Supplement-Human Rabies Prevention
November 1, 1999 6 minutes read
Human Rabies Prevention — United States, 1999 Recommendations of the Advisory Committee on Immunization Practices (Excerpt)
These revised recommendations of the Advisory Committee on Immunization Practices update the previous recommendations on rabies prevention (MMWR 1991; 40:1-14) to reflect the current status of rabies and anti-rabies biologics in the United States.
This report includes new information about a human rabies vaccine approved for U.S. use in 1997, recommendations regarding exposure to bats, recommendations regarding an observation period for domestic ferrets, and changes in the local administration of rabies immune globulin.
Rabies is a viral infection transmitted in the saliva of infected mammals. The virus enters the central nervous system of the host, causing an encephalomyelitis that is almost always fatal. After the marked decrease of rabies cases among domestic animals in the United States in the 1940s and 1950s, indigenously acquired rabies among humans decreased substantially.
In 1950, for example, 4,979 cases of rabies were reported among dogs, and 18 cases were reported among humans. Between 1980 and 1997, 95-247 cases were reported each year among dogs, and only two human cases were reported in which rabies was attributable to variants of the virus associated with indigenous dogs. Thus, the likelihood of human exposure to a rabid domestic animal in the United States has decreased greatly. However, during the same period, 12 cases of human rabies were attributed to variants of the rabies virus associated with dogs from outside the United States. Therefore, international travelers to areas where canine rabies is still endemic have an increased risk of exposure to rabies.
Although rabies among humans is rare in the United States, every year approximately 16,000 to 39,000 persons receive post-exposure prophylaxis. To appropriately manage potential human exposures to rabies, the risk of infection must be accurately assessed. Administration of rabies post-exposure prophylaxis is a medical urgency, not a medical emergency, but decisions must not be delayed. Systemic prophylactic treatments occasionally are complicated by adverse reactions, but those reactions are rarely severe.
Data on the safety, immunogenicity, and efficacy of active and passive rabies immunization have come from both human and animal studies. Although controlled human trials have not been performed, extensive field experience from many areas of the world indicates that post-exposure prophylaxis combining wound treatment, passive immunization, and vaccination is uniformly effective when appropriately applied. However, rabies has occasionally developed among humans when key elements of the rabies post-exposure prophylaxis regimens were omitted or incorrectly administered.
Vaccines Licensed for Use in the United States
Four formulations of three inactivated rabies vaccines are currently licensed for pre-exposure and post-exposure prophylaxis in the United States. When used as indicated, all three types of rabies vaccines are considered equally safe and efficacious. The potency of one dose is greater than or equal to 2.5 international units (IU) per 1.0 mL of rabies virus antigen, which is the World Health Organization's recommended standard.
A full 1.0-mL dose can be used for both pre-exposure and post-exposure prophylaxis. However, only the Imovax Rabies I.D. vaccine (human diploid cell vaccine [HDCV]) has been evaluated and approved by the Food and Drug Administration (FDA) for the intradermal dose and route for pre-exposure vaccination. Therefore, rabies vaccine adsorbed (RVA) and purified chick embryo cell vaccine (PCEC) should not be used intradermally. Usually, an immunization series is initiated and completed with one vaccine product. No clinical studies have been conducted that document a change in efficacy or the frequency of adverse reactions when the series is completed with a second vaccine product.
Human Diploid Cell Vaccine (HDCV)
HDCV is prepared from the Pitman-Moore strain of rabies virus grown on MRC-5 human diploid cell culture, concentrated by ultrafiltration, and inactivated with beta-propiolactone. It is supplied in two forms:
• Intramuscular (IM) administration, a single-dose vial containing lyophilized vaccine that is reconstituted in the vial with the accompanying diluent to a final volume of 1.0 mL just before administration.
• Intradermal (ID) administration, a single-dose syringe containing lyophilized vaccine that is reconstituted in the syringe to a final volume of 0.1 mL just before administration.
Rabies Vaccine Adsorbed (RVA)
RVA was developed and is currently manufactured and distributed in the state of Michigan by BioPort Corp. The vaccine is prepared from the Kissling strain of Challenge Virus Standard (CVS) rabies virus adapted to fetal rhesus lung diploid cell culture. The vaccine virus is inactivated with betapropiolactone and concentrated by adsorption to aluminum phosphate. Because RVA is adsorbed to aluminum phosphate, it is liquid rather than lyophilized. It is approved for IM administration only as a 1.0-mL dose.
Purified Chick Embryo Cell Vaccine (PCEC)
PCEC became available in the United States in autumn 1997. It is prepared from the fixed rabies virus strain Flury LEP grown in primary cultures of chicken fibroblasts. The virus is inactivated with betapropiolactone and further processed by zonal centrifugation in a sucrose density gradient. It is formulated for IM administration only. PCEC is available in a single-dose vial-lyophilized vaccine that is reconstituted in the vial with the accompanying diluent to a final volume of 1.0 mL just before administration.
Rabies Immune Globulin Licensed for Use in the United States
The two RIG products, BayRab and Imogam Rabies-HT, are an anti-rabies immunoglobulin (Ig) preparation concentrated by cold ethanol fractionation from plasma of hyperimmunized human donors. Rabies neutralizing antibody, standardized at a concentration of 150 IU per mL, is supplied in 2-mL (300 IU) vials for pediatric use and 10-mL (1,500 IU) vials for adult use; the recommended dose is 20 IU/kg body weight. Both RIG preparations are considered equally efficacious when used as described in this report.
Post-exposure Prophylaxis
Rationale for Treatment
Administration of rabies post-exposure prophylaxis is a medical urgency, not a medical emergency. Physicians should evaluate each possible exposure to rabies, and if necessary, consult with local or state public health officials regarding the need for rabies prophylaxis. In the United States, certain factors should be considered before specific anti-rabies post-exposure prophylaxis is initiated. (See chart, below.)
| Rabies Post-exposure Prophylaxis Guide, United States, 1999 | ||
| Animal Type | Evaluation and Disposition of Animal | Post-exposure Prophylaxis Recommendations |
| Dogs, cats, and ferrets | Healthy and available | Should not begin prophylaxis for 10 days observation unless animal develops clinical signs of rabies* |
| Rabid or suspected rabid | Immediately vaccinate | |
| Unknown (e.g., escaped) | Consult public health officials | |
| Skunks, raccoons, foxes, and most other carnivores; bats | Regarded as rabid unless animal proven negative by laboratory tests+ | Consider immediate vaccination |
| Livestock, small rodents, lagomorphs (rabbits and hares) large rodents (woodchucks and beavers), and other mammals | Consider individually | Consult public health officials. Bites of squirrels, hamsters,guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require anti-rabies post-exposure prophylaxis. |
| * During the 10-day observation period, begin post-exposure prophylaxis at first sign of rabies in a dog, cat, or ferret that has bitten someone. If the animal exhibits clinical signs of rabies, it should be euthanized immediately and tested. | ||
| + The animal should be euthanized and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative. | ||
Types of Exposure
Rabies is transmitted only when the virus is introduced into bite wounds or open cuts in skin or onto mucous membranes. If no exposure has occurred (i.e., no bite or nonbite exposure), post-exposure prophylaxis is not necessary. The likelihood of rabies infection varies with the nature and extent of exposure. Two categories of exposure — bite and nonbite — should be considered.
• Bite. Any penetration of the skin by teeth constitutes a bite exposure. All bites, regardless of location, represent a potential risk of rabies transmission. Bites by some animals, such as bats, can inflict minor injury and thus be undetected.
• Nonbite. Nonbite exposures from terrestrial animals rarely cause rabies. However, occasional reports of transmission by nonbite exposure suggest that such exposures constitute sufficient reason to consider post-exposure prophylaxis. The nonbite exposures of highest risk appear to be among persons exposed to large amounts of aerosolized rabies virus and surgical recipients of corneas transplanted from patients who died of rabies. Two cases of rabies have been attributed to probable aerosol exposures in laboratories, and two cases of rabies have been attributed to possible airborne exposures in caves containing millions of free-tailed bats (Tadarida brasiliensis) in the Southwest.
The contamination of open wounds, abrasions, mucous membranes, or theoretically, scratches, with saliva or other potentially infectious material (such as neural tissue) from a rabid animal also constitutes a nonbite exposure. Other contact by itself, such as petting a rabid animal and contact with blood, urine, or feces (e.g., guano) of a rabid animal, does not constitute an exposure and is not an indication for prophylaxis. Because the rabies virus is inactivated by desiccation and ultraviolet irradiation in general; if the material containing the virus is dry, the virus can be considered noninfectious.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content