Viral Zoonoses Slide Set

Management and Prevention of Rabies Infection


F. Management and Prevention

Once rabies is established, there is nothing much that could be done except intensive supportive care. To date, only 2 persons with proven rabies have survived, and 3 persons with probable rabies. However, one survivor was left with severe neurological sequelae and all 3 who recovered were vaccinated beforehand. Numerous antiviral agents have been tried with no success.

1. Postexposure prophylaxis

In cases of animal bites, dogs and cats in a rabies endemic area should beheld for 10 days for observation. If signs develop, they should be killed and their tissue examined in the laboratory. Wild animals are not observed but if captured, the animal should be killed and examined. The essential components of postexposure prophylaxis are the local treatment of wounds and active and passive immunization.

  1. Wound treatment - surgical debridement should be carried out. The wound should not be sutured up. Experimentally, the incidence of rabies in animals can be reduced by local treatment alone.
  2. Passive immunization - human rabies immunoglobulin around the area of the wound; to be supplemented with an i.m. dose to confer short term protection. There is convincing evidence that combined treatment with rabies immunoglobulin and active immunization is much more effective than active immunization alone. Equine rabies immunoglobulin (ERIG) is available in many countries and is considerably cheaper than HRIG.
  3. Active immunization - the human diploid cell vaccine is the best preparation available. The vaccine is usually administered into the deltoid region, and 5 doses are usually given.

2. Preexposure prophylaxis

Persons who are regularly at high risk of exposure, such as vets, laboratory workers, animal handlers and wildlife officers should be considered for preexposure prophylaxis by active immunization with the cell culture vaccine. Immunization normally consists of 3 doses of vaccine. Antibody can be demonstrated in the sera of virtually 100% of those vaccinated if the diploid cell culture vaccine is used. Booster doses should be offered to persons at continuing risk every one to three years. Local treatment of wounds should always be carried out in exposed persons who have been vaccinated previously. The WHO expert committee considers that local infiltration with antiserum is optional and systemic passive immunization contraindicated.

3. Rabies Vaccines

Several types of live attenuated vaccines are available for use in animals, but they are considered to be unsuitable for humans. The vaccines which are available for humans are present are inactivated whole virus vaccines.

  1. Nervous tissue preparation - this consisted of a 5% suspension of infected animal nervous tissue which had been inactivated (eg. the Semple vaccine was derived from phenol-inactivated infected rabbit brain), These preparations are now out of date as they were associated with the rare complication of demyelinating allergic encephalitis. This appears to be related to myelin basic protein in the vaccine. This complication was shown to occur in 4.6 case for 1000 persons vaccinated by the Semple vaccine. The case-fatality proportion was 3.13%. The Semple vaccine is still used in some developing countries. A suckling mouse brain vaccine is used in some Central and S.American countries.
  2. Duck Embryo Vaccine - this vaccine strain is grown in embryonated duck eggs and is inactivated with B-propriolactone. This vaccine has a lower risk of allergic encephalitis. However, it is considerably less immunogenic and does have minor side effects. Almost all vaccinees experience local reactions, 33% have constitutional symptoms such as fever, malaise, myalgia, and generalized lymphadenopathy.
  3. Human Diploid Cell Vaccine (HDCV) - HDCV was introduced in 1978. It is a grown on WI-38 (U.S.) or MRC-5 (Europe) cells. The vaccine is highly effective, in several studies, antibodies have been demonstrated in 100% of all recipients. Serious adverse reactions to HDCV are extremely rare. However, the vaccine is very expensive ( $100 for 6 doses), as human cell cultures are more difficult to handle than other animal cell culture systems. 5 or 6 doses of the vaccine is normally i.m. However, several studies suggest than smaller intradermal doses of HDCV may be as effective and thus it may be considered for use in poor developing countries.

Another inactivated vaccine is widely used in China. It is derived from virus grown in primary hamster kidney cells and cost less than the other diploid cell culture vaccines. The vaccine had been shown to be as effective as HDCV. Efforts are being made to use other inexpensive cell culture systems such as VERO cells.

4. Failure of prophylaxis

HDCV has been used to treat many thousands of people exposed to possible rabid animals in the past 12 years and its efficacy has been proven. At least 16 people treated with HDCV after exposure have died of rabies. All of the patients had major exposures and in the majority, the incubation period was short, 21 days or less. Treatment was frequently not started promptly within 24 hours and only half received combined serum and vaccine. At least one person has died despite optimum treatment.  

G. Rabies Control

Urban - canine rabies accounts for more than 99% of all human rabies cases and over 90% of all human post-exposure treatments worldwide. In the past, the Scandinavian countries were able to rid themselves of rabies by sanitary control alone, which included stray dog control. Other countries, such as the UK, have used these techniques allied with quarantine and/or vaccination to eradicate and then maintain freedom from the disease. Currently, the importation of mammals into the UK is controlled by the Rabies order. It applies to a wide range of mammals but livestock including horses, which are covered by separate regulations. The animals must be vaccinated on arrival. Effective animal vaccines are available.

Wildlife - canine rabies can be controlled because in general, dogs live in close association with man and are therefore within physical reach. An attempt was made to vaccinate foxes in an attempt to create an immune barrier at the entrance to the Rhone valley in 1978. The live attenuated virus was contained in small plastic blister packages fixed under the skin of chicken heads used as a bait, and 4050 of these were distributed over an area of 335km2. With continued field trials, Switzerland has been freed of rabies. Other field trials are being set up.  

Viral Zoonoses Slide Set