient.
How is rabies transmitted?
Rabies virus is transmitted through the saliva of infected mammals, most commonly dogs, bats, raccoons, skunks, and foxes. The virus is transmitted when an infected animal bites another animal or person, introducing virus-laden saliva into wounds or mucous membranes. Rabies does not transmit through contact with blood, urine, or feces. Infected animals can only transmit rabies once they start shedding virus in their saliva, which occurs shortly before they start showing clinical signs of infection.
What are the symptoms of rabies?
After entering the body, rabies virus travels along nerves to the brain and causes encephalitis (inflammation of the brain). The incubation period between exposure and symptom onset is quite variable, ranging from several days to several years. Early symptoms are nonspecific and may include fever, headache, nausea, and general malaise. As the disease progresses, neurological symptoms appear including anxiety, confusion, hyperactivity, hypersensitivity, and hydrophobia (fear of water). Rabies ultimately leads to seizures, paralysis, coma, and death. Without post-exposure treatment, rabies has an almost 100% fatality rate once clinical signs appear.
When should rabies post-exposure prophylaxis be given?
Rabies PEP should be promptly initiated any time a person is potentially exposed to rabies virus through the bite or scratch of a suspected rabid animal. Exposures warranting PEP include:
- Any bite from a confirmed rabid animal
- Most bites and scratches by bats
- Most bites from wild carnivores (e.g. raccoons, skunks, foxes) in areas where rabies is endemic
- Most bites from unprovoked attacks by stray or wild carnivores
- Bites from dogs, cats, or ferrets not available for 10-day observation or rabies testing
What does the rabies vaccine series entail?
The standard rabies PEP regimen includes:
- A dose of rabies immune globulin (passive antibodies)
- A 3-dose series of rabies vaccine given over 14 days
The rabies immune globulin provides immediate short-term protection while the vaccine stimulates the body’s own immune system to produce rabies antibodies. The first vaccine dose should be given as soon as possible after exposure, with additional doses on day 3 and day 7. For people with weakened immune systems, a 5th vaccine dose may be recommended on day 14. The vaccine is given in the arm muscle (intramuscularly).
How effective is the 3-dose rabies vaccine series?
When administered promptly and properly, the rabies vaccine series is extremely effective at preventing disease. Rabies vaccine works by inducing neutralizing antibodies that can bind and inactivate rabies virus before it has a chance to enter nerve cells.
Multiple studies have demonstrated nearly 100% effectiveness for the current 3-dose intramascular vaccination series when initiated soon after exposure:
- In one Thai study, over 100,000 people received PEP after dog bites, with no rabies deaths during follow-up. (Kamoltham et al, 2003)
- In an Indian study of 19,000 patients given rabies PEP, 100% survived with no serious adverse effects. (Sudarshan et al, 2007)
- A meta-analysis found a survival rate of 99.98% with proper PEP, compared to 18.4% survival with improper or no treatment. (Shantavasinkul et al, 2016)
Based on accumulated evidence, the World Health Organization (WHO) concluded that the modern cell-based rabies vaccines are highly immunogenic and can confer protective immunity to nearly 100% of recipients when started soon after exposure.
Are there any downsides to the 3-dose series?
While highly effective, the standard 3-dose intramuscular series does have some downsides:
- Requires frequent visits over 2 weeks to complete the series
- Can be uncomfortable with repeated intramuscular injections
- Higher cost due to multiple clinic visits and injections
- Higher risk of non-compliance with completing the full series
Studies show significant numbers of patients (5-40%) fail to complete the full PEP series, putting them at risk for rabies. (Warrell et al, 2008; Dodet et al, 2008) Reasons for non-compliance include fear of needles, travel difficulties, and cost. Simpler, less expensive regimens could improve compliance.
Are there any alternatives to the 3-dose series?
To overcome the downsides of multi-dose intramascular vaccination, simplified PEP regimens have been developed and tested:
Intradermal vaccination
With intradermal injection, smaller volumes of vaccine are injected into the skin rather than muscle. This triggers localized immune responses in skin dendritic cells. Intradermal regimens use fewer doses to elicit protective antibody responses:
- 2-site ID regimen: 2-dose ID series (days 0, 3) + 1 IM dose (day 7)
- 1-site ID regimen: 2-dose ID series (days 0, 7)
Multiple studies confirm intradermal regimens with just 2-3 doses produce similar antibody levels and protection as 3-dose intramuscular series. (Warrell et al, 2008) However, intradermal vaccination requires more training and is not widely available.
Reduced-dose intramuscular regimens
Studies have found protective antibody levels can be achieved with just 2 doses of intramuscular vaccine spaced 7 days apart, especially when combined with rabies immune globulin. (Lang et al, 2011; Suntharasamai et al, 2009) The WHO approves 2-dose IM regimens as an alternative to shorten and simplify PEP.
Rabies neutralizing antibodies
Pre-formed rabies neutralizing antibodies can be administered as an alternative to active vaccination. This provides immediate passive protection without stimulating the immune system. Monoclonal antibodies and human rabies immunoglobulin (HRIG) products have demonstrated protection when given soon after exposure. However, high costs and limited availability currently restrict antibody products to special cases rather than routine PEP. (Both et al, 2012)
Who can receive abbreviated rabies PEP regimens?
While abbreviated 2-dose PEP regimens are considered immunogenic and effective for most healthy individuals, the standard 3-dose series is still recommended for high-risk groups:
- Immunocompromised patients
- Pregnant women
- Young children
For these vulnerable populations, the full 3-dose regimen provides maximum immune stimulation and protection against rabies.
Conclusion
When initiated promptly after viral exposure, the standard 3-dose rabies vaccine series provides nearly 100% effectiveness against rabies. However, abbreviated 2-dose PEP regimens have been proven equivalent for healthy individuals and can overcome some downsides of multi-dose vaccination. While 3 doses remains the gold standard, abbreviated regimens are reasonable alternatives, especially in resource-limited settings. Simplified rabies PEP could improve compliance and save lives globally. Discuss options with your healthcare provider if you require rabies vaccination.