Rabies Awareness by Dr Srikant Sharma

September 28th is World Rabies Day which marks the anniversary of Louis Pasteur's death, the French chemist and microbiologist, who developed the first rabies vaccine. It is celebrated annually to raise "awareness about rabies prevention" and to highlight progress in defeating this horrifying disease.

Rabies in Latin means 'revere' (to rage). In medicine, rabies means acute encephalomyelitis caused by neurotropic viruses belonging to the genus Lyssavirus. Lyssa in Greek means 'frenzy' or Madness. In Greek mythology, Lyssa was the Goddess of rage or fury.

It has been recognized in India since the Vedic period (1500–500 BC) and is described in the ancient Indian scripture Atharvaveda, wherein Yama, the mythical God of Death, has been depicted as attended by 2 dogs as his constant companions, the emissaries of death.

Rabies is present on all continents with the exception of Antarctica, but more than 95% of human deaths occur in Asia and Africa. Canine rabies has been eliminated from Western Europe, Canada, the United States of America, Japan, Malaysia and a few Latin American countries; while Australia is free from carnivore rabies, and many Pacific Islands Nations have always been free from Rabies and related viruses.

While dogs are the major vectors of transmission in Asian countries, transmission by bats and other animals poses a significant threat in America, Africa, and Europe. Infected monkeys, racoons, foxes, skunks, cattle, wolves, bats, and cats are also known to transmit rabies to humans.

Incidence in India:

WHO reports around 50 000 rabies deaths every year, out of which 20000 (36%) are estimated to occur in India. Approximately 17.4 dog bite is there per thousand
population. Canine rabies accounts for 96% of mortality and morbidity in rabies in India. Most of the patient belongs to low socio-economic status, and 40% of dog
bites are in children between age of 5-15 years. In India, every 2 second 1 person bitten by dog & every 30-minute one person is dying from rabies.

Q1. What are the different types of rabies categories?

Exposure to rabies is divided into 3 categories.

Q2. what is the first Aid treatment (wound treatment) for an animal bite?

Wounds should be washed and flushed immediately with soap/detergent and water for 10–15 minutes. Wounds should be cleaned with povidone-iodine/tincture iodine followed by 70% alcohol or spirit.

Avoid:
● Covering the wound with dressings or bandages.
● avoid any traditional maneuvers for wound like leaves, herbs, turmeric, soil, oil, chilies, chalk, betel, etc.
● Do not touch bare hand, without gloves.
● Don't cauterize, as it may leave scar.

● Suturing which facilitates further inoculation of rabies virus. But may be necessary for closing large wounds. Suturing may be done after cleaning and deep infiltration of wound with rabies immunoglobulin (RIG). Suturing may be minimum, loose, and delayed if possible.

Q3. What type of rabies vaccine is available?

Modern rabies vaccines are commercially available as 1. human diploid cell vaccine (HDCV) 2. purified Vero cell rabies vaccine (PVRV) 3. purified chick- embryo cell vaccine (PCECV) and 4. purified duck embryo vaccine (PDEV).

Q4. How vaccine can be used for PEP (post-exposure prophylaxis)?

Intramuscular regimens (I.M.): Both a five-dose and a four-dose (i.m.) regimen are recommended for post-exposure vaccination. Five dose regimens are the more commonly used: administer on days 0, 3, 7, 14 and 28 into the deltoid muscle, or anterolateral thigh for younger children.

The four-dose (3 visits) regimen is to administer, two doses on day 0 (one dose in each deltoid muscles), and then one dose on each of days 7 and 21.

The four dose (4 Visits) regimen is to administer (Canadian immunization schedule): on days 0, 3 ,7 & 14 in immunocompetent patients. And on day 0,3,7,14 and 28 in immunocompromised patients.

Intradermal regimens: Intradermal administration of cell-culture- and embryonated-egg-based rabies vaccines has been successfully used.

Only the anti-Rabies vaccine (lyophilized) approved by DCGI should be used intradermally. Package leaflet should mention safe use of Vaccine by intradermal routes. patient taking chloroquine or immunocompromised patients should take intramuscular vaccine only. Switching from intramuscular to intradermal, or vice versa is not recommended.

The two-site intradermal(i.d.) method: One i.d. injection at every two sites (above 1cm of insertion of deltoid muscle) of lymphatic drainage sites; on days 0, 3, 7 and 28(2,2,2,0,2) are administered. The volume per intradermal injection should be 0.1 ml. The intensity of developing immunity is high with this.

Q5. How to use vaccine and immunoglobulin after exposure?

Q6. When should we start treatment earliest?

As soon as possible, earliest the treatment better the result. Stop treatment if animal remains healthy throughout an observation period of 10 days or if it is proven to be negative for rabies.

Rabies immunoglobulin can be injected up to 7 days after first vaccine dose administration. But preferably be given before vaccination, soon possible.

Q7. Can vaccinated dog transmits rabies?

Dog if adequately vaccinated, will not suffer or transmit the disease. But since laboratory protection of dog immunity is not available, hence irrespective of the vaccination status of the biting dog, PEP is recommended.

Q8. Is PEP recommended for rat bite in India?

In Indian household rat bite PEP is not necessary, but one should consult infectious disease physician if bitten by wild rodents.

Q9. Indication to use rabies vaccine in pregnant and lactating mother?

All modern rabies vaccines are inactivated, safe and potent and can be given to pregnant women or lactating mothers.

Q10. What is the vaccination schedule for rabies pre-exposure prophylaxis?

Modern rabies vaccines are administered for preexposure and post-exposure prophylaxis and the vaccination schedule is determined accordingly.

Pre-exposure prophylaxis Intramuscular administration:
One dose of vaccine is administered intramuscularly/intradermal on each of days 0, 7 and 21 or 28.

To maximize savings, sessions of intradermal pre-exposure prophylaxis should involve enough individuals to use all opened vials within 6 hours. Three doses/three visits IM or ID one dose each on day 0, day 7, and day 21 or 28. Day 0 means day of first vaccination, not necessarily day of bite.

Q11. What is rabies immunoglobulin?

Human rabies immune globulin (HRIG) is infiltrated deep around the bites (diffusion in muscles) and provides rapid passive immune protection with a half- life of approximately 21 days. It is administered only once. No more than the recommended dosage of HRIG should be given because excessive HRIG can partially uppress active production of antibody. It may be diluted (normal saline) if needed for infiltration in multiple wound sites. Infiltration around eyes, fingers, toes, nose, and ar lobule, should be without pressure to prevent developing compression syndrome. Injection adrenaline should be ready for any anaphylaxis reaction (after administration of immunoglobulin 30 minutes watch for any reaction may be done). Care must be taken to avoid injecting into blood vessels and nerves.

The recommended dosage of HRIG is 20 IU/kg body weight for all ages including children.

Administer the remaining HRIG intramuscularly (IM) at a site distant from the first vaccination site.

If there is no wound, such as following a bat-in-the-bedroom exposure, then administer the entire dose of HRIG in the quadriceps or deltoids. The patient should not be given RIG on an empty stomach.
● Pregnancy is not a contraindication for RIG and anti-rabies vaccination.

Q12. What is R-Mab?

This is a novel human rabies monoclonal antibody against rabies G protein (glycoprotein)produced by Recombinant DNA technology (on Chinese hamster ovary cells) for passive prophylaxis of rabies. It is a US-patented product and offers passive immunization against rabies. This antibody, showed strong neutralizing activity, against all rabies serotypes found in India. It precludes chances of transmitting blood-borne infections that are present in rabies immunoglobulin (which is a blood derivative). As RMab dose is lower at 3.33 IU per Kg body weight, the infiltration volume is lower than HRIG making it easier and more convenient to both the doctor and the patient. In India it is available in name of Rabishield.

Q13. Is it necessary to perform a skin sensitivity test while using ERIG?

Yes, and person allergic to ERIG should be preferred to have HRIG/ Rabies Monoclonal Antibody (R-Mab).

Q14. Who should receive routine rabies virus serological testing?

For most persons, completing pre-exposure or postexposure prophylaxis routine serological testing is not necessary to document seroconversion, unless the: the person is immunosuppressed; significant deviations of the prophylaxis schedule have occurred;the person's antibody status is being monitored routinely due to
occupational exposure to rabies virus.

In immunocompetent, immunity remains for more than 5years.

Immunocompromised status may be in HIV suffering, steroids/anticancer/chloroquine drug receiving, cirrhosis, and transplant patients.

Professional working with rabies laboratory may need to check their immune status in 6 months, whereas veterinarian or professional working with animals, may check on 2 years basis.

Protective levels of anti-rabies neutralizing antibody titer of more than 0.5 International unit per ml in serum is protective, which is formed after day 14 of vaccination.

Q15. Is PEP necessary if milk from an infected animal are consumed?

No. There is no laboratory or epidemiological evidence that the consumption of milk or milk products from rabid animals transmits the disease. However, it is not
advisable to consume milk from rabid animals.

Q16. Can consumption of meat from an infected animal transmit rabies?

The consumption of raw meat from an infected animal requires PEP.
Cooked meat does not transmit rabies because heating kills the virus; however, it is not advisable to consume meat from an infected animal.

Q17. Is rabies get transmitted by human bite?

Till now no cases has been found to have human bite transmission.

Q18. What is the mode of death?

Cause of death may be, because of acute neurological phase involvement, resulting in abrupt death or paralysis. Death may occur by cardiorespiratory arrest within a few days of rabies. Without supportive care respiratory arrest usually develop shortly after the onset of coma and leads to death within 5 days for Furious rabies and 13 days for Paralytic rabies.

Q19. How India can prevent rabies?

Rabies is a vaccine-preventable viral disease which occurs in more than 150 countries and territories.

Rabies elimination is feasible through vaccination of dogs and prevention of dog bites. Control of rabies involves two components viz. elimination of human deaths
and control of canine rabies to break down the transmission.

Human Component- The strategy for the human component are: Training of health professionals, implementing use of intra-dermal route of inoculation of cell culture vaccines, strengthening surveillance of human rabies, Information Education & Communication, Laboratory strengthening

Animal Component- which is being pilot tested in the Haryana &

Chennai. The Animal Welfare Board of India, Ministry of Environment & Forests is the Nodal agency for the Animal Component of the program. The strategy for the animal components are: Population survey of dogs, Mass vaccination of dogs, Dog
population management Strengthening surveillance. There must be strict implementation of the legal provisions for licensing and regular vaccination of pet dogs. At the same time, dedicated efforts are needed to control the population of stray dogs, through animal birth control programs(ABC) and mass vaccination, and to eliminate suspected infected animals.

Q20. What is WHO plan for elimination rabies?

WHO, the World Organization for Animal Health (OIE), the Food and Agriculture Organization of the United Nations (FAO) and the Global Alliance for Rabies Control (GARC) have established a global "United Against Rabies" collaboration to provide a common strategy to achieve "Zero human rabies deaths by 030". Built on the five pillars of rabies elimination (STOP-R), the action plan combines socio-cultural, technical, organizational, political, and resource-oriented aspects. And it emphasizes three key aspects of rabies control. First, the most cost-effective way to eliminate rabies is to prevent it at the source, through mass vaccination of dogs.
Second, the human vaccine must be accessible and affordable for those people potentially exposed to rabies. Third, there is a need for education and increased awareness of all aspects of rabies control.

Q21. Where to send sacrificed animal for diagnosis?

India has only one laboratory for diagnosing rabies in animals, located in Bangalore at the Veterinary College of the Karnataka Veterinary, Animal and Fisheries Science University

Q22. Take home message?

Rabies is a 100% fatal disease that has no cure till date but is preventable.
Estimates indicate that Rabies kills 2 people every hour in India. In treating rabies vaccine alone is not enough as, in about 5% of cases the incubation period is less
than 10 days while a vaccine takes up to 14 days to produce adequate antibodies for protection. The only way to protect the victim is by providing passive immunization via rabies immunoglobulins (RIGs) or Monoclonal Rabies Antibody(M-rab). Hence canine rabies almost 100% preventable in India.

The article has been authored by Dr Srikant Sharma, Senior consultant physician, Mool Chand Medicity, New Delhi and Dr Nisarg Patel, Mool Chand Medicity, New Delhi.