Rabies

Rabies is a fatal viral infection that targets the brain and nervous system. The disease is zoonotic i.e. it can be transmitted from one species to another, such as from dogs to humans, commonly following a bite from an infected animal. For a human, rabies is almost always fatal if post exposure prophylaxis (PEP) is not administered immediately following an exposure. The rabies virus infects the central nervous system, ultimately affecting the brain and resulting in death. The rabies virus travels to the brain through the peripheral nerves. The incubation period of the disease i.e. the time lag between the bite/exposure to rabies and onset of symptoms of the disease, is usually about a few days to few months in humans, depending on the site and severity of exposure, the   distance the virus must travel to reach the central nervous system and other factors.

Rabies is a vaccine-preventable disease in both humans and animals. Rabies is present on all continents, except Antarctica. About 80% of human cases occur in rural areas. In India, human rabies is reported from throughout country except Andaman & Nicobar and Lakshadweep Islands. In up to 99% of cases, domestic dogs are transmitting the infection to humans.

National Rabies Control Programme was implemented in India during 12th FYP for rabies control. To achieve zero human deaths from dog-mediated rabies by 2030, National Action Plan based on One Health approach has been launched in 2021 in the country.

Know about:

National Action Plan-Rabies Elimination

National Guidelines for Rabies Prophylaxis, 2019

National Rabies Control Programme

References-

https://ncdc.gov.in/index1.php?lang=1&level=1&sublinkid=146&lid=150

https://ncdc.gov.in/WriteReadData/linkimages/GuidelinesforRabiesProphylaxis.pdf

• Anxiety
• Insomnia
• Confusion
• Agitation
• Fever
• Headache
• Nausea and vomiting 

• Inability to drink water and / or fear for water ( hydrophobia )
• Fear for draught of air ( aerophobia )
• Fear for light ( photophobia ) 
• Abnormal  behaviour
• Hallucinations progressing to delirium 
• Violent behaviour, in some 
• Slight or partial paralysis
• Ultimately leading to cardio-respiratory failure and death 

The rabies virus belongs to a group of viruses called lyssaviruses, which can infect mammals. The virus is present in the saliva of rabid animal.

The primary diagnosis of rabies depends on clinical presentation and history of exposure to a suspect rabid animal or rabies virus (RABV).

The WHO defines a human clinical case of rabies as follows:

A person presenting with an acute neurological syndrome (encephalitis) dominated by forms of hyperactivity (furious rabies) or paralytic signs (paralytic rabies) progressing towards coma and death, usually by cardiac or respiratory failure, typically within 7–10 days after the first sign.

Signs and symptoms of rabies include any of the following: hydrophobia, aerophobia, photophobia, paraesthesia or localized pain, dysphagia, localized weakness, nausea or vomiting.

Tests used to confirm a diagnosis of rabies in its more advanced stages include:

• Saliva test – A sample of saliva is tested for the presence of the rabies virus.
• lumbar puncture – A needle is used to remove a small sample of cerebrospinal fluid (CSF), which can be checked for the rabies antibodies (CSF is the fluid that surrounds brain and spinal cord).
• Blood tests – Blood is checked for the rabies antibodies.
• Skin biopsy – A small sample of skin is removed and checked for the presence of the rabies virus
• Fluorescent antibody testing on brain tissue, direct rapid immunohistochemistry tests, enzyme-linked immunosorbent assays, and reverse transcriptase polymerase chain reaction are some tests for rabies diagnosis.

Reference- https://apps.who.int/iris/bitstream/handle/10665/272371/WER9316.pdf?ua=1

Treatment depends upon the whether the patient has started to show any signs and symptoms. Once clinical symptoms appear, rabies is 100% fatal. Presently the treatment involves providing life-supporting services in intensive care facilities and other palliative measures.

Rabies deaths occur mainly in those who cannot access timely and effective PEP. Prompt PEP following severe exposures is 100% effective in preventing rabies.

Reference:

https://apps.who.int/iris/bitstream/handle/10665/272371/WER9316.pdf?ua=1

Rabies can be prevented in both humans and animals with the vaccine. Mass dog vaccination aiming at 70% coverage in endemic areas, as mentioned in the National action plan for elimination of dog mediated rabies in India can interrupt RABV transmission at its animal source and can save human lives.

In human rabies vaccination is used as post-exposure and pre-exposure prophylaxis for population at high risk of exposure. Active immunization is done by cell culture vaccines (CCVs).

Post exposure prophylaxis (PEP):

Post exposure prophylaxis should be considered in the following conditions:

• Bites by all warm blooded animals.
• Exposure to wild animals need PEP and should be treated as category III exposure.
• Rodents bites in forest area needs PEP, however exposure to domestic rodents, hare and rabbits don’t require PEP.
• Exposure to bats-At present exposure to bats does not warrant PEP as bat rabies has not been proven in India.
• Human to human transmission-people who have been exposed closely to the secretions of a patient with rabies may be given PEP as a precautionary measure.

PEP is a three pronged approach. It includes:

1. Management of animal bite wound(s): The recommended first-aid procedures include immediate thorough cleansing of the wound/s with soap and water (flushing of the wound for approximately 15 minutes) and applying an anti-septic like povidone iodine, alcohol.
2. Administering rabies immunoglobulin (RIG) (passive immunisation): In category III exposure, rabies immunoglobulin (RIG) infiltration into the depth and around the wound is advised. Wounds that require suturing should be sutured several hours after rabies immunoglobulin (RIG) infiltration into the wound. In immunocompromised individuals RIG should be administered in both category II and III exposure.

RIG is a special preparation of anti-rabies antibodies. Two types of RIG are available- Equine Rabies Immunoglobulin (ERIG) and Human Rabies Immunoglobulin (HRIG). 

RIG should be administered only once, preferably at, or as soon as possible after the initiation of PEP. If RIG is not available on first visit, use can be delayed by up to 7 days from the date of the first vaccine dose. RIG should not be given after day 7 following the first rabies vaccine dose, because an active antibody response to rabies vaccine has been already started.

3. Active immunization with ant-rabies vaccines (Rabies Vaccine): Individuals with category II or III exposures should receive rabies vaccine without delay.

Type of exposure:

Category I: Touching or feeding animals; licks on intact skin; contact of intact skin with secretions/excretions of rabid animal/human case

Category II: Nibbling of uncovered skin, minor scratches or abrasions without bleeding;

Category III: Single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, exposures due to direct contact with bats. Bites by wild animals and all bites in forest area should be treated as Category III exposure.

Site and route of administration of rabies vaccine:

Rabies vaccine can be administered by intradermal and intramuscular route. The deltoid region is the ideal site for the administration of these vaccines. anterolateral part of thigh is used for infants and small children. Gluteal region is not used for injection.

Intra dermal route (2-2-2-0-2) (Updated Thai Red Cross Regimen):

It involves total 8 doses in 4 visits. Two injections (each contains 0.1 ml of reconstituted vaccine) are given at two different sites per visit as intradermal injections on days 0, 3, 7 and 28. Day 0 is the date of administration of the first dose of rabies vaccine. Only the rabies vaccines approved by the national health authorities should be used for the intra-dermal route. 

Intramuscular route (1-1-1-1-1) (ESSEN Regimen):

It consists of five intramuscular injections of vaccine each given on 0, 3, 7, 14 and 28 days. Day 0 indicates the date of administration of the first dose of vaccine.

Tetanus and antibiotic prophylaxis: Tetanus prophylaxis is indicated as per national guidelines. A suitable course of antibiotic may be prescribed to prevent wound sepsis.

Counselling of animal/dog bite victim: The dog bite victims should be fully explained about the importance of completion of post exposure prophylaxis.

Pre-exposure prophylaxis (PrEP):

Pre exposure vaccination is provided to high-risk groups such as:

• Laboratory staff handling the infected material, clinicians and individuals attending the human rabies cases
• Veterinarians, animal handlers and dog catchers
• Wild life wardens,
• Travelers from rabies-free area to rabies endemic areas

Vaccination schedule:

Total three doses are recommended for pre-exposure prophylaxis:

• In case of IM route, one site, one full vial has to be given on days 0, 7 and booster either day 21or 28.
• In case of ID route, one site, 0.1ml is given on days 0, 7 and booster either day 21or 28.

Booster doses are indicated in high risk groups based on expert advice and monitoring their periodic anti-rabies antibody titre levels.

Management of re exposure in previously vaccinated person:

For an individual who has a repeat exposure more than three months after the last PEP or PrEP:

• Proper wound care should be done.

• Administration of RIG is not required.
• Give 02 doses, one site intradermal vaccine administration(0.1ml) on days 0 and 3 or
• Give two doses, one –site intramuscular administration of an entire vaccine vial on days 0 and 3

If a person has received pre or post exposure prophylaxis with in last three months of present bite, only adequate wound washing is required; neither vaccine nor RIG is needed.

Newer advancement in post exposure prophylaxis- WHO has recommended the use of Monoclonal Antibodies (mAb) as a cocktail containing at least two antibodies against RABV as an alternative to RIG.

National Action Plan for Dog Mediated Rabies Elimination from India by 2030 (NAPRE) is a multi-pronged strategy based on One Health Approach launched by the Ministry of Health and Family Welfare, Government of India in 2021.

References-

National Guidelines for Rabies prophylaxis, 2019, National Rabies Control Programme, MoHFW, GOI accessed from

https://ncdc.gov.in/WriteReadData/linkimages/GuidelinesforRabiesProphylaxis.pdf

https://apps.who.int/iris/bitstream/handle/10665/272371/WER9316.pdf?ua=1

Rabies can spread to humans from infected animals through bite, scratch, or lick to broken skin or the eye. Once rabies virus enters the body, it multiplies before entering through the nerve endings. It then travels to the central nervous system i.e.  spinal cord and brain. Once the virus is in the central nervous system, it spreads to the salivary glands, lungs, kidneys and other organs. While in theory it is possible for rabies to be transmitted between humans, this has so far only happened as a result of donated infected organs like cornea, kidney and lungs.