Mar 05 2020

Rabies, Or “Werewolf?” “There wolf!”*

One of the most feared, most famous, and oldest known zoonotic diseases is caused by an RNA virus in the “Rhabdovirus” family and “lyssavirus” genus.  It is a short, rod shaped virus that is RNA nucleic acid inside a protein capsule, surrounded by a lipid bilayer with glycoprotein spikes coming out of it.  None of that last sentence is important, except to know that the Rabies virus, when you get right down to it, is kind of cute and cuddly looking.  Getting it is decidedly NOT cuddly.

The name “lyssavirus” is from the Greek spirit of rage or madness, “Lyssa.”  For the classical mythology dorks out there (Ooh, me!  Pick me!), she was the one that drove Herakles mad in the classic Greek stories, and she was adopted by the Romans as “Rabies.”  And honestly, that’s pretty on-the-nose as far as naming a disease goes.  The ancient Greeks and Chinese recommended cautery of a bite wound from a rabid animal as treatment (which might help, if it inactivates the infectious viruses).  The Romans took that idea and added drinking wine to it, which seems like a fine idea if you’ve just been bit by a rabid dog and someone is coming at you with a red-hot poker.  The ancient Egyptians used magic, and in Europe in the Middle Ages, prayer was suggested, as was bathing in the ocean (always nice), putting gallstones from animals in the wound (always NOT nice), and other less than sanitary treatments.  And through it all, people have known that being bitten by a “mad dog” might as well be a death sentence.

It wasn’t until Louis Pasteur’s work in the 1880’s on a vaccine that we could truly say that we could prevent rabies.  Pasteur began by working with anthrax and erispilothrix (in pigs), demonstrating that vaccinating AFTER exposure to prevent clinical disease was effective.  Since rabies has a long period between exposure and disease, it is a natural choice for “Post-Exposure Prophylaxis,” or “PEP.”  Monsieur Pasteur (say it out loud, its fantastic) began by taking saliva from rabid dogs and inoculating other dogs directly into the brain.  (All of that sounds terrible by the way.  Can you imagine your first day working at the lab when they tell you what your job is?)  By attenuating (weakening) samples, in this case from sections of spinal cords from infected rabbits, he managed to prevent infection in exposed dogs.  The first human to successfully receive PEP was a child named Joseph Meister, and the rest, as they say, is history.  Well, actually its “refinement of technique, modification and manufacturing”, but whatever.

[Interesting aside, I remember hearing that the young Joseph Meister, once he grew up, worked as a caretaker at the Pasteur Institute and committed suicide rather than allow the Nazi’s into the Institute.  Wikipedia says the last part isn’t true, but we shouldn’t let the truth get in the way of a good story.]

So now that we have the interesting stuff out of the way, time to talk about the dorky stuff.  As you might have guessed, rabies virus is transmitted from the saliva of an infected animal.  It infects mammals (animals with hair) and there are several strains, mostly defined by who the general host is – dogs, bats, wildlife like racoons, etc.  The virus itself is not very “hardy,” so it takes pretty direct contact to catch it.  That is generally in the form of a bite, but salivary exposure of mucus membranes (eyes, nose, mouth) or through cuts or scrapes on the hands is also possible.

Most of us, when asked to describe rabies, think of the scene in “To Kill a Mockingbird” where Scout’s father shoots the rabid dog on the street, or “Ol’ Yeller.”  That is the “furious form” of rabies, and most common in dogs.  There is also a “dumb form” (as in mute or silent, not like “This is the dumb form and no one likes it.”) in which the affected animal is quiet and still.  They both share the fact that the patient is neurologically abnormal and uncoordinated.  You can find videos of it online, including in people, but I already have enough trouble sleeping, so I’m not going to.  Seriously, don’t do it.

Once you are bit, the virus travels through nerves, up to the spine and from there to the brain, where it causes encephalitis, or swelling of the brain.  Before that though, it travels through the Facial nerve to the salivary glands.  Once the encephalitis begins, the swallowing reflex is paralyzed, ensuring that there are maximum amounts of infectious saliva being spread around.  The ultimate cause of death is related to the virus proliferating in the brain and causing swelling, which is a bad thing in any organ completely surrounded by bone, but especially if it is what you think with.

Alternately, once you are bit, you can get vaccinated.  Since the rabies virus travels so slowly up nerves (clinical signs can show up months or rarely even years after exposure), the body has plenty of time to produce antibodies to the vaccine and confer immunity.  Over time, we have gotten better and better at making effective vaccines, so current recommendations are much nicer than the 5-7 large volume injections that my grandfather got in his abdominal muscles as a child.  Still it is a series of injections, and speaking from personal experience (PRE-exposure vaccination, not POST-exposure), it is one of the rougher vaccines that you can get.  (I hear that smallpox is worse, from one of the veterinary technicians I work with who is in the Army reserves.)

Around the world, the World Health Organization estimates that the are just short of 60,000 (!) human deaths due to rabies every year, mostly in Africa and Asia.  The vast majority is transmitted from dogs and is in children under the age of 15.  I feel like I don’t really need to point this out, but that is bad.  We have a way to prevent disease, what we need is education that prevention is possible and to have the vaccine available where it is needed.  Globally, the goal is to eliminate human deaths from rabies by 2030, and the approach is based on what we have in the US and Europe.

In the United States, our laws for rabies vaccines vary a lot by state, but all are based on protecting HUMAN health, not pet health.  In most areas, vaccination for dogs and cats is required yearly or every 3 years, based on which vaccine is used.  In theory, this means that any dog or cat that is around people (i.e. pets…) won’t transmit rabies from wild populations to the humans they interact with, and thus serve as a buffer.

Regardless of vaccination status, any dog or cat bite to a human in Texas typically results in a 10 day quarantine of the animal, since they can be infectious for up to 10 days before showing obvious clinical signs of rabies.  Any animal that shows neurologic disease prior to release will be euthanized for definitive testing, which is done on brain tissue.  (This also results in any people exposed being given vaccines.)  I have personally been involved in many Rabies quarantine cases, to verify non-rabid status at the end, starting in veterinary school with “Duke,” a 200 pound mastiff who just wanted to cuddle and also had more diarrhea than you can possibly imagine.  Seriously, it was like something you would use to scare your children into going to accounting school.  To many owners, these laws seem overly strict, but the fact of the matter is, it is laws like mandatory vaccination that mean we have only double digit numbers of rabies-related (human) deaths in the United States on a yearly basis, instead of the 5 digit numbers in other parts of the world.

And that, folks, is rabies.  Humans have been dying from it for thousands and thousands of years, and in the last 150 years we have made it something that, at least in the rich parts of the world, most people have forgotten to be afraid of.  The moral is, keep your pets vaccinated and report all bites to Animal Control.  (And don’t pick up bats off the ground.  That’s another good way to get bit.  If one is loose in the house, just ASSUME everyone sleeping was bitten and TELL YOUR DOCTOR!  Seriously, that last part is in all caps because I’m yelling.  People die from rabies in the USA on a yearly basis because they assume they’ll feel a bite from a bat, and they were wrong.)

Eric Vance, DVM

27 Feb, 2020

*  If you’re still wondering about the subtitle, werewolves classically are a person who goes mad about a month after being attacked by a vicious dog or wolf and can themselves transmit that madness on to others.  Sound like any diseases you’ve heard of recently?

 

Schneider MC, Santos-Burgoa C. Tratamiento contra la rabia humana: un poco de su historia [Treatment of human rabies: a summary of its history]. Rev Saude Publica. 1994;28(6):454–463. doi:10.1590/s0034-89101994000600010

Boonsriroj H, Manalo DL, Kimitsuki K, et al. A pathological study of the salivary glands of rabid dogs in the Philippines. J Vet Med Sci. 2016;78(1):35–42. doi:10.1292/jvms.15-0308

https://www.who.int/rabies/epidemiology/en/

Eric Vance, DVM | Zoonotic Disease Blog

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