National Guidelines for Management of Animal Bites
Rabies is an acute viral disease which causes encephalomyelitis in virtually all the warm blooded animals including man. The causative agent is found in wild and some domestic animals, and is transmitted to other animals and to humans through close contact with their saliva (i.e. bites, scratches, licks on broken skin and mucous membranes). In urban areas, Ihe disease is mainly transmitted by dogs, being responsible for about 95% of animal bite cases. Man is the dead end of the infection and hence does not play any role in its spread to new hosts.
Necessity for Formulation of Guidelines
Rabies has plagued man since ancient times and is believed to be as old as our civilization. It is perhaps the most gruesome and dreadful of all human communicable diseases and continues to persist as a major public health problem.
Fortunately, animal bites, if managed appropriately and timely the disease is preventable to a large extent. In this regard the post exposure treatment of animal bite cases is of prime importance. It had been observed that there were no uniform guidelines for addressing various aspects of animal bite management. Some of the important issues like classification of exposure, adequate and appropriate use of rabies immunoglobulins and available anti rabies vaccines and other myths associated with post exposure treatment needed to be addressed.
In view of this, an expert group meeting on reviewing and finalising the national guidelines for management of animal bite cases was held at National Institute of Communicable Diseases, Delhi. The participants in the meeting were clinical practitioners managing anti rabies clinics, laboratory medicine practitioners, neurovirologists & neuro physicians and vaccine producers from both public and private sector.
The main objectives of the meeting were to discuss the current practices of animal bite management and formulate the guidelines for management of animal bite cases, bring about uniformity in post exposure treatment practices and information dissemination by vaccine producers in public and private sector. These guidelines have been drafted by pooling the experience, views and thoughts of the participants.
Because of long incubation period, which is typical of most cases of human rabies, it is possible to institute prophylactic post exposure treatment. This must be started at the earliest to ensure that the individual will be protected before the rabies virus reaches the Central Nervous System.
Decision to treat
In rabies endemic country like India where every animal bite is potentially suspected as a rabid animal bite, the treatment should be started immediately. To bring out uniformity globally.the WHO recommended classification of animal bite for post-exposure treatment should be followed (Table-1).
Although unvaccinated animals are more likely to transmit rabies, vaccinated animals can also do so if the vaccination of the biting animal was ineffective for any reason. The risk of dog being infected with rabies is greatly reduced when it appears healthy and there is confirmed history of vaccination with minimum of two immunizations with potent rabies vaccine in last two years. The treatment should be started immediately after the bite. The treatment may be discontinued if animal involved (dog or cat) remains healthy throughout an observation period of 10 days. The observation period is valid for dogs and cats only. Bite by all wild animals should be treated as Category III exposure. It should be noted that bites by rats, mice, squirrel, hare and rabbits seldom require treatment. Bat rabies has not been conclusively proved in lndia.lt is re-emphasized that the treatment should be started as early as possible after exposure, but it should not be denied to person reporting late for treatment.
The post-exposure treatment is a three-pronged approach. All three carry equal importance and should be done simultaneously.
Management of wound
Management of animal bite wound
Wound Toilet : Since the rabies virus enters the human body through a bite or scratch, it is imperative to remove as much saliva, and thereby the virus, from the wound as is possible by an efficient wound toilet that should not involve additional trauma. Since the rabies virus can persist and even multiply at the site of bite for a long time, wound toilet must be performed even if the patient reports late.
This can be done by prompt and gentle thorough washing with soap or detergent and flushing the wound with running water for 10 minutes. If soap and detergent are not immediately available, wash with running water for at least 10 minutes. Avoid direct touching of wounds with bare hands. Considering the importance of this step the anti rabies clinics should have wound washing facilities.
The application of soil, chillies, oi! etc. is unnecessary and damaging. In case soil, chillies, oil etc. have been applied on the wound, enough gentle washing with soap or detergent to remove the extraneous material, especially oil, should be done followed by flushing with copious amount of water for 10 minutes immediately.
It should be noted that the immediaie washing of the wound is a priority. However, the victim should not be deprived of the benefit of wound toilet as long as there is an unhealed wound which can be washed even if the patient reports late. The maximum benefit of the wound washing is obtained when fresh wound is cleaned immediately. Suturing of wound should be avoided as far as possible. If unavoidable, minimum loose sutures should be applied after adequate local treatment along with proper infiltration of anti rabies serum.
Cauterization of wound is no longer recommended as it leaves a very bad scar, and does not confer any additional advantage over washing the wound with water and soap. Inj. tetanus toxoid should be given to the unimmunized individual. To prevent sepsis in the wound, a suitable course of an antibiotic may be recommended.
Application of antiseptic
After thorough washing and drying the wound, any one of the available chemical agents should be applied: Savlon (in appropriate recommended dilution), Dettol (in appropriate recommended dilution), povidone iodine, alcohol etc.
Table - 1
WHO Guide for post-exposure treatment against rabies
Category Type of contact with
a suspect or
confirmed rabid domestic or wild animal,
or animal unavailable for observation
None, if reliable case history is available
Administer rabies immunoglobulin and vaccine immediately Stop treatment if animal remains healthy throughout an observation period’ of 10 days or if animal is killed humanely and found to be negative for rabies by appropriate laboratory techniques.
Guidelines for post-exposure treatment in 8th Report of the WHO Expert Committee
Local infiltration of rabies immunoglobulins
In Category III bites, rabies immunoglobulins should be infiltrated in the depth and around the wound to inactivate the locally present virus.
Passive Immunization by rabies Immunoglobulins
Antirabies serum/ERIG : The antirabies serum provides passive immunity in the form of ready-made antirabies antibody to tide over the initial phase of the infection. Antirabies serum (ARS) has the property of binding with the rabies virus, thereby resulting in the loss of infectivity of the virus. A purified version of this antirabies serum called as equine rabies immunoglobulins (ERIG) is also now available.
Human Rabies Immunoglobulins (HRIG) : HRIG are free from the side effects encountered in a serum of heterologous origin, and because of their longer half life, are given in half the dose of equine antirabies serum. The antirabies sera should always be brought to room temperature (20 - 25oC) before use.
Dose of rabies Immunoglobulins : The dose of equine anti rabies serum is 40 i.u. per kg body weight of patient and is given after testing of sensitivity, upto a maximum of 3000 i.u. The ARS produced in India contains 300 i.u, per ml. The dose of the human rabies immunoglobulins (HRIG) is 20 i.u. per kg body weigh! (maximum 1500 i.u.). HRIG does not require any prior sensitivity testing. HRIG preparation is available in concentration of 150 i.u. per ml. In Category III of animal bites, the antirabies serum after sensitivity test is infiltrated in and around the wound even if the lesion has begun to heal followed by administration of antirabies vaccine.
Tolerance and side effects: With HRIG, there may be transient tenderness at the injection site and a brief rise in body temperature which do not require any treatment. Skin reactions are extremely rare. HRIG must never be given intravenously since this could produce symptoms of shock, especially in patients with antibody deficiency syndromes. With antisera of equine origin, in addition, anaphylactic shock may occur and thus sensitivity testing is mandatory before giving ERIG. Skin test may be performed as per the manufacturers instructions given in the product insert.
Otherwise as a general guideline the heterologous immunoglobulin may be diluted 1:10 in sterile physiological saline and 0.1-0.2 ml may be given intradermally in the flexor aspect of the forearm. An equivalent intradermal injection of physiological saline solution may be used as a control. The reading made 15 minutes later may be considered to be positive if erythema (>6 mm), local odema or systemic reaction is observed and the control is negative.
A negative skin test must never reassure the physician that no anaphylactic reaction will occur. Those administering ERIG should always be ready to treat early anaphylactic reactions with adrenalin. The dose is 0.5 ml o( 0.1 percent solution (1 in 1000, 1mg/ml) for adults and 0.01 ml/kg body weight for children, injected subcutaneously or IM. If patient is sensitive to ERIG, HRIG should be used.
Serum sickness occurs in 1% to 6% of patients usually 7 to 10 days after injection of ERIG, but it has not been reported after treatment with HRIG.
The total recommended dose of immunoglobulin must not be exceeded as it may reduce the efficacy of the vaccine. If the calculated dose of immunoglobulin is insufficient to cover infiltration in all wounds, sterile saline can be used to dilute 2 or 3 fold to permit thorough infiltration.
If immunoglobulin was not administered when vaccination was begun, it can be administered upto the seventh day after the administration of the first dose of vaccine. Beyond the seventh day, Rabies Immunoglobulin (RIG) is not indicated since an antibody response to anti rabies vaccine is presumed to have occurred.
Immunoglobulin should never be administered in the same syringe or at the same anatomical site as vaccine.
Tissue Culture Vaccines (TCVs)
There has been a growing use of Tissue Culture Vaccines (TCVs) in India. Three type of vaccines that are currently available are :
Human diploid cell strain vaccine (HDCV)
Purifed chick embryo cell vaccine (PCEC)
Purified Vero cell vaccine (PVRV)
As recommended by the WHO Expert Committee on Rabies (1992), the course for postexposure prophylaxis should consist of five injections (Day 0, 3, 7, 14 and 28). The sixth injection (D90) should be considered as optional, but should be considered for those individuals who are immunologically deficient, and are at the extremes of age and on steroid therapy. Day 0 indicates day of first injection.
The dose of the vaccine per injection is 1 ml for HDCV and PCEC vaccines and 0.5 ml for PVRV irrespective of age and weight of vaccinee. The dose of PVRV produced by Pasteur Institute of India, Coonoor is 1 ml per injection.
Indications : All cases of animal bites, irrespective of severity of exposure, require the same number of injections and dose per injection. The Category III requires administration of rabies immunoglobulins as discussed earlier. The general indications remain same as discussed under neural tissue vaccines.
Site of inoculation : The deltoid region is ideal for the inoculation of these vaccines. Gluteal region is not recommended because the fat present in this region retards the absorption of antigen and hence impairs the generation of optimal immune response.
Storage and transportation : Though tissue culture vaccines are marketed in freeze dried (lyophilized) form which is more tolerant of vagaries of temperature, yet it is recommended that these vaccines should be kept and transported at a temperature range of +2°C to +8°C. Freezing does not damage the vaccine but there are chances of breakage of ampoule containing the diluent.
Reconstitution and storage : The lyophilised vaccine should be reconstituted with the diluent provided with the vaccine immediately prior to use. However, in case of unforeseen delay it should not be used after 6-8 hours of reconstitution.
Protective level of antirabies antibody : Humoral antibodies are believed to play important role in protection against rabies and a titre of 0.5 i.u./ml or more in serum is considered as protective.
Adverse effects with tissue culture vaccines : The tissue culture vaccines are widely accepted as the least reactogenic rabies vaccines available today. Various studies have now shown that adverse effects can be either general in nature or allergic in origin. The general adverse reactions include sore arm, headache, malaise, nausea, fever and localised oedema at the site of injection. Symptomatic treatment may be needed.
Switch over from one vaccine to the other Shifting from one brand of TCV to other brand also should nol be encouraged as literature supports that good immunity is best achieved with same brand.
Post exposure therapy for previously vaccinated persons
If re-exposed, persons who have previously received full post-exposure treatment with a potent cell-culture vaccine should be given only two booster doses, intramuscularly on days 0 and 3, but no rabies immunoglobulin.
Managing exposure following pre-exposure prophylaxis with TCV
If after recommended pre-exposure prophylaxis, a vaccinated person is exposed to rabies, a proper wound toileting should be done and two !M doses of Tissue Culture Vaccine be given on days 0 and 3. Treatment with RIG is not necessary.
Pre-exposure prophylaxis may be offered to high risk groups like laboratory staff handling the virus and infected material, clinicians and para-medicals attending to hydrophobia cases, veterinarians, animal handlers and catchers, wildlife wardens, quarantine officers and travellers from rabies free areas to rabies endemic areas. Pre-exposure immunization should be three full IM doses of TCV given on day 0, 7 and 28 or 0, 28 and 56 followed by booster at one year and then a booster every three years.
Laboratory staff and others at high continuing risk of exposure should have their neutralizing antibody titres checked every 6 months. If it is less than 0.5 i.u./ml a booster dose of vaccine should be given. Such individuals on getting exposed to rabies virus after successful pre-exposure immunization require only two booster injections of vaccine given on days 0 and 3 without any anti rabies serum.
Role of Laboratory in Management of Animal Bite Cases
In countries like India where rabies is endemic, the animal bite management should not depend on laboratory results. The treatment should be started immediately as per recommended guidelines.
Indications for carrying out immunoassay
In apparently healthy individuals, who have received adequate doses at appropriate intervals with a potent TCV, no laboratory assessment of treatmenl is required. However, in persons with immuno-compromised status or reactions to vaccine or irregular treatment, antibody assessment may be required for monitoring the treatment.
Approach to a patient requiring Rabies Immunoglobulins when none is available
In circumstances where no immunoglobulins are available greater emphasis should be given to proper wound toileting followed by Essen schedule of Tissue culture vaccine with double dose on day 0 at 2 different sites intramuscularly (0 day - 2 doses, one each on left and right deltoid, 3, 7, 14 and 28 days).
Management of animal bite exposure in pregnant women and lactating mothers
Pregnancy and lactation are no contraindications for rabies vaccination Post-exposure prophylaxis against rabies takes preference over any other consideration since it is a life saving procedure. Moreover, rabies vaccine does not have any adverse effect on fetus, mother-to-be and the course of pregnancy. Hence complete post-exposure treatment should be given depending on the category of the exposure.