Thursday, July 25, 2019

Disease Post: Rabies

Welcome to the Rabies post!

Background:

Rabies is caused by a virus from the rhabdovirus family and is bullet-shaped. The virus has an envelope (a double layer of lipids like those that form our cell membranes). Rabies' genetic material is single-stranded RNA.
Transmisson electron microscopy picture of a rhabdovirus. Image from the Wellcome Collection.

Brief review: in humans, our genetic material is double-stranded DNA (deoxyribonucleic acid) that is kept in the nucleus of our cells. Kind of like the control center. When we need to make a protein, the DNA strands unwind and we have cellular proteins that make a copy of the DNA which is called RNA. Human RNA (ribonucleic acid) is always single-stranded. This strand of RNA then exits the nucleus and into the cytoplasm of the cell where other proteins translate the RNA instructions into a protein.

Since rabies contains single-stranded RNA, it can enter the cytoplasm of our cells and use our cell's machinery to make more viruses.

Rabies is a disease that is present all around the world (except in Antarctica) and has been around for thousands of years (at least). It is thought to have evolved with dogs and wolves as those are usually the most easily affected and infected animals. Most cases in humans occur in Asia and Africa, but it is regularly seen in Europe, Australia, and the Americas, too. In places where dog vaccination is common (like the US), fewer dogs are problems and bats become more likely to spread the disease. There are also vaccination programs in wild animals like foxes and raccoons via food baits, which is great, but there aren't any programs that can easily vaccinate bats, to my knowledge.

How is it spread?

Rabies is often found in wild animals like raccoons, foxes, coyotes, and bats. Domestic animals, like dogs and cats can become infected. And of course, humans. To my knowledge, rabies only infects mammals.

Rabies is spread through the saliva of an infected mammal and enters the new host through broken skin. Infections are usually caused by a bite, but can be transmitted by a scratch.

The virus enters the wound and moves into the local nerve cells or neurons. Once it is in the neurons, it can hide really well from your immune system (obviously your immune system should not normally attack your nervous system because it is so important for all of your normal functions). From the local nerves it makes its way from nerve to nerve to reach the central nervous system (your spinal cord and brain). After that, the virus travels down to the salivary glands where they can shed into the saliva and try to spread further! (Side note: viruses when they multiply are said to be "shed" or released, usually in very large numbers. This is how they enter the environment and spread to other hosts.)

One lucky thing about this virus is that it moves pretty slowly, depending on how far away it is from the central nervous system when it enters the body. For example, if you are bitten on your calf, you will have a lot more time before the virus reaches your brain than someone who is bitten on the neck. Viral load, or how many viruses enter the wound, also plays a role in how quickly it moves. If only a few viruses enter a wound, it will take longer to get to the brain. It's slow movement is important for treatment, which we will discuss later.

Symptoms:

According to the WHO, "incubation period for rabies is typically 2–3 months but may vary from 1 week to 1 year, dependent upon factors such as the location of virus entry and viral load."
Rabid dog. Image from the Wellcome Collection.

Early symptoms are pretty standard: fever, weakness, headache, and body aches. Oftentimes, people will feel tingling, prickling, and/or burning sensations as the virus spreads through the nerve cells. Hydrophobia (fear of water) and sometimes photophobia (fear of light or sensitivity to light) are later symptoms.

There are two forms of the disease: paralytic rabies and furious rabies. Furious rabies is the rabies most of us are familiar with. Furious rabies is a faster moving manifestation of the disease. It is characterized by hyperactivity, excitability, hydrophobia, agitation, confusion, and insomnia.

What is super interesting to me is the hydrophobia. The people who experience this (and not all rabies-infected people/animals do) have pain when they try to swallow. This is a viral strategy (so to speak, they aren't alive) to help spread it. The virus is present in saliva and the virus wants to get out, not be swallowed. Being swallowed defeats the virus' purpose. The virus affects an animal's ability to swallow in order to spread. Much like a cold virus will cause a person to sneeze so that virus can be spread in the air to new hosts.

In paralytic rabies, the disease is slower and not as exciting, so to speak. As the virus spreads, the person becomes paralyzed starting at the site of infection and slowly spreading until the person is completely paralyzed and falls into a coma.

No matter which form you get, the ultimate outcome is almost always death. According to the CDC, "less than 20 cases of human survival from clinical rabies have been documented" and only a few of the survivors had not had any preventative treatment (like the rabies vaccine) or treatment after they were exposed. This shows just how deadly this virus is. It has been noted throughout much of history that if a victim reaches the hydrophobia stage of disease, the outcome will be death.

Prevention and Treatment:

For those of you with dogs, you probably know that rabies vaccines are routine. Generally, they receive the vaccine as puppies and then have a booster every three years, though some areas require a booster every year. Dogs are often vaccinated against rabies, which is good because most cases of human rabies are from domestic dogs. Humans who work closely with animals, like veterinary doctors and staff, or laboratory staff that work with animals may receive the vaccine as prevention. Vaccination against rabies is not standard in humans, though.

If you get bitten or scratched by an animal that can carry rabies, what do you do? Seek care as soon as you can, especially if you do not know the animal or their health state. Cleaning the wound very well can help a person's chances. Normally, people who may have been infected receive the rabies vaccine because the virus moves slowly enough for your body to react to the vaccine and then to react to the actual virus to clear it. Your body just needs a little help from that vaccine. If someone is further along or more at-risk, they may receive rabies immunoglobulin. Immunoglobulin are antibodies specific to a disease, rabies in this case. Antibodies are produced by your immune system to help target and inactivate viruses (or bacteria, and so on). The immunoglobulin is produced in a laboratory and given to people to help their immune system combat the disease until that person's own immune system can catch up and start making its own antibodies.

Miscellaneous Information: 

If you are interested in rabies, I highly recommend the book Rabid: A Cultural History of the World's Most Diabolical Virus by Bill Wasik and Monica Murphy. My favorite parts were about how the rabies virus may have helped inspire the stories of werewolves and vampires. Both horror figures are strongly associated with wolves/dogs. Vampires are also associated with bats. Both involve biting to spread the conditions. Werewolves are often associated with rage and being unpredictable and uncontrollable. And then vampires don't do well (or can't exist at all) in sunlight--photophobia. Many classic vampires also can't cross water--hydrophobia.

The book also goes into the history of the disease, old time treatments (like drinking something containing "the hair of the dog that bit you," which is a common phrase even now) and how it has caused people throughout time to create laws to prevent the spread of rabies.

That is about it for rabies! Please let me know if you have any questions or if I have any information incorrect! Thanks for reading!

And a very special thank you to my friend, Veronica! She edited this post and helped me find things that needed more information or clarification. So thank you for your help!

Sources:
Virology: Principles and Applications by John Carter and Venetia Saunders
World Health Organization
Centers for Disease Control and Prevention
Rabid: A Cultural History of the World's Most Diabolical Virus by Bill Wasik and Monica Murphy
Medical Microbiology 6th Edition by Patrick R. Murray, Ken S. Rosenthal, and Michael A. Pfaller
WebMD Pet Vaccines: Schedules for Cats and Dogs

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