#1 – Rabies Virus: One of the Deadliest Infections

There's only a handful of people who have ever survived rabies infection after they got symptoms. There's ways to treat the infection before symptoms occur, but once the symptoms are there, it's basically game over. Biological with Florian Kramer Hello and welcome to this week's episode of Biological. This episode was recorded on January 11th of 2026 in New York City. 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. Rabies is caused by different Lissa viruses, which are part of the Raptoviridae family. The name Lissa viruses or Lissa virus comes from the name of a Greek spirit, Lissa, just the spirit of mad rage, so that's very fitting. Lissa viruses, there are several genotypes of Lissa viruses out there, but the main culprit for causing rabies is the rabies virus. But again, there's other genotypes of Lissa viruses that can cause rabies as well, including for example the European bed Lissa virus. So these viruses have a single stranded RNA genome that has a negative polarization. And the basically 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 make proteins to code for proteins. The virus basically has a genome on the inside, then there's 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 cheap protein, and the lipid envelope on the inside is stabilized by a matrix protein. The viruses are very interesting shape, a lot of viruses are spherical or biomorphic or filamentous like Ebola viruses, for example. But Lissa viruses and raptor viruses in general look like bullets. So basically it's cylindrical with one point the end. And they're about 75 nanometers in diameter and about 180 nanometers in length. It's interesting this bullet shape because it makes the virus look dangerous and in fact it is a very dangerous virus. Vardust is virus come from, typically is prevalent in animals. Main reservoir are bats and different carnivores. In Europe it's often foxes that it's found in, in North America it's often raccoons, but also foxes and other carnivores as well. 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. It doesn't just infect wild animals, it also infects domesticated animals like cows and pigs. They can also get this virus and it can also infect pets like cats and especially dogs. Dogs can be a big problem. And it's not just that this virus is present in the wild somewhere in the forest. You very often have it in urban areas, specifically in stray dogs which are the main source of human infections. You have a lot of stray dogs in urban areas in many parts of the world. And a few years ago we also had an outbreak in raccoons in central parking Manhattan. So it's not just a problem that exists in the wild. It can also be a big problem in cities. And as I said, most cases globally are actually associated with bites from unvaccinated stray dogs. And so the virus is transmitted by your scratches or bites. It's present in this alive of infected animals and of course we'll get to that disinfected animals are often very aggressive. And typically the disease that follows the infection is uniformly fatal. So typically as soon as you have symptoms you're practically dead. There's, we'll get to that. There's ways to treat the infection before symptoms occur. But once the symptoms are there, it's basically game over. So what's going to happen? How are people getting, or animals are getting infected? Basically it starts with a bite or a scratch and the virus gets into that scratch or bite point and starts to infect muscle tissue and starts to replicate in muscles. And then it typically reaches nerve cells or neurons. The virus is neurotropic, which means it replicates in nervous tissue in neurons. And then it travels slowly through these neurons to the brain. And once it reaches the brain, it causes an infection there and the answer for light is you also get inflammation in the brain. That is really what does the big damage. 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. If you were bitten far away from your brain, let's say on your dough, then incubation time can be very long. If you get bitten in your face or in your neck, so very close to your brain, the incubation time is pretty short. Typically the incubation time is about two to three months, which is already pretty long. 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. The problem is that once the virus reaches the brain, the symptoms start and they include anxiety, often insomnia, confusion, agitation, hallucinations, hypercellivation, which is also how the virus is transmitted in animals, right? There's a lot of saliva with a lot of virus in it, seizures, and then there's this super interesting phenomenon that people get hydrophobia. So they start to be afraid of water and they actually are in the able to drink water and to swallow. That's very interesting phenomenon. Another symptom can be hypersexuality and in males that can lead to involuntary ejaculations many times per day, which sounds interesting, but I don't think in that situation that's enjoyable anymore. And typically if people are exposed or animals are exposed to light and to loud sounds that can trigger aggression as well. And so the disease is pretty similar in humans and infected carnivores. And once the virus spreads reaches the brain, it also spreads to other organs and then is also secreted in this saliva. And typically to do 10 days after symptom onset, people were animals die of the disease. So what I just described is furious rabies. But in 20% of the cases we have paralytic rabies, which comes with weakness and as the name says paralysis and not necessarily aggression. And this is also called dumb rabies. Human to human spread via bites. Well, this is a way of getting infected from animals and from animal to animal for animal transmissions is not really documented for humans, but transmission via organ transplants is documented. So there are cases where people were infected with rabies, the type of other reasons. You know during the incubation time the organ was donated, somebody else got that organ and then that person died or got rabies because of that transplanted organ, that donated organ. How many cases are there? How many deaths are there? There are global estimates and the ideas that are about 60,000 fatalities every year around the globe due to rabies. Most of these cases occur in Africa and in Asia. And as I said, a lot of them are actually associated with straight dogs. In the US we had 15 domestic cases between 2015 and 2024, plus two imported cases. So even though the virus is present throughout the US in many, well, the animal populations, they're actually not that many cases. That may have to do with the fact that pets, specifically dogs are usually vaccinated. And because there's also treatment for rabies, basically when you're exposed, you can get post exposure prophylaxis. And unfortunately that's not available everywhere, but at least in the US that's widely available. There are places that are free of rabies. Western Central Europe, Japan, Australia, New Zealand and Antarctica are free of the restriall rabies. In some of these places you still have it in beds, but not in other carnivores. And I believe Hawaii is also free of the restriall and bed rabies. The main ways to get infected are either by its best trade dogs or other carnivores, or as I mentioned already, exposure to beds. This doesn't have to be vicious a deck by a dog where you get injured badly and you bleed a lot. This can be slight scratches. There's one case, a recent case from last year, where tourists from the UK went to Morocco, and then the person described it got scratched very slightly by a puppy. And did not really think about it, went back home and unfortunately developed symptoms on the diet. Again, it doesn't have to be a bed bite by an animal. It can put just a light scratch and that's often enough. As I mentioned in beds, we have the virus in many places, including in Europe, and people who work with beds, for example, wildlife rehabbers should be vaccinated because there's a very high risk that if you get a scratch or even touch a bed, you could get injured. In fact, in the US, the CDC recommends that even if you just wake up with a bed in the same room, you should seek medical advice. And it's also important to say that in the US, most rabies' deaths are associated with beds. So depending on the region where you are, either a bed somewhere more dangerous and the more common source for rabies, some other areas, it's really dogs and other well-dynamals. The good thing about rabies 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 24 hours of the exposure. This was invented in 1885 already by Louis Pasteur. And it's basically in a way the second vaccine that was ever invented. So what Pasteur did, he was working on a lot of vaccines and a lot of therapies. 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. And so what Louis Pasteur did, he was infecting rabbits with rabies. So rabbit, rabbits. And he killed them and harvested their spine where his humed devirus would be, or the petrogene, would be that caused the disease. And then he tried the spine in the sun and that inactivated the virus. And his idea was that if he would now use that to vaccinate, then the immune system would make an immune response to that petrogene to that rabies virus in the inactivated rabies virus in the trides spine. And because the incubation time was so long, maybe that would be enough to stop the disease. This actually worked. 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 that is to the to the petrogene before we get exposed to the virus. And 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. And so Pasteur tested this in 1885. There was this nine-year-old boy Joseph Meister, who had been bitten by a rabbit dog. And so he treated him with this post-exposure vaccination and the boy survived. And then he tested this number of more times and showed that this really worked. And this was the first rabies vaccine. Now at times, this post-exposure prophylaxis works a little bit different. First of all, you'll get the active vaccine to induce an immune response. So this is basically an inactivated vaccine. It's very similar to the vaccine that you would get as a regular vaccine for rabies. But in this case, you get it after you got bitten. And this is given several times. And in addition to that, you get injections with polyclonal antibodies against rabies. There are preparations that immune-goblin preparations, antibody preparations that are available for that. And so you get these injections. And so what that does is now your immune system is making a response to the vaccine. But in addition to that, you also have neutralizing antibodies against rabies in your body. And those two things together typically stop the virus before it reaches the brain and before it causes symptomatic disease. And that means that most people who get this post-exposure prophylaxis actually survive the infection. What's worth mentioning is a case from 2021 from Illinois where a person woke up in the morning with a bat in the room actually had been injured by that bat around the neck but then unfortunately denied this post-exposure prophylaxis even though the person was informed about it and unfortunately the person died afterwards. I already mentioned that dogs can be vaccinated against rabies. This is actually what we've done in many countries. 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. 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. So you basically take vaccines in this case it's life-at-tenuated 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. And so that's super easy and that worked out super well. Europe of course has relatively small surface area and it's easier to do that there but the similar strategy is used in North America too. 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 and that really helps also to control the infections. What I should mention is I said in the beginning that rabies once you have symptoms is uniformly deadly but there are a handful of people who survive this infection even after symptom onset and I think the most famous case is China Gisa, a teenage girl that got infected in 2004 in Milwaukee and most 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. She recovered 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 to save many lives. Unfortunately it wasn't really effective and probably in this case was just luck that she made it. The protocol or the chemical induced coma might have helped but unfortunately it's not a universal treatment for rabies. The last thing I wanted to mention is that rabies is very old, it has been a problem for humans for a very long time. The disease has been described already 4,000 years ago in Mesopotamia and it left an imprint on culture in general and so these symptoms, this aggressiveness and also the transmission routes through bites probably inspired the myth that exists of vampires and bear wolves and there's really good book that describes that and goes into details about that by Bill Vasek and Monica Murphy. It's called "Rabbit Cultural History of the World's Most Diabolic Virus". I really enjoyed reading that book, I can highly recommend it if you want to learn more about rabies and culture and all these kind of legends and myths that it inspired and I'm going to leave a link to that book in the podcast description. So that was it for today. Rabies is a very interesting, very dangerous virus but 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 and get post-exposure prophylaxis. Yeah, that's it for today from Virulogical. If you have any comments or suggestions or questions feel free to write an email to Virulogical at botcastvirgstod.com. I'm going to leave the email. email address also in the description of the podcast. Thanks for listening and we'll be back in a week. Bye. If you're enjoying the podcast and would like to support our work, visit us on Steady. You'll find the link in the show notes and don't forget to follow and leave a review on your favorite podcast app. [Music] Podcast workstatt.