Rabies Immunoglobulin (RIG)RIG contains specific anti rabies antibodies that neutralize the rabies virus and provide passive protection till active immunity is generated. There are 2 types of RIG: (1) Human rabies immunoglobulin (HRIG dose is 20 U/kg body weight, maximum dose 1500 IU) and (2) Equine rabies immunoglobulin (ERIGdose is 40 U/kg body weight, maximum dose 3000 IU). HRIG is preferred, but if not available/unaffordable, ERIG may be used. Most of the new ERIG preparations are potent, safe, highly purified and less expensive as compared to HRIG but do carry a small risk of anaphylaxis. As per latest recommendations from WHO, skin testing prior to ERIG administration is not recommended as skin tests do not accurately predict anaphylaxis risk and ERIG should be given whatever the result of the test. RIG is indicated in all cases of category 3 wounds where it should be infiltrated thoroughly into and around the wound. The remaining part if any is to be injected IM into the deltoid region or anterolateral aspect of thigh away from the site of vaccine administration to avoid vaccine neutralization. In case RIG dose (quantity) is insufficient for adequate infiltration of extensive or multiple wound, it may be diluted with equal volume of normal saline so that all the wounds can be thoroughly infiltrated. Adverse reactions include tenderness/ stiffness at the injection site, low grade fever; sensitization may occur after repeated injections. If RIG could not be given when antirabies vaccination was began, it should be administered as early as possible but no later than the seventh day after the first dose of vaccine was given. From the eight day onwards, RIG is not indicated since an antibody response to the vaccine is presumed to have occurred. RIG is also not indicated in individuals who have received pre exposure prophylaxis/post exposure prophylaxis in the past. |
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The nerve tissue vaccines are no longer available due to poor efficacy and life threatening adverse effect of neuroparalytic reactions. The currently available vaccines are the modern tissue culture vaccines (MTCV) and include Purified Chick Embryo Cell (PCEC, Rabipur) vaccine, Human Diploid Cell Vaccine (HDCV, Rabivac), Purified Vero Cell Vaccine (PVRV, Verorab, Indirab, Abhayrab), Purified Duck Embryo Vaccine (PDEV, Vaxirab). The vaccines are available in lyophilized form with sterile water as diluent, are stable for 3 years at 2 to 8° C and should be used within 6 hours of reconstitution.
All tissue culture vaccines have almost equal efficacy and any one of these can be used. These vaccines induce protective antibodies in more than 99% of vaccinees following pre/post exposure prophylaxis. The main adverse effects are local pain, swelling and redness and less commonly fever, headache, dizziness and gastrointestinal side effects. Systemic hypersensitivity reactions in vaccinees have been reported with HDCV particularly following booster injections but not with PCEC/ PVRV. Intradermal vaccination may cause more local irritation as compared to the intramuscular route. Along with proper wound care and rabies immunoglobulin (RIG) post exposure prophylaxis is effective in preventing 100% of rabies cases. Failures occur due to delay in initiation or non use of RIG when indicated.
Post exposure prophylaxis is a medical emergency and is indicated following a significant contact (discussed in detail below) with any warm blooded animal. These include dogs, cats, cows, buffaloes, sheeps, goats, pigs, donkeys, horses, camels, foxes, jackals, monkeys, mongoose, bears and others. In case of bites by pet animals, PEP may be deferred only if the pet at the origin of exposure is more than a year old and has a vaccination certificate indicating that it has received at least 2 doses of a potent vaccine, the first not earlier than 3 months of age and the second within 6 to 12 months of the first dose and in the past 1 year.
If vaccination is deferred, the pet should be observed for 10 days; if the dog shows any sign of illness during the observation period, the patient should receive full rabies post-exposure prophylaxis urgently. Rabies due to rodent bites has not been reported in India till date and post exposure prophylaxis is not normally recommended for these bites. Post exposure prophylaxis should be initiated as soon as possible and should not be delayed till results of lab tests or animal observation is available. Infancy, pregnancy and lactation are never contraindications for PEP. Persons presenting several days/months/years after the bite should be managed in a similar manner as a person who has been bitten recently (with RIG if indicated) as rabies may have a long incubation period and the window of opportunity for prevention remains.
Rabies exposure may be classified as per WHO into three categories
| Class | Description | Recommended treatment |
| I | Touching or feeding of animals, licks on intact skin | None if reliable case history is available |
| II | Nibbling of uncovered skin, minor scratches or abrasions without bleeding, licks on broken skin | Administer vaccine |
| III | Single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva (i.e., licks), or exposure to bats | Administer RIG and vaccine immediately |
The first step is thorough cleansing of the wound with soap and flushing under running water for 10 minutes. This should be followed by irrigation with a virucidal agent such as 70% alcohol or povidone iodine. Antimicrobials and tetanus toxoid should be given if indicated. RIG should be infiltrated in and around the wound in category 3 bites as discussed earlier. Any suturing of wound should be avoided. When suturing is unavoidable for purpose of hemostasis, it must be ensured that RIG has been infiltrated in the wound prior to suturing.
All category 2 and 3 bites merit rabies vaccine. Any of the MTCV may be used intramuscularly in anterolateral thigh or the deltoid. Rabies vaccine should never be injected in the gluteal region. The dose is same at all ages and is 1 ml IM for HDCV, PCEV, PDEV and 0.5 ml for PVRV. The standard schedule (Essen protocol) is five doses on days 0, 3, 7, 14 and 30, with day 0 being the day of commencement of vaccination. A sixth dose on day 90 is optional and may be offered to patients with severe debility or those who are immunosuppressed.
Interchange of vaccines is permitted only in special circumstances but should not be done routinely. If RIG is not available then two doses of the vaccine may be given on day 0 (this is however not a substitute for RIG). If the animal remains healthy over a 10 day observation period, further vaccination may be discontinued. It is however desirable to administer one more dose on day 28 in order to convert to the pre exposure prophylaxis schedule.
Several other schedules of rabies vaccination have been proposed. These include the 2-1-1 intramuscular schedule (Zagreb schedule) two IM doses on day 1, one IM dose on day 7 and one IM dose on day 21. This schedule is however not approved for use in India. Intradermal vaccination is cost effective alternative to intramuscular vaccination as the dose required is only 0.1 ml. The intradermal schedules have been used successfully in Thailand, Philippines and Sri Lanka. The unit dose of 0.1ml for ID should have at least 0.25 units.
Based on the recommendations of the expert group as well as WHO, the Drug Controller General of India (DCGI) has recently decided to allow ID route administration of tissue culture based anti rabies vaccine for post exposure prophylaxis in a phased manner in certain government antirabies centres. The schedules permitted in the 1st phase include the Thai Red Cross Regimen (2-2-2-0-1-1, two intradermal doses on the deltoid on days 0,3,7 and 1 dose on day 30 and 90) and the Updated Thai Red Cross Regimen (2-2-2-0-2-0, two doses on days 0, 3, 7 and 30). Another schedule not currently approved by DCGI is the 8 site regimen (8-0-4-0-1-1, 8 intradermal doses on each upper arm, each lateral lower abdominal quadrant, each thighs and each suprascapular regions on day 0, 4 doses on day 7 on each thigh and upper arm and 1 dose on day 30 and 90 on upper arm). Vaccines currently recommended for ID route administration in India are purified vero cell rabies vaccine and purified chick embryo cell vaccine. The intradermal route should not be used for immunocompromised patients and those on chloroquine therapy.
The criteria for selection of Antirabies centre for ID use are
a. Attendance of minimum 50 patients per day for post
exposure prophylaxis
b. Have adequately trained staff to give ID inoculation
c. Can maintain cold chain and ensure adequate supply of
disposable syringes and needles.
Intradermal administration is not recommended in individual practice. Also it does not make economic sense to practice it for individual cases.
Pre-exposure prophylaxis is particularly important where the exposure may be unrecognized (lab) or unreported (children). Pre-exposure prophylaxis eliminates need for RIG (awareness, cost and availability of RIG is a problem). It also reduces post exposure prophylaxis to two doses only. Pre-exposure prophylaxis is recommended for certain high risk groups enumerated below.
Any of the tissue culture vaccines can be given for this purpose three doses are given intramuscularly in deltoid/ anterolateral thigh on days 0, 7 and 28 ( day 21 may be used if time is limited but day 28 preferred). The intradermal schedule of 0.1 ml of any vaccine by the intradermal route on day 0, 7 and 21/28 is currently not approved by DCGI. Routine assessment of anti rabies antibody titer after completion of vaccination is not recommended unless the person is immunocompromised.
It is desirable to monitor antibody titers every
6 months in those with continuous exposure and every year
in those with frequent exposure. A booster is recommended
if antibody levels fall below 0.5 IU/ml. When serologic testing
is not available booster vaccination every 5 years is an
acceptable alternative. For re exposure at any point of time
after completed (and documented) pre or post exposure
prophylaxis two doses are given on days 0 and 3. RIG should
not be used as it may inhibit the relative strength or rapidity
of an expected anamnestic response.