Rabies Medication

Before the onset of rabies symptoms, passive and active immunizations are effective in preventing progression to full-blown rabies.

If the patient has had no prior rabies vaccination, if he or she is of unknown status, or if more than 5 years have passed since his or her last vaccination, rabies vaccine and immunoglobulin should be administered as follows (these dosages being applicable to products available in the United States):

• Rabies vaccine IM (deltoid) - 1 mL on days on days 0, 3, 7, and 14 (if immunocompromised, add an additional dose: 1 mL IM deltoid on days 0, 3, 7, 14, and 28)
• Rabies immunoglobulin - 20 IU/kg infiltrated as much as feasible around and under the bite wound; if any left over, give IM (gluteus)

If the patient has had prior rabies vaccination, vaccine should be administered as follows (this dosage again being applicable to US vaccine): Rabies vaccine IM (deltoid) 1 mL on days on days 0 and 3.

Class Summary

Rabies immunoglobulin is recommended as part of the rabies postexposure regimen for persons not previously immunized against rabies. Vaccine and antiserum should never be mixed or injected in the same limb.

In the United States, passive immunization consists of administration of HRIG pooled from the sera of immunized human donors. In developing countries, equine rabies immunoglobulin (ERIG) is sometimes used but has a higher incidence of adverse effects. ERIG is no longer produced by large pharmaceutical companies. When produced by smaller pharmaceutical firms, its quality cannot be assured. New-generation purified ERIG preparations are under investigation.

Human rabies virus–specific monoclonal antibody preparations are in development, theoretically to decrease the possibility of anaphylaxis.^{[39, 40, 41]}

Because of cost, ERIG and HRIG are not readily available throughout much of the developing world, areas in which rabies is more common than in the United States. If HRIG is available only after more than a week after vaccination has started, then it is probably unnecessary, because an active antibody response has already begun.

Human rabies immunoglobulin (US: Imogam Rabies-HT, HyperRab S/D)

HRIG has been licensed since 1975, and unlike its predecessor, ERIG, it is not associated with significant adverse reactions, anaphylaxis, or serum sickness. Purified ERIG is still used in some developing nations because of cost or availability and is associated with an adverse effect rate of 0.8-6%, which usually involves minor reactions. HRIG is not associated with transmission of viral hepatitis or HIV. Experimentally, infiltration of HRIG at the site of exposure is more protective than IM administration. The current recommendation is that the entire dose be infiltrated, if possible, in and around the site, with any remaining solution administered IM in the gluteus.

Heat-treated and cold alcohol–fractionated immunoglobulin is derived from pooled human plasma from individuals immunized with human diploid cell rabies vaccine.

Class Summary

These agents promote immunity by inducing an active immune response. Two types of rabies vaccines have been produced: cell-cultured vaccines and nerve tissue vaccines.

In developing countries worldwide, nerve tissue vaccines have been the most widely used type for prophylaxis of rabies. They are dangerous because they may induce autoimmune CNS disease and may produce neurologic reactions; they also require multiple injections and are not always effective. WHO has advised discontinuation of nerve tissue rabies vaccines.^[42]

Two types of nerve tissue vaccine exist: the Semple type (STV) and the suckling mouse brain vaccine (SMBV). STV is obtained from inactivated virus prepared on adult animal nerve tissue. It is inexpensive and relatively easy to produce. In India, 3 million people receive postexposure courses of STV each year. STV may produce neurologic reactions, including postvaccination encephalomyelitis, in up to 1 in 220 courses, with a 3% mortality rate.

SMBV is cultured on immature mouse brain tissue, which contains little myelin. It is the most widely used rabies postexposure vaccine in Vietnam. Rare neurologic reactions occur, with complications in 1 in 27,000 treated people, with a 22% mortality rate.

Because SMBV and STV are widely used throughout the developing world, they are the vaccines that are administered to US travelers exposed to animal bites in some countries. It is advisable that US travelers to endemic areas receive pretravel rabies immunization with a cell-cultured vaccine if the itinerary suggests sufficient risk.

Cell-cultured rabies vaccines benefit from efficacy demonstrated in trials and a high level of immunogenicity; this permits a rational dosing schedule, and cell-cultured vaccines are considered the reference standard. The disadvantage of these vaccines is the cost of production.

In the United States, the CDC recommends rabies postexposure prophylaxis only with IM cell-cultured vaccines; intradermal (ID) formulations are not FDA approved for use in the United States.

Outside the United States, in areas where cost and vaccine supply are limiting factors, alternatives to the IM regimens may be more feasible. In addition, rabies vaccination may be the norm in some countries where rabies is endemic, and anamnestic response may permit effective alternative dosing.

In 1998, WHO released guidelines for ID use of HDCV, purified chick embryo cell vaccine, and purified duck embryo cell vaccine.^[26] WHO published updated postexposure prophylaxis guidelines that included ID regimens often used outside the United States.^[27]

In previously vaccinated individuals, studies have shown that single-visit, 4-site ID booster regimens offer satisfactory anamnestic response. A retrospective study at The Queen Saovabha Memorial Institute (QSMI) investigated booster regimens in more than 5000 previously immunized individuals who presented with rabies exposures. The study found that the single-visit, 4-site ID booster regimen using cell-cultured vaccine demonstrated superior anamnestic response, more rapid rise in Nab levels, and more persistently high Nab levels 1 year after prophylaxis than did the standard WHO 2-visit booster regimen.^[33] Advantages of the single-visit booster also included reduced time and reduced costs from loss of work or from delayed travel, along with enhanced compliance.

Booster immunization is indicated for individuals at continuous or frequent risk of rabies, who should undergo periodic rabies antibody testing and who have serum rabies titer of less than 1:5 dilution based on RFFIT results.

Rabies vaccine, adsorbed

This is an inactivated virus vaccine that promotes immunity by inducing an active immune response. It is administered IM only. The vaccine, which has no trade name, is produced by BioPort Corp under a US Department of Defense contract for military use only.

Rabies vaccine (RabAvert, Imovax)

The vaccines RabAvert (grown in chicken fibroblast culture) and Imovax (grown in human diploid cell culture) contain the inactivated virus that promotes immunity by inducing an active immune response. They are indicated for IM use only.