WEBVTT - Ep 121 Tularemia: Hare today, gone tomorrow 0:00:00.320 --> 0:00:05.119 Ef Mail, age forty nine, physician, began investigations of tularemia 0:00:05.280 --> 0:00:09.799 in Delta, Utah, July twenty third, nineteen nineteen. His exposure 0:00:09.840 --> 0:00:12.760 differs from the other cases to be reported in that, 0:00:12.880 --> 0:00:16.360 in addition to exposure to laboratory animals, he took blood 0:00:16.400 --> 0:00:19.880 and puss on two occasions from a human case, which 0:00:20.000 --> 0:00:24.440 terminated fatally. On the thirtieth day of his investigation, August 0:00:24.480 --> 0:00:28.560 twenty third, nineteen nineteen, Ef became ill in the late afternoon, 0:00:28.920 --> 0:00:31.760 feeling tired and weak and having a temperature of one 0:00:31.840 --> 0:00:35.640 hundred two point two degrees. His fever continued until the 0:00:35.720 --> 0:00:39.599 twenty fourth day. During the first twelve days of his illness, 0:00:39.720 --> 0:00:42.479 he packed up his laboratory equipment and animals in Utah 0:00:42.520 --> 0:00:46.800 with great difficulty and proceeded with them to Washington, d c. And, 0:00:46.920 --> 0:00:49.960 after his arrival made a futile attempt to continue work. 0:00:50.800 --> 0:00:53.680 The next fourteen days he spent in the hospital, lying 0:00:53.720 --> 0:00:57.080 on the bed, but not confined to the bed. The 0:00:57.120 --> 0:00:59.560 departure of the patient from the hospital on the twenty 0:00:59.560 --> 0:01:03.320 eighth day was attended with some forced exercise, which resulted 0:01:03.360 --> 0:01:06.399 in a secondary rise of temperature which lasted four days 0:01:06.800 --> 0:01:10.479 after which it remained normal. The second month was spent 0:01:10.600 --> 0:01:13.240 in a hotel, lying on the bed most of the time. 0:01:13.600 --> 0:01:19.040 The third month was one of slow convalescence. Throughout the illness, 0:01:19.080 --> 0:01:22.640 there was an absence of localized pain or tenderness, except 0:01:22.640 --> 0:01:25.040 that on the sixteenth day of illness, a sore throat 0:01:25.080 --> 0:01:28.560 developed on the right side. Practically the only complaint was 0:01:28.600 --> 0:01:31.800 that of languor or weakness and a desire to remain 0:01:31.959 --> 0:01:32.960 quiet on the bed. 0:02:19.760 --> 0:02:26.040 Gosh, well, yeah, long, I know, it's such a long 0:02:26.120 --> 0:02:29.880 and then if you kept reading this paper, there were like, oh, 0:02:29.880 --> 0:02:33.520 and then when it recurred or whatever, relapsed or. 0:02:33.639 --> 0:02:36.400 I don't know what what the technical term is for it, 0:02:36.639 --> 0:02:42.560 for tularimia, but yeah. But the thing that I really 0:02:42.680 --> 0:02:47.200 like about this first hand account is that the initials 0:02:47.320 --> 0:02:56.839 e F that stands for Edward Francis as a Francis. Wow. 0:02:56.960 --> 0:03:00.840 Oh poor guy. I know, I know. And it took 0:03:00.919 --> 0:03:03.640 him like a long time, apparently, according to one paper 0:03:03.680 --> 0:03:06.320 I read to realize that this was tularimia, that what 0:03:06.440 --> 0:03:10.000 he was experiencing was tularimia. But then in retrospect, it 0:03:10.120 --> 0:03:12.680 was like, oh, yeah, and then he tested his blood 0:03:12.760 --> 0:03:16.880 and the blood of several other laboratory workers and found 0:03:16.919 --> 0:03:21.320 that indeed it was your toularimia. Oh my gosh. Yeah, 0:03:21.360 --> 0:03:23.560 so that was from a paper that he and a 0:03:23.680 --> 0:03:28.640 colleague wrote in nineteen twenty two. Wow. Yeah, Hi, I'm 0:03:28.680 --> 0:03:31.960 Aaron Welsh and I'm Erin Alman Updyke and this is 0:03:32.200 --> 0:03:33.639 this podcast Will Kill You. 0:03:34.000 --> 0:03:36.320 And today we're talking about tularimia. 0:03:36.480 --> 0:03:39.880 Yeah, this is kind of a classic one, I would say. 0:03:40.720 --> 0:03:43.600 My guess is that a lot of people have never 0:03:43.640 --> 0:03:47.720 heard of it, which is interesting because I knew the 0:03:47.880 --> 0:03:50.600 name tularimia and then I had this vague association with 0:03:50.760 --> 0:03:53.840 rabbits in my head and that was it. But there 0:03:53.920 --> 0:03:56.880 is so much more I know you this. 0:03:57.320 --> 0:04:00.480 And it's such a big name in terms of public 0:04:00.640 --> 0:04:05.040 health because it is, you know, a potential agent of 0:04:05.080 --> 0:04:11.080 bioterrorism and all. So yeah, it's it's very interesting that 0:04:11.160 --> 0:04:13.640 I also knew very little about it, and I think. 0:04:13.600 --> 0:04:15.480 There's probably a lot of people who've never even heard 0:04:15.480 --> 0:04:19.680 of it. Yeah, and by the end of this episode 0:04:19.760 --> 0:04:22.440 you'll be going, how did I not know about them? 0:04:22.760 --> 0:04:25.599 I hope? So that's the goal. Yeah, Okay, but let's 0:04:25.720 --> 0:04:29.880 let's get into the episode, you know, starting with quarantin 0:04:29.880 --> 0:04:33.279 any time, quarantine anytime. What are we drinking this week? 0:04:34.720 --> 0:04:38.920 We're drinking a drople do you We are. 0:04:40.160 --> 0:04:43.840 So named because the infectious dose is like ten to 0:04:43.880 --> 0:04:52.680 fifty individual bacteria. Yeah, ten bacteria. It's what It's scary, 0:04:53.560 --> 0:04:57.080 but the recipe is not. It is a very did 0:04:57.080 --> 0:05:00.720 you like that segue? Yeah? I sure did, A very 0:05:00.720 --> 0:05:04.880 delicious and fairly simple kind of take on a mohito 0:05:05.279 --> 0:05:09.200 with watermelon and of course mint and lime, a little 0:05:09.200 --> 0:05:13.920 bit of simple syrup and some vodka. This time instead 0:05:13.920 --> 0:05:16.200 of rum right, not change it up. 0:05:16.640 --> 0:05:19.280 We'll post the full recipe for that quarantini, as well 0:05:19.320 --> 0:05:22.039 as our non alcoholic plus se Brita on our website, 0:05:22.080 --> 0:05:25.320 This podcast will kill You dot com and our social media. 0:05:26.200 --> 0:05:31.000 I liked that, thanks, And on our website you can 0:05:31.040 --> 0:05:35.360 find all kinds of things, including, but not limited, certainly 0:05:35.440 --> 0:05:37.240 because I don't have the website in front of me, 0:05:37.720 --> 0:05:40.560 to things like our sources for each and every one 0:05:40.600 --> 0:05:45.400 of our episodes, our transcripts, our merch links, links to 0:05:45.560 --> 0:05:49.279 music by Bloodmobile, links to our bookshop, dot org affiliate account, 0:05:49.320 --> 0:05:53.560 our Goodreads list, Patreon, more stuff. 0:05:53.960 --> 0:05:59.040 Check it out, wonderfully, said Erin on that note, shall 0:05:59.040 --> 0:05:59.920 we get start. 0:06:00.760 --> 0:06:34.720 Let's do it right after this break. 0:06:35.400 --> 0:06:45.080 Franciscella tolerensis is a gram negative, facultatively intracellular Coxobacillus bacterium, 0:06:45.600 --> 0:06:51.200 and the causative agent, of course, of tulaimia. It turns 0:06:51.240 --> 0:06:58.440 out that there are four subspecies of Francessella tolerensis subspecies 0:06:58.480 --> 0:07:06.920 Toulrensis subspecies whole Arctica, media asiatica, and Novacida or Novasida. 0:07:06.839 --> 0:07:11.520 That one I saw sometimes put in its own species 0:07:11.560 --> 0:07:14.600 and sometimes a subspecies, and I was like, there's probably 0:07:14.640 --> 0:07:18.360 some drama behind this, but there is some drama. 0:07:18.560 --> 0:07:20.480 And from what I can tell, it was like in 0:07:20.520 --> 0:07:22.720 two thousand and six they made it a subspecies, and 0:07:22.720 --> 0:07:25.440 then twenty ten people were like, no way, it's its 0:07:25.440 --> 0:07:28.040 own species. But then after that they're like, nana, it's 0:07:28.080 --> 0:07:31.920 it's a subspecies. So that's how we'll call it. In 0:07:31.960 --> 0:07:33.920 any case, we're not going to talk about that one 0:07:34.000 --> 0:07:39.520 very much because it's only francis Ella to lorenzis subspecies Tularensis, 0:07:39.600 --> 0:07:42.480 which is endemic to North America that is the most 0:07:42.680 --> 0:07:47.480 virulent and the cause of the most severe disease, and 0:07:47.680 --> 0:07:51.600 Holarctica is found throughout Eurasia. And in North America, and 0:07:51.760 --> 0:07:55.560 is the other major subspecies of franciscella to lorenzis that 0:07:55.600 --> 0:08:00.000 causes disease in humans. So those are the two subspect 0:08:00.480 --> 0:08:03.360 that I'm going to be focused on. They're also sometimes 0:08:03.400 --> 0:08:07.560 called type A and type B in the literature, but realistically, 0:08:07.600 --> 0:08:10.560 I'm just going to be talking about francisselo toulorensis, or 0:08:10.560 --> 0:08:12.880 I might even just say tulaimia for the rest of 0:08:12.880 --> 0:08:13.360 this section. 0:08:13.880 --> 0:08:18.000 Sounds good, great, So, like we said at the. 0:08:17.920 --> 0:08:20.400 Top, erin I kind of knew that this was going 0:08:20.440 --> 0:08:23.160 to be an interesting episode because I at least knew 0:08:23.160 --> 0:08:27.040 that Tularemia was a potential agent of bioterrorism or a 0:08:27.040 --> 0:08:32.120 potential bioweapon. But as I often do with this podcast, 0:08:32.200 --> 0:08:36.200 I really underestimated just how interesting of a bacterium this is. 0:08:36.640 --> 0:08:40.480 We're always underestimating how you would think I'm going by. Now. 0:08:40.760 --> 0:08:46.160 Yeah, well let's get into it, shall we. So, like 0:08:46.200 --> 0:08:50.719 I said off the top, this is a facultatively intracellular bacterium. 0:08:50.880 --> 0:08:53.319 What that means is that it can live both freely 0:08:53.559 --> 0:08:57.520 in the environment as well as live in and replicate 0:08:57.559 --> 0:09:02.600 within other ie hosts cells. And we'll talk a little 0:09:02.600 --> 0:09:05.440 bit more about that what sells it's replicating in in detail, 0:09:06.440 --> 0:09:10.280 But as far as hosts go, this is a bacterium 0:09:10.320 --> 0:09:15.840 that can infect hundreds of animal species, mammals and birds 0:09:16.440 --> 0:09:21.319 and many different species of invertebrates which end up serving 0:09:21.400 --> 0:09:23.040 as arthropod vectors. 0:09:23.440 --> 0:09:26.600 It was giving me Shaga disease vibes in that. 0:09:26.640 --> 0:09:31.960 Regard, Yeah, totally, totally, But even shagas disease, it's mostly 0:09:32.559 --> 0:09:36.160 really just one vector, right, I mean exactly, yeah, multiple species, 0:09:36.200 --> 0:09:37.680 but on one vector. 0:09:37.800 --> 0:09:38.000 Yeah. 0:09:38.000 --> 0:09:42.040 I Meanwhile, to lorensis is just like anytime anywhere, anything, 0:09:42.520 --> 0:09:43.800 you know, let's make it happen. 0:09:44.800 --> 0:09:47.079 So I am going to focus on what the disease 0:09:47.280 --> 0:09:51.600 tulurimia looks like in humans and therefore how the life 0:09:51.679 --> 0:09:55.120 cycle ends up spilling over into human populations, how we 0:09:55.160 --> 0:09:59.440 get infected. But this is by no means primarily a 0:09:59.480 --> 0:10:03.880 disease humans. It's fortunately quite a rare disease of humans 0:10:03.920 --> 0:10:07.559 and primarily a zoonotic disease of many different wildlife species. 0:10:08.120 --> 0:10:11.560 And like we mentioned early on France, Assella is also 0:10:12.160 --> 0:10:16.600 highly infectious. So as I talk about how it gets 0:10:16.600 --> 0:10:19.600 into us and does all of these party tricks, keep 0:10:19.600 --> 0:10:23.800 in mind that as few as ten individual bacteria can 0:10:23.840 --> 0:10:26.160 cause infection in humans. 0:10:26.920 --> 0:10:31.200 Uh, did you just describe causing disease in humans as 0:10:31.320 --> 0:10:35.520 party tricks? Yes? Is that not a party trick for 0:10:35.559 --> 0:10:40.720 a bacteria? I guess technically, Yeah, look what I can do? Yeah, 0:10:40.920 --> 0:10:42.000 look at me, mom. You know. 0:10:43.840 --> 0:10:46.600 So, let's get into this nitty gritty of how this 0:10:46.760 --> 0:10:49.560 bacterium lives its life, how it infects ourselves, and what 0:10:49.679 --> 0:10:53.439 it actually looks like when we get sick to begin 0:10:53.720 --> 0:10:56.800 the life cycle of france Assella to lorensis. It's a 0:10:56.840 --> 0:11:01.400 little bit difficult because we don't fully know ecological niche 0:11:01.440 --> 0:11:04.840 of this bacterium at all. We don't know the major 0:11:04.920 --> 0:11:10.160 natural reservoir hosts or the major environments even that are 0:11:10.200 --> 0:11:14.640 conducive to the growth of this bacterium. And keep in mind, 0:11:14.760 --> 0:11:18.360 like I said, there are several different subspecies that can 0:11:18.440 --> 0:11:22.720 all persist in the environment and live intracellularly inside of 0:11:22.760 --> 0:11:27.440 host cells. Because it's a pretty difficult bacterium to grow 0:11:27.559 --> 0:11:30.680 in the lab in culture, there is some thought that 0:11:30.800 --> 0:11:34.400 perhaps in the environment it's not just persisting on its own, 0:11:34.960 --> 0:11:39.520 maybe it's in a host like an amiba or a protozoa. 0:11:40.120 --> 0:11:45.160 Who knows it's unclear, but it can infect and be 0:11:45.240 --> 0:11:48.359 a pathogen of a whole bunch of different animal species. 0:11:48.960 --> 0:11:51.840 One paper I read said over two fifty other papers 0:11:51.840 --> 0:11:54.200 said over one hundred and ninety, So like a lot 0:11:54.240 --> 0:11:59.680 of animals, a lot including mammals and birds and arthropods. 0:11:59.480 --> 0:12:03.800 Which is amazing. I like just the different Like how 0:12:03.840 --> 0:12:09.400 diverse the animal species are right, That this spacterium can infect. 0:12:09.160 --> 0:12:12.120 All of our different cell types, different immune systems that 0:12:12.120 --> 0:12:15.920 it's having to evade, it's really impressive. Yeah, when it 0:12:15.960 --> 0:12:20.160 comes to spillover from animals into humans, the two biggest 0:12:20.160 --> 0:12:23.160 groups of animals that are commonly found infected and thought 0:12:23.200 --> 0:12:27.959 to be kind of like the culprits of spillovers are lagomorphs, 0:12:28.000 --> 0:12:31.839 so rabbits and hares, and rodents, so things like mice 0:12:31.880 --> 0:12:37.240 and rats, but also prairie dogs, voles, even aquatic rodents 0:12:37.280 --> 0:12:40.000 like muskrats and beavers and things. And I had to 0:12:40.040 --> 0:12:41.640 look up to make sure that all of these things 0:12:41.640 --> 0:12:47.599 were really rodents. What a diverse group the rodents are, really, truly, Yeah, 0:12:47.720 --> 0:12:51.360 but in many of these species, this bacterium seems to 0:12:51.400 --> 0:12:54.439 cause an acute infection and make all of these animals 0:12:54.600 --> 0:12:58.640 quite sick. So it's perhaps less likely that any of 0:12:58.760 --> 0:13:03.400 these species that we commonly find Francissella toulrensis in are 0:13:03.520 --> 0:13:08.240 actually the natural reservoir host in the environment, So we 0:13:08.320 --> 0:13:12.000 don't really know. But then how do we actually get exposed? 0:13:12.000 --> 0:13:14.360 If these are the animals getting infected, we should at 0:13:14.400 --> 0:13:18.560 least have an answer for how humans get sick, And 0:13:18.600 --> 0:13:21.560 it turns out that that's more complicated too. Of course, 0:13:21.600 --> 0:13:26.560 it is like we alluded to already, Francissella toulrensis has 0:13:26.600 --> 0:13:29.760 been shown to be transmitted not by one or two 0:13:30.600 --> 0:13:35.320 or three, but many different arthropod vectors. And by that 0:13:35.440 --> 0:13:38.600 I mean it can be transmitted by ticks a whole 0:13:38.600 --> 0:13:42.200 bunch of different species, horse flies or to bannids a 0:13:42.240 --> 0:13:45.679 bunch of different species, and mosquitoes a whole bunch of 0:13:45.720 --> 0:13:46.760 different species. 0:13:48.120 --> 0:13:49.720 Normally, when we talk about. 0:13:49.600 --> 0:13:52.120 Vector borne diseases on this podcast, I have this whole 0:13:52.120 --> 0:13:57.600 section on the life cycle of the pathogen in the vector. Right, 0:13:57.679 --> 0:14:00.880 we go over, a mosquito sucks up can staminated blood. 0:14:00.960 --> 0:14:04.440 The pathogen travels through the guts, bursts out, goes to 0:14:04.480 --> 0:14:08.480 the salivary glands. The mosquito bites another host and injects 0:14:08.520 --> 0:14:12.560 the pathogen. Blah blah blah. That's how most vector born 0:14:12.600 --> 0:14:18.240 diseases work with whatever species or few species that are 0:14:18.280 --> 0:14:20.200 able to serve as vectors. 0:14:20.920 --> 0:14:26.960 But this is not that are there different vectorial capabilities 0:14:27.040 --> 0:14:31.560 among these different vector species? Like are some mosquitoes better 0:14:31.600 --> 0:14:35.160 than others? I'm sure that there are probably differences between 0:14:35.320 --> 0:14:42.120 the two subspecies of Tularensis of human health importance. Yeah, yeah, 0:14:42.200 --> 0:14:43.560 great question. Who knows. 0:14:46.480 --> 0:14:50.880 So Different geographical regions do have different arthropods that seem 0:14:50.960 --> 0:14:54.480 to serve as the primary vector. For example, in Russia 0:14:54.560 --> 0:14:58.400 and Finland and Sweden it's mostly various species of mosquito. 0:14:59.120 --> 0:15:01.760 Throughout most the rest of Europe it's thought to be 0:15:01.880 --> 0:15:06.440 primarily tabanids, so horseflies and ticks, and in the US 0:15:06.520 --> 0:15:10.560 there are a few species of tick and tabanids that 0:15:11.120 --> 0:15:15.440 seem to be the primary vectors. It's not strictly based 0:15:15.480 --> 0:15:19.440 on just which subspecies of franciscella to Lorenzis we're talking about, 0:15:19.480 --> 0:15:23.880 since in Europe we really only see subspecies Holarctica. And 0:15:24.000 --> 0:15:27.280 North America we see both Holarctica and Toulrensis, as well 0:15:27.320 --> 0:15:28.920 as a little bit of the other ones that are 0:15:29.080 --> 0:15:34.120 less important for human infections. But what's really interesting is 0:15:34.160 --> 0:15:36.840 that when it comes to the life cycle of Francissella 0:15:36.920 --> 0:15:41.520 in these arthropods. From one paper that I read, they 0:15:41.600 --> 0:15:46.520 noted that it has never been demonstrated that this bacterium 0:15:46.720 --> 0:15:51.160 is found in the salivary glands of any arthropod, and 0:15:51.200 --> 0:15:54.960 so it's thought that maybe the spread is just mechanical. 0:15:55.160 --> 0:15:58.480 You have mouth parts becoming infected when a fly or 0:15:58.520 --> 0:16:06.240 a mosquito bites, but ticks are found infected throughout their 0:16:06.320 --> 0:16:10.320 life cycle. So if a tick gets infected as a larva, 0:16:10.960 --> 0:16:13.840 they remain infected as they become a nymph and an adult, 0:16:14.160 --> 0:16:16.880 et cetera. And we really have very little data on 0:16:17.480 --> 0:16:20.400 what is going on in these ticks, which ticks are 0:16:20.400 --> 0:16:23.920 really the best vectors, and all of that we just 0:16:24.200 --> 0:16:30.200 simply don't know. Because here's the thing, transmission doesn't stop there. 0:16:31.560 --> 0:16:36.320 Vector born transmission is one way that people can become infected, 0:16:37.000 --> 0:16:41.720 but human infection with tulurimia is also associated with waterborne 0:16:41.720 --> 0:16:46.880 transmission from contaminated water sources, and perhaps the scariest and 0:16:46.960 --> 0:16:51.720 most severe possible route of transmission is aerosolized bacteria that 0:16:51.800 --> 0:16:56.600 we inhale, and this can come from contaminated soil or grasses, 0:16:56.720 --> 0:17:00.760 or even directly from animal carcasses that were infected it themselves. 0:17:01.840 --> 0:17:05.679 This is the way that makes francissela to lorensis a 0:17:05.720 --> 0:17:10.280 potential bioweapon agent that combined with the very low infectious dose. 0:17:11.040 --> 0:17:15.320 Right, do we know how long francisla to lorensis is? 0:17:15.840 --> 0:17:15.919 Like? 0:17:15.960 --> 0:17:18.000 How durable is it in the environment? 0:17:18.320 --> 0:17:21.440 Excellent question. It's been isolated. I love when you ask 0:17:21.480 --> 0:17:23.560 a question that I actually have the answer. 0:17:23.200 --> 0:17:24.000 For it right away. 0:17:24.040 --> 0:17:28.800 It's like that rarely happens, So love it. It's been 0:17:28.840 --> 0:17:32.359 isolated from water and mud that has been stored like 0:17:32.400 --> 0:17:35.879 in laboratory conditions in a fridge, nice and cold, for 0:17:36.000 --> 0:17:38.920 up to fourteen weeks, so pretty long time. 0:17:39.560 --> 0:17:40.399 Yeah, it's been. 0:17:40.280 --> 0:17:44.919 Isolated from tap water after three months and then in 0:17:45.000 --> 0:17:46.640 like dry straw. 0:17:46.320 --> 0:17:50.440 For six months. My it's a long time. 0:17:52.240 --> 0:17:56.280 It's unclear how long it might persist under real environmental conditions, 0:17:56.320 --> 0:18:01.320 like not ideal conditions, especially in the world health organizations. 0:18:01.600 --> 0:18:04.359 Estimates of what would happen in the case of a 0:18:04.359 --> 0:18:08.879 bioterrorism attack where you're just aerosolizing dried bacteria and spreading it, 0:18:09.119 --> 0:18:11.800 then you'd probably have a lot more like UV decay, 0:18:11.920 --> 0:18:15.640 and things wouldn't probably persist quite as long, is the thought. 0:18:16.000 --> 0:18:20.280 Hmmmm, we don't know really, So that is that is 0:18:20.480 --> 0:18:24.360 definitely an interesting thing in the column of mechanical transmission 0:18:24.520 --> 0:18:27.320 for non tick arthropod vectors. 0:18:27.720 --> 0:18:32.680 Yeah, it's maybe. There's also been suggested that maybe it's 0:18:32.920 --> 0:18:37.400 water that becomes contaminated and that's a reservoir where flies 0:18:37.480 --> 0:18:41.440 and especially mosquitoes during their larval stage could become infected, 0:18:41.520 --> 0:18:42.920 so not necessarily from. 0:18:42.760 --> 0:18:43.760 Biting a host. 0:18:45.080 --> 0:18:47.280 But we really just don't know, and so there's a 0:18:47.320 --> 0:18:48.600 lot of these different theories. 0:18:49.400 --> 0:18:52.919 What route of transmission is the most common or like 0:18:53.000 --> 0:18:56.080 how does that how is that pie sliced? That's such 0:18:56.119 --> 0:18:56.879 a good question. 0:18:57.720 --> 0:19:02.720 I don't really know because surprisingly the epidemiological data that 0:19:02.800 --> 0:19:08.600 I found didn't really break out infections by different type. 0:19:08.640 --> 0:19:12.120 As we'll see, there's different symptoms that you see depending 0:19:12.119 --> 0:19:15.359 on the root of transmission. One paper that I read 0:19:15.440 --> 0:19:20.080 suggested that the form that you see after vectoral transmission, 0:19:20.440 --> 0:19:24.760 or like direct contact with a mucous membrane or like 0:19:24.800 --> 0:19:28.600 a wound, say, which would be a very similar route 0:19:28.680 --> 0:19:31.680 of transmission from like an infected animal through the skin 0:19:31.760 --> 0:19:34.800 through a break in the skin, that that might account 0:19:34.840 --> 0:19:37.720 for up to ninety percent of cases, but I didn't 0:19:37.720 --> 0:19:40.400 see that number reported in very many papers, so. 0:19:40.400 --> 0:19:42.639 I'm not sure. Interesting. 0:19:43.640 --> 0:19:49.240 Yep, Honestly, almost the only way that this is not transmitted, 0:19:49.400 --> 0:19:52.359 and this is a good thing, is directly person to person. 0:19:52.480 --> 0:19:55.840 So human to human transmission is incredibly rare, if not 0:19:56.119 --> 0:19:58.600 entirely non existent, which is very good. 0:19:59.080 --> 0:19:59.399 Yeah. 0:19:59.600 --> 0:20:04.520 Yeah, imagine it would be terrifying, absolutely terrifying. So once 0:20:04.560 --> 0:20:10.080 we are exposed again to even incredibly low bacterial lodes. 0:20:10.800 --> 0:20:17.800 Francissella tularensis exists mostly intracellularly, and it predominantly infects our macrophages, 0:20:18.000 --> 0:20:21.479 which are white blood cells. But it is capable of 0:20:21.520 --> 0:20:24.959 infecting a really wide range of cell types, both in 0:20:25.080 --> 0:20:28.320 animals as well as in humans, which kind of makes 0:20:28.359 --> 0:20:30.960 sense when we think about just how many animals it's 0:20:31.000 --> 0:20:32.960 infecting overall. It's just really versatile. 0:20:33.080 --> 0:20:35.639 Yeah, but like, how like how is it so good 0:20:35.800 --> 0:20:40.960 at doing this when then most other bacteria are not. Yeah, 0:20:41.080 --> 0:20:45.239 great question. Do you want to guess my answer? We 0:20:45.320 --> 0:20:49.600 don't know. We know some things, Okay. 0:20:51.000 --> 0:20:54.600 Part of what they do is they disrupt what's called 0:20:54.680 --> 0:20:59.120 the phagosome. And so this is when something like a macrophage, 0:20:59.200 --> 0:21:04.720 especially in gulfs, a bacterium in order to try and 0:21:05.160 --> 0:21:08.960 you know, our immune response get rid of these bacteria 0:21:09.000 --> 0:21:12.040 or other substances that are potentially pathogenic or just non 0:21:12.160 --> 0:21:16.960 self they form this structure called the phagosome. It's just 0:21:17.240 --> 0:21:21.480 like phase means eat, right. So what franciscella to lorensis 0:21:21.520 --> 0:21:24.480 is able to do is kind of like stabilize this 0:21:24.560 --> 0:21:29.680 phagosome initially prevent it from doing its normal thing of 0:21:30.119 --> 0:21:36.560 killing those bacteria, and then escape and replicate in the cytoplasm. 0:21:37.400 --> 0:21:40.720 While we don't fully understand all the mechanisms by which 0:21:40.760 --> 0:21:45.560 they do this, it's not entirely uncommon compared to other 0:21:45.640 --> 0:21:50.399 intracellular bacteria. A lot of other intracellular bacteria are able 0:21:50.440 --> 0:21:51.960 to do kind of similar things. 0:21:52.920 --> 0:21:53.840 One thing that's. 0:21:53.800 --> 0:21:58.560 Interesting and cool about Francescella to lorensis is that after 0:21:59.320 --> 0:22:02.920 they've you know, burst out of the fagosome replicated a 0:22:02.960 --> 0:22:08.240 whole bunch in the cytoplasm, they then induce apoptosis aka 0:22:08.400 --> 0:22:12.440 cell death in the cells that they've infected, which allows 0:22:12.480 --> 0:22:15.359 for them to be released go throughout the body and 0:22:15.400 --> 0:22:20.200 infect for their cells virus style exactly, and the exact 0:22:20.280 --> 0:22:24.479 mechanism by which they induce this cell death we don't know, 0:22:24.760 --> 0:22:28.520 but it does seem to be unique to francissella to lorensis, 0:22:28.880 --> 0:22:36.360 meaning it's a different method than other intracellular pathogens like Coxiella, legionella, salmonella. 0:22:35.800 --> 0:22:36.320 Et cetera. 0:22:37.240 --> 0:22:42.680 So yeah, we don't fully understand, and that actually continues 0:22:42.760 --> 0:22:46.680 in terms of we don't fully understand our immune response 0:22:46.880 --> 0:22:51.400 to this pathogen either, which then has implications for our 0:22:51.440 --> 0:22:53.440 development of things like vaccines. 0:22:54.800 --> 0:23:00.320 Dark Dawn question. Answer, maybe, if you become infected with 0:23:00.440 --> 0:23:06.399 one of these subspecies, do you then have immunity to 0:23:06.640 --> 0:23:10.000 the second subspecies or to reinfection with the first. 0:23:10.640 --> 0:23:14.000 It's a good question. I don't know the direct answer 0:23:14.119 --> 0:23:16.360 to that. What I can tell you is that the 0:23:16.440 --> 0:23:23.919 initial vaccines that were developed were based on the subspecies Holarctica. Yeah, 0:23:23.960 --> 0:23:29.080 and they provided at least some protection against the Toularensis subspecies, 0:23:29.119 --> 0:23:31.439 which is of course the more virulent subspecies and the 0:23:31.440 --> 0:23:33.679 one that people really wanted to be able to develop 0:23:33.720 --> 0:23:34.680 a vaccine against. 0:23:35.240 --> 0:23:35.760 Yeah. 0:23:36.040 --> 0:23:39.960 So yes, at least some how long does that immunity persist? 0:23:40.440 --> 0:23:40.960 Unclear? 0:23:41.560 --> 0:23:44.200 And that's been one of the big issues is trying 0:23:44.240 --> 0:23:46.520 to develop a vaccine that really does a good job 0:23:46.560 --> 0:23:54.720 of protecting against Tularensis subspecies toulorensis rather than just wlearctica. 0:23:54.800 --> 0:23:57.400 And in the past the vaccines that have been developed 0:23:57.400 --> 0:24:00.159 have been mostly based on Holarctica because it's safer to 0:24:00.200 --> 0:24:06.200 work with, because it's less pathogenic. Right, Okay, gotcha, So yeah, 0:24:06.240 --> 0:24:11.000 that's what it's doing. Let's get to what does this 0:24:11.400 --> 0:24:13.480 illness actually look like? What is tulaimia? 0:24:14.040 --> 0:24:17.000 Right? In general? 0:24:17.160 --> 0:24:20.879 After exposure, the incubation period initially is about three to 0:24:20.960 --> 0:24:29.320 five days. Symptoms often start with a fever, oh and 0:24:29.359 --> 0:24:35.760 then some nonspecific symptoms like chills, malaise, headache. But there 0:24:35.840 --> 0:24:40.119 are multiple different forms of this disease that vary based 0:24:40.160 --> 0:24:44.239 on the root of transmission. So in addition to just 0:24:44.480 --> 0:24:48.040 nonspecific symptoms, let's look at all of the different kind 0:24:48.040 --> 0:24:53.880 of types of tulaimia. The first, and what like I mentioned, 0:24:53.960 --> 0:24:57.280 is in some papers at least reported as the most common, 0:24:57.440 --> 0:25:00.679 like up to ninety percent of cases, is called the 0:25:00.840 --> 0:25:04.679 ulcero glandular form, or less commonly, there can be a 0:25:04.760 --> 0:25:07.920 glandular form without the ulcer at the beginning, What does 0:25:07.960 --> 0:25:12.200 this mean. This happens with vector borne transmission, so from 0:25:12.240 --> 0:25:14.880 a tick or a mosquito or a fly that bit 0:25:14.960 --> 0:25:18.600 you on your skin somewhere, or from direct contact with 0:25:18.640 --> 0:25:22.119 an infected animal with like a break in the skin. 0:25:23.520 --> 0:25:27.119 What you see with this form of tuluremia is at 0:25:27.200 --> 0:25:31.119 the sight of the bite or the infection an ulcer. 0:25:32.400 --> 0:25:35.520 So it usually starts as a papule like a little 0:25:35.600 --> 0:25:39.840 bump that then progresses to a pustule like a blister 0:25:40.040 --> 0:25:44.560 with pus in it that looks inflamed, maybe warm, maybe tender, 0:25:45.080 --> 0:25:48.159 and can often kind of open to form this open ulcer. 0:25:48.920 --> 0:25:51.400 It might just look like a bug bite. It might 0:25:51.480 --> 0:25:55.560 not be that gnarly looking of an ulcer, and it 0:25:55.680 --> 0:25:59.880 usually heals within a week or so. But if it does, 0:26:00.680 --> 0:26:03.400 then what that means is that this infection has spread 0:26:03.440 --> 0:26:06.480 to the lymph nodes nearest the bite, which will then 0:26:06.560 --> 0:26:10.160 start to get enlarged. That's the glandular part of the name. 0:26:11.359 --> 0:26:15.640 These lymph nodes will get swollen and tender, and if 0:26:15.680 --> 0:26:20.160 this infection becomes severe, you can have such severe swelling 0:26:20.359 --> 0:26:23.040 of these lymph nodes that they actually begin to drain 0:26:23.480 --> 0:26:26.639 pus from the lymph nodes to the skin, which is 0:26:26.920 --> 0:26:27.880 very very serious. 0:26:28.800 --> 0:26:31.159 It sounds so painful, I know. 0:26:31.720 --> 0:26:35.640 And on top of that, you're having these systemic symptoms 0:26:35.720 --> 0:26:39.080 right like just fever and chills and feeling very sick. 0:26:39.080 --> 0:26:43.880 In general, that's the ulcero glandular or in rarer cases 0:26:43.920 --> 0:26:47.200 you can have just the lymph nodes without that ulcer 0:26:47.359 --> 0:26:55.000 to begin with. Then there's the respiratory form respiratory meaning 0:26:55.320 --> 0:27:00.800 that most commonly you have inhaled and aerosolized bacteria, which 0:27:00.840 --> 0:27:04.879 is often happening from farming activities where hay or grasses 0:27:05.000 --> 0:27:08.919 or something are mode or dealt with, or from hunting 0:27:08.960 --> 0:27:12.840 activities where you're dealing with carcasses and maybe aerosolizing something 0:27:12.880 --> 0:27:17.920 from a carcass. Now, if you have a respiratory infection 0:27:18.240 --> 0:27:24.439 from Francissela Toulurance's subspecies whole Arctica, usually it's a pretty 0:27:24.560 --> 0:27:32.960 mild flu like nonspecific respiratory illness, but with subspecies tolurensis 0:27:33.560 --> 0:27:39.040 what we see are those fevers, chills, add on a cough, 0:27:40.440 --> 0:27:45.639 very severe chest pain. It can progress then to hemoptosis, 0:27:45.680 --> 0:27:49.359