#1 – Rabies Virus: One of the Deadliest Infections

00:00:06: There's only a handful of people who have ever survived rabies infection after they got symptoms.

00:00:12: There's ways to treat the infection before symptoms occur, but once the symptoms are there, it's basically game over.

00:00:46: Hello and welcome to this week's episode of Virological.

00:00:50: This episode was recorded on January eleventh of two thousand twenty six.

00:00:57: in New York City.

00:00:58: And so in this episode, we're going to talk about rabies, which is one of the deadliest, if not the deadliest infectious diseases that exists.

00:01:09: Rabies is caused by different Lissa viruses, which are part of the Raptoviridae family.

00:01:16: The name Lissa viruses or Lissa virus comes from the name of a Greek spirit, Lissa.

00:01:23: just the spirit of mad rage, so that's very fitting.

00:01:29: There are several genotypes of Lysoviruses out there, but the main culprit for causing rabies is the rabies virus.

00:01:37: But again, there's other genotypes of Lysoviruses that can cause rabies as well, including, for example, the European bed Lysovirus.

00:01:47: These viruses have a single-stranded RNA genome that has a negative polarization.

00:01:54: Basically, it just means that when the virus enters the cell, the viral polymerase, the protein that transcribes and amplifies the genome, has to convert the negatively polarized genome into a positive-strand genome, and that can then basically be used to... to make proteins, to code for proteins.

00:02:18: The virus basically has the genome on the inside, then there is a nuclear protein that is associated with the genome and protects it, and this whole complex is covered or protected by a lipid envelope, and in that lipid envelope we have one spike protein, the G protein, and the lipid envelope on the inside is stabilized by a matrix protein.

00:02:43: The viruses are very interesting shape.

00:02:45: A lot of viruses are spherical or pleomorphic or filamentous like Ebola viruses for example.

00:02:54: But Lissa viruses and Raptor viruses in general look like bullets.

00:02:59: So basically it's cylindric with one point the end and they're about seventy-five nanometers in diameter and about a hundred eighty nanometers in length.

00:03:09: It's interesting this bullet shape because it makes the virus look dangerous and in fact it is a very dangerous virus.

00:03:17: Where does this virus come from?

00:03:19: Typically is prevalent in animals.

00:03:23: Main reservoirs are bats and different carnivores.

00:03:28: In Europe it's often foxes that it's found in.

00:03:31: In North America it's often raccoons, skunks, but also foxes.

00:03:36: and other carnivores as well.

00:03:38: It depends on which area of the globe you're looking at and actually the virus is very prevalent in many parts of the world.

00:03:46: It doesn't just infect wild animals, it also infect domesticated animals like cows and pigs.

00:03:53: They can also get this virus and it can also infect pets like cats and especially dogs.

00:04:00: Dogs can be a big problem.

00:04:02: It's not just that this virus is present in the wild somewhere in the forest.

00:04:08: You very often have it in urban areas, specifically in stray dogs, which are the main source of human infections.

00:04:16: You have a lot of stray dogs in urban areas in many parts of the world.

00:04:20: And a few years ago, we also had an outbreak in raccoons in Central Park in Manhattan.

00:04:25: So it's not just a problem that exists in the wild.

00:04:29: It can also be a big problem in cities.

00:04:32: And as I said, most cases globally are actually associated with bites from unvaccinated stray dogs.

00:04:39: And so the virus is transmitted via scratches or bites.

00:04:43: It's present in the saliva of infected animals.

00:04:45: And of course we'll get to that.

00:04:47: disinfected animals are often very aggressive.

00:04:50: And typically the disease that follows the infection is uniformly fatal.

00:04:56: So typically as soon as you have symptoms, you're practically dead.

00:05:01: There's only a handful of people who have ever survived rabies infection after they got symptoms.

00:05:07: We'll get to that.

00:05:09: There's ways to treat the infection before symptoms occur, but once the symptoms are there, it's basically game over.

00:05:16: So what's going to happen, how people or animals are getting infected, basically it starts with a bite or a scratch and the virus gets into that scratch or bite wound and starts to infect muscle tissue and starts to replicate in muscles and then it typically reaches nerve cells or neurons.

00:05:36: The virus is neurotropic which means it replicates in nervous tissue, in neurons.

00:05:42: and then it travels slowly through these neurons to the brain.

00:05:46: And once it reaches the brain, it causes an infection there, an encephalitis.

00:05:54: You also get inflammation in the brain and that is really what does the big damage.

00:05:58: The interesting thing here is that the incubation time, so the time from when you get infected to when symptoms occur depends on where you were bitten.

00:06:08: If you were bitten far away from your brain, let's say, on your dough, then the incubation time can be very long.

00:06:15: If you get bitten in your face or on your neck, so very close to your brain, the incubation time is pretty short.

00:06:22: Typically the incubation time is about two to three months, which is already pretty long.

00:06:26: It can be as short as a few days, but there are cases where it's actually very long, even years, which is pretty remarkable because typically you don't have these long incubation times with viruses.

00:06:40: The problem is that once the virus reaches the brain, the symptoms start and they include anxiety, often insomnia, confusion, agitation, hallucinations, hyper salivation, which is also how the virus is transmitted in animals, right?

00:06:57: There's a lot of saliva, there's a lot of virus in it, seizures, and then there's this super interesting phenomenon that people get hydrophobia.

00:07:07: So they start to be afraid of water.

00:07:10: and they actually are unable to drink water and to swallow.

00:07:13: And that's a very interesting phenomenon.

00:07:16: Another symptom can be hypersexuality and in males that can lead to involuntary ejaculations many times per day.

00:07:27: which sounds interesting but I don't think in that situation that's enjoyable anymore.

00:07:32: And typically if people are exposed or animals are exposed to light and to loud sounds that can trigger aggression as well.

00:07:41: And so the disease is pretty similar in humans and in infected carnivores.

00:07:47: and you know once the virus spreads reaches the brain It also spreads to other organs and then is also secreted in the saliva.

00:07:57: And typically, two to ten days after the symptom onset, people or animals die of the disease.

00:08:05: So what I just described is furious rabies.

00:08:08: That's about eighty percent of the cases.

00:08:11: But in twenty percent of the cases we have paralytic rabies, which comes with weakness and as the name says, paralysis.

00:08:19: and not necessarily aggression, and this is also called dump rabies.

00:08:23: Human to human spread via bites, while this is a main way of getting infected from animals and from animal to animal, for animal to animal transmissions, is not really documented for humans, but transmission via organ transplants is documented.

00:08:40: So there are cases where people were infected with rabies, they died of other reasons.

00:08:46: During the incubation time the organ was donated.

00:08:49: Somebody else got that organ and then that person died or got rabies because of that transplanted organ, that donated organ.

00:08:57: How many cases are there?

00:08:58: How many deaths are there?

00:09:00: There are global estimates and the idea is that there are about sixty thousand fatalities every year around the globe due to rabies.

00:09:08: Most of these cases occur in Africa and in Asia.

00:09:13: And as I said, a lot of them are actually associated with stray dogs.

00:09:18: In the US, we had fifteen domestic cases between two thousand fifteen and two thousand twenty four plus two imported cases.

00:09:26: So even though the virus is present throughout the US in many wild animal populations, there are actually not that many cases.

00:09:34: that might have to do with the fact that that pets, specifically dogs are usually vaccinated.

00:09:41: And because there's also treatment for rabies, basically when you're exposed, you can get both exposure prophylaxis.

00:09:50: And unfortunately, that's not available everywhere, but at least in the US that's widely available.

00:09:56: There are places that are free of rabies.

00:10:00: Western Central Europe, Japan, Australia, New Zealand and Antarctica are free of terrestrial rabies.

00:10:08: In some of these places you still have it in bats, but not in other carnivores.

00:10:14: And I believe Hawaii is also free of terrestrial and bat rabies.

00:10:21: The main ways to get infected are either bites by stray dogs or other carnivores or as I mentioned already exposure to bats.

00:10:30: This doesn't have to be vicious attack by a dog where you get injured badly and you bleed a lot.

00:10:36: This can be slight scratches.

00:10:38: There's one case, a recent case from last year where a tourist from the UK went to Morocco and then the person described it got scratched very slightly by a puppy.

00:10:51: and did not really think about it and went back home and unfortunately developed symptoms and died.

00:10:56: So again, it doesn't have to be a bad bite by an animal.

00:11:01: It can be just a light scratch and that's often enough.

00:11:07: As I mentioned in bats, We have the virus in many places, including in Europe.

00:11:14: And people who work with bats, for example, wildlife rehabbers, should be vaccinated because there is a very high risk that if you get a scratch or even touch a bat, you could get infected.

00:11:27: In the US, the CDC recommends that even if you just wake up with a bat in the same room, you should seek medical advice.

00:11:40: It's also important to say that in the US most ravis' deffs are associated with bats.

00:11:46: So depending on the region where you are, either bats are more dangerous and the more common source for ravis, some other areas it's really dogs and other wild animals.

00:12:00: The good thing about ravis is that There is a post-exposure prophylaxis that works really well and stops infections before symptoms start and that saves a lot of lives in areas where people have access to that and you're supposed to get that within twenty four hours of the exposure.

00:12:22: This was invented in eighteen eighty five already by Louis Pasteur and it's basically in a way the second vaccine that was ever invented.

00:12:33: So what Pasteur did, he was working on a lot of vaccines and a lot of therapies.

00:12:39: And so he, rabies was of course already known back then, maybe not the molecular details about the virus but the disease and that it was transmissible.

00:12:49: And so what Louis Pasteur did, he was infecting rabbits with rabies.

00:12:54: So rabbit, rabbits.

00:12:57: And he killed them and harvested their spine.

00:13:00: where he assumed the virus would be or the pathogen would be that caused the disease.

00:13:06: And then he tried the spine in the sun and that inactivated the virus.

00:13:12: And his idea was that if he would now use that to vaccinate, then the immune system would make an immune response to that pathogen, to that rabies virus in the inactivated rabies virus in the tried spine.

00:13:26: And because the incubation time was so long, maybe that would be enough to stop the disease.

00:13:33: This actually worked.

00:13:35: He proved that a number of times and in a way this is a very special case because typically we have to vaccinate before we get exposed to the better gen, before we get exposed to the virus.

00:13:48: But in this case, because the incubation time is so long, it works even after exposure, after infection that you still vaccinate, get an immune response that then stops the virus before you get symptoms.

00:14:00: And so Pasteur tested this in eighteen eighty five.

00:14:04: There was this nine year old boy Joseph Meister who had been bitten by a rapid dog.

00:14:10: And so he treated him with this post-exposure vaccination and the boy survived.

00:14:15: And then he tested this a number of more times and showed that this really worked.

00:14:20: And this was the first rabies vaccine.

00:14:22: Now at times this post-exposure prophylaxis works a little bit different.

00:14:26: First of all, you'll get the active vaccine.

00:14:29: to induce an immune response.

00:14:31: So this is basically an inactivated vaccine.

00:14:33: that's very similar to the vaccine that you would get as regular vaccine for rabies.

00:14:39: But in this case, you get it after you got bitten.

00:14:43: And this is given several times.

00:14:45: And in addition to that, you get injections with polyclonal antibodies against rabies.

00:14:50: There are preparations that immune globulin preparations, antibody preparations that are available for that.

00:14:56: And so you get these injections.

00:14:58: And so what that does is now your immune system is making a response to the vaccine.

00:15:04: But in addition to that, you also have neutralizing antibodies against rabies in your body.

00:15:10: And those two things together, typically stop the virus before it reaches the brain and before it causes symptomatic disease.

00:15:19: and that means that most people who get this post-exposure prophylaxis actually survive the infection.

00:15:27: What's worth mentioning is a case from two thousand twenty one from Illinois where a person woke up in the morning with a bat in the room actually had been injured by that bed around the neck but then unfortunately denied this post-exposure prophylaxis even though the person was informed about it and unfortunately the person died afterward.

00:15:52: I already mentioned that dogs can be vaccinated against rabies.

00:15:56: This is actually routinely done in many countries.

00:15:59: Cats are typically vaccinated against rabies too and That is very helpful because that means that the animals that surround us or pets cannot get rabies and that means that people who interact with them are not in danger of getting the infection.

00:16:14: The interesting thing is that you can vaccinate wildlife too and In Europe this has been done and this was actually how rabies was eliminated from west and central Europe and this is done using baits.

00:16:27: So you basically take vaccines, in this case it's life attenuated so weakened vaccines or viral vector vaccines and you put them inside baits and then you basically just distribute these baits in the forest and foxes for example just eat the bait and that vaccinate them.

00:16:48: And so that's super easy and it worked out super well.

00:16:52: Europe, of course, has a relatively small surface area and it's easier to do that there.

00:16:59: But a similar strategy is used in North America too.

00:17:02: And in Canada, for example, these vaccine baits are distributed in the wild by flying over forests with a plane or a helicopter and just throwing them out.

00:17:14: And that really helps also to control the infections.

00:17:18: What I should mention is, I said in the beginning that rabies, once you have symptoms, is uniformly deadly.

00:17:25: But there are a handful of people who survived this infection even after symptom onset.

00:17:32: And I think the most famous case is Gina Gisse, a Danish girl that got infected in a Milwaukee in and was already symptomatic and because there was no other choice I think her physicians came up with a plan and put her in a chemical-induced coma and she survived the infection.

00:17:55: She recovered to a certain degree but not fully which makes sense because the virus does a lot of damage to the nervous system and the hope was that this protocol would now work and this could be used for to save many lives.

00:18:12: Unfortunately it wasn't really effective and probably in this case was just luck that she made it.

00:18:18: The protocol or the chemical induced coma might have helped but unfortunately it's not the universal treatment for rabies.

00:18:26: The last thing I wanted to mention is that rabies is very old.

00:18:30: It has been a problem for humans for a very long time.

00:18:34: The disease has been described already four thousand years ago in Mesopotamia and it left an imprint on culture in general.

00:18:42: And so these symptoms, this aggressiveness and also the transmission route through bites probably inspired the myth that exists of vampires and bear walls.

00:18:52: And there's a really good book that describes that and goes into details about that by Bill Vasek and Monica Murphy.

00:19:01: That's called Rabbit.

00:19:03: cultural history of the world's most diabolic virus.

00:19:06: I really enjoyed reading that book.

00:19:08: I can highly recommend it if you want to learn more about rabies and culture and all these all these kind of legends and myths that it inspired and I'm going to leave a link to that book in the in the podcast description.

00:19:27: So that was it for today.

00:19:30: Ravis is a very interesting, very dangerous virus but in many places it's not really an imminent danger and if you get exposed to it there is something that can be done about it if you act quickly enough.

00:19:45: and get post-exposure profile access.

00:19:47: Yeah, that's it for today from Virological.

00:19:50: If you have any comments or suggestions or questions, feel free to write an email to Virological at podcastwerkstatt.com.

00:19:59: I'm going to leave the email address also in the description of the podcast.

00:20:02: Thanks for listening and we'll be back in a week.

00:20:06: Bye.

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