WEBVTT - Ep 123 Hand, Foot, and Mouth (and Butt?) Disease 0:00:00.200 --> 0:00:02.600 On a Saturday in the late summer of twenty eighteen, 0:00:02.759 --> 0:00:04.520 I went to visit two of my best friends to 0:00:04.519 --> 0:00:06.440 have dinner and play with their little ones, who were 0:00:06.440 --> 0:00:08.600 about two and four years old at the time. My 0:00:08.600 --> 0:00:10.640 friend is a teacher and had recently gone back to 0:00:10.680 --> 0:00:13.360 school in preparation for the coming fall semester, so her 0:00:13.440 --> 0:00:15.440 kids had just started going back to daycare after a 0:00:15.440 --> 0:00:17.880 summer home with mom. My friends told me that there 0:00:17.880 --> 0:00:20.240 had been an outbreak of handfoot, and mouth disease at 0:00:20.280 --> 0:00:22.640 their daycare, and both of the little ones had gotten sick. 0:00:23.120 --> 0:00:25.200 They said it was super contagious for kids, but not 0:00:25.239 --> 0:00:28.120 to worry, as it doesn't really affect adults. I saw 0:00:28.120 --> 0:00:30.159 a couple of little red bumps near their ankles, but 0:00:30.160 --> 0:00:32.440 thought nothing of playing with the tots or kissing them 0:00:32.440 --> 0:00:36.239 good night as usual. The following Wednesday, around two am, 0:00:36.520 --> 0:00:39.360 I sat straight up in bed, shaking with violent chills 0:00:39.400 --> 0:00:41.920 and experiencing what might have been the worst sore throat 0:00:42.000 --> 0:00:44.240 of my life. I checked my temp and had a 0:00:44.240 --> 0:00:46.560 fever around a one hundred and two, so I loaded 0:00:46.560 --> 0:00:48.720 myself with niq will and stayed home sick from work 0:00:48.760 --> 0:00:49.040 for the. 0:00:48.960 --> 0:00:50.000 Next two days. 0:00:50.320 --> 0:00:52.360 By that Friday, I was starting to feel a little 0:00:52.400 --> 0:00:54.560 better and I returned to work, but that day the 0:00:54.560 --> 0:00:58.600 blister started. They were mostly painless, just empty bubbles of 0:00:58.640 --> 0:01:00.800 skin on my hands and feet that would rise to 0:01:00.840 --> 0:01:03.320 the surface and then tear off in chunks. At that point, 0:01:03.360 --> 0:01:04.920 I was pretty sure that I had a case of 0:01:04.959 --> 0:01:08.200 handfoot in mouth. Remembering that the disease was very contagious 0:01:08.200 --> 0:01:10.280 for kids, I did my best to be conscientious and 0:01:10.319 --> 0:01:12.560 avoid my coworkers with children at home at the team 0:01:12.600 --> 0:01:15.759 meeting that morning. As the days went by, my sore 0:01:15.800 --> 0:01:18.040 throat eased and I was feeling like my normal self, 0:01:18.080 --> 0:01:20.319 but the bubbly blisters on the palms of my hands 0:01:20.319 --> 0:01:23.559 and soles of my feet kept coming. A little after 0:01:23.600 --> 0:01:26.600 a month after initially feeling sick, I shared a kombucha 0:01:26.760 --> 0:01:29.000 with my mom, really thinking nothing of it as I 0:01:29.080 --> 0:01:32.280 had felt fine for weeks at that point. Three days later, however, 0:01:32.360 --> 0:01:34.680 she was hit with a terrible sore throat, in fever, 0:01:34.880 --> 0:01:37.320 and then blisters. I had given her hand foot and 0:01:37.360 --> 0:01:40.040 mouth five whole weeks after I first got sick. I 0:01:40.080 --> 0:01:42.560 was shocked, so I did a quick google and discovered 0:01:42.560 --> 0:01:45.039 that once infected, a person can be contagious for up 0:01:45.080 --> 0:01:48.320 to eleven weeks. That's almost three months a fiscal quarter. 0:01:48.560 --> 0:01:51.520 I was floored, and after that I got serious about 0:01:51.560 --> 0:01:53.760 making sure I didn't get anyone else sick. I remember 0:01:53.800 --> 0:01:55.760 putting a reminder in my phone for a date in 0:01:55.840 --> 0:01:58.120 late October that would have been around eleven weeks after 0:01:58.160 --> 0:02:00.680 my initial infection, and in the me time, I was 0:02:00.720 --> 0:02:03.320 not going to be swapping spit with anyone. I went 0:02:03.320 --> 0:02:05.120 to the lake with my girlfriends around then, and I 0:02:05.200 --> 0:02:07.280 vividly remembered that I had taken a piece of duct 0:02:07.320 --> 0:02:09.400 tape and covered the label of a jar of salsa 0:02:09.760 --> 0:02:12.239 and scrawled the word infected on it in sharpie so 0:02:12.320 --> 0:02:15.360 that I could double dip safely. One of my girlfriends 0:02:15.400 --> 0:02:17.079 remarked that she felt like if she didn't catch hand, 0:02:17.120 --> 0:02:18.480 foot and mouth for me, that we must not be 0:02:18.520 --> 0:02:21.000 that good of friends. But thankfully I didn't get anyone 0:02:21.000 --> 0:02:24.160 else sick. The blisters did stop around that eleven week mark, 0:02:24.200 --> 0:02:26.560 and the course of disease was pretty similar for my mom. 0:02:26.919 --> 0:02:29.680 I think most people, especially parents, are at least vaguely 0:02:29.680 --> 0:02:31.800 aware of the disease, but I hope that more people 0:02:31.840 --> 0:02:34.080 come to realize that adults can get sick too, And 0:02:34.120 --> 0:02:36.160 I also hope that more people become aware of just 0:02:36.240 --> 0:02:56.880 how long an infected person remains contagious. 0:02:49.639 --> 0:03:31.000 Oh my gosh, I yeah, that sounds awful, you know, 0:03:31.480 --> 0:03:36.080 Like I know about hand foot in mouth because I 0:03:36.120 --> 0:03:38.320 have a lot of friends who have had it or 0:03:38.360 --> 0:03:39.480 their kids have had it. 0:03:39.960 --> 0:03:42.880 But I guess I just like didn't really it never 0:03:42.920 --> 0:03:46.480 really registered how long it can last and how long 0:03:46.520 --> 0:03:51.360 you're infectious. Yeah, so how awful it is to just 0:03:51.360 --> 0:03:53.480 have your skin sloughing off? 0:03:53.600 --> 0:03:58.560 Like it doesn't sound fun. Let's say that. 0:03:57.840 --> 0:04:02.520 That is the understatement of the century for sure. 0:04:05.320 --> 0:04:08.480 Thank you so much, Libby for being willing to share 0:04:08.520 --> 0:04:09.400 that story with us. 0:04:09.760 --> 0:04:13.600 Yes, yeah, oh sorry you had to relive it on 0:04:13.640 --> 0:04:16.120 the podcast, but we all appreciate it. 0:04:16.360 --> 0:04:18.480 Hi. 0:04:18.839 --> 0:04:20.520 I'm Aaron Welsh. 0:04:20.000 --> 0:04:22.039 And I'm Erin Almond Updyke and. 0:04:21.920 --> 0:04:23.800 This is this podcast Will Kill You. 0:04:24.040 --> 0:04:26.000 And today we're talking about handfoot and mouth. 0:04:26.760 --> 0:04:30.080 Yeah, and we've gotten so many requests for this one. 0:04:30.520 --> 0:04:32.840 I mean, it is so common. 0:04:32.839 --> 0:04:35.480 It is, and I don't think I even realized how 0:04:35.520 --> 0:04:36.839 common it was. 0:04:37.880 --> 0:04:39.520 Do you know if you had it as a kid. 0:04:39.839 --> 0:04:41.960 You know, I was thinking about asking my mom because 0:04:42.000 --> 0:04:43.560 I have no recollection of it. 0:04:44.000 --> 0:04:48.960 Yeah, yeah, the same no idea, mom, Mom, can you 0:04:49.000 --> 0:04:49.719 text me time? 0:04:49.800 --> 0:04:50.240 He knows. 0:04:53.360 --> 0:04:55.880 Yeah, but it seems like it's everywhere. Maybe it's just 0:04:55.960 --> 0:04:59.440 like because that's the age we're at, where you just 0:04:59.560 --> 0:05:00.520 hear about you. 0:05:00.480 --> 0:05:04.080 Know, everyone's toddler's bringing it home from daycare exactly. 0:05:04.279 --> 0:05:07.919 Yeah, but there's a lot to unpack about this episode. 0:05:08.240 --> 0:05:09.520 I'm excited to dive. 0:05:09.320 --> 0:05:10.120 In me too. 0:05:10.680 --> 0:05:14.200 But first, it's quarantine any time it is, So what 0:05:14.240 --> 0:05:15.600 are we drinking this week? 0:05:15.880 --> 0:05:22.040 We're drinking out of the mouths of babes? Get it? 0:05:22.880 --> 0:05:25.279 I do get it? Yeah, you get it if you 0:05:25.320 --> 0:05:29.000 don't listeners, it's because it can be transmitted by respiratory 0:05:29.040 --> 0:05:35.800 droplets and it's mostly little kids. Okay, what is in 0:05:36.400 --> 0:05:37.560 the mouths of babes? 0:05:38.200 --> 0:05:40.280 I didn't expect this one to crack me up as 0:05:40.360 --> 0:05:42.680 much as it did, Like we were talking about it 0:05:42.720 --> 0:05:43.120 all day. 0:05:43.320 --> 0:05:44.640 Why is it so funny now? 0:05:44.760 --> 0:05:44.960 You know? 0:05:45.160 --> 0:05:49.480 Because it's the moment it is. It's a pretty delicious drink. 0:05:50.040 --> 0:05:54.960 It is gin and cherry juice and some lime juice 0:05:55.160 --> 0:05:56.279 and some tonic. 0:05:56.040 --> 0:06:01.240 Water, so refreshing. We'll post it's the full recipe for 0:06:01.320 --> 0:06:04.560 that quarantine as well. As our non alcoholic plusy Brita 0:06:04.680 --> 0:06:07.279 on our website, This podcast will Kill You dot com 0:06:07.400 --> 0:06:09.200 and our social media Do you follow us there? You 0:06:09.200 --> 0:06:10.159 should follow us there? 0:06:10.320 --> 0:06:11.520 You should follow us there? 0:06:12.480 --> 0:06:15.240 On our website This podcast will Kill You dot com? 0:06:15.800 --> 0:06:18.839 Must I go through the spiel? There's lots of good stuff. 0:06:19.040 --> 0:06:24.280 There's transcripts, and there's bookshop dot org and our goodreads 0:06:24.320 --> 0:06:28.719 list and merch and music by Bloodmobile and resources or 0:06:28.760 --> 0:06:30.960 the citations for all of our episodes. 0:06:31.480 --> 0:06:34.479 What do I normally say? References? You know, there's lots 0:06:34.520 --> 0:06:37.280 of stuff there. Check it out. It's a great time. 0:06:37.720 --> 0:06:42.840 It is. It is Wow with that. Shall we get 0:06:42.880 --> 0:06:45.040 into the biology of this disease? 0:06:45.279 --> 0:06:46.800 Let's do it, short and sweet intro. 0:06:46.960 --> 0:06:47.600 I'm loving it. 0:06:48.240 --> 0:06:50.120 Let's dive in right after this break. 0:07:22.760 --> 0:07:26.559 Handfoot and mouth disease not to be confused with hoof 0:07:26.600 --> 0:07:30.360 and mouth or foot and mouth, which is something different 0:07:30.400 --> 0:07:31.480 that affects animals. 0:07:32.000 --> 0:07:32.280 It is. 0:07:33.960 --> 0:07:35.920 The naming is confusing. 0:07:36.280 --> 0:07:40.400 Yeah, I don't know. I didn't do it, but anyways, 0:07:42.120 --> 0:07:46.920 handfoot and mouth disease is an extremely common viral infection 0:07:47.360 --> 0:07:52.160 of humans. It's caused by any one of a number 0:07:52.280 --> 0:07:56.520 of different viruses in the group enterovirus, which I think 0:07:57.080 --> 0:08:01.600 the only other enterovirus that we've covered so far is poliovirus. 0:08:01.800 --> 0:08:03.920 If I'm remembering correctly. 0:08:03.720 --> 0:08:04.520 I think that's right. 0:08:04.800 --> 0:08:08.200 Yeah, So, as usual, viruses are going to get a 0:08:08.240 --> 0:08:11.760 little confusing in this episode, but we'll do our best. 0:08:12.080 --> 0:08:12.200 So. 0:08:12.720 --> 0:08:18.880 Enteroviruses are a group of single stranded, non enveloped RNA 0:08:18.960 --> 0:08:23.480 viruses that are all in the family Picornaviridae. And this 0:08:23.560 --> 0:08:29.240 includes a lot of different zero types and subtypes of enteroviruses. 0:08:29.600 --> 0:08:32.280 And by a lot, I mean over ninety or over 0:08:32.320 --> 0:08:34.760 one hundred and a lot of these are viruses that 0:08:34.760 --> 0:08:37.920 people have probably heard of because they cause disease in humans. 0:08:38.360 --> 0:08:46.600 These include COCKSACKI viruses, polioviruses, enteroviruses, echoviruses, and enteroviruses actually 0:08:46.640 --> 0:08:50.280 also include rhinoviruses like the cause of common colds. 0:08:50.520 --> 0:08:54.480 I learned about that, but also what's an echovirus? Because 0:08:54.480 --> 0:08:56.480 I kept seeing that and I was like, this must 0:08:56.480 --> 0:08:59.440 be of public health importance in some regard, But I 0:08:59.440 --> 0:08:59.959 just don't know what. 0:09:00.360 --> 0:09:03.560 Echoviruses cause other viral illnesses. 0:09:03.600 --> 0:09:07.880 That's that's that's cause illnesses. 0:09:08.559 --> 0:09:11.880 Yeah, there's like a whole bunch of different types of 0:09:11.920 --> 0:09:16.520 illnesses that all of these enteroviruses can cause, including echoviruses 0:09:16.600 --> 0:09:20.640 and ones called par echo or pair echoviruses as well. 0:09:21.360 --> 0:09:23.920 There's a whole bunch there's it's too much, and the 0:09:24.040 --> 0:09:28.280 organization and like subtyping system has changed in recent years. 0:09:28.880 --> 0:09:33.760 So now all of the human enteroviruses in the genus 0:09:33.960 --> 0:09:41.240 enterovirus are four major species A through D. Within each 0:09:41.280 --> 0:09:43.520 of these A through D, there are a bunch of 0:09:43.559 --> 0:09:47.760 different zero types that used to be always called say, 0:09:47.920 --> 0:09:51.360 Koksaki virus A one, two, three, four, five blah blah 0:09:51.360 --> 0:09:54.960 blah blah blah, and Cooksaki virus B blah blah blah. 0:09:55.000 --> 0:09:57.000 They used to have a bunch of different names, and 0:09:57.040 --> 0:10:02.400 now they've all been grouped within these A through D species. 0:10:03.280 --> 0:10:08.160 Yeah, that was interesting because when I was looking at 0:10:08.160 --> 0:10:11.040 old papers and then new papers, and I was just 0:10:11.160 --> 0:10:15.000 trying to reconcile, like what are they talking about? 0:10:15.240 --> 0:10:18.640 How are these things related? You know, it's hard. 0:10:18.720 --> 0:10:20.440 Well, the good news is that we don't have to 0:10:20.440 --> 0:10:24.400 talk about every single enterovirus in the world's wonderful, wonderful 0:10:25.440 --> 0:10:28.320 handfoot and mouth is most commonly caused by a few 0:10:28.480 --> 0:10:32.720 of these human enteroviruses, specifically ones in enterovirus group A. 0:10:33.640 --> 0:10:38.080 These ones have names Koksaki virus A sixteen and human 0:10:38.240 --> 0:10:42.880 enterovirus seventy one, although there are a few others as well, 0:10:43.040 --> 0:10:47.120 including Koksaki virus A six which we'll talk about, and 0:10:47.320 --> 0:10:50.120 A ten, A eight, and a few others. All of 0:10:50.160 --> 0:10:53.640 these that cause handfoot in mouth tend to be in 0:10:53.720 --> 0:10:57.560 this enterovirus group A species. 0:10:57.160 --> 0:11:02.520 But there are B group species that cause or cocksacke 0:11:02.679 --> 0:11:07.080 Group B that cause handfoot in mouth occasionally soft some papers. 0:11:08.080 --> 0:11:11.320 Probably yes, not to an extent that I'm going to 0:11:11.320 --> 0:11:14.679 talk about them in any great detail. But as we'll see, 0:11:15.600 --> 0:11:18.840 what handfoot in mouth disease really is is kind of 0:11:18.960 --> 0:11:23.880 a presentation of a generalized viral illness. And so that's 0:11:24.040 --> 0:11:28.120 why you can have a variety of different virus subtypes, 0:11:28.440 --> 0:11:32.040 call them subspecies, call them serotypes, what have you, that 0:11:32.120 --> 0:11:35.400 are all slightly different. Some of them are more virulent 0:11:35.520 --> 0:11:38.360 than others, so they might have a tendency to cause 0:11:38.360 --> 0:11:41.640 more severe disease. Some of them might be less virulent 0:11:41.760 --> 0:11:45.560 than others so cause a less severe disease. But overall, 0:11:45.760 --> 0:11:48.720 there is a group of these viruses that cause very 0:11:48.760 --> 0:11:52.400 similar signs and symptoms, and that group of signs and 0:11:52.440 --> 0:11:54.920 symptoms is what we call handfoot and mouth disease. 0:11:55.160 --> 0:11:55.920 Does that make sense? 0:11:56.320 --> 0:11:59.440 Yeah, it's interesting because you know, I think that a 0:11:59.440 --> 0:12:02.679 lot of the time we think about one disease, one pathogen, 0:12:03.280 --> 0:12:07.160 but we've also covered many that don't follow that rule. 0:12:07.360 --> 0:12:07.520 Right. 0:12:07.760 --> 0:12:10.440 For some reason, I feel like this handfoot and mouth 0:12:10.480 --> 0:12:15.080 in particular, because there's such variation in those signs and 0:12:15.160 --> 0:12:18.560 symptoms associated with different viruses that I. 0:12:18.440 --> 0:12:20.880 Was like, why are we calling this all the same thing? 0:12:22.320 --> 0:12:25.080 I think that that's a really valid point, honestly, Like 0:12:25.240 --> 0:12:28.960 how we define these different viruses to begin with, and 0:12:29.320 --> 0:12:32.559 then how we define the clinical syndrome that we call 0:12:32.640 --> 0:12:35.640 a disease. It's really interesting to think about, like how 0:12:35.760 --> 0:12:40.000 which came first and yesh, maybe you'll tell us sered 0:12:40.960 --> 0:12:45.440 and also how we make those distinctions. I think it's 0:12:45.440 --> 0:12:49.640 really valid. Today, I'm going to focus on Coxsacki virus 0:12:49.640 --> 0:12:54.320 A sixteen, enterovirus seventy one, and a little bit about 0:12:54.400 --> 0:12:57.400 Koksaki virus A six because those are the three that 0:12:57.480 --> 0:13:01.760 I found the most information about as well. Say, but first, 0:13:01.800 --> 0:13:03.640 let's keep it a little bit more general, shall we 0:13:04.200 --> 0:13:09.160 Love that enteroviruses as a group are transmitted in a 0:13:09.280 --> 0:13:15.360 number of different ways. Think back to our poliovirus episode. Poliovirus, 0:13:15.400 --> 0:13:18.600 by the way, is enterovirus group C, so not very 0:13:18.600 --> 0:13:23.680 closely related to all these a group enteroviruses, but kind 0:13:23.679 --> 0:13:29.240 of closely related. So enteroviruses are transmitted by direct contact 0:13:29.640 --> 0:13:36.040 with things containing the virus, like secretions. The blisters that 0:13:36.160 --> 0:13:39.240 we'll get to talking about with handfoot and mouth disease 0:13:39.320 --> 0:13:42.600 are full of virus, so direct contact with these blisters 0:13:42.640 --> 0:13:48.800 or that fluid can transmit the disease. Respiratory droplets are 0:13:48.920 --> 0:13:53.439 a huge source of transmission for a lot of different enteroviruses, 0:13:53.520 --> 0:13:58.280 including those that cause handfoot in mouth and importantly fecal 0:13:58.559 --> 0:14:03.439 oral as with polioviivirus, And this is especially an important 0:14:03.880 --> 0:14:09.560 way of transmission for kids and between family groups. And 0:14:10.160 --> 0:14:17.959 because interoviruses are really hardy little viruses environmentally stable, they 0:14:17.960 --> 0:14:23.160 can also be transmitted via fomites so infected surfaces as well. 0:14:23.640 --> 0:14:25.520 I mean, they're hardy little beasts. 0:14:25.840 --> 0:14:27.040 You have to admire them. 0:14:27.800 --> 0:14:31.400 You can also be horrified, Yeah, of course by them too. 0:14:32.000 --> 0:14:33.040 How long are we talking? 0:14:33.280 --> 0:14:34.840 I knew you were going to ask that I have 0:14:34.920 --> 0:14:39.080 like star starsar how long, I don't know as usual, 0:14:39.440 --> 0:14:42.880 but I can tell you these are very environmentally stable viruses. 0:14:42.920 --> 0:14:45.960 They can be recovered from water sources, including ocean water. 0:14:46.400 --> 0:14:49.840 HI did my masters on some of that. They're resistant 0:14:49.880 --> 0:14:53.520 to freezing, they're resistant to most alcohol based hand sanitizers 0:14:53.520 --> 0:14:56.600 that we use. They're resistant to a lot of cleansers. Yep. 0:14:58.920 --> 0:15:02.720 So they are the point one percent. 0:15:03.000 --> 0:15:08.160 Exactly because they're because they're non enveloped viruses. They have 0:15:08.320 --> 0:15:11.440 evolved to withstand the acidity of our stomach and be 0:15:11.520 --> 0:15:16.600 transmitted fecal oral so they are very hardy. Yeah, it's great. 0:15:18.080 --> 0:15:20.880 The incubation period, so the time between when you get 0:15:20.920 --> 0:15:25.600 exposed to when symptoms develop for most enterra viruses, including 0:15:25.840 --> 0:15:28.680 the ones that cause handfoot and mouth disease, is generally 0:15:28.680 --> 0:15:32.840 between three and five days. And as we'll see, and 0:15:32.880 --> 0:15:35.320 as you heard in our first hand account, the whole 0:15:35.440 --> 0:15:38.880 course of handfoot and mouth disease usually lasts between a 0:15:38.920 --> 0:15:44.280 week and ten days. But you can continue shedding virus, 0:15:44.560 --> 0:15:50.640 especially in your stool, but also even in your throat secretions, 0:15:50.720 --> 0:15:56.680 so in your saliva, for weeks at a time. It's gnarly, 0:15:57.640 --> 0:16:02.480 and these are incredibly contigued viruses. So if we look 0:16:02.520 --> 0:16:04.840 at studies that have tried to estimate they are not 0:16:05.440 --> 0:16:09.520 which listeners likely remember, is the reproductive number, the average 0:16:09.640 --> 0:16:13.280 number of new cases that become infected by a single 0:16:13.560 --> 0:16:16.080 index case like how many people get sick from one 0:16:16.120 --> 0:16:21.360 sick person. The estimates range between two and five, which 0:16:21.600 --> 0:16:26.360 varies by virus subtype, but anything over one means you 0:16:26.480 --> 0:16:29.680 have like exponential growth and outbreak potential. 0:16:30.600 --> 0:16:34.720 And these studies did they look like within different populations, 0:16:34.720 --> 0:16:37.040 because I would imagine daycares would be on the higher 0:16:37.160 --> 0:16:38.440 end of that exactly. 0:16:38.480 --> 0:16:41.920 So these very based on population, they vary based on 0:16:42.000 --> 0:16:46.360 virus subtypes. So for enterovirus seventy one, it's estimated usually 0:16:46.760 --> 0:16:51.720 closer to five, and then for Coxsacki virus A sixteen, 0:16:51.880 --> 0:16:55.280 it's like an average of two and a half or so. 0:16:55.280 --> 0:16:58.360 So yes, and then also if you look specifically in 0:16:58.480 --> 0:17:04.040 like household transmission, in some studies, household transmission is like 0:17:04.359 --> 0:17:07.400 fifty two percent of households are going to get infected, 0:17:07.520 --> 0:17:11.040 and other studies as high as eighty five percent, especially 0:17:11.080 --> 0:17:18.160 for kids under six. So it's incredibly infectious, really easy 0:17:18.200 --> 0:17:22.600 to spread around. But what actually are the symptoms like 0:17:22.680 --> 0:17:28.840 what is handfoot and mouth disease. For the most part, 0:17:29.520 --> 0:17:34.600 handfoot and mouth disease is considered a relatively benign, self 0:17:34.680 --> 0:17:39.360 limited disease, as we heard in our first hand account. 0:17:39.600 --> 0:17:44.320 That doesn't mean it's not miserable to have, but it 0:17:44.359 --> 0:17:49.200 does tend to be self limited and not very severe. However, 0:17:49.760 --> 0:17:52.160 I am going to get into some of what the 0:17:52.200 --> 0:17:56.800 potential complications are because it's always important to talk about 0:17:56.800 --> 0:18:00.520 these complications because they're real and they do exist even 0:18:00.560 --> 0:18:06.000 when they're incredibly rare, and because it's also fascinating from 0:18:06.000 --> 0:18:09.520 a virology perspective, how something can cause such a mild 0:18:09.560 --> 0:18:14.760 illness and such a severe illness with the same virus. Yeah, 0:18:14.840 --> 0:18:17.320 So I don't want to fear monger too much in 0:18:17.359 --> 0:18:22.320 this episode because the whole group of enteroviruses we're talking 0:18:22.359 --> 0:18:25.280 about over ninety different viruses. A lot of them have 0:18:25.359 --> 0:18:29.560 the potential to cause severe disease, but the vast majority 0:18:29.600 --> 0:18:32.520 of cases of what we call handfoot in mouth are 0:18:32.840 --> 0:18:37.600 relatively low virulence. Pathogens or for whatever reason, are causing 0:18:37.760 --> 0:18:40.720 self limited disease in the vast majority of people that 0:18:40.760 --> 0:18:45.600 they infect. In fact, many people who become infected are 0:18:45.640 --> 0:18:49.639 asymptomatic entirely and are just happily shedding virus to everyone 0:18:49.640 --> 0:18:51.000 else without getting sick at all. 0:18:52.560 --> 0:18:56.399 What do we know what proportion of those are asymptomatic. 0:18:56.520 --> 0:18:58.520 It's a great question. It does depend a lot on 0:18:58.880 --> 0:19:02.600 the virus and also what age group we're talking about. 0:19:02.680 --> 0:19:06.159 Much more common in adults to be asymptomatic compared to kids. 0:19:06.920 --> 0:19:11.960 Estimates range between ten and seventy percent of people become symptomatic, 0:19:12.040 --> 0:19:16.520 which is like a huge range. But for example, with poliovirus, 0:19:16.600 --> 0:19:19.600 about seventy five percent of people are asymptomatic and only 0:19:19.640 --> 0:19:22.679 twenty five percent of people show symptoms of polio, so 0:19:22.920 --> 0:19:25.240 it's likely on the low end of people who show 0:19:25.280 --> 0:19:27.200 any symptoms whatsoever after exposure. 0:19:27.920 --> 0:19:32.440 Okay, I have a couple of like, immunity questions and 0:19:32.560 --> 0:19:33.920 infectiousness questions. 0:19:34.000 --> 0:19:35.000 Should I hold those? 0:19:35.960 --> 0:19:38.560 Meant, you can ask them now if you like, before 0:19:38.600 --> 0:19:39.680 we get into the symptoms. 0:19:39.800 --> 0:19:45.200 Okay, about the infectiousness, you said that you can shed 0:19:45.320 --> 0:19:50.560 virus for weeks and weeks after first showing symptoms. Are 0:19:50.600 --> 0:19:53.480 you infectious only once you start showing symptoms? 0:19:53.920 --> 0:19:58.400 Great question. I believe, like with many enteroviruses, you can 0:19:58.480 --> 0:20:01.920 potentially shed virus before you realize that you're symptomatics, say, 0:20:01.960 --> 0:20:05.280 before your fever starts. 0:20:05.520 --> 0:20:11.720 Spoilers, ah, And then this, I think this actually is 0:20:11.800 --> 0:20:13.119 really sort of jumping ahead. 0:20:13.160 --> 0:20:14.720 But in terms of. 0:20:14.720 --> 0:20:20.320 Reinfection or immunity, is there any sort of cross serotype 0:20:20.400 --> 0:20:27.960 or cross species immunity? And I guess maybe not enough 0:20:28.040 --> 0:20:29.280 because there's no vaccine. 0:20:29.680 --> 0:20:30.880 Spoilers, I don't. 0:20:30.720 --> 0:20:35.000 Know, a few spoilers, jumping ahead just a little. But 0:20:35.240 --> 0:20:38.560 in general, because we are talking about a whole bunch 0:20:38.600 --> 0:20:42.720 of different viruses, you can certainly get infected and have 0:20:42.880 --> 0:20:46.359 handfoot and mouth disease multiple times in your life, yay wohoo. 0:20:48.280 --> 0:20:51.280 But it's very likely that there is some degree of 0:20:51.320 --> 0:20:56.040 cross protection among different say COCKSACKI virus strains and enterovirus 0:20:56.200 --> 0:21:01.680 numbered enterovirus strains. Because a, adults are much less likely 0:21:01.760 --> 0:21:04.520 to have symptomatic handfoot and mouth disease, and it's not 0:21:04.640 --> 0:21:08.840 that that's very likely due to previous exposure. The most 0:21:08.880 --> 0:21:13.200 susceptible people for handfoot and mouth disease, both severe disease 0:21:13.320 --> 0:21:17.960 and just symptomatic disease in general are little kids, especially 0:21:18.080 --> 0:21:24.000 under age five, especially under age two. Really, So yeah, 0:21:24.680 --> 0:21:27.480 so there's likely some degree, but certainly not enough that 0:21:28.160 --> 0:21:31.239 we have like the potential for one vaccine for all 0:21:31.240 --> 0:21:31.600 of it. 0:21:31.920 --> 0:21:35.520 Right well, and also like the fact that these are 0:21:35.640 --> 0:21:36.919 RNA viruses that. 0:21:36.960 --> 0:21:40.480 Right, they're just take yeah, mutation happy. 0:21:40.240 --> 0:21:44.600 And yeah, it's fun, good stuff. Okay, So let's talk 0:21:44.600 --> 0:21:46.040 about what this looks like, shall we? 0:21:46.480 --> 0:21:48.120 Yeah, very finally there. 0:21:50.200 --> 0:21:54.400 So, most cases of handfoot and mouth happen in little kids, 0:21:54.760 --> 0:21:58.880 that's the stereotype for a reason, mostly kids underage five 0:21:59.760 --> 0:22:03.720 and and so this illness starts as many childhood illnesses do, 0:22:04.000 --> 0:22:08.560 and that is with a fever. Likely this goes hand 0:22:08.560 --> 0:22:11.479 in hand with some general malaise. The kid is probably 0:22:11.480 --> 0:22:15.439 feeling pretty crappy, and they probably have a sore throat. 0:22:15.920 --> 0:22:18.760 They're probably eating or drinking a lot less than usual 0:22:18.840 --> 0:22:22.159 because of that sore throat. And because we're talking about 0:22:22.440 --> 0:22:26.160 little kids, a lot of these kids are pre verbal, 0:22:26.600 --> 0:22:28.720 they might not be able to tell you that something 0:22:28.800 --> 0:22:31.400 is wrong, So that eating and drinking a little bit 0:22:31.480 --> 0:22:34.840 less and maybe being crankier than usual might be the 0:22:34.880 --> 0:22:38.040 first signs that something is wrong. Since they can't tell 0:22:38.080 --> 0:22:44.600 you my throat hurts, then it'll start with the rash. 0:22:44.680 --> 0:22:49.440 And this rash happens in three major places, the hands, 0:22:49.880 --> 0:22:55.440 the feet, and the butt. I'm gonna say that, actually, yeah, 0:22:55.480 --> 0:22:57.439 a lot of people call this hand, foot, mouth, and 0:22:57.520 --> 0:22:58.240 butt disease. 0:23:00.640 --> 0:23:03.480 Can we like shorten the disease name somehow? 0:23:03.560 --> 0:23:03.879 Please? 0:23:04.160 --> 0:23:06.520 We'll make you to keep adding body parts to it. 0:23:08.119 --> 0:23:11.200 And fingernail disease part of the end. 0:23:11.359 --> 0:23:15.720 But those are the main places where we tend to 0:23:15.760 --> 0:23:18.119 see this rash. It can be across the whole arms 0:23:18.119 --> 0:23:20.320 and legs, It can go onto the genitals as well. 0:23:20.960 --> 0:23:24.480 One thing that's interesting and kind of specific about handfoot, 0:23:24.520 --> 0:23:27.199 in mouth is that on the hands and feet, this 0:23:27.359 --> 0:23:31.200 rash is often found on the palms and souls. Specifically, 0:23:32.080 --> 0:23:34.320 this is a place that not a lot of other 0:23:34.440 --> 0:23:37.880 viruses or pathogens cause a rash. And I know you're 0:23:37.920 --> 0:23:41.920 going to ask, because you've asked in previous episodes, And no, 0:23:42.359 --> 0:23:44.960 I still don't know why. 0:23:46.800 --> 0:23:49.440 What are the other ones? I was hoping you weren't 0:23:49.440 --> 0:23:50.840 going to quiz me because I don't know? 0:23:51.960 --> 0:23:55.200 Syphilis? Can? I think that's probably one of the main 0:23:55.240 --> 0:23:58.800 ones that we've covered on this podcast, ricketsia or Rocky 0:23:58.800 --> 0:24:02.760 Mountain spotted fever, and yeah, rat bite fever. Can. We 0:24:02.800 --> 0:24:05.199 haven't done that there's a number of other pathogens, but 0:24:06.280 --> 0:24:10.760 it's kind of a relatively short list. Okay, so it 0:24:11.080 --> 0:24:14.120 makes people who are trying to figure out what's going 0:24:14.160 --> 0:24:17.119 on clue in that, oh, this might be handfoot and 0:24:17.200 --> 0:24:23.760 mouth disease. The rash itself usually starts as little red spots, flat, 0:24:23.960 --> 0:24:27.440 little red spots that progress into blisters that are filled 0:24:27.520 --> 0:24:31.320 with fluid. And again this fluid is full of virus. 0:24:32.880 --> 0:24:36.400 The ones on the hands and feet and but usually 0:24:36.440 --> 0:24:40.119 don't itch, They usually don't hurt that bad. But the 0:24:40.119 --> 0:24:42.840 ones that are in the mouth can be quite sore 0:24:43.040 --> 0:24:45.040 and like I said, can make it so that you 0:24:45.040 --> 0:24:47.880 don't want to eat or drink a lot, or little 0:24:47.960 --> 0:24:50.280 kids might have a lot of drooling just because of 0:24:50.320 --> 0:24:51.600 how uncomfortable they are. 0:24:52.760 --> 0:24:55.520 Why is it that the ones in the mouth, and like, 0:24:55.520 --> 0:24:56.680 why does your throat hurt? 0:24:57.320 --> 0:25:01.439 So because you're not just having like soores in that area, 0:25:01.480 --> 0:25:05.479 you're also having a lot of generalized inflammation because that 0:25:05.560 --> 0:25:08.160 infection is there in your throat essentially. 0:25:08.400 --> 0:25:12.800 Yeah, yeah, okay, yeah. 0:25:11.320 --> 0:25:14.680 So adults and older kids certainly can get hand foot 0:25:14.680 --> 0:25:16.760 in mouth like you heard in our first hand account, 0:25:17.760 --> 0:25:20.800 but it's more common in little kids, likely because of 0:25:20.840 --> 0:25:24.359 both exposure. The list of things that small children will 0:25:24.359 --> 0:25:27.200 not lick is much shorter than the list of things 0:25:27.240 --> 0:25:30.800 that they will put in their mouth, and like I mentioned, 0:25:30.800 --> 0:25:34.000 because of cross protection that you get from prior exposure. 0:25:34.040 --> 0:25:36.440 As we grow up, so by the time you're grown up, 0:25:36.520 --> 0:25:40.359 you've been exposed. Now most of the time. That is 0:25:40.440 --> 0:25:45.600 how this infection goes. It'll run its course. Kids and 0:25:45.680 --> 0:25:52.240 adults need symptomatic treatment, popsicles, rest, hydration, that sort of thing, 0:25:52.400 --> 0:25:55.760 and then people tend to recover over a pretty long 0:25:55.800 --> 0:25:59.840 course of seven to ten days. But that's not where 0:25:59.840 --> 0:26:04.560 we're going to end. That uncomplicated form of handfoot in 0:26:04.640 --> 0:26:08.320 mouth can be caused by any of the pathogens that 0:26:08.400 --> 0:26:12.760 I mentioned that cause handfoot and mouth disease. Coxsacky virus 0:26:12.840 --> 0:26:16.320 A sixteen is probably one of the most common causes 0:26:16.359 --> 0:26:21.160 of uncomplicated handfoot in mouth. Enterovirus seventy one is the 0:26:21.200 --> 0:26:25.760 other most common cause of handfoot in mouth, but enterovirus 0:26:25.760 --> 0:26:28.920 seventy one can also cause a much more severe infection. 0:26:29.480 --> 0:26:32.639 All of these can, but enterovirus is more likely to 0:26:32.680 --> 0:26:35.680 cause a more severe infection, and one of the main 0:26:35.720 --> 0:26:39.399 ways that does this is by invading the central nervous system. 0:26:41.160 --> 0:26:46.160 Many viruses, including our friend polio, which again is related 0:26:46.280 --> 0:26:51.119 to these viruses, can invade our central nervous system and 0:26:51.200 --> 0:26:56.280 cause a number of different severe neurologic manifestations. In the 0:26:56.320 --> 0:27:00.600 case of entiovirus seventy one, it's often a viral mentaingitis 0:27:00.800 --> 0:27:05.320 or encephalitis, So infection and inflammation of the brain or 0:27:05.440 --> 0:27:09.600 meninges the lining of the central nervous system, So this 0:27:09.880 --> 0:27:12.639 instead of just looking like a fever and sore throat 0:27:12.680 --> 0:27:17.600 and feeling sick, would look like a fever, stiff neck, headache, 0:27:18.400 --> 0:27:22.240 potentially loss of consciousness or behavioral change. These are very 0:27:22.280 --> 0:27:27.800 typical viral meningitis symptoms and they're very serious. In the 0:27:27.840 --> 0:27:31.840 case of entervirus seventy one, if it invades the nervous system, 0:27:32.080 --> 0:27:36.919 it tends to cause a brain stem encephalitis specifically, so 0:27:37.080 --> 0:27:39.680 our brain stem is the bottom part of our brain 0:27:39.760 --> 0:27:43.840 that controls a lot of our basic functions like breathing 0:27:44.440 --> 0:27:48.160 and our heart being able to function properly. So when 0:27:48.200 --> 0:27:51.040 you have inflammation of this part of our brain, what 0:27:51.160 --> 0:27:53.480 we can see is then issues in the way that 0:27:53.560 --> 0:27:57.800 our heart and lungs are able to actually function. So 0:27:57.920 --> 0:28:00.399 this can lead to a lot of a debas or 0:28:00.440 --> 0:28:03.560 swelling and fluid in the lungs because they're not working 0:28:03.600 --> 0:28:07.720 the way that they're supposed to neurologically, and that actually 0:28:07.760 --> 0:28:12.760 can lead to death in severe neurologic terovirus seventy one infections, 0:28:14.480 --> 0:28:18.520 this virus can also affect the spinal cord and cause 0:28:18.600 --> 0:28:23.440 an acute flacid paralysis, which really looks a lot like poliomyelitis. 0:28:24.280 --> 0:28:27.800 So this is an infection and inflammation of the sheath 0:28:28.040 --> 0:28:31.760 around our nerves that then cause our nerves to our 0:28:31.840 --> 0:28:35.359 muscles to not be able to function and a flacid paralysis. 0:28:37.440 --> 0:28:41.160 I want to stress that these are not common manifestations 0:28:41.680 --> 0:28:44.800 of enterovirus seventy one of hand foot and mouth disease, 0:28:45.480 --> 0:28:49.920 but they are really important because these are potentially deadly 0:28:50.080 --> 0:28:54.600 infections and in some cases can result in lifelong complications 0:28:54.640 --> 0:28:59.640 from a severe neurologic infection. To put some numbers into 0:28:59.680 --> 0:29:03.920 pive though, in some of the larger enterovirus outbreaks that 0:29:03.960 --> 0:29:07.280 we've seen, for example, in Malaysia in the late nineties, 0:29:07.640 --> 0:29:10.600 there was over two thy six hundred cases of handfoot 0:29:10.640 --> 0:29:14.280 in mouth disease that were reported and thirty four deaths, 0:29:14.600 --> 0:29:19.040 so a very small number comparatively, but still a number. 0:29:20.120 --> 0:29:23.320 In Taiwan in the late nineties and estimated one point 0:29:23.360 --> 0:29:26.880 five million people were infected with handfoot in mouth disease, 0:29:27.400 --> 0:29:30.120 four hundred and five admitted to the hospital with some 0:29:30.320 --> 0:29:34.360 type of neurologic complications, and seventy eight children died in 0:29:34.400 --> 0:29:35.360 that big outbreak. 0:29:35.880 --> 0:29:36.320 Geez. 0:29:36.760 --> 0:29:39.920 Yeah. And then in two thousand and eight in Madeland China, 0:29:40.120 --> 0:29:43.000 just under five hundred thousand cases and one hundred and 0:29:43.000 --> 0:29:45.640 twenty six deaths in children were reported due to handfoot 0:29:45.640 --> 0:29:48.560 in mouth disease, and the vast majority of those cases 0:29:48.800 --> 0:29:52.320 were likely or confirmed to be enterovirus seventy one, which 0:29:52.360 --> 0:29:56.160 is really common in Asia but is present around the world. 0:29:56.960 --> 0:30:02.200 How like, for a typical outbreak, or like a suspected 0:30:02.200 --> 0:30:07.400 outbreak of handfoot in mouth, how often is virus testing 0:30:07.960 --> 0:30:10.760 done to know which strain it is. 0:30:11.240 --> 0:30:14.680 It's a really good question. It's going to vary so 0:30:14.880 --> 0:30:17.280 much by place that I don't have a great answer 0:30:17.320 --> 0:30:25.120 to that. Yeah. Here in the US, the vast majority 0:30:25.240 --> 0:30:28.960 of people who get handfoot and mouth disease probably never 0:30:29.000 --> 0:30:32.000 even go to a doctor, so we might not even 0:30:32.000 --> 0:30:34.840 know that they had it. If they do go to 0:30:34.880 --> 0:30:38.640 a doctor, it's probably not the emergency room, so they 0:30:38.720 --> 0:30:41.680 probably don't even have the capacity to do that viral testing. 0:30:41.720 --> 0:30:47.120 Maybe they do, maybe they don't, but if they're not 0:30:47.400 --> 0:30:51.720 that sick, then they're likely to not get testing anyways. 0:30:52.480 --> 0:30:55.800 So it's really very likely that it's only the severe cases, 0:30:55.960 --> 0:30:58.960 the ones who are very sick, who have these maybe 0:30:59.000 --> 0:31:02.960 neurologic signs or signs of just a more severe infection, 0:31:03.680 --> 0:31:06.760 that end up in emergency rooms that end up getting testing, 0:31:07.440 --> 0:31:11.160 and that testing would probably need like multiple rounds of 0:31:11.200 --> 0:31:14.480 testing to be able to determine exactly which strain of 0:31:14.520 --> 0:31:18.040 an enterovirus or which species of an enterovirus we're dealing with. 0:31:18.800 --> 0:31:23.080 Right, Yeah, And so it's possible. 0:31:24.240 --> 0:31:30.280 Is it possible, I'll rephrase that, to have multiple circulating 0:31:30.840 --> 0:31:34.160 viruses that are the cause or contributing to the outbreak 0:31:34.680 --> 0:31:35.440 at the same time? 0:31:35.840 --> 0:31:39.880 For sure? Yeah? Yeah, yeah, because these all pretty much 0:31:39.960 --> 0:31:43.840 exist across the globe. There's of course geographic variation in 0:31:43.880 --> 0:31:48.160 what's most common, but all of these enteroviruses that can 0:31:48.200 --> 0:31:52.440 cause handfoot in mouth are pretty widespread and becoming more 0:31:52.520 --> 0:31:54.120 so because of globalization. 0:31:54.680 --> 0:31:57.480 So how likely is it that if you repeatedly get 0:31:57.720 --> 0:31:59.360 hand foot in mouth or you get hand foot in 0:31:59.400 --> 0:32:02.000 mouth multiple times? How likely is it that those are, 0:32:02.400 --> 0:32:05.520 you know, Cocksacki virus A sixteen and then a six 0:32:05.720 --> 0:32:08.080 or just a mutated version of A sixteen. 0:32:08.720 --> 0:32:13.760 I think that's an impossible question to answer for fun 0:32:13.800 --> 0:32:22.400 one though. I'm not even done though, because there's one 0:32:22.440 --> 0:32:25.720 more specific virus that I want to shout out. And 0:32:25.760 --> 0:32:28.960 when I'm shouting out these specific ones, do know that 0:32:29.680 --> 0:32:32.800 any and all of these viruses that cause the disease 0:32:33.440 --> 0:32:37.000 or the clinical syndrome that we call handfoot in mouth disease, 0:32:38.120 --> 0:32:41.640 Any of them can cause severe infection or can cause 0:32:41.960 --> 0:32:45.400 mild infection. It's just that some of them are have 0:32:45.480 --> 0:32:48.080 been shown so far to be more likely to cause 0:32:48.120 --> 0:32:51.840 a severe infection than others. So enterovirus seventy one is 0:32:51.960 --> 0:32:55.720 more likely to cause neurologic manifestations if there are going 0:32:55.760 --> 0:33:00.080 to be neurologic manifestations. Cocksacki virus A sixteen more like 0:33:00.240 --> 0:33:04.560 to just cause uncomplicated, regular run of the mill handfoot 0:33:04.560 --> 0:33:09.720 in mouth. And then there is cocksacky A six This 0:33:09.800 --> 0:33:14.040 is yet another strain of Koksaki virus which really recently 0:33:14.160 --> 0:33:16.920 has been found to cause handfoot in mouth disease, like 0:33:16.960 --> 0:33:20.520 two thousand and eight was the first big outbreak. Correct 0:33:20.560 --> 0:33:21.960 me historically if I'm wrong. 0:33:22.600 --> 0:33:25.400 I thought, hold on, I'm looking at my notes, but 0:33:25.480 --> 0:33:28.960 I swear I have a paper from nineteen sixty. 0:33:29.440 --> 0:33:31.040 I thought that's entrovirus seventy one. 0:33:33.560 --> 0:33:34.280 A five. 0:33:35.320 --> 0:33:37.480 Oh, I don't even talk about A five. 0:33:38.000 --> 0:33:41.080 Yeah, I mean I mentioned it briefly, but that's it. 0:33:41.120 --> 0:33:44.560 Must have come and gone. It had its time or not. 0:33:44.720 --> 0:33:47.640 Who knows, I guess well. 0:33:47.640 --> 0:33:51.400 In any case, this particular virus seems to be more 0:33:51.560 --> 0:33:56.400 likely to cause both severe disease in the form of 0:33:56.480 --> 0:34:01.840 severe skin manifestations and more likely to cause symptoms and 0:34:01.920 --> 0:34:06.480 severe disease in adults. So remember, most of the time, 0:34:06.840 --> 0:34:10.000 adults don't end up getting symptoms even if they become 0:34:10.040 --> 0:34:14.680 infected and are shedding these various viruses, but Koksaki virus 0:34:14.680 --> 0:34:20.080 A six seems to be an exception. This virus has 0:34:20.520 --> 0:34:23.560 been making its way across the globe and is now 0:34:23.640 --> 0:34:29.600 present pretty much worldwide, and cases associated with this particular 0:34:29.760 --> 0:34:35.719 virus have caused extensive cutaneous or skin variants, some of 0:34:35.760 --> 0:34:41.239 which were not previously seen in Koksaki virus infections. So 0:34:41.320 --> 0:34:47.040 these include things like very very large blisters like deep 0:34:47.200 --> 0:34:54.440 blistering eruptions, they include much more extensive involvement of the skin, 0:34:54.600 --> 0:34:58.840 so not just hands, feet, but but across the entire arms, 0:34:59.360 --> 0:35:03.759 especially in areas that you tend to get eggzema, so 0:35:03.840 --> 0:35:07.040 like in your elbow folds and things like that. This 0:35:07.080 --> 0:35:11.560 is called egzima cocksackium. It has also been shown to 0:35:11.640 --> 0:35:18.680 cause these lesions that look like very very thick blisters, 0:35:19.160 --> 0:35:22.560 kind of crustier looking than a normal blister, not quite 0:35:22.600 --> 0:35:27.320 a fluid filled situation, but a really widespread, very itchy rash, 0:35:27.440 --> 0:35:32.520 which normally a handfoot in mouth disease rash is not itchy. 0:35:32.600 --> 0:35:36.360 It also can cause what's called a delayed on a 0:35:36.440 --> 0:35:41.640 comadsis if I'm saying that correctly, aka, your nails fall off. 0:35:43.960 --> 0:35:47.120 It sounds like a much lovelier way of saying, and 0:35:47.160 --> 0:35:48.440 then your fingernails fall off. 0:35:48.440 --> 0:35:50.919 Your fingernails fall and toenails. 0:35:50.800 --> 0:35:54.040 Toenails potentially too. This happens from a rest of the 0:35:54.160 --> 0:35:57.680 nail matrix growth plate, so it stops your nails growing 0:35:57.719 --> 0:36:00.520 for a little while, and then a few weeks months 0:36:00.560 --> 0:36:03.399 after you get the infected, that nail just falls off. 0:36:03.880 --> 0:36:09.160 It'll go back and this one is really horrible. Image 0:36:09.840 --> 0:36:14.160 palm o planter desquamation, aka the skin of your hands 0:36:14.160 --> 0:36:17.279 and feet just fluff off, the same way that we 0:36:17.360 --> 0:36:20.040 might see in a fungal infection or in like a 0:36:20.160 --> 0:36:22.480 masderation if a foot has been in like a wet 0:36:22.520 --> 0:36:28.160 boot for too many days. Sorry your face, Oh yeah, yeah, 0:36:28.239 --> 0:36:32.040 I mean just the word sluff alone is enough to 0:36:32.440 --> 0:36:37.799 just it's bad. Yeah, And this is not only in adults. 0:36:38.640 --> 0:36:41.480 Cocksacuars A six has been found to cause these more 0:36:41.520 --> 0:36:48.160 severe skin manifestations in both kids and adults. Why great question, me, 0:36:48.560 --> 0:36:55.200 I don't know. Presumably it's something about the difference in 0:36:55.239 --> 0:36:58.760 these virulence factors, but we don't know the specific ones, 0:36:58.880 --> 0:37:03.440 and the same is true true for enterovirus seventy one. 0:37:03.520 --> 0:37:06.400 With all of these, it's also very likely that host 0:37:06.480 --> 0:37:10.840 factors are playing a role as well, whether that's differences 0:37:10.960 --> 0:37:15.040 in the way that we respond, for example, in our 0:37:15.080 --> 0:37:19.359 T cell response to these various viruses, that certain individuals 0:37:19.440 --> 0:37:22.120 might be more likely to have a severe case than 0:37:22.160 --> 0:37:25.360 other individuals, But again we don't know what those host 0:37:25.360 --> 0:37:30.719 factors are either, right, But in general, all of the 0:37:30.840 --> 0:37:34.120 variety of viruses that can cause handfoot in mouth disease. 0:37:34.680 --> 0:37:38.400 While they vary here and there, some being more virulent, 0:37:38.640 --> 0:37:42.840 some less, so in general, these are all human specific 0:37:43.000 --> 0:37:47.719 viruses that have a pretty wide tropism. That is, they 0:37:47.719 --> 0:37:51.080 can infect a pretty wide range of cell types, and 0:37:51.160 --> 0:37:54.360 that is how they can end up causing disease across 0:37:54.360 --> 0:37:57.680 this wide spectrum our skin as well as our nervous system, 0:37:58.120 --> 0:38:02.120 giving us fevers, etc. No matter how we get exposed, 0:38:02.120 --> 0:38:10.879 whether it's fecal, oral, or respiratory. So yeah, yeah, any 0:38:10.880 --> 0:38:12.040 more questions. 0:38:12.360 --> 0:38:17.759 I mean, treatment I assume is supportive if necessary, like 0:38:17.800 --> 0:38:19.760 you said, hydrate chill. 0:38:23.040 --> 0:38:26.400 Yeah, we don't have any specific intivirals at this point, 0:38:27.640 --> 0:38:33.320 but especially in the case of severe infections or neurologic manifestations, 0:38:33.680 --> 0:38:36.959 hospitalization with just supportive care is kind of the only 0:38:37.000 --> 0:38:42.760 thing that's available. Right, But that is handfoot in mouth. 0:38:43.400 --> 0:38:43.600 You know. 0:38:43.719 --> 0:38:46.840 It's funny because I thought I would be very feeling 0:38:46.920 --> 0:38:50.960 very strongly about needing there to be multiple names, but 0:38:50.960 --> 0:38:55.640 it seems pretty consistent. I mean there's like degrees, Yes, 0:38:56.280 --> 0:38:58.040 there's degrees. I think that that's a good way of 0:38:58.080 --> 0:39:01.799 looking at there's degrees and then there's implications, right, Yeah, 0:39:01.840 --> 0:39:06.840 but they all share this sort of clinical picture of fever, 0:39:07.800 --> 0:39:15.160 feeling crappy, this rash that's pretty specific. Usually there's throat involvement, 0:39:15.560 --> 0:39:21.200 lesions in the mouth, and then there's complications therein there's 0:39:21.360 --> 0:39:24.880 this can invade further and cause what a lot of 0:39:24.960 --> 0:39:29.200 viruses can cause in terms of neurologic manifestations, or it 0:39:29.239 --> 0:39:32.680 can cause really bad skin rashes that might look a 0:39:32.680 --> 0:39:35.920 little bit different and make it harder to diagnose, but 0:39:36.120 --> 0:39:38.560 at the end of the day, are still hand foot 0:39:38.560 --> 0:39:43.200 in mouth disease. I do think that, And again I 0:39:43.239 --> 0:39:47.440 am not a virus genetics expert by any means, but 0:39:48.400 --> 0:39:51.520 the fact that they're all named different viruses I think 0:39:51.600 --> 0:39:54.040 makes them seem like they are more distant from each 0:39:54.080 --> 0:39:57.759 other than in actuality. Right, So it's like more like 0:39:57.800 --> 0:40:02.319 along the lines of like a salmonella exactly, stererotype, the 0:40:02.440 --> 0:40:04.600 numbered serotype or whatever precisely. 0:40:04.680 --> 0:40:07.880 So now you can think of these all as variants 0:40:07.920 --> 0:40:13.240 of human enterovirus group A, right, right, and then you think, oh, okay, 0:40:13.239 --> 0:40:17.360 that kind of makes sense. But we also don't fully 0:40:17.440 --> 0:40:20.799 understand why why this one and not that one? 0:40:21.120 --> 0:40:24.080 Right, And there are more viruses that cause it, which 0:40:24.440 --> 0:40:27.919 just adds a little bit more flavor to the whole thing, 0:40:28.239 --> 0:40:31.319 and like, what's cocksacky group B doing in there? 0:40:31.520 --> 0:40:37.000 You know, well, that's just enterovirus group B. So yeah, but. 0:40:37.520 --> 0:40:38.320 How is it different? 0:40:38.320 --> 0:40:38.920 Why is there A? 0:40:39.080 --> 0:40:39.799 Why is there B? 0:40:43.040 --> 0:40:43.160 So? 0:40:44.080 --> 0:40:48.400 Yeah, but Aaron, where did these things come from? Why 0:40:48.680 --> 0:40:50.320 did they do this to us? 0:40:50.960 --> 0:40:56.200 Or maybe not that fart philosophical question. I don't know, 0:40:56.239 --> 0:40:56.719 it could be. 0:40:58.360 --> 0:41:01.520 Yeah, let's let's le's figure out how we got from 0:41:01.840 --> 0:41:02.560 there to hear? 0:41:03.160 --> 0:41:04.840 Right after this break. 0:41:39.560 --> 0:41:43.520 Handfoot and mouth disease, what have we gotten ourselves into? 0:41:46.880 --> 0:41:49.319 I mean, and I say this because you know, just 0:41:49.400 --> 0:41:52.600 like we talked about the biology of this disease is 0:41:52.920 --> 0:41:56.640 it's a teeny tiny bit more complicated than this one microbe, 0:41:56.680 --> 0:42:00.799 one disease model that we're used to hearing about, that 0:42:00.800 --> 0:42:05.840 we're used to learning about. And because of this, the 0:42:05.880 --> 0:42:10.440 way this disease can manifest is sometimes like it depends, 0:42:10.440 --> 0:42:12.880 it depends, like you said, on the host, It depends 0:42:12.920 --> 0:42:16.480 on the type of virus, It depends on the age 0:42:16.480 --> 0:42:19.080 of the individual, like it depends on lots of different things, 0:42:20.000 --> 0:42:23.320 and as will likely learn about in the current events section, 0:42:23.600 --> 0:42:26.719 the nature of some hand foot in mouth disease outbreaks 0:42:26.880 --> 0:42:31.920 has been changing in kind of major ways with some epidemics, 0:42:32.080 --> 0:42:35.479 like you talked about Aaron, involving never before seen case 0:42:35.560 --> 0:42:42.160 numbers or these new symptoms fingernails or mortality rates. And 0:42:42.680 --> 0:42:44.839 it's interesting to see if in the future, you know, 0:42:44.880 --> 0:42:47.680 as we gain more resolution on the role that these 0:42:47.680 --> 0:42:51.400 different viruses play in disease manifestation, like maybe we will 0:42:51.480 --> 0:42:54.600 get some sort of like separating out of names, kind 0:42:54.640 --> 0:42:57.560 of in the way that the naming or classification of 0:42:57.640 --> 0:43:04.719 kokshaki viruses has been revised confusingly, but it's not all 0:43:04.960 --> 0:43:09.040 NonStop complications and well yes, but also no, we're going 0:43:09.120 --> 0:43:12.680 to get a little mid episode break here because the 0:43:12.719 --> 0:43:16.600 history of hand foot and mouth disease is fortunately, like 0:43:16.800 --> 0:43:22.160 pretty darn straightforward, so much so in fact, that it's 0:43:22.280 --> 0:43:25.000 not even going to take up this whole history section. 0:43:25.320 --> 0:43:26.480 Ooh yeah. 0:43:26.520 --> 0:43:30.120 So this gives me a chance to explore something that 0:43:30.160 --> 0:43:33.439 I've been wanting to on this podcast for a very 0:43:33.520 --> 0:43:34.080 long time. 0:43:34.200 --> 0:43:35.440 Oh my gosh, I'm so excited. 0:43:35.440 --> 0:43:37.960 I have no idea, ida, and I'm going to keep 0:43:38.000 --> 0:43:41.640 you in suspense on what exactly that something is. And 0:43:41.800 --> 0:43:44.560 first we're going to talk about the history of handfoot and. 0:43:44.520 --> 0:43:45.800 Mouth disease Okay. 0:43:46.840 --> 0:43:50.480 In nineteen fifty seven, nineteen fifty eight and nineteen fifty nine, 0:43:51.000 --> 0:43:55.799 outbreaks of a highly infectious disease seemingly never before described 0:43:56.160 --> 0:44:01.440 were reported in New Zealand, Canada, and England, respect The 0:44:01.520 --> 0:44:05.640 disease seemed to affect primarily children and was very mild, 0:44:05.960 --> 0:44:08.520 with many parents not even feeling like they needed to 0:44:08.560 --> 0:44:11.319 call a doctor. So a lot of the cases in 0:44:11.360 --> 0:44:13.640 some of these outbreaks were only like the case numbers 0:44:13.719 --> 0:44:16.560 only went up after the fact, after the outbreak was over. 0:44:16.560 --> 0:44:20.239 When they started to like survey the community, parents were like, 0:44:20.360 --> 0:44:24.040 oh yeah, but like you know, my kid was fine. Popsicles, 0:44:24.640 --> 0:44:31.759 popsicles delicious. Infections involved lesions in the mouth and on 0:44:31.840 --> 0:44:35.600 the hands and the feet, and sometimes rashes on other 0:44:35.640 --> 0:44:38.840 parts of the body. Sometimes there was a fever, but 0:44:39.040 --> 0:44:43.640 in general recovery was rapid and complete. While only eight 0:44:43.760 --> 0:44:47.080 children were involved in the earliest New Zealand outbreak, or 0:44:47.120 --> 0:44:50.920 at least discussed in this paper, a total of sixty 0:44:50.960 --> 0:44:54.200 cases occurred in the Toronto one and eighty three in 0:44:54.280 --> 0:44:59.160 the Birmingham, England outbreak, again including all or predominantly children. 0:45:00.239 --> 0:45:01.840 If we had to give. 0:45:01.880 --> 0:45:05.480 Like metals out for each of these outbreaks and what 0:45:05.520 --> 0:45:09.080 they contributed it would go like this. Nineteen fifty seven, 0:45:09.120 --> 0:45:13.160 New Zealand the first recognized outbreak of handfoot in mouth, 0:45:13.360 --> 0:45:16.600 though only like in retrospect was it recognized as handfoot 0:45:16.640 --> 0:45:18.520 and mouth because they didn't test for the virus at 0:45:18.560 --> 0:45:24.000 the time. Nineteen fifty eight Toronto, first time that Cocksacki 0:45:24.120 --> 0:45:27.680 virus A sixteen was found in samples from people who 0:45:27.719 --> 0:45:31.520 were infected, showing that this was a viral infection caused 0:45:31.520 --> 0:45:36.280 by an enterovirus. And nineteen fifty nine Birmingham the first 0:45:36.320 --> 0:45:39.640 time the name handfoot in mouth was used to describe 0:45:39.640 --> 0:45:42.680 this disease. So kind of like boom boom boom, here 0:45:42.719 --> 0:45:45.920 we go done. So the nineteen it's the mid twentieth 0:45:46.000 --> 0:45:50.120 century virology is like just cruising. We'll really getting on 0:45:50.239 --> 0:45:54.560 at start. But yeah, pretty cool stuff. But even at 0:45:54.560 --> 0:45:58.120 the time that these early outbreaks were reported, none of 0:45:58.120 --> 0:46:01.200 the researchers involved thought that, like, this must be the 0:46:01.239 --> 0:46:04.440 first time that humans have been infected with this disease. 0:46:05.320 --> 0:46:08.320 They just figured that previous cases or outbreaks had probably 0:46:08.360 --> 0:46:10.759 been chalked up to foot and mouth disease or some 0:46:10.960 --> 0:46:14.760 other viral infection. The timing of the discovery of handfoot 0:46:14.760 --> 0:46:17.879 in mouth disease seems likely to be a combination of 0:46:18.640 --> 0:46:21.239 this is a very mild illness that has flown under 0:46:21.239 --> 0:46:25.399 the radar. This looks like something that has already been 0:46:25.480 --> 0:46:28.440 described and so didn't really encourage a closer look. 0:46:29.360 --> 0:46:31.240 And we only just now. 0:46:31.080 --> 0:46:33.520 Have the molecular tools to be able to identify and 0:46:33.560 --> 0:46:34.680 classify viruses. 0:46:34.920 --> 0:46:36.640 Yeah, ding, ding makes it makes sense. 0:46:36.719 --> 0:46:41.439 Yeah, But as it always happens, once handfoot in mouth 0:46:41.480 --> 0:46:45.640 disease was a known entity, a reported entity, it began 0:46:45.680 --> 0:46:47.080 popping up all. 0:46:46.960 --> 0:46:50.400 Over the world, like seriously global. 0:46:51.360 --> 0:46:54.719 The same year of that Birmingham outbreak in nineteen fifty nine, 0:46:54.960 --> 0:46:58.719 there was an outbreak of cocksacky A sixteen described in California, 0:46:59.239 --> 0:47:07.640 and in the years that followed, Hawaii, Arizona, Japan, China, Vietnam, Malaysia, Australia, Thailand, Spain, Sweden, Bulgaria, Brazil, Kenya, 0:47:07.719 --> 0:47:12.520 basically everywhere, like within I don't know how many years exactly, 0:47:12.600 --> 0:47:18.160 but everywhere was reporting outbreaks of handfoot in mouth disease. 0:47:19.320 --> 0:47:23.239 As the distribution of this disease spread and as the 0:47:23.280 --> 0:47:27.640 case numbers climbed, researchers quickly realized that this was not 0:47:27.880 --> 0:47:31.000 the mild, mannered, predictable virus that they had assumed at 0:47:31.000 --> 0:47:35.000 the beginning. For one, the nineteen sixty discovery that a 0:47:35.040 --> 0:47:38.479 different virus, cocksacky virus A five there's my shout out, 0:47:39.239 --> 0:47:43.719 was responsible for a small outbreak changed it from the 0:47:43.800 --> 0:47:47.279 handfoot and mouth virus to the hand foot and mouth viruses, 0:47:47.520 --> 0:47:51.560 with more to be added to that over the following decades, 0:47:52.600 --> 0:47:55.520 and the mild nature of this disease was called into 0:47:55.600 --> 0:47:58.640 question with the report that two infants had died during 0:47:58.640 --> 0:48:03.800 the nineteen fifty nine out in California. Over the decades 0:48:03.920 --> 0:48:07.719 since the discovery of handfoot in mouth disease, it continues 0:48:07.760 --> 0:48:13.040 to surprise US Epidemics involving hundreds of thousands or even 0:48:13.200 --> 0:48:15.600 you talked about one that was over a million people 0:48:16.280 --> 0:48:21.600 have occurred, Like those are huge numbers. Strange outbreaks quote 0:48:21.680 --> 0:48:24.000 unquote strange. I'll call them atypical. Strange is not a 0:48:24.080 --> 0:48:25.000 very scientific word. 0:48:25.040 --> 0:48:26.000 I suppose. 0:48:27.680 --> 0:48:32.120 That target teenagers or older adults rather than young children 0:48:32.280 --> 0:48:35.440 have also happened, like I read about one at a 0:48:35.960 --> 0:48:42.239 university I think Loyola maybe. Anyway, new virus serotypes have 0:48:42.320 --> 0:48:45.560 been linked to more virulent forms of the disease. Viral 0:48:45.640 --> 0:48:49.600 recombination has also thrown a wrench in the predictability of 0:48:49.640 --> 0:48:54.360 this disease. Researchers are investigating the potential effect of climate 0:48:54.440 --> 0:48:59.120 change on shifting or expanding handfoot in mouth disease season 0:48:59.280 --> 0:49:00.359 in certain redis. 0:49:00.440 --> 0:49:01.960 Oh yeah, I mean. 0:49:01.840 --> 0:49:04.839 Because like, like you talked about how the environment can 0:49:04.880 --> 0:49:08.400 play a big role in how long it can survive, 0:49:08.760 --> 0:49:12.920 not survive, but how long it can stay viable on surfaces. 0:49:13.600 --> 0:49:16.759 I saw one paper that was investigating how long they 0:49:16.800 --> 0:49:22.000 can live and accumulate in clams. Oh boy, which was 0:49:22.040 --> 0:49:26.880 actually something that my lab was studying. Like it's terrifying. 0:49:26.920 --> 0:49:32.319 Actually, yeah, yeah, it really. I think like as I 0:49:32.400 --> 0:49:35.400 was reading, it started to feel more and more like 0:49:35.440 --> 0:49:39.720 a tip of the Iceberg situation with foot and mouth disease. 0:49:40.000 --> 0:49:40.960 Yeah. 0:49:41.000 --> 0:49:43.240 And I know that you're going to talk about where 0:49:43.280 --> 0:49:48.000 we go from here, vaccines, changing epidemiology of outbreaks, research 0:49:48.040 --> 0:49:51.040 on prevention, whatever else there is to talk about in 0:49:51.120 --> 0:49:54.440 terms of the current and future world of handfoot and 0:49:54.480 --> 0:49:58.360 mouth disease. But I still need to talk about where 0:49:58.400 --> 0:49:59.480 this came from. 0:49:59.760 --> 0:50:00.440 Yeah. 0:50:00.840 --> 0:50:03.879 Of course, now that we've learned about the many players 0:50:03.880 --> 0:50:07.799 involved or possibly involved in handfoot and mouth disease. You 0:50:07.800 --> 0:50:09.880 could understand why that might be a little bit of 0:50:09.880 --> 0:50:14.400 a tricky question to answer. If you interpret that question 0:50:15.040 --> 0:50:19.160 as where does this group of viruses that cause handfoot 0:50:19.160 --> 0:50:23.240 and mouth disease come from? We can say that enteroviruses 0:50:23.480 --> 0:50:26.759 are an ancient group, and there are ana viruses, so 0:50:26.840 --> 0:50:30.320 it's easy to underestimate the time scale of viral evolution, 0:50:31.000 --> 0:50:33.600 and they recombine with each other, so it's also difficult 0:50:33.640 --> 0:50:38.360 to trace evolutionary relationships. There's not very much specific research 0:50:38.400 --> 0:50:43.600 that I could find on terraviruses, so I don't know where, when, 0:50:43.719 --> 0:50:49.120 how those sorts of steps, unfortunately. But you could also 0:50:49.560 --> 0:50:53.000 interpret that question where does this thing come from as 0:50:53.200 --> 0:50:56.239 where does the name handfoot and mouth disease or the 0:50:56.360 --> 0:50:59.800 name cocksacky virus come from. We know the answer to 0:50:59.840 --> 0:51:04.320 the first the nineteen fifty nine outbreak, and the second 0:51:04.640 --> 0:51:08.680 is that Koksaki viruses were named after a small village 0:51:08.719 --> 0:51:12.480 on the Hudson River south of Albany, where two children 0:51:12.560 --> 0:51:17.160 lived from whom Koksacki viruses were first extracted or isolated 0:51:17.239 --> 0:51:20.880 in nineteen forty eight by Gilbert Dohldorf, a director in 0:51:20.920 --> 0:51:23.920 the New York State Department of Health. So there's a 0:51:23.960 --> 0:51:26.040 town called Koksaki. 0:51:25.920 --> 0:51:26.719 Oh New York. 0:51:26.880 --> 0:51:28.640 Yeah, how funny, right? 0:51:29.239 --> 0:51:29.880 Or a village? 0:51:29.920 --> 0:51:33.160 I don't know the difference. But for the rest of 0:51:33.200 --> 0:51:37.960 this history section, I am choosing a third interpretation of 0:51:38.000 --> 0:51:43.600 your question. Ooh okay, not where does this disease or 0:51:43.920 --> 0:51:48.399 where do the viruses that cause it come from? But 0:51:48.640 --> 0:51:50.840 where do viruses come from? 0:51:51.360 --> 0:51:51.920 Stop it? 0:51:52.960 --> 0:51:56.279 What do we think the very first viruses looked like 0:51:56.719 --> 0:52:02.560 acted like? Did they pre date cells? Or did they 0:52:02.600 --> 0:52:05.879 come from cells? How do we even begin to form 0:52:06.000 --> 0:52:11.919 hypotheses around the origins of viruses? Should I go back 0:52:11.960 --> 0:52:14.799 to grad school to get a degree in paleovirology because 0:52:14.840 --> 0:52:17.960 I kind of want to do it? What is paleovirology? 0:52:18.200 --> 0:52:18.919 We'll get there. 0:52:21.320 --> 0:52:21.920 I love it. 0:52:25.080 --> 0:52:26.200 I was very. 0:52:26.040 --> 0:52:28.480 Excited to get to go down this rabbit hole, which 0:52:28.520 --> 0:52:29.480 I have. 0:52:29.520 --> 0:52:30.600 Never gotten to go down. 0:52:30.960 --> 0:52:31.240 Yeah. 0:52:31.320 --> 0:52:34.480 I feel like we've talked about it. Yeah, now's our moment. 0:52:35.520 --> 0:52:36.280 Now's the moment. 0:52:37.040 --> 0:52:39.680 I was going to say that everyone listening to this 0:52:39.719 --> 0:52:43.080 podcast is no doubt familiar with viruses, but then I 0:52:43.160 --> 0:52:46.799 remembered the last few years, and so instead I will 0:52:46.800 --> 0:52:50.080 say that, no doubt everyone in the world is familiar 0:52:50.320 --> 0:52:54.560 with viruses. The vast majority of the viruses that we 0:52:54.640 --> 0:52:58.799 are familiar with are pathogenic, either to humans or to 0:52:58.880 --> 0:53:02.000 humans and other animals, or to animals, or to plants, 0:53:02.280 --> 0:53:06.200 or to bacteria bacteria phases. And that makes sense given 0:53:06.239 --> 0:53:09.920 that identifying those you know more deadly, those super harmful 0:53:10.000 --> 0:53:13.840 viruses is top of the priority list. But the world 0:53:14.040 --> 0:53:18.880 of viruses is much much larger than just those pathogenic ones, 0:53:19.719 --> 0:53:24.279 and being harmful to humans or the animals that we 0:53:24.520 --> 0:53:30.160 have or wildlife is by no means a requirement. Probably 0:53:30.560 --> 0:53:34.440 nobody needs this definition, but just in case. A virus 0:53:34.719 --> 0:53:37.520 is simply a teeny tiny or in other words, sub 0:53:37.520 --> 0:53:43.200 microscopic infectious agent made up of genetic information wrapped in 0:53:43.239 --> 0:53:48.840 a protein coat. Viruses are not considered living organisms because 0:53:48.960 --> 0:53:52.759 they rely on living cells to multiply, which they do 0:53:52.960 --> 0:53:56.360 by invading a cell and hijacking the cells machinery to 0:53:56.400 --> 0:53:59.920 make more viruses they turn into like viral production factory. 0:54:01.520 --> 0:54:05.160 Viruses can be characterized by what type of genetic material 0:54:05.200 --> 0:54:08.000 they have, Like we've talked a lot about RNA viruses, 0:54:08.440 --> 0:54:12.640 and we've talked about DNA viruses and also how they 0:54:12.680 --> 0:54:19.000 replicate in infected cells. The number and diversity of viruses 0:54:19.040 --> 0:54:24.360 on this planet is beyond imagination. It's just too big 0:54:24.440 --> 0:54:28.799 for us to even try to imagine. But Carl's immergize 0:54:29.360 --> 0:54:34.000 in his book Planet of Viruses, he writes that, quote, 0:54:34.280 --> 0:54:38.640 there are one hundred billion times more viruses in the 0:54:38.680 --> 0:54:42.920 oceans than the grains of sand on all the world's beaches. 0:54:45.000 --> 0:54:48.319 If you lined up all the viruses in the oceans 0:54:48.719 --> 0:54:52.320 end to end, they would stretch out forty two million 0:54:52.600 --> 0:54:53.760 light years. 0:54:55.360 --> 0:54:58.360 It is, in fact, too much to comprehend. 0:54:58.560 --> 0:54:59.080 You can't. 0:54:59.239 --> 0:55:02.759 We need we need one of those grains of rice videos. 0:55:02.880 --> 0:55:05.120 Yeah, you know, I do know. 0:55:07.160 --> 0:55:07.440 What. 0:55:08.320 --> 0:55:09.640 And that's just the ocean. 0:55:09.840 --> 0:55:13.400 That's just the ocean. Yeah, that's not even all. 0:55:13.360 --> 0:55:14.640 The biomass on. 0:55:16.080 --> 0:55:18.680 Earth. Wow, Oh my goodness. 0:55:20.840 --> 0:55:23.680 Since the discovery of the tobacco mosaic virus in the 0:55:23.760 --> 0:55:26.719 late eighteen nineties, which was the first to be described, 0:55:26.840 --> 0:55:29.200 I know I've mentioned that at least once or twice 0:55:29.280 --> 0:55:33.120 or three or four times on the podcast, scientists have 0:55:33.239 --> 0:55:37.640 classified and named a few thousand species, but there are 0:55:38.040 --> 0:55:43.520 likely billions, trillions, even more viruses out there waiting to 0:55:43.560 --> 0:55:48.840 be discovered. Like virus species, viruses are found on every 0:55:49.000 --> 0:55:52.840 corner of the earth, infecting every cell you can think of. 0:55:53.760 --> 0:55:59.040 There are even giant viruses with genomes larger than scientists 0:55:59.160 --> 0:56:03.080 ever thought for a virus, and these viruses can be 0:56:03.120 --> 0:56:11.120 infected by a virus a viral phage. That's like one 0:56:11.120 --> 0:56:16.279 of my favorite fun facts. Blows my mind. Research is 0:56:16.440 --> 0:56:18.919 in its infancy for sure when it comes to these 0:56:18.960 --> 0:56:23.440 giant viruses and their viral phages. And really research is 0:56:23.480 --> 0:56:27.560 in its infancy when it comes to viruses period. Although 0:56:27.600 --> 0:56:30.799 we may have observed and written about viral infections for 0:56:30.880 --> 0:56:34.400 thousands of years, we only made the connection between disease 0:56:34.480 --> 0:56:39.719 and infectious agent relatively recently. We are in a thrilling 0:56:40.280 --> 0:56:45.959 and sometimes terrifying time for virology research. Thrilling for how 0:56:46.000 --> 0:56:48.960 often it seems like there is a discovery made that 0:56:49.120 --> 0:56:53.080 completely upends what we thought we knew about viruses or 0:56:53.320 --> 0:56:57.120 the borders around what it means to be a virus, 0:56:58.280 --> 0:57:03.480 and terrifying for the same reason right the insidious long 0:57:03.600 --> 0:57:06.759 term effects of a viral infection, the increasing number of 0:57:06.800 --> 0:57:10.960 links made between viral infections and autoimmune conditions and cancers 0:57:11.160 --> 0:57:18.120 or other conditions, The sheer unpredictability of viruses even when 0:57:18.120 --> 0:57:22.120 we can predict certain things about them, they still continue 0:57:22.160 --> 0:57:27.200 to surprise us, surprise us in sometimes not so pleasant ways. Right, 0:57:29.400 --> 0:57:32.360 we are learning about the world of viruses at an 0:57:32.480 --> 0:57:37.520 unprecedented rate, and it has given us profound insight into 0:57:37.960 --> 0:57:41.520 slash spurred debate on what it means to be alive, 0:57:42.080 --> 0:57:46.240 the surprising ways that evolution can work, the blurred line 0:57:46.320 --> 0:57:52.280 between help and harm, even what it means to be human. Because, 0:57:52.920 --> 0:57:57.400 as you can probably imagine, viruses like bacteria and other 0:57:57.480 --> 0:58:01.200 pathogens don't really turn into fall at least in the 0:58:01.240 --> 0:58:05.200 traditional sense. A select few can leave behind traces of 0:58:05.240 --> 0:58:09.800 infection in their host skeleton, like remnants of smallpox virus 0:58:09.920 --> 0:58:14.360 in the teeth of vikings, but even those are somewhat 0:58:14.400 --> 0:58:18.000 limited in how long they can last without degrading past 0:58:18.040 --> 0:58:22.240 the point of recognition. But there is another way that 0:58:22.360 --> 0:58:26.439 ancient viruses can be detected and studied millions of years 0:58:26.560 --> 0:58:30.120 post infection, and that is through our genome. 0:58:30.600 --> 0:58:31.520 I'm so excited. 0:58:33.280 --> 0:58:37.320 We've talked about retroviruses on the podcast before, and the 0:58:37.320 --> 0:58:40.320 way that these viruses work is that when they infect 0:58:40.320 --> 0:58:44.000 our cells, they end up inserting their genetic material into 0:58:44.120 --> 0:58:47.880 our cells DNA, so that our cells end up replicating 0:58:47.880 --> 0:58:51.120 that genetic material and then producing a whole lot more 0:58:51.240 --> 0:58:55.080 of those viruses. But what's super cool about this is 0:58:55.080 --> 0:58:58.720 that if one of these viruses ends up infecting a 0:58:58.880 --> 0:59:03.840 germ cell like egg or sperm, that viral DNA can 0:59:03.880 --> 0:59:10.120 be inherited and then inherited and then inherited. What this 0:59:10.280 --> 0:59:16.480 process I know right, is called indogenization, and it has 0:59:16.600 --> 0:59:21.520 happened over and over and over again in our species history, 0:59:21.600 --> 0:59:26.000 in many, many species history, all species history, some more 0:59:26.040 --> 0:59:30.760 than others. That's also very interesting. And it's estimated that 0:59:31.320 --> 0:59:36.560 up to eight percent of our human genome is comprised 0:59:36.600 --> 0:59:38.680 of sequences of viral origin. 0:59:39.520 --> 0:59:42.400 So we are all virus, we are all virus. 0:59:42.800 --> 0:59:47.800 We are eight percent virus. Isn't that amazing? 0:59:47.920 --> 0:59:52.360 Like we're just hanging out living life. Well, we've got 0:59:52.360 --> 0:59:54.320 this huge amount of viral DNA in our. 0:59:54.240 --> 0:59:56.480 Genomes and it's like just being there. 0:59:57.080 --> 0:59:58.560 Well is it? 0:59:58.600 --> 0:59:58.680 Is? 0:59:58.720 --> 1:00:00.040 It? Is it? 1:00:02.600 --> 1:00:07.439 These sequences are called human indogenous retroviruses. But side note, 1:00:07.440 --> 1:00:11.600 apparently it's not just retroviruses that can become indogenized. That's 1:00:11.680 --> 1:00:12.600 just my own little like. 1:00:14.320 --> 1:00:14.880 Especially. 1:00:15.080 --> 1:00:19.560 Yeah, while most of this eight percent is inactive, as 1:00:19.560 --> 1:00:21.760 in it's just like doesn't code for anything, It just 1:00:21.880 --> 1:00:26.760 chills there. Some parts do still have an impact from 1:00:27.240 --> 1:00:31.680 regulating when certain genes turn off or turn on, or 1:00:32.040 --> 1:00:37.960 even say coding for proteins that are crucial for placental development. 1:00:38.240 --> 1:00:39.560 What uh huh. 1:00:39.360 --> 1:00:44.040 Yep sincyitan soh uh huh. 1:00:44.120 --> 1:00:44.920 We talked about that. 1:00:45.320 --> 1:00:49.040 We talked about this. Yeah, like it has played a 1:00:49.080 --> 1:00:55.120 tremendous role in placental development and many other aspects. 1:00:55.840 --> 1:01:02.360 And that gene, that sequence, that protein is from a virus. 1:01:03.400 --> 1:01:03.680 M h. 1:01:05.360 --> 1:01:13.360 What so yes, I not only that, but since cyiton 1:01:13.440 --> 1:01:16.680 one and since cyiton two may play a role in 1:01:16.840 --> 1:01:22.200 pre eclampsia and even some preliminary hypotheses on the development 1:01:22.280 --> 1:01:29.000 of other conditions unrelated to pregnancy. Other human hodogenous retroviruses 1:01:29.040 --> 1:01:32.200 may affect our immune system and have been linked to 1:01:32.560 --> 1:01:36.480 various autoimmune diseases and als, among other things. 1:01:38.760 --> 1:01:45.480 You know, I feel very conflicted about this, Aaron. Is 1:01:45.560 --> 1:01:50.040 that because I feel like, on the one hand, this 1:01:50.240 --> 1:01:58.640 is the most incredible information, like it's so my brain 1:01:59.240 --> 1:02:04.240 can't hand it's incredible. And then on the other hand, 1:02:04.280 --> 1:02:11.600 I'm like that makes sense because I mean especially because like, yeah, 1:02:11.640 --> 1:02:14.960 there are viruses that that you know still today that 1:02:15.160 --> 1:02:19.160 make their way into our DNA. We've talked about some 1:02:19.600 --> 1:02:23.640 like of the hepatitis viruses that do that. HIV can 1:02:23.680 --> 1:02:27.840 do that, and so of course it makes sense that 1:02:27.840 --> 1:02:32.520 that viruses have been doing this forever, and I mean, 1:02:32.560 --> 1:02:35.440 evolution is so random that of course if that happens 1:02:35.480 --> 1:02:37.600 and there's some benefit to it, then it's going to 1:02:37.640 --> 1:02:40.680 become a part of you. Like, but so it's so 1:02:40.880 --> 1:02:44.880 logical and so mind blowing at the same. 1:02:44.640 --> 1:02:47.840 Time, I think that what really blows my mind too 1:02:47.920 --> 1:02:50.840 is that some of these are still having an effect, 1:02:51.360 --> 1:02:55.160 whereas like, for the most part, these viral genetic sequences 1:02:55.200 --> 1:02:58.680 have been like turned off because they were probably so 1:02:58.920 --> 1:03:01.520 that's sort of the turn off was selected for It 1:03:01.600 --> 1:03:03.280 was like, OK, we're going to do better if we 1:03:03.320 --> 1:03:07.160 don't do whatever those virus is instructing us to do. 1:03:08.120 --> 1:03:10.240 But the fact that there are many out there that 1:03:10.520 --> 1:03:12.600 do still play a role, and it's like, I think 1:03:12.640 --> 1:03:18.520 it's also really probably challenging. Like this field of this 1:03:18.600 --> 1:03:24.040 is paleovirology involves studying ancient viruses as well as the 1:03:24.160 --> 1:03:28.600 impact that these endogenous retroviruses and other extinct viruses have 1:03:28.720 --> 1:03:31.800 had on the evolution of their hosts. And it sounds 1:03:31.800 --> 1:03:34.160 like an incredibly cool field of research, which is why 1:03:34.200 --> 1:03:36.400 I want to go back to grad school kind of 1:03:36.440 --> 1:03:39.760 and research it, but we'll just end up reading papers 1:03:39.800 --> 1:03:43.800 about it instead. But it also seems really challenging, like 1:03:43.880 --> 1:03:48.320 how do we know what is a viral like an 1:03:48.400 --> 1:03:50.960 endogenous retrovirus versus not? 1:03:51.400 --> 1:03:52.200 That's my question. 1:03:52.280 --> 1:03:52.960 How do we know? 1:03:53.320 --> 1:03:55.400 How do you what's the tag? Do they have a 1:03:55.400 --> 1:03:56.760 little sign that they waive? 1:03:57.080 --> 1:03:59.040 So I think that there are, and also like this 1:03:59.160 --> 1:04:01.280 is now I am like way out of my depth 1:04:01.280 --> 1:04:03.600 because I'm like, Okay, this is not what I prepared for, 1:04:03.720 --> 1:04:06.000 but I did do it like a little bit of 1:04:06.040 --> 1:04:09.400 extra reading, and so there do seem to be there's 1:04:09.440 --> 1:04:13.840 a growing database where people have identified indigenous retroviruses, and 1:04:13.880 --> 1:04:17.520 then you can look for similarities across other species that 1:04:17.680 --> 1:04:21.400 have these sort of genetic sequences. Okay, and I think 1:04:21.440 --> 1:04:23.400 that there might You're right that there might be like 1:04:23.440 --> 1:04:26.400 little tags or something that indicates like this looks like 1:04:26.440 --> 1:04:30.520 a viral sequence. Okay, But there's a program I think 1:04:30.560 --> 1:04:33.520 that you can also, like a bioinformatic program that you 1:04:33.560 --> 1:04:37.760 can run genomes through to be like where's my indogenous retrovirus. 1:04:37.880 --> 1:04:42.040 Oh wow, Yeah, so I don't really know much about 1:04:42.080 --> 1:04:44.200 like at all about the mechanics, and so if that 1:04:44.560 --> 1:04:47.680 was completely wrong, which it very well could be, I'm 1:04:47.760 --> 1:04:48.320 very sorry. 1:04:48.360 --> 1:04:49.360 Please correct me. 1:04:49.440 --> 1:04:52.360 Send an email, yeah, just send us infots so we 1:04:52.400 --> 1:04:53.320 can read more about it. 1:04:53.800 --> 1:04:54.480 Yeah. 1:04:54.680 --> 1:04:59.280 So I promise you that this will definitely not be 1:04:59.400 --> 1:05:02.560 like I'm gonna stop talking about indigenous retroviruses here, but 1:05:02.760 --> 1:05:05.120 it will not be the last time on the podcast 1:05:05.120 --> 1:05:09.000 that we go into them, because I do want to 1:05:09.120 --> 1:05:11.919 take us further down the rabbit hole, like as deep 1:05:11.960 --> 1:05:17.680 as it can go with indogenous retroviruses, maybe in an 1:05:17.720 --> 1:05:20.400 episode on pre eclampsia, Like that seems like it would 1:05:20.440 --> 1:05:21.880 be really I mean, that's on. 1:05:21.800 --> 1:05:24.680 Our short list of episodes to do for sure. 1:05:24.760 --> 1:05:27.520 So and then we can get sort of up close 1:05:27.560 --> 1:05:30.760 and personal with like what does this gene do? There 1:05:30.800 --> 1:05:33.200 are other genes that seem to be involved as well, 1:05:33.240 --> 1:05:37.120 like how do we determine the functions that they have 1:05:37.480 --> 1:05:40.560 or don't have? I mean, just also like trying to 1:05:40.560 --> 1:05:43.040 tease a part regulatory functions. 1:05:42.520 --> 1:05:44.520 Of I love things. 1:05:44.880 --> 1:05:49.600 I love it, very cool, love it, okay, love it, 1:05:49.720 --> 1:05:50.640 kind of scared of it. 1:05:50.680 --> 1:05:51.600 Seems overwhelming. 1:05:52.960 --> 1:06:00.400 That's life, okay. But today, for the rest of this 1:06:00.520 --> 1:06:04.120 history section, I want to take you even further back. 1:06:05.000 --> 1:06:09.959 By comparing endogenous retroviruses across different animal species, like who 1:06:10.040 --> 1:06:14.160 has what? How different are those sequences? We can learn 1:06:14.200 --> 1:06:19.160 a lot about the evolutionary relationships among those animals, and 1:06:19.360 --> 1:06:21.920 we can also learn a lot about the evolutionary history 1:06:21.960 --> 1:06:26.760 of those viruses. How closely do they resemble viruses or 1:06:26.880 --> 1:06:30.800 viral genes that are around today. How long ago do 1:06:30.840 --> 1:06:34.160 we think they were incorporated into the host genome? What 1:06:34.280 --> 1:06:38.120 purpose do we think this viral gene held for the virus, 1:06:38.680 --> 1:06:41.200 like it had to have done something, it had to 1:06:41.200 --> 1:06:42.720 have benefited it in some way. 1:06:43.440 --> 1:06:44.200 What was it doing? 1:06:45.360 --> 1:06:50.800 These endogenous retroviruses, often referred to as molecular fossils, can 1:06:50.840 --> 1:06:54.960 give us valuable insight into what viruses may have looked 1:06:55.040 --> 1:06:58.480 like or how they acted millions of years in the past, 1:06:58.560 --> 1:07:04.240 even hundreds of millions of years. But millions is not billions, 1:07:04.840 --> 1:07:08.280 and if we want to explore the possible origins of viruses, 1:07:08.640 --> 1:07:12.440 we're gonna need to go back billions. So let's get 1:07:12.480 --> 1:07:15.720 into some of the hypotheses on the origin of viruses. 1:07:16.680 --> 1:07:20.240 All of these hypotheses have to try to reconcile these 1:07:20.640 --> 1:07:27.680 two kind of paradoxical statements about viruses. Number one, viruses 1:07:27.800 --> 1:07:32.360 infect organisms across the three domains of life, the archaea, 1:07:32.480 --> 1:07:36.960 the bacteria, and the eukaria, and some viruses, even though 1:07:37.000 --> 1:07:41.440 they infect super distantly related hosts, share some of the 1:07:41.480 --> 1:07:46.240 same proteins or some very similar proteins, and this suggests 1:07:46.280 --> 1:07:51.040 to scientists that viruses emerged really early on, like before 1:07:51.160 --> 1:07:56.120 these domains split from one another, possibly before cells existed. 1:07:57.920 --> 1:08:03.600 Number two, This is the conflicting contradictory statement. Viruses infect 1:08:03.720 --> 1:08:09.720 organisms period like they have to infect cells in order 1:08:09.760 --> 1:08:15.720 to replicate, So viruses both needed cells to exist and 1:08:15.960 --> 1:08:20.200 had to exist before cells to display the diversity they have. 1:08:22.040 --> 1:08:23.240 So how do we explain this? 1:08:23.680 --> 1:08:28.880 Yeah, yeah, well, traditionally three different scenarios are proposed, and 1:08:28.920 --> 1:08:31.200 I'm going to try to go through each of these, 1:08:31.320 --> 1:08:33.280 but in not too much detail because I'm not a 1:08:33.360 --> 1:08:37.200 virologist by any means. And I'll also try to mention 1:08:37.280 --> 1:08:40.120 a few of the hybrid hypotheses that have been proposed 1:08:40.200 --> 1:08:43.479 more recently. And my goal with this is not to 1:08:43.560 --> 1:08:46.880 convince you of any one hypothesis or even give you 1:08:47.000 --> 1:08:50.080 what you need to draw your own conclusions. This is 1:08:50.080 --> 1:08:53.559 an area of active research where there doesn't seem to 1:08:53.600 --> 1:08:57.680 be any strong consensus. So my goal here is just 1:08:57.800 --> 1:09:02.160 to introduce some of these ideas and kind of get 1:09:02.160 --> 1:09:05.320 you to think about how cool and incredible and weird 1:09:05.439 --> 1:09:08.720 viruses are, and to think about a time that you 1:09:09.120 --> 1:09:10.559 may not think about that often. 1:09:11.720 --> 1:09:15.080 Deep time, baby. Okay. 1:09:16.040 --> 1:09:22.679 The three hypotheses are virus first, escape, and reduction. Okay, 1:09:23.360 --> 1:09:26.639 let's start with the virus first hypothesis, which is more 1:09:26.760 --> 1:09:30.520 or less exactly what it sounds like. Under this hypothesis, 1:09:30.880 --> 1:09:35.439 viruses came before cells. They emerged from a soup of 1:09:35.600 --> 1:09:41.120 RNA molecules and had proteins to help them replicate once 1:09:41.360 --> 1:09:45.759 cells assembled. Later on, these sort of proto viruses evolved 1:09:45.760 --> 1:09:51.200 to infect them. There's wide agreement among biologists that RNA 1:09:51.280 --> 1:09:55.240 molecules existed before DNA, and that they were the first 1:09:55.320 --> 1:10:01.320 replicating molecules, in which case today's single stran did RNA viruses, 1:10:01.800 --> 1:10:05.639 like the anenteroviruses that cause handfoot in mouth disease, are 1:10:05.640 --> 1:10:11.320 representatives of the descendants of these ancient ancient viruses. Okay, 1:10:11.880 --> 1:10:15.360 Another thing in the support column for this hypothesis is 1:10:15.360 --> 1:10:18.280 that in a huge number of viral genomes there are 1:10:18.320 --> 1:10:23.120 genetic sequences that aren't found in cells, which might suggest 1:10:23.320 --> 1:10:27.360 that viruses came before cells rather than deriving from cells, 1:10:29.000 --> 1:10:30.520 because otherwise, where. 1:10:30.240 --> 1:10:32.439 Did these genetic sequences come from? 1:10:32.640 --> 1:10:32.760 Right? 1:10:34.280 --> 1:10:37.280 There are a couple of problems with this virus first idea. 1:10:38.240 --> 1:10:41.720 One is that there is no gene or coding sequences 1:10:42.000 --> 1:10:47.160 found in all viruses, and another is just the mechanics 1:10:47.200 --> 1:10:50.679 of it, like how can a virus replicate without a cell? 1:10:51.360 --> 1:10:56.280 How can it get that protective protein shell that capsid 1:10:56.520 --> 1:11:00.120 around its genetic material to find its next host and 1:11:00.200 --> 1:11:06.280 replicate more. The next hypothesis can help answer that, the 1:11:06.479 --> 1:11:12.879 escape or sometimes called vagrancy hypothesis. Under this hypothesis, cells 1:11:13.040 --> 1:11:17.719 predated viruses and viruses actually derived from cells. 1:11:18.560 --> 1:11:19.439 How do they do this? 1:11:20.680 --> 1:11:21.600 Well? 1:11:21.640 --> 1:11:25.160 In the genomes of our cells, there are these super 1:11:25.160 --> 1:11:30.880 cool things called retro transposons, which are genetic elements that 1:11:31.080 --> 1:11:34.759 move around the genome, cutting and pasting genetic code. 1:11:35.040 --> 1:11:39.280 Like how ah, what oh I just beat up around? 1:11:39.720 --> 1:11:41.519 I can't I just can't get over it. 1:11:42.040 --> 1:11:42.160 Who. 1:11:43.200 --> 1:11:47.400 So, some scientists think that viruses could have emerged from 1:11:47.439 --> 1:11:52.920 a similar process where a mobile genetic element got wrapped 1:11:53.000 --> 1:11:56.160 up in a nice little protein coat and escaped the cell, 1:11:56.800 --> 1:11:59.320 like in a little vesicle or something, along with the 1:11:59.400 --> 1:12:02.879 tools it needed to cut and paste itself into another 1:12:03.000 --> 1:12:07.799 cell's genome and make more of itself and voila virus. 1:12:08.080 --> 1:12:09.280 Okay, okay, okay. 1:12:09.680 --> 1:12:13.960 And there are viruses that have actually formed this way 1:12:14.160 --> 1:12:17.559 or are thought to have formed this way through gene escape, 1:12:18.200 --> 1:12:23.639 one of which is the human hepatitis delta virus, which 1:12:23.680 --> 1:12:27.639 can only infect humans and requires the hepatitis B virus 1:12:27.680 --> 1:12:32.280 to replicate, and it probably came from human genetic material 1:12:32.439 --> 1:12:33.960 hepatitis delta virus. 1:12:34.320 --> 1:12:36.759 Oh that's so interesting because when you were talking about 1:12:37.880 --> 1:12:42.240 the viruses that infect other viruses, hepatitized d was the 1:12:42.240 --> 1:12:45.080 first thing that I thought of, because it's like, it's 1:12:45.120 --> 1:12:47.080 not a virus that infects other viruses, but it's a 1:12:47.160 --> 1:12:51.760 virus that requires another virus to already exist in the 1:12:51.840 --> 1:12:53.720 cell for it to be able to infect that cell. 1:12:54.080 --> 1:13:01.840 It's like hyper dependent, yeah, hyperterocyte. Yeah, so very cool, right, 1:13:03.160 --> 1:13:07.920 And with this scenario, these so called pickpocketing or gene 1:13:07.960 --> 1:13:12.759 robbing viruses could have been formed from escaped genes from 1:13:12.880 --> 1:13:17.880 each of the domains Bacteria, Archaea, and Eukarya, which helps 1:13:17.880 --> 1:13:23.400 to explain the existence of bacterial viruses, bacteriophases from bacterial genomes, 1:13:23.760 --> 1:13:29.720 eukaryotic viruses from eukaryotic genomes, and archaeoviruses from archaeo genomes. Okay, 1:13:29.760 --> 1:13:33.920 but if this were the case, we shouldn't find viral 1:13:34.000 --> 1:13:37.760 genes or genes of viral origin because they would have 1:13:37.840 --> 1:13:39.760 all come from these cells. 1:13:40.240 --> 1:13:41.320 Yet we do. 1:13:42.880 --> 1:13:46.960 So. Here enters the third hypothesis, or the reduction hypothesis. 1:13:48.280 --> 1:13:51.960 This idea was revived when in the early two thousands, 1:13:52.000 --> 1:13:56.600 scientists discovered giant DNA viruses. The first of these to 1:13:56.640 --> 1:14:02.000 be described Mimi virus because it mimics micro is bigger 1:14:02.040 --> 1:14:05.439 than anyone thought viruses could be. So, you know how, 1:14:05.680 --> 1:14:07.920 like on the podcast when we talk about the history 1:14:07.960 --> 1:14:10.800 of the discovery of viruses, we talk about how they 1:14:10.840 --> 1:14:14.560 were called filterable transmissible agents because you filter all the 1:14:14.600 --> 1:14:19.720 bacteria out and yet there's still something there. These would 1:14:19.760 --> 1:14:27.280 get filtered out. Some of these viruses are bigger than bacteria. What, yeah, 1:14:28.000 --> 1:14:31.840 than some bacteria. Bacteria range in size whatever, But it's 1:14:31.880 --> 1:14:38.479 so cool, and this giant virus than this. Mimivirus has 1:14:38.640 --> 1:14:43.480 also an incredibly large genome, which goes against this conventional 1:14:43.560 --> 1:14:47.960 idea that viruses have small genomes and they're restricted to 1:14:48.000 --> 1:14:51.759 having small genomes because the larger the genome, the more 1:14:52.040 --> 1:14:55.920 likely that mistakes are made in replication, and since they 1:14:56.000 --> 1:14:59.360 don't have proof reading abilities, those mistake written, large genome 1:14:59.439 --> 1:15:04.080 viruses would die out right. So if you're like imagining typing, 1:15:04.720 --> 1:15:08.599 trying to copy a paragraph, the longer the paragraph is, 1:15:09.000 --> 1:15:11.479 the more likely you are to make mistakes. And let's 1:15:11.479 --> 1:15:13.599 say that you can't proofread your mistakes. 1:15:13.920 --> 1:15:14.120 Right. 1:15:14.640 --> 1:15:20.880 Yeah, but these giant viruses still exist, and they not 1:15:20.960 --> 1:15:24.880 only have these big genomes, but they also appear to 1:15:24.960 --> 1:15:29.839 have genes or forms of genes that may have coded 1:15:29.920 --> 1:15:33.960 for protein synthesis or may have been involved in protein synthesis. 1:15:34.640 --> 1:15:39.040 It's wild, it's wild. Also, they have very low mutation rates, 1:15:39.360 --> 1:15:43.080 which is really cool because you would think larger the 1:15:43.080 --> 1:15:47.320 genome even though it's DNA, but still, and because of 1:15:47.400 --> 1:15:51.439 how much they resemble cells and rely less on hosts 1:15:51.479 --> 1:15:55.240 for a replication compared to other viruses, some scientists have 1:15:55.320 --> 1:15:59.760 speculated that these giant viruses evolved from more complex and 1:16:00.120 --> 1:16:04.400 esters losing their free living ability. So I like to 1:16:04.439 --> 1:16:06.800 think of it as like, this giant virus started out 1:16:06.800 --> 1:16:10.080 as a free living, independent being, just happy being itself, 1:16:10.160 --> 1:16:13.599 going through eons chillin', and then it meticell and was like, 1:16:13.640 --> 1:16:17.080 oh hey, you me me you, maybe we could like 1:16:17.120 --> 1:16:20.880 form a partnership work together. And over time that virus 1:16:20.880 --> 1:16:23.080 grew to be more and more dependent on its partner. 1:16:23.400 --> 1:16:25.679 It stopped working on itself and didn't care about living 1:16:25.680 --> 1:16:33.120 freely and eventually turned into a Parasite's that's the story 1:16:33.160 --> 1:16:33.679 in my head. 1:16:34.479 --> 1:16:35.880 I really love it. 1:16:37.840 --> 1:16:41.240 And so it's even been proposed. I think it's pretty controversial, 1:16:41.560 --> 1:16:44.320 but it has been proposed that these giant viruses are 1:16:44.439 --> 1:16:47.880 the descendants of an extinct fourth domain of life. 1:16:48.240 --> 1:16:50.599 Oh mg, yeah, or. 1:16:50.560 --> 1:16:55.240 Maybe not, because their genomes don't show the same degradation 1:16:55.760 --> 1:17:01.760 that obligately intracellular bacteria like Ricketsia and chlamydia, and so 1:17:02.000 --> 1:17:06.880 it's possible some scientists think that they evolved from smaller 1:17:06.960 --> 1:17:14.040 DNA viruses through genome expansion wild wild. So at this point, though, 1:17:14.320 --> 1:17:18.400 these giant viruses don't really seem to hold the complete 1:17:18.439 --> 1:17:23.360 answer for viral origins. Did viruses come before cells? Did 1:17:23.400 --> 1:17:26.840 they escape from modern cells about four billion years ago, 1:17:27.000 --> 1:17:31.040 which is when the last universal common ancestor was thought 1:17:31.080 --> 1:17:35.560 to have originated, or did they derive from more complex 1:17:35.640 --> 1:17:43.600 ancestors now extinct. These three hypotheses have been revised, championed, abandoned, revisited, 1:17:43.920 --> 1:17:48.400 and will probably continue to be debated forever. They do 1:17:48.439 --> 1:17:54.040 seem to be mutually exclusive in their traditional forms, yet 1:17:54.120 --> 1:17:57.840 none explains the origin of viruses in a completely satisfactory way, 1:17:58.960 --> 1:18:03.519 and it's possible, but no single hypothesis ever will. Some 1:18:03.680 --> 1:18:08.520 people have proposed hybrids of these scenarios, like viruses evolving 1:18:08.560 --> 1:18:12.160 from ancient cells which later gave rise to modern cells, 1:18:12.400 --> 1:18:14.680 which is why we see genes or elements that are 1:18:14.760 --> 1:18:17.559 unique to viruses yet are not found in these more 1:18:17.600 --> 1:18:24.759 modern domains, or protoviruses that could replicate themselves came first, 1:18:24.840 --> 1:18:29.840 and then ancient cells emerged, and they stole protective proteins 1:18:29.920 --> 1:18:33.040 from those cells, So it's sort of like step wise, 1:18:34.000 --> 1:18:38.640 or that there were multiple origins of viruses, especially separately 1:18:38.800 --> 1:18:44.439 for RNA and DNA viruses. At this point, it mostly 1:18:44.520 --> 1:18:48.880 seems like a philosophical question, albeit one that we'll keep 1:18:49.000 --> 1:18:51.839 changing the more that we learn about the viruses around 1:18:51.920 --> 1:18:55.680 us as well as those within us in our genomes. 1:18:57.200 --> 1:18:59.200 And I know that I probably gave you a lot 1:18:59.280 --> 1:19:02.200 more than you bargained for when you asked, where did 1:19:02.200 --> 1:19:03.080 this thing come from? 1:19:03.479 --> 1:19:03.719 Hah? 1:19:04.240 --> 1:19:09.640 But hopefully you found this little foray into viral origins 1:19:09.920 --> 1:19:14.559 fun or at least somewhat interesting. And now I'm going 1:19:14.600 --> 1:19:16.840 to turn it over to you to bring us out 1:19:16.840 --> 1:19:19.519 of deep time into what's going on with handfoot in 1:19:19.560 --> 1:19:20.719 mouth disease today. 1:19:21.080 --> 1:19:22.880 Oh my gosh, Aaron, I want to stay in deep 1:19:22.920 --> 1:19:24.400 time and just ponder. 1:19:26.640 --> 1:19:29.479 Let's do that. Let's have a deep time hour, can we? 1:19:29.640 --> 1:19:33.600 That sounds great? Okay, But right now we'll take a 1:19:33.640 --> 1:19:36.479 quick break and then I'll bring us back to twenty 1:19:36.640 --> 1:19:37.680 twenty three. Ish. 1:19:39.040 --> 1:19:40.400 Don't sound so disappointed. 1:19:41.439 --> 1:19:43.599 I know, I'm excited. It's gonna be great. Okay, good 1:19:43.720 --> 1:20:15.120 right after this break. At this point, all of these 1:20:15.560 --> 1:20:22.080 modern viruses and taroviruses that cause handfoot in mouth disease 1:20:22.560 --> 1:20:27.639 have been seen pretty much across the globe in my reading, 1:20:27.720 --> 1:20:31.320 at least, Koksaki virus A six is perhaps the newest 1:20:31.360 --> 1:20:35.760 one to be spreading and making headlines about it. With 1:20:35.840 --> 1:20:38.640 epidemics that started, like I mentioned, in two thousand and 1:20:38.640 --> 1:20:42.519 eight in Europe, spread throughout Asia and made their way 1:20:42.640 --> 1:20:47.720 across the Atlantic to the US. Enterovirus seventy one is 1:20:47.840 --> 1:20:52.960 also globally distributed, but seems to cause the largest and 1:20:53.200 --> 1:20:59.200 most severe epidemics in Asia for reasons we don't really understand, 1:20:59.360 --> 1:21:07.040 because it's not limited to Asia, certainly, but across all 1:21:07.160 --> 1:21:12.000 of its range, especially in temperate regions, handfoot in mouth 1:21:12.080 --> 1:21:16.639 tends to be a seasonal disease. It usually occurs in 1:21:16.840 --> 1:21:20.759 summer as well as having smaller peaks in spring and fall, 1:21:22.439 --> 1:21:26.479 and across the globe, infections are by far most common 1:21:26.600 --> 1:21:31.559 in kids under five years old. It's also probably not 1:21:31.640 --> 1:21:36.240 that surprising, both given how infectious this is and just 1:21:36.360 --> 1:21:39.760 the ways that it's spread, that it's really common for 1:21:39.880 --> 1:21:43.919 handfoot in mouth disease to cause outbreaks. Whether those outbreaks 1:21:43.920 --> 1:21:48.400 are small or incredibly large just depends on the certain 1:21:48.439 --> 1:21:53.400 set of circumstances surrounding it. But what that means is 1:21:53.439 --> 1:21:59.040 that we don't have great numbers on global prevalence. Yeah, 1:21:59.280 --> 1:22:02.519 it's also not a reportable disease for most of the globe. 1:22:03.040 --> 1:22:07.759 A lot of Asia does actually report, especially ento ravirus 1:22:07.960 --> 1:22:11.600 seventy one infections. So we have some numbers and we 1:22:11.640 --> 1:22:15.800 can really see those seasonal trends, and from there we 1:22:15.880 --> 1:22:20.040 can see that there are tens to hundreds of thousands 1:22:20.080 --> 1:22:24.479 of reported cases during these peak seasons, depending on the 1:22:24.479 --> 1:22:27.960 country that we look at. So if we extrapolate that 1:22:28.080 --> 1:22:33.080 data using not quite air and math, but just guessing, 1:22:35.160 --> 1:22:38.679 it's almost certain that there are hundreds of thousands, if 1:22:38.720 --> 1:22:42.759 not millions, of cases of hand foot in mouth across 1:22:42.760 --> 1:22:49.520 the globe every year. This is a very common infection. Yeah, 1:22:49.800 --> 1:22:52.880 So then the question is why does it seem like 1:22:53.000 --> 1:22:58.559 perhaps some subtypes, especially those that maybe cause more severe infection, 1:22:59.280 --> 1:23:03.519 are on the right eye, like Koksaki virus A six. 1:23:05.360 --> 1:23:05.840 I don't know. 1:23:07.840 --> 1:23:08.599 I was waiting. 1:23:08.800 --> 1:23:12.760 I was like, oh, I don't ever have an answer there, 1:23:12.920 --> 1:23:15.960 but it's fun to think about. Is it because it's 1:23:16.080 --> 1:23:19.599 out competing the other Cooksaki viruses because it's a more 1:23:19.680 --> 1:23:23.280 virulent infection somehow? Is it just that most of us 1:23:23.360 --> 1:23:26.400 haven't yet been exposed, so there's a lot more susceptible 1:23:26.439 --> 1:23:31.799 individuals in the population. Is it some combination thereof Probably, 1:23:33.479 --> 1:23:36.679 but it's important that we try and get a handle 1:23:36.720 --> 1:23:40.320 on this, especially as we're looking at these viruses that 1:23:40.400 --> 1:23:43.160 seem to be causing more severe illness. 1:23:43.680 --> 1:23:43.880 Right. 1:23:46.040 --> 1:23:50.839 Another thing that's interesting just about the general epidemiology of handfoot, 1:23:50.840 --> 1:23:55.400 and mouth disease is that in addition to seasonal variation, 1:23:55.800 --> 1:24:00.920 there also tends to be these cyclical epidemics where every 1:24:01.040 --> 1:24:06.080 two to five years, larger outbreaks and epidemics tend to happen. 1:24:07.439 --> 1:24:10.040 That may not be that surprising to anyone who listened 1:24:10.120 --> 1:24:13.320 to our poliovirus episode recently, because that used to happen 1:24:13.320 --> 1:24:17.040 with poliovirus as well, and it's likely related to just 1:24:17.360 --> 1:24:21.800 the how many kids have been born and how many 1:24:21.880 --> 1:24:25.640 susceptible young babies you now have in a population that 1:24:25.680 --> 1:24:28.440 have never been exposed to any of these viruses. 1:24:29.640 --> 1:24:34.600 Yeah, it's it's interesting, Like I wonder what the susceptible 1:24:34.640 --> 1:24:39.120 population requirements are, you know, in order to be sustained. 1:24:39.160 --> 1:24:41.800 I feel like we talked about this in different episodes, 1:24:41.840 --> 1:24:44.760 and like our measles episode, compared to other things like 1:24:44.840 --> 1:24:48.040 chicken pox, you don't really need to have a certain 1:24:48.520 --> 1:24:51.320 you know, threshold of individuals to maintain infection. 1:24:52.600 --> 1:24:56.200 Well, one of the at least one paper that I read, 1:24:56.360 --> 1:25:01.280 I remember seeing that they estimated that to heard immunity, 1:25:01.960 --> 1:25:05.240 you would need to have well over eighty percent of 1:25:05.360 --> 1:25:10.080 people no longer susceptible, so immune to the infection. 1:25:10.880 --> 1:25:13.120 Wow, it's a lot, right, it's a lot. 1:25:13.200 --> 1:25:17.200 It's not as high as for something like measles, but 1:25:18.000 --> 1:25:20.800 it's also that much more complicated because there are so 1:25:20.840 --> 1:25:26.120 many different viruses that can cause this. So yeah, so 1:25:26.120 --> 1:25:29.920 there's definitely a lot of variation within that. The good 1:25:29.960 --> 1:25:33.040 news is that even though we talked about the severe 1:25:33.080 --> 1:25:36.880 complications of handfoot and mouth disease, if we look at 1:25:36.920 --> 1:25:40.960 the case fatality rate of all cases from all causes 1:25:41.000 --> 1:25:44.960 of handfoot and mouth disease that are uncomplicated, the case 1:25:44.960 --> 1:25:49.040 fatality rate is incredibly low, between point zero six and 1:25:49.160 --> 1:25:54.080 point one percent, which is very low. When it comes 1:25:54.120 --> 1:25:58.320 to more complicated cases that have neurologic involvement, the mortality 1:25:58.400 --> 1:26:01.800 rate can be between ten twenty five percent, which is 1:26:02.040 --> 1:26:09.080 significantly higher. So I think that right now, in terms 1:26:09.080 --> 1:26:13.240 of current research, there is a lot of interest, understandably 1:26:13.320 --> 1:26:17.280 in these more severe subtypes, not only in what is 1:26:17.439 --> 1:26:22.120 causing this increased virulence with say enterovirus seventy one and 1:26:22.320 --> 1:26:26.680 cocksacky A six, but also what are the drivers of 1:26:26.720 --> 1:26:31.200 this seemingly increase in outbreaks that we've been seeing year 1:26:31.360 --> 1:26:35.080 after year. There's also, of course a lot of work 1:26:35.120 --> 1:26:40.040 to be done on vaccines which do exist. There are 1:26:40.200 --> 1:26:43.280 at least three that have existed, at least one that 1:26:43.360 --> 1:26:47.439 is licensed, but they've only ever been licensed in China. 1:26:47.600 --> 1:26:51.439 The vaccine that exists only exists against enterovirus seventy one, 1:26:51.520 --> 1:26:55.719 which again is more common across Asia, so it's licensed 1:26:55.720 --> 1:26:59.439 in China. It does seem that it's quite effective. The 1:26:59.439 --> 1:27:01.680 study that I I saw said that it's estimated to 1:27:01.680 --> 1:27:05.160 have ninety to ninety seven percent efficacy even over a 1:27:05.200 --> 1:27:09.120 couple of years, which is pretty incredible. But other than that, 1:27:09.240 --> 1:27:11.439 I don't know a ton about it, and I don't 1:27:11.479 --> 1:27:14.719 know the likelihood that it would be licensed anywhere else. 1:27:16.000 --> 1:27:19.320 But there's certainly a lot of research to be done. 1:27:19.520 --> 1:27:26.559 As always as always, and that is hand, foot in 1:27:26.600 --> 1:27:28.880 mouth and butt disease. 1:27:29.320 --> 1:27:31.400 And fingernail and to fingernail. 1:27:34.040 --> 1:27:37.400 Yeah, we did. 1:27:37.360 --> 1:27:40.080 It, we did. I mean this was I really loved 1:27:40.080 --> 1:27:42.200 that deep dive. Arin. I'm just not going to stop 1:27:42.200 --> 1:27:44.679 thinking about viruses in my body. 1:27:46.280 --> 1:27:49.880 Well, I'm glad and if for anyone out there who 1:27:49.920 --> 1:27:53.880 wants to maybe read more and because there's idea so 1:27:54.120 --> 1:27:56.599 much more out there than what I even touched on 1:27:56.960 --> 1:27:57.360 at all. 1:27:57.560 --> 1:28:00.320 So go to our sources. 1:28:01.000 --> 1:28:03.679 And I'm going to shout out a few right now. 1:28:04.800 --> 1:28:06.600 If you want to learn more about the history of 1:28:06.680 --> 1:28:10.800 handfoot and mouth disease, there are several great papers. One 1:28:11.320 --> 1:28:15.639 is by Richardson and Leibovitz from nineteen sixty five. And 1:28:15.960 --> 1:28:19.920 if you want to learn more about the origin of 1:28:20.000 --> 1:28:25.280 viruses like where to even begin, there are many different sources. 1:28:25.439 --> 1:28:29.800 One is by Drzinska at All from twenty fifteen called 1:28:29.920 --> 1:28:33.679 Viruses and Cells Intertwined Since the Dawn of Evolution. 1:28:34.960 --> 1:28:35.880 There's just a lot. 1:28:35.960 --> 1:28:38.960 There are a lot of sources for this one, I 1:28:39.000 --> 1:28:43.760 can imagine. For the biology, there was a few papers 1:28:43.840 --> 1:28:47.320 that were really nice overviews and a lot of papers 1:28:47.360 --> 1:28:51.680 that I had on enterovirus seventy one specifically, So for 1:28:51.840 --> 1:28:54.439 more on that, you can check a paper in the 1:28:54.520 --> 1:28:59.720 Lancet Neurology called Clinical Features, Diagnosis and Management of Entrovirus 1:29:00.080 --> 1:29:04.120 A new one. Really loved that one, and I used 1:29:04.160 --> 1:29:08.840 the American Academy of Pediatrics red Book, which had information 1:29:08.960 --> 1:29:12.840 on all of the different enteroviruses, and I even threw 1:29:12.880 --> 1:29:16.320 in a fun paper about all of the skin rashes 1:29:16.360 --> 1:29:19.599 that involve palms and souls, just for. 1:29:19.520 --> 1:29:20.760 Fun to check that one out. 1:29:20.960 --> 1:29:23.800 Yeah, it's pretty cool, pretty cool. Not a lot of 1:29:23.840 --> 1:29:27.760 the path of physiology, but just less of all the different. 1:29:27.439 --> 1:29:28.759 Ones and it's so interesting. 1:29:29.720 --> 1:29:33.240 You can find the list of all of our sources 1:29:33.240 --> 1:29:37.400 because there's many more from this episode and all of 1:29:37.439 --> 1:29:39.680 our episodes on our website This podcast will Kill You 1:29:39.760 --> 1:29:41.400 dot com under the episodes tap. 1:29:42.400 --> 1:29:45.760 Thank you to Libby again for sharing your first hand 1:29:45.800 --> 1:29:49.520 account like oh oh, thank you yeah. 1:29:49.560 --> 1:29:52.160 Thank you to Bloodmobile for providing the music for this 1:29:52.280 --> 1:29:54.080 episode and all of our episodes. 1:29:54.320 --> 1:29:57.960 Thank you to Leana Scolacci for our amazing audio mixing. 1:29:58.080 --> 1:29:59.719 Thank you, we love it. You're the best. 1:30:00.280 --> 1:30:02.520 Thank you to the Exactly Right Network. 1:30:02.360 --> 1:30:03.840 And thank you to you listeners. 1:30:04.040 --> 1:30:06.840 For anyone out there who requested this, we hope that 1:30:06.960 --> 1:30:09.400 you got your questions answered. 1:30:10.040 --> 1:30:14.240 I hope you so yeah felt validated. I don't know, 1:30:14.560 --> 1:30:17.800 yeah yeah that too. And a special shout out to 1:30:17.840 --> 1:30:20.920 our patrons as always, thank you so much. Your support 1:30:21.080 --> 1:30:22.400 means everything to us. 1:30:22.479 --> 1:30:25.080 It really does. Well. 1:30:25.640 --> 1:30:28.080 Until next time, wash your hands 1:30:28.360 --> 1:30:31.200 You filthy animals, and your feet and you really do 1:30:31.680 --> 1:30:36.360 really and the changing pad scrum it everywhere,