What are the guidelines for rabies vaccination, including post-exposure prophylaxis (PEP) and pre-exposure prophylaxis?

From the Guidelines

Rabies vaccination guidelines include both post-exposure prophylaxis (PEP) and pre-exposure prophylaxis protocols, with the most recent and highest quality study recommending a 4-dose schedule for PEP 1. For PEP, immediate treatment is essential after potential rabies exposure and consists of wound cleansing with soap and water, rabies immune globulin (RIG) infiltrated around the wound (20 IU/kg), and a series of rabies vaccines. The standard PEP vaccine schedule includes four doses of rabies vaccine (HDCV or PCECV) given intramuscularly in the deltoid on days 0,3,7, and 14 after exposure, as recommended by the Advisory Committee on Immunization Practices (ACIP) 1. Some key points to consider in the administration of PEP include:

• Wound cleansing with soap and water, and if available, a virucidal agent such as povidine-iodine solution should be used to irrigate the wounds 1.
• RIG should be administered at a dose of 20 IU/kg body weight, with the full dose infiltrated around and into the wound(s), and any remaining volume administered at an anatomical site (intramuscular) distant from vaccine administration 1.
• The combination of HRIG and vaccine is recommended for both bite and nonbite exposures reported by persons who have never been previously vaccinated for rabies, regardless of the interval between exposure and initiation of prophylaxis 1.
• For persons previously vaccinated with a cell culture vaccine or who have previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, a 2-dose PEP vaccination series is recommended 1. Pre-exposure prophylaxis is recommended for high-risk individuals like veterinarians, laboratory workers handling rabies virus, and travelers to rabies-endemic regions with limited medical access, and consists of two doses of rabies vaccine given on days 0 and 7, or a 3-dose series on days 0,7, and 21 or 28 1. This pre-exposure vaccination doesn't eliminate the need for additional treatment after exposure but reduces the number of doses needed and eliminates the need for RIG. The effectiveness of these protocols is based on the ability of the vaccines to stimulate neutralizing antibodies before the virus reaches the central nervous system, which is critical since rabies is nearly always fatal once symptoms develop, as noted in the study by 1. Timely administration is crucial, as the incubation period varies from days to months depending on wound location and viral load. It is also important to consider the specific recommendations for immunocompromised individuals, who may require a fifth dose of vaccine on day 28, as well as the recommendations for persons with altered immunocompetence, who should continue to receive a 5-dose vaccination regimen with 1 dose of RIG 1.

From the FDA Drug Label

Pre-exposure immunization should be offered to rabies researchers, certain laboratory workers and other persons in high-risk groups, such as veterinarians and their staff, and animal handlers Pre-exposure prophylaxis consists of three 1. 0 mL doses of Imovax Rabies vaccine administered intramuscularly, using a sterile needle and syringe, one injection per day on Days 0,7, and 21 or 28. The essential components of rabies post-exposure prophylaxis are wound treatment and, for previously unvaccinated persons, the administration of both human rabies immune globulin (RIG) and vaccine. Post-exposure antirabies vaccination should always include administration of both passive antibody and vaccine, with the exception of persons who have ever previously received complete vaccination regimens (pre-exposure or post-exposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer.

The rabies vaccination guidelines include:

• Pre-exposure prophylaxis: three 1.0 mL doses of Imovax Rabies vaccine administered intramuscularly on Days 0,7, and 21 or 28, for individuals in high-risk groups such as rabies researchers, laboratory workers, veterinarians, and animal handlers.
• Post-exposure prophylaxis: wound treatment and administration of both human rabies immune globulin (RIG) and vaccine for previously unvaccinated persons.
• Booster doses: administration of booster doses depends on exposure risk category and serologic testing.
• Special considerations: immunosuppressed persons should postpone pre-exposure vaccinations and consider avoiding activities for which rabies pre-exposure prophylaxis is indicated. 2 2 2

From the Research

Rabies Vaccination Guidelines

The guidelines for rabies vaccination include both post-exposure prophylaxis (PEP) and pre-exposure prophylaxis.

• Post-exposure prophylaxis (PEP) is critical in preventing rabies after an exposure to the virus, and it typically consists of immediate wound cleansing, injection of human rabies immunoglobulin, and a series of rabies vaccinations 3, 4.
• The administration of a rabies immune globulin is generally recommended in conjunction with the first dose of the rabies vaccine 4.
• Pre-exposure prophylaxis is recommended for individuals at risk of exposure to the virus, such as those working with animals or traveling to areas where rabies is common 4.
• Pre-exposure prophylaxis consists of 3 doses of an approved rabies vaccine administered either intramuscularly or intradermally on days 0,7, and 21 or 28, with periodic booster doses or titre determination depending on the level of risk of potential exposure to the virus 4.

Post-Exposure Prophylaxis (PEP) Schedules

• The World Health Organization (WHO) recommends PEP schedules that require up to 5 clinic visits over the course of approximately one month 5.
• Abridged schedules with fewer doses have the potential to save costs, increase patient compliance, and improve equitable access to life-saving PEP for at-risk populations 5.
• The 1-week, 2-site ID PEP schedule has been found to be safe, immunogenic, and cost-effective, and it involves the least direct costs compared to other schedules 5.
• Changes in the rabies vaccine product and/or the route of administration during PEP are possible, and evidence suggests that this does not affect the safety and immunogenicity of the vaccine 6.

Vaccine Administration

• Rabies vaccines can be administered intramuscularly or intradermally, and the choice of route depends on various factors, including the vaccine product and the individual's risk of exposure 4, 7.
• The four-site intradermal schedule (4-0-2-0-1-1) has been found to be immunogenic, cost-effective, and practical, and it reduces the cost of PEP by up to 80% compared to the standard intramuscular Essen regimen 7.
• Both purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccine (PVRV) have been found to be well-tolerated and effective in inducing rabies virus neutralizing antibody titers above 0.5 IU/mL 7.