Rabies - Continued Reactions

Local reactions to postexposure treatment with DEV are very common. Most patients experience pain, erythema, and induration at the injection site. Approximately 13% have itching at the site. Systemic symptoms (fever, malaise, myalgia) occur in 33%, usually after 5-8 doses. Anaphylaxis develops in less than 1% of persons receiving DEV and may occur after the first dose, particularly in persons previously sensitized with vaccines containing avian tissue. Neuroparalytic reactions occur rarely with DEV. Between 1958 and 1975, 5 cases of transverse myelitis, 7 cases of cranial or peripheral neuropathy, and 9 cases of encephalopathy (2 fatal) were reported among an estimated 595,000 recipients of DEV. Neuroparalytic reactions were estimated to occur at the rate of 1 case for every 2,000 of the now discontinued NTV.

Local pain and slight febrile response may follow receipt of RIG. Although not reported for RIG, angioneurotic edema, nephrotic syndrome, and anaphylaxis have been reported but rarely after routine injection of immune serum globulin (ISG). These reactions occur so rarely that the causal relationship between ISG and these reactions is not clear.

ARS produces serum sickness in at least 40% of adult recipients; reaction rates for children are lower. Anaphylactic reactions may occur. When ARS is indicated, the patient

should be tested for sensitivity to equine serum. (In rare instances the sensitivity test has induced anaphylactic reaction.)

Because adverse reactions are associated more frequently with ARS than with RIG, and ARS might sensitize recipients to equine protein, RIG is the product of choice. ARS should be used only when RIG cannot be obtained within 24 hours.

RATIONALE OF TREATMENT

Every possible exposure to rabies infection must be individually evaluated.

In the United States the following factors should be considered before specific antirabies treatment is initiated: Species of Biting Animal

Carnivorous animals (especially skunks, foxes, coyotes, raccoons, dogs, and cats) and bats are more likely than other animals to be infected with rabies. Bites of rabbits, squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, and other rodents have never resulted in human rabies in the United States and almost never call for antirabies prophylaxis.

Circumstances of Biting Incident

An UNPROVOKED attack is more likely to mean that 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 commonly transmitted by inoculation with infectious saliva. The likelihood that rabies infection will result from exposure to a rabid animal varies with the nature and extent of the 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. Vaccination Status of Biting Animal

A properly immunized animal has only a minimal chance of contracting rabies and transmitting the virus. Presence of Rabies in Region

If adequate laboratory and field records indicate that there is no rabies infection in a domestic species within a given region, local and state health officials are justified in considering this in making recommendations on antirabies treatment for bites by particular species. Such officials should be consulted for current interpretations.

MANAGEMENT OF BITING ANIMALS

A healthy domestic dog or cat that bites a person should be confined and observed by a veterinarian for 10 days. Any illness in the animal should be reported immediately to the local health department. If signs suggestive of rabies develop, the animal should be humanely killed and its head removed and shipped under refrigeration to a qualified laboratory designated by the local or state health department for examination. Stray or unwanted dogs or cats should be killed immediately and their heads submitted for rabies examination by flourescent microscopy.

Signs of rabies in wild animals cannot be interpreted reliably; therefore, any wild animal that bites or scratches a person should be killed at once (without unnecessary damage to the head) and the brain examined for evidence of rabies.

If the brain is negative by flourescent antibody examination for rabies, one can assume that the saliva contains no virus, and the bitten person need not be treated.

LOCAL TREATMENT OF WOUNDS

Immediate and thorough local treatment of all bite wounds and scratches is perhaps the most effective rabies preventive. Experimentally the incidence of rabies in animals can be markedly reduced with local therapy alone. First-Aid Treatment to be Carried Out Immediately

The wound should be thoroughly cleansed immediately with soap and water.

Treatment by or under Direction of Physician

1. The wound should be thoroughly cleansed immediately with soap solution.

2. Tetanus prophylaxis and measures to control bacterial infection should be given as indicated.

POSTEXPOSURE PROPHYLAXIS

THE FOLLOWING RECOMMENDATIONS ARE INTENDED AS ONLY A GUIDE. THEY MAY BE MODIFIED ACCORDING TO KNOWLEDGE OF THE SPECIES OF BITING ANIMAL, CIRCUMSTANCES SURROUNDING THE EXPOSURE INCIDENT, VACCINATION STATUS OF THE ANIMAL, AND PRESENCE OF RABIES IN THE REGION.

RIG and DEV: Passive antibody, RIG (ARS only if RIG is not available), is administered only once, at the beginning of antirabies therapy. The recommended dose of RIG is 20 IU/kg or approximately 9 IU/lb body weight. (When ARS must be used, the recommended dose is 40 IU/kg, approximately 18 IU/lb or 1 vial of 1,000 IU/55 lb body weight.) Up to half the dose of RIG (or ARS) should be thoroughly infiltrated around the wound and the rest administered intramuscularly in the buttocks.

Twenty-three 1-ml doses of DEV should be given, beginning the day passive antibody is administered. Vaccine may be given as 21 daily doses or 14 doses in the first 7 days (2 injections each day) and then 7 daily doses. This should be followed by the 2 "booster" doses, the first booster 10 days after the 21st dose and the second booster 10 days later. Vaccine should be injected subcutaneously in the abdomen, lower back, or lateral aspect of the thigh; rotation of sites is recommended.

All persons who receive vaccine and RIG (or ARS) should have serum collected for rabies antibody testing at the time of the second booster. Testing for rabies antibody can be arranged by state health department laboratories. If no antibody is detected, additional boosters should be given.

Precautions

Since RIG (or ARS) partially suppresses active production of antibody, no more than the recommended dose of RIG (or ARS) should be given, and the 2 "booster" doses of vaccine must be given.

Local reactions to vaccine (DEV) are common and do not contraindicate continuing treatment.

Rabies - Continued

When rabies vaccine must be given to a person with a history of hypersensitivity, especially to avian tissues, antihistamine drugs may be given. Epinephrine is indicated to counteract anaphylactoid reactions. If serious allergic manifestations preclude continuing prophylaxis with DEV, state health departments can advise physicians about possible use of experimental vaccines.

If neurologic reactions, develop, vaccine treatment should be discontinued. Corticosteroids may interfere with development of active immunity and should be used only to treat life-threatening neuroparalytic reactions when the possibility of clinical rabies has been ruled out. The Center for Disease Control, Bureau of Epidemiology, Viral Diseases Division, should be contacted for additional information on the differential diagnosis of rabies.

Two 1-ml injections of DEV given subcutaneously in the deltoid area 1 month apart should be followed by a dose 6-7 months after the second dose. This series of 3 injections can be expected to produce neutralizing antibody in 80%90% of vaccinees.

For more rapid immunization, 3 injections of DEV, 1-ml each, should be given at weekly intervals with the fourth dose 3 months later. This schedule elicits an antibody response in about 80% of the vaccinees.

All who receive the preexposure vaccination should have serum collected for rabies antibody testing 3-4 weeks after the last injection. Testing for rabies antibody can be arranged by state health department laboratories. If no anti

body is detected, booster doses should be given until a response is demonstrated. Persons with continuing exposure should receive boosters every 2 years.

When an immunized person with previously demonstrated rabies antibody is bitten by a rabid animal, he or she should receive 5 daily doses of vaccine plus a booster dose 20 days after the fifth dose. Passive immunization should not be given in this case; it might inhibit a rapid anamnestic response. For non-bite exposures, an immunized person with antibody needs only one 1-ml dose of vaccine. If the immune status of a previously vaccinated person is not known, postexposure antirabies treatment may be necessary. In such cases, if antibody can be demonstrated in a serum sample collected before vaccine is given, treatment can be adjusted accordingly.

MANAGEMENT OF PERSONS WHO FAIL TO DEVELOP ANTIBODY FOLLOWING VACCINATION

Some individuals receiving postexposure or preexposure prophylaxis fail to develop demonstrable antibody after completion of the recommended regimens. Additional booster doses of DEV may produce the desired seroconversion. The patient's serum should be tested for antibody 2-3 weeks after each booster dose of DEV. If 2 additional booster doses of vaccine do not result in demonstrable antibody, authorities at the state health department or CDC should be consulted to determine if alternative procedures, such as the use of experimental vaccines, may be indicated.

ACCIDENTAL INOCULATION WITH LIVE RABIES VIRUS VACCINE

Persons exposed to Flury or the SAD (formerly ERA) vaccine should not be considered at risk, and antirabies prophylaxis is not indicated. There is no reliable information on which to judge the risk associated with accidental human exposure to new animal vaccines incorporating these strains in other substrates or to animal vaccines incorporating other rabies virus strains, and they should be regarded as potentially virulent for purposes of managing the treatment of exposed humans.

Current Trends

Worldwide: Influenza B has been isolated from 2 children in Montreal. These are the first confirmed isolates of influenza in Canada this winter.

Reported by Canada Diseases Weekly Report 2(-50):197, 1976. United States: No evidence of secondary cases has been uncovered to date in the investigation of the second case of A/New Jersey/76 influenza reported from Wisconsin (MMWR 25 [50]).

A/Victoria/75-like virus has been isolated from sporadic cases of influenza in an adult in Michigan, a 2-year-old child in Alaska, a 12-year-old child in South Carolina, and an adult in North Carolina. In each of these cases clinical illness occurred in late November or early December. While there have been increases in visits for febrile respiratory isease to sentinal physicians in Anchorage and Fairbanks,

there have been no other indications of influenza activity in any of these states.

Isolates of influenza B from sporadic cases of influenza have been made in Texas, Tennesses, and Pennsylvania. Influenza surveillance does not indicate significant influenza activity in these locations.

Reported by NS Hayner, MD, State Epidemiologist, Michigan Dept of Public Health; MP Hines, DVM, State Epidemiologist, North Carolina Division of Health Services; AR Hinman, MD, State Epi demiologist, Tennessee Dept of Public Health; JP Middaugh, MD, Acting State Epidemiologist, Alaska Dept of Health and Social Ser vices; RL Parker, DVM, State Epidemiologist, South Carolina Dept of Health and Environmental Control; W Parkin, DVM, Acting State Epidemiologist, Wisconsin Dept of Health and Social Services; CR Webb Jr, MD, Acting State Epidemiologist, Texas Dept of Health Resources; and the National Influenza Immunization Program, CDC.