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The Morbidity and Mortality Weekly Report is prepared by the Centers for Disease Control, Atlanta, Georgia, and available on a paid subscription basis from the Superintendent of Documents, U.S. Govemment Printing Office, Washington, D.C. 20402, (202) 783-3238.

The data in this report are provisional, based on weekly reports to CDC by state health departments. The reporting week concludes at close of business on Friday; compiled data on a national basis are officially released to the public on the succeeding Friday.

The editor welcomes accounts of interesting cases, outbreaks, environmental hazards, or other public health problems of current interest to health officials. Such reports and any other matters pertaining to editorial or other textual considerations should be addressed to: ATTN: Editor, Morbidity and Mortality Weekly Report, Centers for Disease Control, Atlanta, Georgia 30333.

Director, Centers for Disease Control
James O. Mason, M.D., Dr.P.H.
Director, Epidemiology Program Office
Carl W. Tyler, Jr., M.D.

Editor

Michael B. Gregg, M.D. Assistant Editor

Karen L. Foster, M.A.

*U.S. Government Printing Office: 1984-746-149/10003 Region IV

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These revised recommendations of the Immunization Practices Advisory Committee (ACIP) on rabies prevention update the previous recommendations (MMWR 1980;29: 65-72,277-80) to reflect the current status of rabies and antirabies biologics in the United States. For assistance on problems or questions about rabies prophylaxis, call local or state health departments.*

INTRODUCTION

Although rabies rarely affects humans in the United States, every year, approximately 25,000 persons receive rabies prophylaxis. Appropriate managment of those who may have been exposed to rabies infection depends on the interpretation of the risk of infection and the efficacy and risk of prophylactic treatment. All available methods of systemic prophylactic treatment are complicated by instances of adverse reactions. These are rarely severe. Decisions on management must be made immediately; the longer treatment is postponed, the less likely it is to be effective.

Data on the efficacy of active and passive immunization after rabies exposure have come from both human and animal studies. Evidence from laboratory and field experience in many areas of the world indicates that postexposure prophylaxis combining local wound treatment, vaccine, and rabies immune globulin, is uniformly effective when appropriately used. However, rabies has occasionally developed in humans who had received postexposure antirabies prophylaxis with vaccine alone.

In the United States, rabies in humans has decreased from an average of 22 cases per year in 1946-1950 to zero to five cases per year since 1960. The number of rabies cases among domestic animals has decreased similarly. In 1946, more than 8,000 rabies cases were reported among dogs; 153 cases were reported in 1982. Thus, the likelihood of human exposure to rabies in domestic animals has decreased greatly, although bites by dogs and cats continue to be the principal reasons given for antirabies treatments.

The disease in wildlife-especially skunks, foxes, raccoons, and bats-has become more prevalent in recent years, accounting for approximately 85% of all reported cases of animal rabies every year since 1976. Wild animals now constitute the most important potential source of infection for both humans and domestic animals in the United States. Rabies among animals is present throughout the United States; only Hawaii remains consistently rabies-free. Four of the six rabies fatalities in U.S. citizens occurring between 1980 and 1983 were related to exposure to rabid dogs outside the United States. In much of the world, including *If these are unavailable, call the Division of Viral Diseases, Center for Infectious Diseases, CDC ([404] 329-3095 during working hours, or [404] 329-2888 nights, weekends, and holidays).

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES/PUBLIC HEALTH SERVICE

ACIP: Rabies - Continued

most of Asia and all of Africa and Latin America, the dog remains the major source of human exposure.

RABIES IMMUNIZING PRODUCTS

There are two types of immunizing products: (1) vaccines that induce an active immune response, which requires about 7-10 days to develop but may persist for as long as a year or more, and (2) globulins that provide rapid passive immune protection, which persists for a short period of time, with a half-life of about 21 days. Both types of products should be used concurrently for rabies postexposure prophylaxis.

Vaccines for Use in the United States

Human diploid cell rabies vaccine (HDCV)†: HDCV is an inactivated virus vaccine prepared from fixed rabies virus grown in WI-38 or MRC-5 human diploid cell culture. The vaccine grown on WI-38 cells and developed in the United States is inactivated with tri-n-butyl phosphate and B-propiolactone (Wyeth Laboratories' WYVAC®), while that grown in MRC-5 cells and developed in Europe is inactivated with B-propiolactone (Merieux Institute's RABIES VACCINE®). Both vaccines are supplied as 1.0 ml, single-dose vials of lyophilized vaccine with accompanying diluent.

Globulins

Rabies Immune Globulin, Human (RIG): RIG (Cutter Laboratories' HYPERAB® and Merieux Institutes' IMOGAM®) is antirabies gamma globulin concentrated by cold ethanol fractionation from plasma of hyperimmunized human donors. Rabies neutralizing antibody content is standardized to contain 150 international units (IU) per ml. It is supplied in 2-ml (300 IU) and 10-ml (1,500 IU) vials for pediatric and adult use, respectively.

Antirabies Serum, Equine (ARS): ANTIRABIES SERUM® (Sclavo) is a refined, concentrated serum obtained from hyperimmunized horses. Neutralizing antibody content is standardized to contain 1,000 IU per vial. Volume is adjusted by the manufacturer on the basis of antibody potency in each lot. Currently, a 1,000-IU vial contains approximately 5 ml. RATIONALE FOR CHOICE OF RABIES IMMUNIZING PRODUCTS

Both types of HDCV rabies vaccines are considered equally efficacious and safe when used as indicated on the labels. Only the Merieux Institute vaccine has been evaluated by the intradermal (ID) dose/route for preexposure immunization. No data are available on ID use with the Wyeth Laboratories vaccine. RIG is preferred over ARS, because the latter has a much higher risk of adverse reactions.

Vaccines

The effectiveness of rabies vaccines is measured by their ability to protect persons exposed to rabies and to induce antibodies to rabies virus. HDCV has been used concurrently with RIG or ARS to treat 45 persons bitten by rabid dogs or wolves in Iran, 31 persons bitten by a variety of rabid animals in Germany, and 511 persons bitten by a variety of rabid animals in the United States. In these studies, no person contracted rabies after receiving HDCV in combination with RIG.

All persons treated with RIG and five 1.0-ml intramuscular (IM) doses of HDCV and tested have developed a rabies antibody titer. The definition of a minimally acceptable antibody titer varies between laboratories and is influenced by the type of test conducted. CDC currently specifies a 1:5 titer by the rapid fluorescent-focus inhibition test (RFFIT) as acceptable. The World Health Organization (WHO) specifies a titer of 0.5 I.U.

Serious adverse reactions associated with rabies vaccines include systemic, anaphylactic, and neuroparalytic reactions. Serious adverse reactions occur at lower rates in the HDCV vaccine than with previously available types of rabies vaccine.

*Official name: Rabies Vaccine. The duck embryo vaccine which was used from 1957-1982 is no longer available in the United States.

ACIP: Rabies - Continued

Globulins

RIG and ARS are both effective; however, ARS causes serum sickness in over 40% of adult recipients. RIG rarely causes adverse reactions and should be the product of choice when available.

RATIONALE OF TREATMENT

Physicians must evaluate each possible rabies exposure. Local or state public health officials should be consulted if questions arise about the need for prophylaxis.

In the United States, the following factors should be considered before specific antirabies treatment is initiated:

Species of Biting Animal

Carnivorous wild animals (especially skunks, raccoons, foxes, coyotes, and bobcats) and bats are the animals most commonly infected with rabies and have caused most of the indigenous cases of human rabies in the United States since 1960. Unless an animal is tested and shown not to be rabid, postexposure prophylaxis should be initiated upon bite or nonbite exposure to the animals. (See definition in "Type of Exposure" below.) If treatment has been initiated and subsequent testing in a competent laboratory shows the exposing animal is not rabid, treatment can be discontinued.

The likelihood that a domestic dog or cat is infected with rabies varies from region to region; hence, the need for postexposure prophylaxis also varies.

Rodents (such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are rarely found to be infected with rabies and have not been known to cause human rabies in the United States. In these cases, the state or local health department should be consulted before a decision is made to initiate postexposure antirabies prophylaxis.

Circumstances of Biting Incident

An unprovoked attack is more likely than a provoked attack to indicate the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as provoked.

Type of Exposure

Rabies is transmitted by introducing the virus into open cuts or wounds in skin or via mucous membranes. The likelihood of rabies infection varies with the nature and extent of exposure. Two categories of exposure should be considered.

Bite: Any penetration of the skin by teeth.

Nonbite: Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or other potentially infectious material, such as brain tissue, from a rabid animal. Casual contact, such as petting a rabid animal (without a bite or nonbite exposure as described above), does not constitute an exposure and is not an indication for prophylaxis. There have been two instances of airborne rabies acquired in laboratories and two probable airborne rabies cases acquired in a bat-infested cave in Texas.

The only documented cases of rabies from human-to-human transmission occurred in four patients in the United States and overseas who received corneas transplanted from persons who died of rabies undiagnosed at the time of death. Stringent guidelines for acceptance of donor corneas should reduce this risk.

Bite and nonbite exposures from humans with rabies theoretically could transmit rabies, although no cases of rabies acquired this way have been documented. Each potential exposure to human rabies should be carefully evaluated to minimize unnecessary rabies prophylaxis. MANAGEMENT OF BITING ANIMALS

A healthy domestic dog or cat that bites a person should be confined and observed for 10 days and evaluated by a veterinarian at the first sign of illness during confinement or before

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