RABIES TREATMENT REVIEW

The PEP should be started immediately after the bite. The observation period of 10 days is valid for dogs and cats only. The natural history of rabies in mammals other than dogs and cats is not fully understood and therefore the 10-day observation period is not applicable. The treatment may be modified if dog or cat involved remains healthy throughout the observation period of 10 days by converting post-exposure prophylaxis to pre-exposure vaccination by skipping the vaccine dose on day 14 and administering it on day 28 while using Essen Schedule. While using ID administration complete course of vaccination should be given irrespective of status of animal.

Vaccination status of the biting animal: 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. A history of rabies vaccination in an animal is not always a guarantee that the biting animal is not rabid.

Provoked versus unprovoked bite: A provoked dog bite should also be managed as an exposure and PEP started immediately. A provoked bite does not mean that the biting animal is not rabid. It is difficult to understand what provokes a dog so it is prudent to start PEP at the earliest.

Bite by wild animals: Bite by all wild animals should be treated as category III exposure. All animal bites in forest or in the wild should be treated as category III exposure

Bite by rodents: Exposure to domestic rodents, squirrel, hare and rabbits do not ordinarily require PEP.

Bat rabies: Bat rabies has not been conclusively proved in India and hence, at present, exposure to bats does not warrant PEP.

Post-exposure prophylaxis of immune-compromised patients: Several studies of patients with HIV/AIDS have reported that those with low CD4 (<200 counts) will mount a significantly lower or no detectable neutralizing antibody response to rabies. In such patients and those in whom the presence of immunological memory is no longer assured as a result of other causes (patients on chemotherapy, long term steroid therapy, cancer patients, etc) proper and thorough wound management and antisepsis accompanied by local infiltration of rabies immunoglobulin followed by complete course of anti-rabies vaccination by intramuscular route in both category II and III exposures are of utmost importance. Preferably, if the facilities are available, anti-rabies antibody estimation should be done 14 days after the completion of course of vaccination to assess the need of additional doses of vaccine

Contraindications and precautions: As rabies is nearly 100% fatal disease, there is no contraindication to PEP

Approach to Post-Exposure Prophylaxis (PEP)

The post-exposure prophylaxis is a three-pronged approach. All three carry equal importance and should be done simultaneously as per the category of exposure

1.Management of animal bite wound(s)

2.Passive immunization with Rabies Immunoglobulin (RIG)

3.Active immunization with Anti-Rabies Vaccines (ARV)

Management of animal bite wound(s)

Wound(s) 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(s) as is possible by an efficient wound(s) toilet that should not involve additional trauma. Washing of wound(s) should be carried out as soon as possible with soap and water. Since the rabies virus can persist and even multiply at the site of bite for a long time, wound(s) toilet must be performed even if the patient reports late.

Local infiltration of rabies immunoglobulin: In category III exposures rabies immunoglobulin should be infiltrated in the depth and around the wound(s) to neutralize the locally present virus as described in section 3.2.

Suturing of wound(s) should be avoided as far as possible. If surgically unavoidable, after adequate cleansing, rabies  immunoglobulin should be infiltrated in the depth and around the wound(s) and suturing should be delayed by a few hours. The delay in suturing allows diffusion of antibodies in the tissues. Minimum loose sutures should be applied for arresting the bleeding in life threatening situations.

Rabies Immunoglobulin (RIG) The anti-rabies serum/Rabies Immunoglobulin (RIG) provides passive immunity in the form of ready-made anti-rabies antibodies, before it is physiologically possible for the victim to begin producing his/her own antibodies following anti-rabies vaccination. Anti-rabies serum or RIG has the property of binding with the rabies virus, thereby resulting in neutralization and thus loss of infectivity of the virus and hence it is most logical to infiltrate RIG locally at the site of exposure. Two types of RIGs are available:

Equine Rabies Immunoglobulin (ERIG): ERIG is of heterologous origin produced by hyper-immunisation of horses. Currently manufactured ERIGs are highly purified Fab 2′ fragments and the occurrence of adverse events has been significantly reduced. These are produced in the country in public and private sectors.

Dose of rabies immunoglobulin: The dose of ERIG is 40 IU per kg body weight of patient. The ERIG produced in India contains 300 IU per ml. The dose of the HRIG is 20 IU per kg body weight. HRIG preparation is available in concentration of 150 IU per ml.

Administration of rabies immunoglobulin: The RIG should be brought to room temperature (25ºC to 30ºC) before administration to the patient. As much of the calculated dose of RIG as is anatomically feasible should be infiltrated into and around the wound/s. Multiple needle injections into the wound(s) should be avoided. After all the wound(s) has been infiltrated, if any volume of RIG is remaining, it should be administered by deep intramuscular inj

Anti-Rabies Vaccines

Active immunization is achieved by administration of safe and potent cell culture vaccines (CCVs) or purified duck embryo vaccine (PDEV). Currently available CCVs could be administered by IM regimen and CCVs approved for ID use shall be administered by ID regimen.

Anti-rabies vaccines are produced as one single intramuscular dose with potency of > 2.5IU per IM dose for post exposure and pre-exposure prophylaxis. It is absolutely essential that every batch of CCVs have minimum potency of 2.5IU per IM dose, irrespective of whether the vaccine is administered by IM or ID route.

Indications: All animal bite victims of Category II and III exposures irrespective of age and body weight require the same number of injections and dose per injection. All Category III exposures and Category II exposures in immuno-compromised individuals, in addition, require administration of RIG as discussed previously ection at a site distant from the vaccine injection site.

Intra-dermal (ID) Regimen

Post-exposure regimen

Updated Thai Red Cross Schedule (2-2-2-0-2).

This involves injection of 0.1ml of reconstituted vaccine per ID site and on two sites per visit (one on each deltoid area, an inch above the insertion of deltoid muscle) on days 0, 3, 7 and 28. The day 0 is the date of first dose administration of anti-rabies vaccine and may not be the date of rabies exposure/animal bite.

Intra-muscular (IM) Regimen

The currently available vaccines and regimen in India for IM administration are described below.

Vaccines

1. Cell Culture Vaccines

Human Diploid Cell Vaccine (HDCV), Liquid (Adsorbed), 1ml: Produced locally in private sector Purified Chick Embryo Cell Vaccine (PCECV), 1ml: Produced locally in private sector

Purified Vero Cell Rabies Vaccine (PVRV), 0.5ml and 1ml: Imported and also produced locally in public & private sectors

2. Purified Duck Embryo Vaccine (PDEV), 1ml: Produced locally in private sector and is currently being exported.

Regimen

Essen regimen (1-1-1-1-1): Five dose intramuscular schedule – The course for post-exposure prophylaxis consists of intramuscular administration of five injections, one dose each given on days 0, 3, 7, 14 and 28. Day 0 indicates date of administration of first dose of vaccine.

Management of re-exposure in previously vaccinated individuals

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after complete pre-exposure vaccination or post-exposure vaccination with potent cell culture vaccines is an important factor in the establishment of long lasting immunity against rabies.

Several studies have indicated that persons who have previously received complete pre- or post-exposure prophylaxis will elicit an anamnestic response to one or more booster doses of rabies vaccine even if the initial series of vaccination was administered several years previously. This response will occur whether:

the initial vaccination regimen was administered IM or ID;

the booster dose is given IM or ID

the previously vaccinated person has detectable rabies virus neutralizing antibodies or not.

Based on the above if re-exposed persons who have previously received and documented full pre- or post-exposure prophylaxis (either by IM or ID route) with a cell-culture vaccine or PDEV should now be given only two booster doses intramuscularly (0.5ml/1ml) or CCVs intra-dermally (0.1 ml at 1 site) on days 0 and 3. Proper wound toilet should be done. Treatment with RIG is not required.

Persons who have previously received full post-exposure treatment with NTV or vaccine of unproven potency or cannot document previous pre- or post-exposure treatment should be treated as fresh case and given treatment as per merits of the case

REFERENCE : NATIONAL RABIES GUIDELINES 2015