The Deadliest Virus

by Gertrud U. Rey

Rabies virus infection in mammals is nearly 100% fatal if left untreated. The signs and symptoms that precede death – agitation, anxiety, hallucinations, hydrophobia, excessive salivation, and biting – have inspired countless fictional characters and narratives. The recent death of a British woman who was scratched by a rabid stray puppy while vacationing in Morocco has brought this virus back into the spotlight, and it highlights the importance of practicing caution when interacting with feral animals.

Stray dogs are by far the largest natural reservoir for rabies virus globally, and they also pose the biggest danger to humans. Mass vaccination campaigns for domestic dogs and oral rabies vaccines distributed to wild dogs through food baits have drastically reduced the incidence of canine rabies in the U.S. Nevertheless, rabies virus still circulates in other wildlife, including in bats, raccoons, skunks, foxes, and coyotes.

Rabies virus is typically transmitted through the bite of an infected animal, but exposure can also occur through indirect contact with the animal’s saliva. Initial infection leads to viral replication in muscle cells at the site of infection. The virus then infects neurons of the peripheral nervous system and travels to the central nervous system (the brain and spinal cord), from where it spreads to other organs and the oral mucosa. The saliva of an infected animal contains high concentrations of virus, and projectile salivation – one of the possible symptoms of infection – can promote transmission to another individual. Symptoms usually begin when the virus has reached the brain, and by then it is too late to intervene. Most infected mammals die within days to weeks of exposure, depending on the distance of the infecting bite from the brain. A bite on the neck allows less time for medical intervention than a bite on the foot, because of the proximity of the infected site to the brain and the potential for faster viral transmission to the central nervous system.

Fortunately, rabies can be prevented through vaccination, which can be administered before and/or after exposure to the virus. A vaccine developed by Louis Pasteur in 1885 was initially tested on a 9-year-old boy who had been mauled by a rabid dog. The vaccine consisted of different preparations of rabbit-derived rabies virus-containing spinal cord tissue, which had been dried for various lengths of time. Over the course of ten days, the boy received a series of thirteen injections, which consisted of progressively more virulent spinal cord tissue preparations. In other words, earlier inoculations consisted of less virulent material that had been dried longer, and later inoculations consisted of more virulent material that had been dried for shorter periods of time. Although the vaccine was effective and Pasteur saved the boy’s life, it is no longer in use today because it causes severe side effects.

Today there is still misunderstanding of the treatment for possible rabies virus exposure that may lead to hesitation in getting treatment. The treatment is much more tolerable than when many adults were young. The vaccines can be delivered after exposure to people who were previously not vaccinated. These individuals receive an initial dose along with an injection of rabies immunoglobulin, a composition containing antibodies against rabies virus, followed by three more doses of vaccine over a two-week period. Post-exposure vaccination should begin as early as possible, ideally the day of the incident. The vaccine is more than 99% effective if administered within the recommended post-exposure timeline.

The rabies vaccines in current use consist of inactivated rabies virus that has been grown in embryonated chicken eggs or in cell culture (African green monkey kidney cells). Virus isolated from the infected eggs or cells is concentrated, purified, and inactivated using chemicals, irradiation, or heat. These vaccines are therefore very safe. To prevent rabies prior to exposure, typically in individuals living in areas where the virus is common, or in veterinarians or researchers who are at high risk of exposure, the vaccines are administered in three doses over the course of one month. Vaccinated individuals who are later infected should receive one additional vaccine dose after exposure.

There are only two documented cases of recovery from rabies without vaccination. Both of these individuals were subjected to induced coma to suppress brain activity and potentially slow the progression of the virus to the brain. They were then given antiviral medications and underwent intensive supportive care; which included ventilation and monitoring/managing numerous possible complications. This treatment approach is also known as the “Milwaukee Protocol,” and it is not endorsed by the scientific community or the World Health Organization because it is costly and has not met with consistent success.

An estimated 60,000 people die from rabies each year worldwide, although the number is likely higher because of inadequate reporting. Illness and mortality in infected individuals are highly preventable if vaccines are given promptly after exposure. If you come in contact with an animal that could potentially be infected with rabies virus, you should seek immediate medical attention. Even if you aren’t certain of exposure (for example, if you find a wild animal in your house and you are unaware of contact), it is better to receive the treatment for the 100% fatal rabies disease.

[The material in this blog post is also covered in Catch This Episode 72.]