Administration of Anti-Rabies vaccine stimulates production of neutralizing antibodies by the patient`s immune system. Protective levels of antibodies (of more than 0.5 IU/ml of serum) are seen 7 to 14 days after the initial dose of vaccine (window period). Moreover when the bites are on the head, neck, face & hands, the incubation period will be shorter.

Thus the patients are vulnerable to develop rabies during this window period of 7 to 14 days. RIGs are readymade anti-rabies antibodies and provide passive immunity to rabies.

Following situations need RIG:-

• 1. All Category III exposures.
• 2. Bites by all wild animals viz. by mongoose, jackal, fox etc.
• 3. Even Category II exposures in immuno-compromised/immunosuppressed individuals including HIV infected people & AIDS patients.
• 4. RIGs should also be administered in Category III exposures even by vaccinated pet animals.
• 5. RIGs can be used in pregnant women and lactating mothers.

There are two types of RIGs:-

• (1) Human RIG (HRIG): Available as 2 ml. vial with a potency of 150 IU/ml.
• (2) Equine RIG (ERIG): Available as 5 ml. vial with a potency of 300 IU/ml.

Availability of different RIGs in India:- HRIG Brands

• 1. BERIRAB-P- manufactured by CSL Behring GmbH, Germany and marketed by Bharat Serum & Vaccines Ltd.
• 2. KAMRAB - manufactured by Kamada Ltd., Israel and marketed by Synergy.

ERIG Brands

• 1. Anti Rabies Serum - manufactured by CRI - Kasauli.
• 2. EQUIRAB - manufactured and marketed by Bharat Serum & Vaccines Ltd.
• 3. ABHAYRIG - manufactured by VINS Bioproducts and marketed by Human Biologicals Ltd.
• 4. VINIRIG - manufactured and marketed by VINS Bioproducts.

• 1. Patient should not be on an empty stomach.
• 2. RIGs vial taken out from the refrigerator should be kept outside for a few minutes to warm it to room/body temperature.
• 3. While infiltrating RIGs into the bite wound, care must be taken to avoid injecting into blood vessels and nerves.
• 4. While injecting into finger tips, care must be taken to avoid compartment syndrome.
• 5. All emergency drugs and facilities for managing any adverse reactions must be available.
• 6. For ERIG, keep the patient under observation for at least one hour after ERIG administration and then send home.
• 7. RIGs can be infiltrated even to already sutured wounds without disturbing the sutures.

Majority of reactions to ERIG result from complement activation and are not IgE mediated and will not be predicted by skin testing.

The recent WHO recommendation states that there are no scientific grounds for performing a skin test prior to the administration of ERIG, because testing does not predict reactions and ERIG should be given whatever the result of the test.

However skin test is mandatory to avoid any possible litigation under consumer protection Act (COPRA) in India.

Inject 0.1 ml ERIG diluted 1:10 in physiological saline intra-dermally into the flexor surface of the forearm to raise a bleb of about 3-4 mm diameter.
Inject an equal amount of normal saline as a negative control on the flexor surface of the other forearm After 15 minutes an increase in diameter to > 10 mm of indurations surrounded by flare is taken as positive skin test, provided the reaction on the saline test was negative.

An increase or abrupt fall in blood pressure, syncope, hurried breathing, palpitations and any other systemic manifestations should be taken as positive test.

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 of 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.

Most ERIGs that are manufactured presently are highly purified and the occurrence of adverse events has been significantly reduced. Unlike the original unpurified rabies antisera which resulted in adverse reactions in as many as 40% of recipients, the adverse-reaction rate of patients receiving highly purified ERIGs has been reduced to <1-2%. However adverse event like anaphylaxis cannot be completely ruled out.

In rare cases the following adverse reactions may occur:

• 1. Allergic reactions including fall in blood pressure, dyspnoea, cutaneous reactions, in isolated cases reaching as far as anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration of Immunoglobulins.
• 2. Generalized reactions such as chills, fever, headache, malaise, nausea, vomiting, arthralgia and moderate back pain
• 3. Cardiovascular reactions particularly if HRIG is inadvertently injected intravascularly.

Local reactions:

• At the injection site local pain, tenderness or swelling can be observed in rare cases.

It is important to infiltrate all wounds with RIGs. Intra-muscular (IM) administration of RIGs is of very little value. The previous recommendation was to give anti rabies serum half into wounds and half IM, which is no longer recommended and may lead to treatment failure. As much of the calculated dose of RIG, as is anatomically feasible, should be infiltrated into & around all the wounds. In the event that some volume of RIGs is left over after all wounds have been infiltrated, it should be administered by deep IM at a site distant from the vaccine injection site.

If the calculated dose of RIG is insufficient to infiltrate all wounds, sterile saline can be used to dilute it 2 or 3 fold to permit thorough infiltration.

If a person has consumed milk of a rabid animal, counseling should be done. If counseling is not effective, then PrEP by IM or ID route or as a last resort a course of PEP (only vaccine) should be given.

If the milk is boiled or heated then only counseling or at the most a course of PrEP should be given only due to compulsions in medical practice in Indian setting.

Kissing a rabies patient may transmit disease because there may be contact with rabies patient's saliva. Full post-exposure immunization must be given either by Intramuscular (IM) or Intradermal (ID) route.

If there are ulcers in the mouth of the exposed person, then RIGs must be given by IM route.

• 1. Thorough wound cleansing.
• 2. ESSEN IM vaccination with double dose on day 0 and refer the patient to RIG center.

• 1. Any change in normal behavior suggesting either undue aggression or depression.
• 2. Running aimlessly and attacking others without provocation.
• 3. Becomes too drowsy and withdraws to a corner.
• 4. Change in voice/bark.
• 5. Excessive salivation.
• 6. Refusal to feed or eating objects like stone, paper, wood, metal pieces etc.

The clinical course of rabies in animals is divided into three phases:-

• 1. Prodromal,
• 2. Excitative
• 3. Paralytic.

However, the signs are variable and the lengths of phases may be irregular.

Vaccinating the pet dog is primarily to protect it against contracting rabies following bites by stray rabid dogs/animals. No veterinary vaccine offers 100% protection against rabies. Rabies is enzootic in our stray animal/dog population. The facility of protective antibody titre test (in vaccinated dog) is available only at a few centers in the country. The facility to quarantine the bitten vaccinated pet is limited and difficult. In view of the above facts and practical realities, rabies being 100% fatal, we take no chances and start PEP (immunization) in the bitten person and presume the vaccinated dog to be incubating rabies (and infective) and simultaneously observe the dog.

However, in extremely rare situations exception to the above thumb rule can be made at the professional discretion of the treating physician.

If a potent veterinary vaccine is given correctly as per pre-exposure schedule, it will mostly prevent rabies in the vaccinated dog, unless the exposure is severe. Ideally, its sera should be tested for protective antibody titre level but this is rarely practicable due to scare facilities in our country. Consequently, PEP vaccination is recommended following bites even by vaccinated dogs. It has been noted that:-

• 1. 6% of dogs found rabid have a reliable pre-exposure rabies vaccine history and that
• 2. 40% of dogs' vaccinated only one time lost most of their immunity 4-6 months later.
• 3. Post Exposure Prophylaxis (PEP) vaccination is not very successful in dogs.

As rabies is enzootic, that is, widely prevalent in stray dogs in India, if unvaccinated pet dog/cat is bitten by a stray dog, the pet may develop rabies and later pose threat at home to all family members.

Dogs effectively vaccinated against rabies ordinarily do not suffer and transmit the disease. But it is very difficult to say with certainty that a particular dog immunized with a specific vaccine is immune against rabies. If a tissue culture vaccine is regularly given to a healthy dog, it should develop sufficient protection. However, following severe and extensive bites (challenge dose of virulent virus infection) by a rabid dog, it may still succumb to rabies.

Ideally, the pet dog should be put to sleep (Euthanasia). The usual method of euthanasia for dogs is by IV injection of either concentrated Magnesium Sulphate solution or concentrated pentabarbitone.

No. Neither the age nor the breed or sex of the dog is important in transmission of rabies.

It is important to establish if the biting animal is healthy or diseased, bearing in mind that a rabid animal excretes the virus in its saliva not just throughout the illness but also several days before the appearance of the first signs. An unknown animal, which has disappeared, must be considered as rabid and full course of PEP must be given. Cats and dogs, which can be identified, must be kept under observation. The risk of rabies can be considered as slight if the animal shows no sign of disease after 5 days, and non-existent if the animal is still healthy on the 10th day (The European Standards recommend an observation period of 15 days).

All wild animals, and those domestic animals suspected of having rabies must be put down and the rabies diagnosis must be carried out in the laboratory.

If it is proven that the animal is not rabid - and only then - the anti-rabies treatment may be halted.

Yes. The rabies virus after multiplying in the brain spreads to other organs of the body like the heart, muscles, skin, etc. So the dog can definitely get infected because the virus can spread through oral mucous membrane.

Following severe and extensive bites which mean injection of very high challenge dose of virulent virus by a rabid dog, a vaccinated dog can still succumb to rabies.

A dog effectively vaccinated against rabies ordinarily will not suffer and transmit rabies. But it is very difficult to say with certainty that a particular dog immunized with specific vaccine is immune against rabies, more so in a rabies-endemic area.

Animal lovers and pet owners are always at high risk of rabies, and therefore, pre-exposure vaccination is recommended for all the family members.

"World Rabies Day" is on 28th September.

• 1. Talking to your dog like he/she is a person.
• 2. Treating your dog like he/she is a person.
• 3. Allowing dogs to do what they want because it will hurt their "feelings."
• 4. Dressing them up in little doggie clothes.

Remember, humanizing your dog is fulfilling your own human needs, not your dogs. Humanizing dogs does more harm than good.

• 1. The number one way to communicate to a dog that you are his pack leader is to take him or her for a Pack walk daily, where the dog is made to heel beside or behind the human who is holding the lead. This is most important for all dogs, as in a dog's mind, the leader always leads the way.
• (a) A dog must not be allowed to sniff or eliminate anywhere he wishes, but where you allow him.
• (b)The dog should be concentrating on following the human.
• 2. All humans must eat before the dogs.
• 3. No table scraps should be fed to the dogs during a meal.
• 4. Feedings must be at a scheduled time.
• 5. Humans must not let the dog go through any doorways first.
• 6. When you have left the house or the room, even for a minute and come back, ignore the dog for a few minutes.
• 7. A simple obedience command should be given before any pleasurable interaction with the dog. A child in the house should give the dogs command at least once a day and reward with a treat when the command is followed.
• 8. You should not lie on the floor to watch TV when the dog is around, as a human should never put himself in an equal or lesser height position than the dog.
• 9. You are the first one who greets new comers; the dog is the last that gets attention.
• 10. If a dog is lying in your path, do not walk around the dog, either make the dog move or step over the dog.
• 11. If you establish eye contact with the dog, the dog must avert his gaze first. Tell the children not to have staring contest with the dog.
• 12. Dogs must not sleep in your bed.
• 13. Games of fetch or play with toys must be Started and Ended by the Human.
• 14. Dog should not be allowed to lie on your furniture.
• 15. No tug-of-war, as this is a game of power and you may lose the game giving the dog reinforcement (in the dog's mind) of top dog.
• 16. Dogs need to be taught a drop it or release command.
• 17. Dogs should not be allowed to pull on the leash.
• 18. When you put his food dish down, he must wait until you give the "OK" to eat it.
• 19. Small dogs or puppies who demand to be picked up or put down should not get what they want until they sit or do another acceptable quiet behavior.
• 20. Dogs should never be left unsupervised with children or anyone who cannot maintain leadership over the dog.
• 21. Last but certainly not least... when you are around your dog avoid emotions. Your dog can sense these emotions and will see you as weak.

Dogs do not sweat through the skin. They exchange most of their heat through the mouth, and extend the tongue to increase the surface exposed to the air.

• 1. Study of passive immunity in the prevention of rabies discusses the advances in passive immunoprophylaxis, most notably the shift from the recommended polyclonal human or equine immunoglobulin to monoclonal antibody therapies. The first rabies-specific monoclonal antibodies are undergoing clinical trials, so passive immunization might finally become an accessible, affordable, and routinely used part of global health practices for rabies.
• 2. A report on use of a reduced (4-dose) vaccine schedule for post exposure prophylaxis to prevent human rabies summarized new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for post exposure prophylaxis (PEP) to prevent human rabies.
• 3. Human rabies can be very effectively prevented, and animal control is an important component in reducing the public health risk to humans. Dog rabies can be eliminated by well established control methods and routine dog rabies vaccination programs.

A rabies patient can make a valid will.
According to Section 59 in the Indian Succession Act, 1925

Person capable of making will:-

• 1. Every person of sound mind not being a minor may dispose of his property by will.
• 2. A married woman may dispose by will of any property which she could alienate by her own act during her life.
• 3. Persons who are deaf or dumb or blind are not thereby incapacitated for making a will if they are able to know what they do by it.
• 4. A person who is ordinarily insane may make a will during interval in which he is of sound mind.
• 5. No person can make a will while he is in such a state of mind, whether arising from intoxication or from illness or from any other cause that he does not know what he is doing.

Monoclonal antibodies (mAb) are important reagents used in biomedical research, in diagnosis of diseases, and in treatment of such diseases as infections and cancer. These antibodies are produced by cell lines or clones obtained from animals that have been immunized with the substance that is the subject of study. The cell lines are produced by fusing B cells from the immunized animal with myeloma cells.

Monoclonal antibodies against rabies virus have been widely used in the diagnosis and immunological analysis of rabies. Human monoclonal antibodies to rabies virus G protein are also expected to be used as a replacement for rabies immunoglobulin (RIG) in the post-exposure treatment of rabies. In 1978, Wiktor reported the preparation of rabies virus monoclonal antibodies. Since then, rabies virus monoclonal antibody (mAb) technology has been more and more widely used in basic research and diagnosis of rabies.

The Milwaukee protocol is an experimental course of treatment of an acute infection of rabies in a human being. The treatment involves putting the patient into a chemically induced coma and administering antiviral drugs. It was developed and named by Dr. Rodney Willoughby, following the successful treatment of Jeanna Giese, a teenager from Wisconsin who became the first of only six patients known to have survived symptomatic rabies without receiving the rabies vaccine.

Medical history has shown most rabies deaths are caused by temporary brain dysfunction with little to no damage occurring to the brain itself. Using this information, Willoughby's team devised an experimental treatment for rabies. Giese's parents agreed to the experimental treatment. Dr. Willoughby's goal was to put Giese into an induced coma to essentially protect herself from her brain, with the hope she would survive long enough for her immune system to produce the antibodies to fight off the virus. Giese was given a mixture of ketamine and midazolam to suppress brain activity, and the antiviral drugs ribavirin and amantadine, while waiting for her immune system to produce antibodies to attack the virus. Giese was brought out of the coma after six days, once signs of the immune system's progress became apparent. After 31 days in the hospital, Giese was declared virus-free and removed from isolation.The reasons for Giese's survival under the Milwaukee protocol remain controversial.

Recent WHO expert consultation did not recommend this protocol to be tried.

Important rabies websites are:-

• 1. http://rabies.org.in/
• 2. http://www.who-rabies-bulletin.org/
• 3. www.who.int/rabies
• 4. www.cdc.gov.in
• 5. www.apcri.org
• 6. www.rabiesinasia.org
• 7. www.rabiescontrol.net
• 8. www.worldrabiesday.org
• 9. www.drakgupta.in