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Rabies is acute viral encephalitis caused by a RNA virus (Genus: Lyssavirus, Family: Rhabdoviridae). The genus name derives from lyssa, the Greek goddess of frenzy. The virus is bullet shaped and can be seen through an electron microscope only. Rabies is a zoonotic disease (i.e., transmitted by animals) that affects all mammals and is endemic in India.

Rabies is one of the oldest and most feared zoonotic diseases, and has been a threat to human health for more than 4000 years. Rabies is a neglected and severely under-reported disease killing each year worldwide (WHO 2007) an estimated 55,000people (24,000 to 90,000 deaths). All mammals, but mainly carnivores and bats, are susceptible and can transmit rabies virus. Human exposures are most frequently associated with bites by rabid dogs and transmission of virus from dogs' saliva. The Association for the Prevention and Control of Rabies in India (APCRI) estimated in 2004 that in India, there were 20,565 reported human deaths every year. Rabies is practically 100% fatal even today but easily preventable.
About half of the world's population lives in areas in which rabies is enzootic.

The virus is bullet shaped and can be seen through an electron microscope only. These viruses have a phospholipids envelope with glycoprotein surface spikes and a negative polarity strand; single chain RNA. The rabies virus genome encodes five proteins: the nucleoprotein, the matrix protein, the glycoprotein, the phosphorylated protein and a large polymerase protein.

The existence of lyssaviruses that are closely related to rabies virus and that can also cause clinical disease (Duvenhage virus, Lagos bat virus, Mokola virus, Shimoni bat virus, and Ikoma virus) has been known for several decades.

Street virus is a type of rabies virus which is virulent, having a long and variable incubation period of about 3 weeks to 3 months.

When first isolated from natural human or animal hosts, rabies virus preserves its natural properties and is referred to as street virus. Most of the street virus isolates generally cause a lethal CNS infection.

It is a rabies virus that has been passaged in tissue culture or animals. The term fixed indicates only that the incubation period and virulence has been stabilized. It is least virulent, and has a fixed short incubation period of 5-9 days. It is used as seed.

Rabies virus is inactivated:-
  • (1) By heat (1 hour at 50°C)
  • (2) On exposure to ultraviolet radiation
  • (3) By exposure to 70% ethanol, phenol, formalin, trypsin, ß-propiolactone
  • (4) Detergents
  • (5) By lipid solvents
  • (6) At pH below 3 or above 11
  • (7) Rabies virus is inactivated rapidly in sunlight and does not survive for long periods out of the host (in dried blood and secretions) as it is susceptible to sunlight and desiccation.
  • (8) X-rays

Rabies virus is resistant to cold and freeze drying.

Till date only seven survivors have been recorded. These patients survived not due to any specific anti-rabies therapy but following intensive life support and excellent nursing care. These patients survived for variable periods with residual neurological deficits. All the survivors had paralytic form of rabies and majority had history of some anti-rabies vaccination in the past.

REGION COUNTRIES
Africa Cape Verde, Libya, Mauritius, Réunion, São Tomé and Príncipe, and Seychelles
Americas North: Bermuda, St. Pierre and Miquelon
Caribbean: Antigua and Barbuda, Aruba, The Bahamas, Barbados, Cayman Islands, Dominica, Guadeloupe, Jamaica, Martinique, Montserrat, Netherlands Antilles, Saint Kitts (Saint Christopher) and Nevis, Saint Lucia, Saint Martin, Saint Vincent and Grenadines, Turks and Caicos, and Virgin Islands (UK and US)
Asia and the Middle East Hong Kong, Japan, Kuwait, Lebanon, Malaysia (Sabah), Qatar, Singapore, United Arab Emirates
Europe Austria, Belgium, Cyprus, Czech Republic,2 Denmark,2 Finland, Gibraltar, Greece, Iceland, Ireland, Isle of Man, Luxemburg, Netherlands,2 Norway, Portugal, Spain2 (except Ceuta and Melilla), Sweden, Switzerland.
Oceania3 Cook Islands, Fiji, French Polynesia, Guam, Hawaii, Kiribati, Micronesia, New Caledonia, New Zealand, Northern Mariana Islands, Palau, Papua New Guinea, Samoa, and Vanuatu.
1. Bat rabies may exist in some areas that are reportedly free of rabies in other mammals.
2. Bat lyssaviruses are known to exist in these areas that are reportedly free of rabies in other mammals.
3. Most of Pacific Oceania is reportedly "rabies-free."
In India the islands of Andaman and Nicobar and Lakshadweep are free of rabies.

Rabies is transmitted by infected secretions. Most commonly, transmission to humans takes place through exposure to saliva following a bite by an infected animal. Rabies virus can be excreted in saliva, urine, nasal discharge and respiratory secretions.

  1. Rabies is most commonly transmitted to humans via the bite of a rabies-infected animal.
  2. Humans usually contract rabies through bite wounds from rabid animals (bite exposure) because the rabies virus is highly concentrated in the saliva of infected animals.
  3. The amount of virus reaching the lesion is also a factor in transmission; for example, when a bite has to penetrate clothing, the saliva may be retained in the fabric and be prevented from entering the wound.
  4. It can also be transmitted through non-bite exposure, although this rarely occurs. Airborne infections, such as inhaling an aerosol of infected animal brain tissue in virus laboratories, or of contaminated air in bat-inhabited caves, have been reported.
  5. Iatrogenic rabies cases have occurred in patients who received cornea, kidney, liver, or blood vessel graft transplantation from donors who had undiagnosed rabies.
  6. To date, the only medically verified cases of human-to-human rabies transmission are the cases infected through organ transplantation from undiagnosed rabies patients
  7. Potential non-bite modes of transmission include contamination of a pre-existing wound, contact of mucous membrane or respiratory tract with the saliva of an infected animal, exposure to aerosolized rabies virus in the laboratory (or from bats), or via organ transplantation from an infected donor.

Animal bites are very common in India.
The annual incidence of animal bites is high, 1.7% and it was more in rural areas (1.8%), children (2.6%) and poor/low income group (75%). The main biting animal was dog (91.5%), mostly stray (63%), followed by cat (4.7%).

Rabies infection can be transmitted through aerial (by aerosol) route. Airborne infections, such as inhaling an aerosol of infected animal brain tissue in virus laboratories, or of contaminated air in bat-inhabited caves, have been reported.

Man-to-man transmission of rabies is possible. Rabies can be transmitted following bite by a rabies patient.
In 2004, three cases of human rabies were reported in U.S. following liver and kidney transplantation from rabies patients.
Transplantation of rabies infected cornea can cause rabies in recipient. Therefore a careful neurological history of donor must be taken before cornea transplantation.

As per Centre for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report (MMWR), no confirmed case of rabies has ever been reported in persons who performed a postmortem examination of people or animals, although contact with decedents with confirmed or suspected rabies can cause anxiety. Even from living patients with rabies, human-to-human transmission has been documented only rarely, (in cases of organ or tissue transplantation).

Both CDC and the World Health Organization (WHO) have stated that the infection risk to health-care personnel from human rabies patients is no greater than from patients with other viral or bacterial infections. In addition, rabies post-exposure prophylaxis (PEP) is available for exposed personnel. Nevertheless, because of the nearly universal fatal outcome from rabies, both CDC and WHO recommend that all personnel working with rabies patients or decedents adhere to recommended precautions. Even the minimal risk for rabies virus transmission at autopsy can be reduced by using careful dissection techniques and appropriate personal protective equipment, including an N95 or higher respirator, full face shield, goggles, gloves, complete body coverage by protective wear, and heavy or chain mail gloves to help prevent cuts or sticks from sharp instruments or bone fragments.

Participation in the autopsy should be limited to persons directly involved in the procedure and collection of specimens. Previous vaccination against rabies is not required for persons performing such autopsies. PEP of autopsy personnel is recommended only if contamination of a wound or mucous membrane with patient saliva or other potentially infectious material (e.g., neural tissue) occurs during the procedure.

Rabies exists in two forms:-
  • (1) Urban Rabies, propagated chiefly by unimmunized dogs.
  • (2) Sylvatic rabies, propagated by skunks, foxes, raccoons, mongooses, wolves, bats etc.

Worldwide the most common cause by far of human rabies infections is dog bites. The host animals of the rabies virus differ among regions, even though almost every mammal is capable of contracting rabies. The main vectors are foxes in Europe and Canada, raccoons, skunks, and fruit-eating and insectivorous bats in the United States, dogs in Asia, mongooses, jackals, and dogs in Africa, and dogs and vampire bats in Latin America.

In India, the animals commonly responsible for transmission of rabies are dogs and cats (97%) followed by wild animals like mongoose, foxes & jackals (2%) and occasionally by horses, donkeys, monkeys, cows, goats, sheep and pigs.

India has approximately 25 million dogs, with an estimated dog: man ratio of 1:36.2. The dogs fall into 4 broad categories: pets (restricted and supervised); family dogs (partially restricted, wholly dependent); community dogs (unrestricted, partially dependent); and undomesticated stray dogs (unrestricted, independent). Most dogs in India, perhaps 80%, would fall into the last 3 categories. The majority of the stray dog population is found in rural areas.

In India most rodents, rats, squirrel, rabbits, birds and bats have been found to be free of rabies. However, following exposure to mongoose, PEP is recommended. Rat bite cases do not require rabies vaccination but this is a right opportunity to start pre-exposure vaccination.

Human exposures to rabies can generally be categorized as bite, open wound, mucous membrane, or other types of exposure:

Bite exposure: Any penetration of the skin of a person by the teeth of a rabid or potentially rabid animal.

Open wound exposure: Introduction of saliva or other potentially infectious material (cerebrospinal fluid, spinal cord, or brain tissue) from a rabid or potentially rabid animal into an open wound (e.g., broken skin that bled within the past 24 hours).

Mucous membrane exposure: Introduction of saliva or other potentially infectious material (cerebrospinal fluid, spinal cord, or brain tissue) from a rabid or potentially rabid animal onto any mucous membrane (eyes, nose, mouth).

Other exposure: Any interaction with a rabid or potentially rabid animal where a bite, open wound, or mucous membrane exposure cannot be definitively ruled out.

A person does not acquire immunity against natural rabies infection, as it occurs in other viral infections because there is no viremia in rabies and the virus is not accessible to the normal immune mechanism of the body. The antibody production starts only after travelling efferently from CNS via mostly autonomic nerves to different target organs. But by that time, the neuronal cells of patient`s brain stem are affected.

Hydrophobia and aerophobia are pathognomonic for rabies and occur in 50% of patients. Attempting to drink or having air blown in the face produces severe laryngeal or diaphragmatic spasms and a sensation of asphyxia. This may be related to a violent response of the airway irritant mechanisms. Even the suggestion of drinking may induce hydrophobic spasm. Hydrophobia is typically unique to human beings.

The incubation period of rabies that is the time interval between the exposure to virus and the onset of symptoms, is usually from 03 weeks to 03 months (rarely 04 days to 02 years). An incubation period as long as 19 years has been reported. Children are at an increased risk of a shorter incubation period because of their short stature and bites are often closer to CNS. Multiple bites to the head and neck are associated with very short incubation periods less than 1 month.

The incubation period varies with the amount of virus transmitted, virus strain, site of inoculation (bites closer to the head have a shorter incubation period), host immunity and nature of the wound.

During most of the long incubation period of rabies, the virus likely remains close to the site of viral entry. Centripetal spread to the central nervous system and spread within the central nervous system occur by fast axonal transport.

People who are immuno-compromised will most likely be more susceptible to rabies. Rabies is usually undetectable during the incubation period, and infections can also be difficult to diagnose when the clinical signs first appear.

  • 1.Pain or paraesthesiae at the site of the bite is well known as a diagnostically useful prodromal symptom occurring in one-third to two-thirds of cases.
  • 2. In Thailand, however, a specific type of paraesthesiae-itching-was the earliest symptom in >40% of cases. Itching occurred at the site of the healed bite wound or involved the whole bitten limb and was sometimes so intense as to provoke frenzied scratching and excoriation of the skin. The explanation for local paraesthesiae may be the multiplication of virus in the dorsal root ganglion of the sensory nerve supplying the area of the bite.
  • 3. Pain behind the grafted eye was an early symptom in three of the four patients who developed rabies following corneal transplants.
  • 4. Priapism with frequent spontaneous orgasms was the first symptom in one Thai patient.
  • 5. Fever, malaise, nausea and vomiting.
  • 6. The skin becomes sensitive to changes of temperature, especially air currents.

There are mainly two types of rabies:-
  • a) Two-third of rabies patients suffer from typical furious (encephalitic) type of rabies. The virus replicates in portions of the brain including the hippocampus, amygdala, anterior thalamic nuclei and limbic cortex. Furious rabies has three cardinal signs:-
    • 1. Fluctuating consciousness, episodes of excitement and hallucinations.
    • 2. Phobic spasms - Aerophobia, Hydrophobia and Photophobia.
    • 3. Autonomic dysfunctions like increased salivation, excessive sweating, priapism & pupillary abnormalities.

    • It is typically believed that salivation and vomiting are linked, and contribute to the apparent hydrophobia (fear of water) in patients. These symptoms can last for few days, after which the patient may suffer from the second type of rabies, or may slip into a coma and die. It is when suffering from furious rabies that a person or animal is likely to attack those near them, and spread the disease.

  • b) Dumb (paralytic) type which is characterized by flaccid muscle weakness, constipation, urinary retention, stupor, coma. Hydrophobia is usually absent in these cases. This is a condition resembling Guillain Barre Syndrome. Dumb Rabies occurs as the result of the virus replicating in the brain's neocortex. It is much harder for a doctor to diagnose rabies in its "dumb" form than it is in its "furious" form, because the symptoms are less indicative of a specific medical issue.
    • Both forms are progressive and will lead to death, usually within 7 days in patients with encephalitic rabies and 3 weeks in those with paralytic rabies.

A study on management of human rabies concluded that the dismal outcome of patients with rabies provides little optimism for heroic efforts. Palliative therapy is of paramount importance in this fatal disease.

Maximum dog bites were observed in the autumn months. It is observed that there is an increase during warm-weather months (May through August) and a corresponding decrease during colder months (November through March).

Following myths about rabies are very much prevalent in India:-
  • 1. In India, there are many myths and wrong practices concerning the management of an animal bite. People apply turmeric, salt and sometimes ghee over the wound area. Chilies, hydrogen- peroxide and cow dung are some other wrong practices followed mainly in the rural parts of India.
  • 2. Some herbal extracts will cure rabies.
  • 3. In rural areas, people also resort to witchcraft and religious practices.
  • 4. Washing of wound(s) can cause hydrophobia.
  • 5. Dietary changes can cure, that is, shift from vegetarianism to non-vegetarianism or vice versa; stopping consumption of white things etc.
  • 6. A single dose vaccine will prevent rabies.
  • 7. Vaccines are more effective if taken on empty stomach.
  • 8. One should not take bath; eat meat and eggs during vaccination.
  • 9. Gems and stones have magical properties against rabies.

There is no specific treatment for clinical rabies. Key to survival after exposure to rabies virus is administration of post-exposure prophylaxis (PEP) as soon as possible. Death is virtually inevitable once clinical signs develop. Medical management is supportive and palliative.

Theoretically, the richly innervated areas like head, neck, face, hands and genitals are the most dangerous sites of bite in man. But practically, it is often the wounds on legs, which are ignored/neglected, that cause rabies.

It includes:-
  • (1) Local treatment of wound(s)
  • (2) Categorization of animal bite wound(s)
  • (3) Anti Rabies Vaccination. (ARV)
  • (4) Administration of Rabies Immunoglobulin (RIG)
  • (5) In addition, Tetanus prophylaxis, analgesics & systemic antibiotics may be given.

As rabies is 100% fatal, there are no contraindications to post exposure prophylaxis.

By mere washing of wounds and application of antiseptics, the risk of rabies will reduce by about 50%. The maximum benefit of the wound washing is obtained when fresh wound is cleaned immediately. It is important to remove saliva containing rabies virus at the site of bite by physical or chemical means. This can be done by prompt and gentle thorough washing with ordinary soap or detergent and flushing the wound with running tap water for at least 15 minutes.

Washing of the wound must be done as long as the wound is raw; irrespective of the time elapsed since the exposure. Care must be taken not to disturb the scab, if formed.

After washing with water & soap, disinfectants like Povidone Iodine or Surgical Spirit must be applied.

In extraneous circumstances, other alcoholic (>40%) preparations like Rum, Whisky or after-shave lotion may be applied on the wound. If soap or antiviral agent is not available, the wound should be thoroughly washed with water.

After cleansing of the bite wounds, local antimicrobial agents can be applied. Discourage local wound applicants like turmeric, neem, red chili, lime, plant juices, coffee powder etc.

Cauterizing the wound is not advisable as it leaves a very bad scar and also does not confer any additional advantage over washing the wound with water and soap. It amounts to malpractice and the doctor can be sued for compensation under COPRA.

Do not bandage the wound as far as possible and if unavoidable, apply non-adherent, absorbent dressings (paraffin gauze or Melolin) to absorb the discharge from the wound. Tincture iodine should not be used.

Avoid Suturing of the bite wound as a rule since it may risk inoculation of the virus deeply into the wound. However, if the wound has to be sutured, it should be done as late as possible from several hours to 3 days after infiltration of RIGs. If RIGs is not available, as a last resort, the wound must be flushed with povidone iodine before suturing. The suture should be loose and not interfere with free bleeding and drainage.

Human and animal bite wounds are best closed by secondary sutures after one week and after proper cleansing and daily wound care. Primary surgical intervention must be avoided if possible.

We should never try to deepen the bite wound. Deepening of wound for cleaning depends on area of injury, extent of injury and the aim should be to preserve as much tissue as possible and to excise dead tissue only.

Only 15 to 20 percent of dog bite wounds become infected. Puncture wounds and hand wounds are more likely to become infected than scratches.

Using antibiotics may be helpful, particularly in high-risk wounds such as those of the hand.
Antimicrobials effective in the empiric treatment of patients with animal bite and human bite wounds
  Animal bite Human bite
Amoxicillin-clavulanate (PO) + +
Ampicillin-sulbactam (IV) + +
Moxifloxacin (PO, IV) + +
Gatifloxacin (PO, IV) + +
Doxycycline (PO, IV) + +
Most mammalian bites are caused by dogs, cats or humans. Cat and human bites often become infected, so antibiotic prophylaxis should be considered in addition to wound management. Amoxycillin with clavulanate is suitable for prophylaxis in most cases. Prophylaxis is usually continued for 5–7 days.

WHO Guide for treatment against rabies post-exposure:-
Category (Type of contact with a suspect or confirmed rabid domestic or wild animal, or animal unavailable for observation) 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, Administer 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.
III. Single or multiple transdermal bites or scratches, Contamination of mucous membrane with saliva (i.e. licks), Licks on broken skin. 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.
When in doubt of degree of exposure to rabies risk, it is safer to over treat than under treat.

  • It is very important to elicit information about biting animal.
  • Low risk category includes healthy pets and regularly vaccinated dogs/cats.
  • Moderate risk category includes healthy pets but vaccination status doubtful or not done.
  • High risk category includes rabid, sick, died, stray dogs/cats, or wild animals.

These are:-

  • (1) Purified vero cell rabies vaccine (PVRV)
  • (2) Purified chick embryo cell vaccine (PCECV)
  • (3) Human diploid cell vaccine (HDCV)
  • (4) Purified duck embryo vaccine (PDEV)

Response to rabies vaccination is a unique mix of specificities to rabies virus antigens. Antibodies develop out of intrinsic host responses and in response to extrinsic factors such as the amount of antigen given, type of antigen, and route of exposure or vaccination. There may be substantial variation in the neutralizing activity and quantity of rabies virus neutralizing antibodies (RVNA) produced. Therefore, the strain of virus used in antirabies vaccine plays a role in eliciting the required response.

Compared to other continuous cell lines based rabies vaccines, PCEC vaccine with Pitman-Moore (PM) strain has several advantages, these includes:

  • 1. This method provides vaccine with high yield, greater potency and immunogenicity which makes the vaccine comparatively cost effective and unique.
  • 2. It is more readily scalable to large scale commercial vaccine production.

In the past, rabies vaccine was a sheep brain derived Nerve Tissue Vaccine (NTV) and used to have considerable side effects. Large volumes and number of injection were required. So, rabies vaccine acquired the bad reputation of a dangerous vaccination. However, these fears are no longer justified with modern rabies vaccines that are very safe.

Of the currently available TCVs such as HDCV, PCECV, PVRV, and PDEV, all are equally good and approved by WHO. All are interchangeable following non availability of one brand or due to allergy to one of the CCVs or PDEV. All are considered protective throughout the world against different strains of rabies viruses in different parts of the world.

The modern anti-rabies vaccines should not be diluted with tetanus toxoid or any other diluents other than that provided with the vaccine.

Following animal bite, rabies vaccine can be given to a pregnant woman. Medical termination of pregnancy should not be done as a routine clinical practice.

Modern Anti-rabies vaccines being used now are Tissue Culture Vaccines (TCV) inactivated by beta-propiolactone (BPL) and can safely be given to a lactating mother.

There is no single dose vaccine or a vaccine that gives lifelong immunity.

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All modern rabies vaccines have a uniform dosage for all age groups.

As rabies is 100% fatal, there is no contraindication for anti-rabies vaccination. Rabies vaccine can be given to a child with chicken pox or measles and it is effective. If possible administration of measles vaccine should be postponed by a fortnight after the completion of antirabies immunization.

Rabies vaccine can be given to HIV or AIDS patient. It is recommended to administer RIGs even in category II exposures in such patients and double dose of anti-rabies vaccine must be given on day 0 of vaccination.

Rabies vaccine can be given to a patient with jaundice.

A person receiving/completed antirabies immunization can donate blood. However, the recipient does not benefit from the transfer of rabies-neutralizing antibodies due to hemodilution.

There is no contraindication for any surgery along with anti-rabies vaccination and a full course of anti-rabies immunization should be given, irrespective of the surgery or other procedures.

It is the time taken by Anti-Rabies vaccine to produce protective levels of antibodies in the patient. The window period is of 7-14 days.

The criterion for protection after immunization is that the rabies virus neutralizing antibody (RVNA) titer of > or = 0.5 IU/ml of serum in the vaccinated person is considered protective.

The facility for this test is available at NCDC, Delhi, CRI, Kasauli, Pasteur institute, Coonnor, NIV, Pune and NIMHANS, Bangalore.

WHO recommends that the vaccine potency should be at least 2.5 IU per dose. The potency is the capacity of the vaccine to induce immune response.

Vaccine must be stored at +20 C to + 80 C. It should not be stored at room temperature. Besides, the vaccine should not be exposed to sunlight and heat.

There are no risks with vaccine with a higher potency.

There are no risks with vaccine with a higher The post-exposure (WHO ESSEN-IM) Schedule is I.M. vaccination on days 0(day of first dose of vaccine and not the day of bite), 03, 07, 14 and 28.
Vaccine should be injected deep into deltoid muscle (in Adults) or antero-lateral aspect of thigh (in Children)..

Rabies vaccine must not be administered in gluteal region as the gluteal fat may retard vaccine absorption resulting in delayed and lower seroconversion.

The vaccine on day 0 (first injection) must be doubled and given at two sites (deltoids or thigh in young children). In category II exposures, it is recommended to administer even RIGs along with vaccine. Rest of the schedule is same as for any other patient.

Only two doses of vaccine at days 0 & 3 are required. RIGs are not required (WHO 2007). However, in laboratory confirmed rabies exposures, irrespective of past rabies immunization, full course of PEP and RIGs is recommended. In rabies, it is safer to over treat than under treat.

An early and correct administration of modern anti-rabies vaccine is life saving. The vaccination must be started immediately irrespective of the status of the biting animal. Patients who seek treatment after a delay of 48 hours or even months after having been bitten should be dealt in the same manner as if the exposure occurred recently.

In case the mother develops rabies, the rabies virus is not known to cross placental barrier, and as a result, the fetus is safe. Hence, the pregnant woman with rabies should be clinically managed and if induction of pregnancy or caesarean section is possible, the obstetrician should do it with some "personal precautions" and immuno-prophylaxis (usually three doses of modern vaccine or if any accidental exposure is there, then full course of post-exposure vaccination either by IM or ID route should be given to the obstetrician.) Later the new born may be given full course of rabies PEP vaccination.

Antibody tests, that is, rapid fluorescent focus inhibition test (RFFIT), mouse neutralization test (MNT) are done only at selected few reference centers in India. Antibody tests are not required on a routine basis following antirabies vaccination if vaccination is correct and reliable.

Observing the dog for 10 days without initiating treatment is risky and not at all justifiable. It is mandatory to start treatment soon after exposure. The vaccination must be started immediately irrespective of the status of the biting animal. Improper treatment to animal bite victims may lead to rabies death and litigation under Consumer Protection Act (COPRA). According to Consumer Protection Act, the animal bite should be considered as "medical urgency" and treated with due care.

Carrier state of rabies in dogs/cats is not yet conclusively proven and established.

In case, day 0 and 3 inj. were given and inj. due on day 7 was postponed because the dog was kept under observation but the dog dies between 8 and 15 days, three doses of vaccine must be given as close to the original dates of the schedule and all five inj. must be completed by day 28.

First three doses of modern rabies vaccine must be very timely and for the fourth and fifth, one or two days of variation is permissible.

All anti-rabies vaccines are considered protective against different strains of rabies viruses in different parts of the world.

It is advisable to abstain from alcoholic drinks during the course of rabies vaccination as it may affect the immune response.

Pre-exposure (Prebite) vaccination means immunization before the bite.

The regimen is three IM injections on days 0, 7 & 28.

Pre-exposure vaccination simplifies post-exposure vaccination because after bite, those who have received full Pre-exposure vaccination, only two doses of vaccine at days 0 & 3 are required. RIG is not required (WHO 2007).

Although no teratogenicity or other adverse effects are reported with modern rabies vaccines, pre-exposure vaccination should be avoided in pregnant woman.

Immunosuppressive drugs, such as steroids, antimalarials, anticancer drugs are generally contraindicated during rabies immunizations. However if these drugs cannot be avoided, then day 0 dose of vaccine should be doubled.

For PEP, the modified "TRC ID" schedule (2-2-2-0-2) is the only schedule approved by the DCGI at present. ID vaccine is given on days 0, 03, 07, and 28.
The dose of each ID shot has been specified to be of 0.1 ml. of the permitted vaccines.
For pre-exposure vaccination, 0.1 ml of ID-approved vaccine is to be given ID over one deltoid on days 0, 7 and 21 or 28 days.

One dose of 0.1 ml is administered intradermally at eight different sites (Either upper arms, lateral thighs, supra-scapular region, and lower quadrant of abdomen) on day 0. On day 7, four 0.1 ml injections are administered intradermally into each upper arm (deltoid region) and each lateral thigh. Following these injections, one additional 0.1 ml dose is administered on days 28 and 90. This regimen lowers the cost of vaccine administered by intramuscular regimens and generally produces a higher antibody response than the other recommended schedules by day 14. It does not result in a significantly earlier antibody response and in order to ensure optimal treatment, a passive immune product must be administered to patients presenting with severe exposures.
However, it is not approved for use in India by DCGI.

The ID dosage of all approved vaccines is uniformly 0.1 mL per ID site irrespective of their IM dosage.

It is deposition of approved modern rabies vaccine (or antigen) in the layers of dermis of skin by which the immuno-receptive Langerhan cells present within the dermis are stimulated. Subsequently the antigen is carried by antigen presenting cells via the lymphatic drainage to the regional lymph nodes and later to the reticulo-endothelial system eliciting a prompt and highly protective antibody response. Immunity is believed to depend mainly upon the CD 4 + T- cell dependent neutralizing antibody response to the G protein. In addition, cell-mediated immunity has long been reported as an important part of the defense against rabies. Cells presenting the fragments of G protein are the targets of cytotoxic T- cells and the N protein induced T helper cells. The immune response induced by IDRV is adequate and protective against rabies.

Not all vaccines produced in India are at present fit for Intra-dermal usage. The following vaccines have been approved by DCGI for use by intra-dermal route.

  • (1) Purified chick embryo cell vaccine (PCEC) - Rabipur and Vaxirab-N.
  • (2) PVRV (Purified verocell rabies vaccine) - Verorab-vial of 0.5 ml,
  • (3) PVRV - Abhayrab - vial of 0.5 ml., Human Biological Institute
  • (4) PVRV - Indirab, vial of 0.5 ml/1.0 ml. Bharath Biotech, Hyderabad.

PDEV (Vaxirab) and HDCV (Rabivax) are approved for IM use only and not for IDRV. Rabies vaccines formulated with an adjuvant should not be administered intradermally.

As far as possible, the same vaccine should be used throughout a course of IDRV. However, in exigencies, the permitted vaccines are interchangeable.

It is recommended by many internationally reputed experts that the phenomenon of mixing of IM and ID schedules is not to be practiced and must be avoided as far as possible.

WHO recommends that in cases where the wheal over the skin is not formed then the patient should receive another dose of vaccine at a site nearby. If the IDRV fails in any one of the sites after two attempts, then the vaccine must be given by IM route and the remaining doses of the schedule given by IM route only.

IDRV can be given in deltoid region, supra-scapular, anterior abdominal wall and the upper part of thigh.

Cell culture vaccines have proved remarkably safe and free of significant adverse events. However, mild symptoms of pain, erythema, irritation or swelling at the intradermal injection sites occur in 3% to 92% of patients. The most frequent symptom is local irritation in 7% to 64% of vaccines. Generalized symptoms reported by 3% to 14% of recipients include headache, fever and influenza- like illness. Transient macula papular and urticarial rashes are occasionally seen. All these adverse effects are mild, transient and self limiting and rarely call for the use of anti-histamines (tablet or syrup Avil) and analgesics.

  • 1. The ID injections must be administered by staff trained in this technique.
  • 2. The Vaccine vials must be stored at +20 C to + 80 C after reconstitution and
  • 3. The total content should be used as soon as possible, but at least within 8 hours.
  • 4. The 0.1 ml. ID administration of cell-culture vaccine should create a wheal of at least 5 mm diameter with "peau de orange" appearance.
  • 5. If ID dose is given sub-cutaneously then there is a possibility of poor immune response due to low antigen load. This may be life threatening

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