Morning Report: 3/15/2013

Thanks to Dr. Melendez for today’s Morning Report!

Rabies Post Exposure Treatment

In the United States, there has been an average of two fatal human rabies cases annually since 1980, the majority associated with exposure to bats.

Timing of prophylaxis — Rabies postexposure prophylaxis is an urgent medical intervention and should begin as soon as possible after the presumed exposure.

What to administer — Rabies immunoglobulin is referred to as “passive immunization”; rabies vaccine is referred to as “active immunization”. The choice of rabies biologics (eg, vaccine and rabies immunoglobulin) will depend on whether the patient is receiving pre- or postexposure prophylaxis and on the previous immunization history:

Vaccine alone is given for preexposure prophylaxis
Post-exposure rabies prophylaxis, in previously unimmunized persons, should always include both passive and active immunization.
Vaccine alone is indicated in persons who have had preexposure prophylaxis with a cell culture vaccine series or who had been vaccinated with other types of rabies vaccine with a documented neutralizing antibody response.

The CDC guidelines for vaccine administration for postexposure prophylaxis in unvaccinated persons exposed to rabies changed in 2010, from a five-dose schedule of vaccine (given intramuscularly) starting immediately (day 0) after exposure and on days 3, 7, 14, and 28 after the first dose to a four-dose schedule eliminating the day 28 dose of the series. However, the 5 dose regimen is still recommended for immunocompromised hosts.

Postexposure prophylaxis for previously vaccinated persons — A previously vaccinated person who has had a potential rabies exposure should receive two intramuscular doses of vaccine; the first dose should be given on day 0, as soon after exposure as possible, and the other three days later.

Individuals who qualify as previously immunized include those who have received one of the vaccines according to either preexposure or postexposure immunization schedules recommended in the United States, or those who had a documented adequate rabies antibody titer following another vaccine product or schedule.

Wound care — One of the most important initial steps to prevent rabies is wound care. Thorough washing of bite wounds, scratches, and non-bite exposures with soap and water is recommended, if feasible. When available, a virucidal agent such as povidone-iodine should also be used. In animal studies of rabies, wound cleansing alone reduced the likelihood of rabies up to 90 percent

Other preventive care — Tetanus prophylaxis, as well as antibiotics, should also be considered depending on the type of wound.

Rabies immune globulin — Rabies immune globulin (RIG) is derived from pooled plasma samples of hyperimmunized human donors (human RIG; HRIG) or from horses (equine RIG; ERIG). Although both preparations are considered equally potent and effective, only HRIG is recommended for use in the United States. Although these products are derived from human donors or horses, they are treated in ways that eliminate infectious agents, and no transmission of infectious agents has yet been documented from either product. The administration of RIG provides immediate virus-neutralizing antibodies until protective antibodies are generated in response to vaccine. HRIG has a half-life of approximately three weeks.

Rabies vaccines — Rabies vaccine induces the production of protective virus-neutralizing antibodies within approximately 7 to 10 days that persist for several years. It is administered intramuscularly in doses of 1 mL according to the recommended schedules for pre- or postexposure prophylaxis.

Rabies immune globulin — As noted above, RIG is only given for postexposure prophylaxis. The recommended dose of HRIG in all age groups is 20 IU/kg while the recommended dose of ERIG (including F(ab”)2 products) is 40 IU/kg body weight. RIG can partially suppress antibody production, so no more than the single recommended dose should be administered.

RIG should always be given in a different syringe from the vaccine, and at a different intramuscular site, such as the deltoid muscle opposite the vaccine dose or the anterior thigh.

As much of the RIG dose as is anatomically feasible should be infiltrated in the area around and in the wounds. Any remaining dose should be given intramuscularly. If there is no obvious wound (eg, suspected bat exposure), the large volume of RIG is best administered into the gluteal muscle. When this area is used for injection, RIG should be administered carefully in the upper outer quadrant of the gluteus to avoid possible damage to the sciatic nerve.

Rabies vaccines — Rabies vaccine is given for pre- or postexposure prophylaxis. The dosing schedule is determined by the intended use.

Antibody responses in normal volunteers are uniform and relatively long lived. All persons tested during CDC studies have had adequate titers two to four weeks after completion of the recommended vaccine schedule. Thus, routine testing after preexposure prophylaxis is not recommended.

Vaccine should never be administered in the gluteal area, because this may result in lower antibody titers. The deltoid is the only acceptable site of administration in adults and older children, but the outer aspect of the thigh can be used in young children

SAFETY OF RABIES BIOLOGICS

Rabies immunoglobulin (RIG) — HRIG is associated with local reactions including pain and tenderness, erythema, and induration. Headache is the most commonly reported systemic side effect. There has never been evidence of transmission of any known virus or infectious agent by HRIG approved for use in the United States.

Human diploid cell vaccine (HDCV) — Local reactions, including pain at the injection site, redness, swelling, and induration, have been reported in many patients. Most are mild and resolve in a few days. Systemic reactions are less common and include mild fever, headache, dizziness, and gastrointestinal symptoms