Rabies: A vaccine preventable death

Rabies a vaccine preventable death

Rabies is present all over the world and it kills thousands of people each year. It is a major health concern in poor countries or countries and islands which are isolated. In India, it is a major health concern killing at least 30 thousand people each year. These deaths can be prevented by a vaccine. Rabies disease if occurs to anyone the death is almost certain as there is no remedy or medicines for the disease. Let’s discuss rabies and rabies vaccine in detail here.

About rabies disease:

Rabies is present all over the world in all continents except Antarctica continent.

The rabies virus can infect any mammal at least in theory, and any mammal animal can transmit the rabies virus to humans. In reality on terrestrial carnivores and bats are natural reservoirs of the rabies virus. 

Humans get infected by rabies most commonly through dogs. More than 90 percent of cases of human rabies are through dog bites. The next most common are cats. 

Jackal, mongoose, Raccoons are some other animal reservoirs. Wild animals can also spread the rabies virus.

Bats are also known to cause spread of rabies virus.

Infection in mice, squirrels, and rabbits is rare and yet no case has been documented of rabies being spread to humans from these small animals.

In developed countries, the deaths because of rabies are decreasing as pets are vaccinated and humans get post-exposure prophylaxis for the bites.

Still in developing countries like India, it is a major health concern as the immunization in pets and post-exposure prophylaxis in humans too yet not accepted or not affordable to the majority of the population.

About Rabies virus: 

Rabies disease is caused by infection of rabies virus through infected animal bites or scratches and these animals can be asymptomatic carriers of the rabies virus.

Rabies virus is a bullet shaped virus.

It is negative sense, single stranded enveloped single stranded RNA virus.

Rabies virus is from family Rhabdoviridae and genus lyssavirus.

There are at least 7 genotypes of rabies virus.

Of all genotypes, type 1 is most extensively spread all across the world and causes the majority of rabies cases in humans.

Other genotypes are animal species-specific but they too can infect humans as the cross-species infection is possible.

How the Rabies virus is transmitted to human?

Rabies virus is found in large quantities in saliva of infected animals.

The animals can be asymptomatic carriers of the rabies infection.

When rabies-infected animals bite or scratch the human the virus is inoculated into the skin and there is a 35-50 percent chance that a person who hasn’t received post-exposure prophylaxis will get infected with the rabies virus.

The virus cannot infect if animal licks intact skin but can infect intact mucous membrane.

The more the bites in number and the more severe are the bites more are the chances of rabies infection transmission.

Body parts that have reach nerve innervations readily are infected if animal bites such part.

There are some reports of lab workers getting infected by route of inhalation.

Spread by route of fomites is not possible as the virus is rapidly dead when exposed to the environment.

Nosocomial spread to healthcare workers from human patients is not yet reported but healthcare workers should use barrier protective person equipment while providing care.

How does rabies affects the humans, pathogenesis?

As discussed earlier rabies virus infects humans through bite or scratch by an infected mammal animal, most commonly a dog or cat.

When such a bite or scratch occurs the virus is inoculated into the skin and subcutaneous tissue or muscles.

The virus multiplies at a very low rate at these sites that is the reason why the incubation period of rabies can belong.

After multiplying enough in number in these sites the virus then infects the motor nerves.

Rabies virus gains entry into these nerves by nicotinic acetylcholine receptors and multiple other receptors.

Once entered the nerve axons it is carried proximally by axonal carrier system rapidly.

Rabies virus crosses synapses rapidly at rate 12 hours.

Rabies virus enters the ganglion it multiplies there and cause radiculitis. 

Then infection spinal cord it goes further up proximally to reach to brain stem.

Rabies virus stays in brainstem sparing the cortex thus patient is conscious in initial phases.

Though the patient may be conscious as the rabies virus is in the brain stem there are autonomic symptoms and autonomic storms-like conditions intermittently.

Through nerves then rabies virus spreads to all other innervated organs infecting every organ.

Thus it reaches to salivery glands and cornea too through this route.

Tetrahydrobiopterin deficiency occurs in the course of the illness. This molecule is utilized for the synthesis of dopamine, norepinephrine, and serotonin.

Tetrahydrobipterin deficiency also causes decreased synthesis of nitrous oxide.

Decreased synthesis of nitrous oxide leads to autonomic symptoms.

Nitrous oxide is potent vasodilator. Its absence leads to severe spasm in basilar arteries.

As it causes autonomic imbalance cardiac arrhythmia is frequent cause of death in rabies disease.

After 5-6 days of hospitalization usually patient goes to coma.

The death invariably comes in the patient with rabies disease there no cure. The chances of dying are 100 percent.

What are the clinical manifestations of rabies disease?

Most commonly incubation period is generally 1-3 months after bites.

If the bite is near face incubation period can be as little as 5 days.

In some cases, the incubation period is longer than 6 months, indeed so long that the history of minor bite or scratch is forgotten.

Rabies disease has two types of clinical presentation mainly the furious disease and dumb rabies.

Furious rabies disease is also called as encephalitis.

Initially, there are non-specific symptoms of fever, malaise, nausea, vomiting, sore throat, and weakness.

These symptoms are often accompanied by pruritus and paraesthesia at the site of the bite which then extends to the affected limb.

Soon the manifestations of encephalitis supervene in form of agitation, decreased consciousness, and also seizures.

Hydrophobia and aerophobia are cardinal signs in humans with rabies but they are neither specific nor universal.

Phobic spasms are induced by agitation and fear produced by the mere sight of water or airflow on the face.

These spasms may lead to choking and aspirations and increased in frequency over time.

The patient invariably sleeps into a coma followed by death in 1-2 days may last up to 18-20 days in ICU setups.

The anterograde progression occurs from the brainstem and there is the dissociation of electroencephalograph and electrophysiological activities of the brain.

Dumb rabies is also called as paralytic rabies.

In this form the fever and ascending progressive motor weakness are the characteristics.

There are generally some manifestations of encephalopathy in dumb rabies form too.

Few reports of rabies survivors are known but they are only 16 cases.

Death is invariable end result in rabies.

Diagnostic tests for rabies: 

RT PCR that is a reverse transcriptase-polymerase chain reaction is the most reliable and rapid test to detect virus RNA. The virus can be detected in saliva and skin and brain tissue.

Virus can be grown in cell culture and animal after injection but these are very slow.

Rabies antigen can be detected in saliva and hairy skin, brain, by immunofluorescence.

Rabies antibodies can be detected in patients. Most of the patients die before they could develop antibodies. Serum antibodies can indicate insufficient vaccination in past. The antibodies in CSF are confirmatory of rabies disease irrespective of vaccinated or not.

CSF findings such as protein, glucose and cell number are minimally affected.

MRI findings in brain are very late and by the time patient may be dead.

What is treatment for rabies?

Unfortunately there is currently no treatment that cures rabies.

Rabies is invariably fatal no anti viral drug is effective against rabies.

Only supportive care is given when patient is hospitalized for rabies.

The care is taken in special noise free environment with life support.

But any care provided to save life fails ultimately.

The care providers should use all barrier precautions by providing the care though no transmission from patient to healthcare worker is recorded yet.

As there is no treatment and rabies is invariably fatal only option left is have to prevent it rather than treating it with futile efforts.

Post exposure prophylaxis:

· Currently rabies vaccination is not included in universal vaccination for all.

· It is recommended after the animal bite that is after the human is exposed to the animal bite so it is called as post exposure prophylaxis.

· Considering the incubation period of the rabies vaccine post exposure prophylaxis is a medical urgency.

· Depending on category of wound and whether the animal was vaccinated and also whether animals age the recommendations are different.

· Let’s see different category of exposure, category 1 is no exposure it includes feeding, touching animals and animal licks on intact skin. For this category of exposure no PEP is needed only wash the exposed skin even in case of previously unvaccinated patients.

· Category 2 exposure means nibbling of uncovered skin and minor scratches or abrasion without bleeding. For this category of exposure wound washing with immediate vaccination with Rabipur on day 0, 3, 7, 14-28 days is needed for previously unvaccinated children. For previously vaccinated children 2 doses of rabipur is given intramuscular on day 0 and 3. Also inj TT is needed.

· Category 3 exposure in trans-dermal bites or scratches, contamination of mucosal membrane or broken skin, broken skin with saliva of the animal licks, exposure due to direct contact with bats(sever exposure). For this category of exposure Inj Rabipur vaccine is given im on day 0, 3, 7 and 14-21 along with RIG that is rabies immunoglobulin for unvaccinated patients. For vaccinated patients 2 doses of Inj Rabipur is needed im on day 0 and 3. No need of RIG. Also inj TT is needed.

· RIG – Rabies immunoglobulin are antibodies against this virus that are injected in category 3 wound of dog bite that provides protection against the disease. As this is passive method the protection provided is immediate and also Rabipur vaccine is injected along with it first dose next doses to be followed subsequently along with inj TT. Rabishield is latest and human monoclonal antibodies or antibodies obtained from horse that are used for this purpose. They are very safe and devoid of reactions or very rare reactions if at all. It is given at bite site and systemically in dose 3.33 iu/kg. It is very effective in its purpose of preventing this disease.

· Rabipur is inactivated rabies virus vaccine. Inactivated means the virus in it is inactive so it cannot cause the disease but it is similar to the virus. So when the vaccine is injected to a person the immunity acts against it and so also develops the memory in the process so when exposed to the real virus it is successfully able to fight against the this virus.

· Rabipur is indicated prophylacticaly before the bite when the bite is expected like those who work in circus or zoo or those who are likely to come in contact of wild animals and also for pet breeders.

CategoryType of contactType of exposureRecommended post exposure prophylaxis
ITouching or feeding of animalsLicks on intact skinNoneNone if reliable case history is available.
IINibbling on uncovered skinMinor scratches or abrasion without bleedingMinorWound management and antirabies vaccine.
IISingle or multiple trans-dermal bites or scratches, licks on brocken skinContamination of the mucous membrane with saliva.SevereWound management + Antirabies immunoglobulin + Antirabies vaccine

Apart from rabipur, other brands of rabies virus vaccine are Rabivax s, Verorab, Rabavert, Abhayrab, Imovax.

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