1 00:00:02,333 --> 00:00:04,033 - Welcome, everyone to Wednesday Nite @ the Lab. 2 00:00:04,133 --> 00:00:05,300 I'm Tom Zinnen. 3 00:00:05,400 --> 00:00:07,433 I work here at the UW-Madison Biotechnology Center. 4 00:00:07,533 --> 00:00:11,733 I also work for the Division of Extension and Wisconsin 4-H, 5 00:00:11,833 --> 00:00:14,100 and on behalf of those folks and our other co-organizers, 6 00:00:14,200 --> 00:00:17,633 PBS Wisconsin, the Wisconsin Alumni Association, 7 00:00:17,733 --> 00:00:20,100 and the UW-Madison Science Alliance, 8 00:00:20,200 --> 00:00:22,966 thanks again for coming to Wednesday Nite @ the Lab. 9 00:00:23,066 --> 00:00:26,566 We do this every Wednesday night, 50 times a year. 10 00:00:26,666 --> 00:00:29,433 Tonight, it's my pleasure to introduce to you Katie Schmit. 11 00:00:29,533 --> 00:00:32,766 She's a physician in the Department of Pediatrics here. 12 00:00:33,966 --> 00:00:36,500 She was born in St. Charles, Illinois, 13 00:00:36,600 --> 00:00:39,833 which is right down Illinois 38 from Dixon, Illinois. 14 00:00:41,100 --> 00:00:43,366 She went to St. Charles North High School, 15 00:00:43,466 --> 00:00:47,066 and then came here to UW-Madison to study biochemistry. 16 00:00:47,166 --> 00:00:49,800 Then she went to St. George's University 17 00:00:49,900 --> 00:00:53,033 to get her medical degree on the island of Grenada, 18 00:00:53,133 --> 00:00:55,466 then she did her clinical work in Brooklyn 19 00:00:55,566 --> 00:00:58,600 and lived in Bedford-Stuyvesant. 20 00:01:00,233 --> 00:01:03,500 Then she came here to UW-Madison to do her residency. 21 00:01:03,600 --> 00:01:05,533 She's currently here doing a fellowship 22 00:01:05,633 --> 00:01:08,033 in pediatric infectious disease, 23 00:01:08,133 --> 00:01:12,166 and she's also doing a primary care research fellowship 24 00:01:12,266 --> 00:01:14,266 with the Department of Family Medicine. 25 00:01:14,366 --> 00:01:16,466 Tonight, she's going to talk to us about something 26 00:01:16,566 --> 00:01:18,066 that's near and dear to all of us 27 00:01:18,166 --> 00:01:19,566 who have ever had children, 28 00:01:19,666 --> 00:01:22,900 respiratory viruses of children and adults. 29 00:01:23,000 --> 00:01:24,966 The focus is on influenza. 30 00:01:25,066 --> 00:01:27,566 It's gonna be interesting to see how the numbers stack up 31 00:01:27,666 --> 00:01:31,500 to this competing virus that we have going around right now. 32 00:01:31,600 --> 00:01:34,100 I think influenza may win. 33 00:01:34,200 --> 00:01:36,133 Please join me in welcoming Dr. Katie Schmit 34 00:01:36,233 --> 00:01:37,466 to Wednesday Nite @ the Lab. 35 00:01:37,566 --> 00:01:40,266 [audience applauding] 36 00:01:45,200 --> 00:01:46,366 - All right. 37 00:01:49,233 --> 00:01:51,266 Thank you, Tom, for that introduction. 38 00:01:51,366 --> 00:01:54,466 Today, I'll be discussing influenza, like Tom mentioned. 39 00:01:54,566 --> 00:01:57,500 I will focus on three key concepts that will help us 40 00:01:57,600 --> 00:02:00,500 follow influenza from the virus itself 41 00:02:00,600 --> 00:02:02,833 to the infection that it causes. 42 00:02:02,933 --> 00:02:06,033 So my goal is to help you guys enhance your knowledge 43 00:02:06,133 --> 00:02:08,500 about influenza you hear so much about, 44 00:02:08,600 --> 00:02:10,966 and the flu virus you hear so much about. 45 00:02:11,066 --> 00:02:12,600 I recognize that everyone in this room 46 00:02:12,700 --> 00:02:14,833 is starting from different backgrounds. 47 00:02:14,933 --> 00:02:17,633 There may be some virologists in the audience, 48 00:02:17,733 --> 00:02:19,666 but I'm trying to keep it quite basic 49 00:02:19,766 --> 00:02:22,966 with talking about key concepts about influenza 50 00:02:23,066 --> 00:02:27,100 that transfers over to different respiratory viruses. 51 00:02:28,533 --> 00:02:30,600 So before I get started, I have no financial disclosures. 52 00:02:30,700 --> 00:02:33,333 [audience chuckling] I will not be addressing 53 00:02:33,433 --> 00:02:36,233 any non-FDA medications during this talk. 54 00:02:38,233 --> 00:02:39,966 So these are the three key concepts 55 00:02:40,066 --> 00:02:42,033 that I'll be going through today to talk about 56 00:02:42,133 --> 00:02:43,966 in addressing influenza. 57 00:02:44,066 --> 00:02:46,700 So even though some of these are very specific and unique 58 00:02:46,800 --> 00:02:49,900 to influenza, overarching respiratory viruses, 59 00:02:50,000 --> 00:02:53,400 a lot of this is the same in regards to transmission 60 00:02:53,500 --> 00:02:56,100 and immunity, and within transmission, 61 00:02:56,200 --> 00:02:57,833 animal to human transmission 62 00:02:57,933 --> 00:03:01,400 as well as human to human transmission. 63 00:03:01,500 --> 00:03:05,400 So the first concept I'll go over is viral properties 64 00:03:05,500 --> 00:03:07,233 that are unique to influenza, 65 00:03:07,333 --> 00:03:10,000 dealing with some surface antigens called hemagglutinin 66 00:03:10,100 --> 00:03:13,233 and neuraminidase, and then going to antigenic drift 67 00:03:13,333 --> 00:03:16,300 and shift, which really helps us understand epidemics 68 00:03:16,400 --> 00:03:18,700 and pandemics and how they occur. 69 00:03:18,800 --> 00:03:21,333 Second concept I'll go to is transmission. 70 00:03:21,433 --> 00:03:24,066 So this is focusing more on the human to human transmission 71 00:03:24,166 --> 00:03:27,200 that occurs with droplets transmission mainly, 72 00:03:27,300 --> 00:03:29,766 and then also discussing some of the environmental changes 73 00:03:29,866 --> 00:03:32,033 that allow influenza to replicate. 74 00:03:33,233 --> 00:03:35,000 The third concept that I'll go through 75 00:03:35,100 --> 00:03:36,500 has to do with immunity. 76 00:03:36,600 --> 00:03:38,233 So not only population immunity, 77 00:03:38,333 --> 00:03:41,066 but I will talk about influenza vaccine overall. 78 00:03:43,466 --> 00:03:46,500 So I know I listed a whole bunch of things on that slide. 79 00:03:46,600 --> 00:03:47,933 Some things may be familiar to you, 80 00:03:48,033 --> 00:03:50,233 some things may be completely foreign, 81 00:03:50,333 --> 00:03:52,233 so I really don't want you guys thinking like this 82 00:03:52,333 --> 00:03:53,466 at this point. 83 00:03:53,566 --> 00:03:56,166 I really want us to take this journey together 84 00:03:56,266 --> 00:03:57,700 and have a better understanding idea 85 00:03:57,800 --> 00:04:00,066 of some of these concepts that come through 86 00:04:00,166 --> 00:04:01,700 when we talk about influenza. 87 00:04:01,800 --> 00:04:06,700 So my goal is to put you more in this realm. 88 00:04:06,800 --> 00:04:09,600 Being able to talk to family and friends about influenza, 89 00:04:09,700 --> 00:04:11,000 being more informed, yourself, about influenza 90 00:04:11,100 --> 00:04:13,366 and some other respiratory viruses. 91 00:04:13,466 --> 00:04:16,533 Realistically, I know that you may feel more like this 92 00:04:16,633 --> 00:04:20,600 after my talk, and that's okay, but I'm hoping that we land 93 00:04:20,700 --> 00:04:23,133 more on this, where we just really understand 94 00:04:23,233 --> 00:04:25,366 the importance of hand washing and the key things 95 00:04:25,466 --> 00:04:27,900 with influenza and other respiratory viruses 96 00:04:28,000 --> 00:04:30,233 to reduce transmission overall. 97 00:04:32,900 --> 00:04:36,200 So before I go into those key concepts that I talked about, 98 00:04:36,300 --> 00:04:38,800 I'm gonna start with the burden of influenza. 99 00:04:38,900 --> 00:04:40,033 So this is important, 100 00:04:40,133 --> 00:04:41,933 and why I'm talking about influenza today 101 00:04:42,033 --> 00:04:44,366 has to do with the burden of disease that we see 102 00:04:44,466 --> 00:04:46,400 in the United States and throughout the world. 103 00:04:48,600 --> 00:04:50,866 So these statistics here, I'll try not to bore you 104 00:04:50,966 --> 00:04:53,500 with a ton of statistics, but these statistics here 105 00:04:53,600 --> 00:04:56,066 are just from this influenza season. 106 00:04:56,166 --> 00:04:59,266 So starting from September to this is the most recent one 107 00:04:59,366 --> 00:05:02,166 on the CDC from February 22nd. 108 00:05:02,266 --> 00:05:04,733 These are the numbers that we're dealing with. 109 00:05:04,833 --> 00:05:07,766 So when we talk about flu illnesses overall, 110 00:05:07,866 --> 00:05:12,766 we're at 45 million flu illnesses in the United States. 111 00:05:12,866 --> 00:05:14,366 Okay. 112 00:05:14,466 --> 00:05:16,600 So this isn't world, this is in the United States, here. 113 00:05:16,700 --> 00:05:20,866 We're talking about 500,000 influenza hospitalizations. 114 00:05:20,966 --> 00:05:22,433 So to put that in perspective, 115 00:05:22,533 --> 00:05:25,600 that's about the size of Milwaukee. 116 00:05:25,700 --> 00:05:27,966 A little bit less than the size of Milwaukee, overall. 117 00:05:28,066 --> 00:05:32,000 So the entire city of Milwaukee 118 00:05:32,100 --> 00:05:33,966 would be hospitalized with influenza. 119 00:05:35,366 --> 00:05:37,433 In addition to that, when we look at flu deaths 120 00:05:37,533 --> 00:05:39,400 so far this season alone, 121 00:05:39,500 --> 00:05:43,133 we're at 18,000 to 46,000 influenza deaths, 122 00:05:44,266 --> 00:05:46,366 which is quite a lot when we're comparing it 123 00:05:46,466 --> 00:05:48,966 to some other things that are going on at this time. 124 00:05:50,400 --> 00:05:54,100 Overall, the CDC tracks all of the leading causes of death, 125 00:05:54,200 --> 00:05:56,500 and in 2017, which is the most updated ones 126 00:05:56,600 --> 00:05:59,566 that they have, it is the eighth leading cause of death. 127 00:05:59,666 --> 00:06:01,433 So influenza and pneumonia combined 128 00:06:01,533 --> 00:06:03,800 are the eighth leading cause of death overall. 129 00:06:03,900 --> 00:06:06,066 So this is really important, and something I think 130 00:06:06,166 --> 00:06:09,100 a lot of us forget about, is how big of a burden this is. 131 00:06:10,533 --> 00:06:13,633 This is also from the CDC, the Center for Disease Control. 132 00:06:13,733 --> 00:06:16,733 I'll abbreviate it as the CDC going forward. 133 00:06:16,833 --> 00:06:18,900 This has to do with the median incidence 134 00:06:19,000 --> 00:06:23,500 of symptomatic influenza throughout the influenza years 135 00:06:23,600 --> 00:06:27,200 from 2010 to 2015 influenza seasons. 136 00:06:27,300 --> 00:06:29,266 So the seasons' severity change quite a bit 137 00:06:29,366 --> 00:06:33,366 from moderate, to low, to high depending on certain types 138 00:06:33,466 --> 00:06:35,633 of viruses that are circulating that year, 139 00:06:35,733 --> 00:06:38,900 but overall, with all ages, this is the amount of people 140 00:06:39,000 --> 00:06:40,900 that have symptoms because of influenza. 141 00:06:41,000 --> 00:06:47,033 So 8.3% of the total population has influenza symptoms 142 00:06:47,133 --> 00:06:48,933 throughout the influenza season. 143 00:06:49,033 --> 00:06:52,933 Then, when we look at specific age groups overall, 144 00:06:53,033 --> 00:06:56,400 we notice that the children less than five years of age 145 00:06:56,500 --> 00:07:01,266 have a higher percentage, and also adults age 50 to 64 146 00:07:01,366 --> 00:07:03,333 also have a higher percentage. 147 00:07:03,433 --> 00:07:05,466 Again, every season it changes a little bit, 148 00:07:05,566 --> 00:07:07,766 there's some certain seasons that it shifts, 149 00:07:07,866 --> 00:07:10,700 but really these are the ages that are affected the most. 150 00:07:12,333 --> 00:07:14,466 The deaths per year in the United States, 151 00:07:14,566 --> 00:07:15,966 it's 12,000 to 61,000. 152 00:07:16,066 --> 00:07:18,433 Again, that changes depending on the circulating viruses 153 00:07:18,533 --> 00:07:21,766 and some of the other things I'll talk about moving forward. 154 00:07:21,866 --> 00:07:28,566 But worldwide, there is 290,000 to 646,000 deaths per year. 155 00:07:28,666 --> 00:07:29,833 The entire world. 156 00:07:31,033 --> 00:07:33,766 Okay, so that addresses just some of the burden, 157 00:07:33,866 --> 00:07:36,166 and why I think it's important to talk about influenza, 158 00:07:36,266 --> 00:07:39,466 and why we should be educated about influenza overall. 159 00:07:39,566 --> 00:07:41,100 So now I'll go into the viral properties 160 00:07:41,200 --> 00:07:42,266 I was talking about. 161 00:07:42,366 --> 00:07:44,066 So these are specific to influenza 162 00:07:44,166 --> 00:07:46,733 and help with influenza being virulent, 163 00:07:46,833 --> 00:07:49,633 and how it gets transmitted to others. 164 00:07:49,733 --> 00:07:52,533 So first, I'm gonna talk about the two surface proteins 165 00:07:52,633 --> 00:07:55,433 that are important, hemagglutinin and neuraminidase. 166 00:07:57,233 --> 00:08:00,500 So this is a depiction of the influenza virus 167 00:08:00,600 --> 00:08:02,166 that really graphically helps. 168 00:08:02,266 --> 00:08:04,766 So influenza virus is an RNA virus. 169 00:08:04,866 --> 00:08:07,900 This is important when we talk about some of the changes 170 00:08:08,000 --> 00:08:10,200 that the virus can have moving forward. 171 00:08:10,300 --> 00:08:13,300 So its genome, so the genetic makeup of this virus 172 00:08:13,400 --> 00:08:17,533 is RNA instead of DNA, which our genetic makeup is made of. 173 00:08:19,933 --> 00:08:22,800 So now, moving onto some surface proteins. 174 00:08:22,900 --> 00:08:25,866 So the first one I wanna talk about is hemagglutinin, 175 00:08:25,966 --> 00:08:27,700 which is, really how you think about it 176 00:08:27,800 --> 00:08:32,366 is this the virus here, and how it sticks to cells, 177 00:08:32,466 --> 00:08:34,100 and how it's glued to a cell 178 00:08:34,200 --> 00:08:37,033 is the protein called hemagglutinin. 179 00:08:37,133 --> 00:08:40,500 So this is the reason that the influenza viruses 180 00:08:40,600 --> 00:08:42,500 attaches to cells. 181 00:08:42,600 --> 00:08:46,966 Moving forward, it's abbreviated as HA or H. 182 00:08:47,066 --> 00:08:50,600 I'll come into influenza naming in a little bit. 183 00:08:51,966 --> 00:08:55,166 The second surface protein that you can see 184 00:08:55,266 --> 00:08:58,333 on this picture here is something called neuraminidase, 185 00:08:58,433 --> 00:09:01,133 which helps release the virus from the cell. 186 00:09:01,233 --> 00:09:03,300 So after the virus is attached, 187 00:09:03,400 --> 00:09:06,566 it gets engulfed into the cell, it makes new virus, 188 00:09:06,666 --> 00:09:08,833 and then prior to it getting out of the cell, 189 00:09:08,933 --> 00:09:10,566 it needs to be released by something. 190 00:09:10,666 --> 00:09:13,533 And this is what is releasing it, the neuraminidase. 191 00:09:13,633 --> 00:09:15,533 So you can think about the neuraminidase 192 00:09:15,633 --> 00:09:17,166 as a scissor, okay? 193 00:09:17,266 --> 00:09:21,066 So the hemagglutinin glues it to the cell, 194 00:09:21,166 --> 00:09:24,966 the neuraminidase cuts it off from the cell. 195 00:09:25,066 --> 00:09:28,633 Moving forward, this will be abbreviated as NA or N. 196 00:09:28,733 --> 00:09:30,833 And so, these are important when we talk about 197 00:09:30,933 --> 00:09:32,900 some of the naming of influenza viruses. 198 00:09:33,000 --> 00:09:35,233 So if you guys have heard of influenza viruses 199 00:09:35,333 --> 00:09:41,033 named H1N1, H3N2, H2N2, 200 00:09:41,133 --> 00:09:42,733 those are why they're named that way 201 00:09:42,833 --> 00:09:44,733 is based on these surface proteins. 202 00:09:44,833 --> 00:09:47,100 So the H refers to hemagglutinin, 203 00:09:47,200 --> 00:09:49,666 the N refers to neuraminidase. 204 00:09:52,933 --> 00:09:55,466 So now, we'll go through the life cycle of influenza. 205 00:09:55,566 --> 00:09:58,533 So once it attaches to the epithelial cell 206 00:09:58,633 --> 00:10:03,000 of either humans or animals, what it does is that virus 207 00:10:03,100 --> 00:10:06,800 goes into the cell, over on the second portion here, 208 00:10:07,966 --> 00:10:10,300 and that is facilitated, the actual attachment 209 00:10:10,400 --> 00:10:12,233 like we talked about, is the hemagglutinin, 210 00:10:12,333 --> 00:10:16,066 goes into the cell, and then it releases its viral contents 211 00:10:16,166 --> 00:10:18,733 in that third stage, in the uncoating stage. 212 00:10:20,633 --> 00:10:23,533 Once its viral contents are in the human cell 213 00:10:23,633 --> 00:10:27,466 or animal cell, it then transfers its RNA material 214 00:10:27,566 --> 00:10:29,800 into the nucleus of that cell, 215 00:10:29,900 --> 00:10:31,933 and then what it does is it replicates it. 216 00:10:32,033 --> 00:10:33,966 So it makes more of itself, 217 00:10:34,066 --> 00:10:36,600 making more of these infectious viral particles 218 00:10:36,700 --> 00:10:39,566 that you can see within the cell, here. 219 00:10:39,666 --> 00:10:43,500 And then, once it's ready, it goes to the cell's surface 220 00:10:43,600 --> 00:10:44,733 and then it gets released, 221 00:10:44,833 --> 00:10:46,300 and that's where the neuraminidase comes in 222 00:10:46,400 --> 00:10:48,066 and it helps with the process. 223 00:10:52,033 --> 00:10:54,833 So there are three different types of influenza, 224 00:10:56,000 --> 00:10:58,066 type A, type B, and type C. 225 00:10:59,066 --> 00:11:00,766 So first I'll mention type C. 226 00:11:00,866 --> 00:11:03,733 Type C is not something we hear about very often, 227 00:11:03,833 --> 00:11:06,900 but it is a subtype of influenza. 228 00:11:07,000 --> 00:11:09,366 It typically causes very mild respiratory illnesses 229 00:11:09,466 --> 00:11:10,533 in children. 230 00:11:10,633 --> 00:11:12,033 We don't focus on it as much 231 00:11:12,133 --> 00:11:14,333 because it doesn't lead to pandemics or epidemics, 232 00:11:14,433 --> 00:11:17,433 so it doesn't lead to mass people having infections 233 00:11:17,533 --> 00:11:19,800 because of it, and the symptoms are quite mild 234 00:11:19,900 --> 00:11:22,466 so we don't see deaths associated with it. 235 00:11:22,566 --> 00:11:24,466 This is the last time I'll talk about type C, 236 00:11:24,566 --> 00:11:26,566 'cause really, the importance of the influenza 237 00:11:26,666 --> 00:11:28,766 has to do with type A and B. 238 00:11:30,400 --> 00:11:34,266 So now, talking about type A, as I mentioned previously, 239 00:11:34,366 --> 00:11:38,300 type A is named by the H#*N#* 240 00:11:38,400 --> 00:11:42,133 or H#N# subtypes. 241 00:11:42,233 --> 00:11:45,800 When we look at different subtypes like I had mentioned, 242 00:11:45,900 --> 00:11:49,333 there are certain subtypes that infect different types 243 00:11:49,433 --> 00:11:51,700 of animals and different types of humans. 244 00:11:52,700 --> 00:11:55,166 So influenza A is quite unique 245 00:11:55,266 --> 00:11:58,566 because it can infect birds, can infect pigs, 246 00:11:58,666 --> 00:12:00,800 and it can infect humans. 247 00:12:00,900 --> 00:12:03,066 So this becomes important when we talk a little bit later 248 00:12:03,166 --> 00:12:05,833 about some of the pandemics that have happened in the past. 249 00:12:05,933 --> 00:12:08,733 And concern for pandemics happening in the future 250 00:12:08,833 --> 00:12:11,266 really has to do with multiple species 251 00:12:11,366 --> 00:12:14,700 being able to be infected with influenza A virus. 252 00:12:15,866 --> 00:12:18,466 Humans, at this time, have only been known 253 00:12:18,566 --> 00:12:23,266 to have H1N1, H2N2, and H3N2, 254 00:12:23,366 --> 00:12:24,666 so those are the most common ones 255 00:12:24,766 --> 00:12:26,200 that you'll hear over and over again. 256 00:12:26,300 --> 00:12:28,066 They're the most common ones that are covered 257 00:12:28,166 --> 00:12:29,800 in our vaccines as well. 258 00:12:33,266 --> 00:12:34,333 Now, type B. 259 00:12:34,433 --> 00:12:36,666 So type B infects humans only, 260 00:12:36,766 --> 00:12:39,466 so it does not infect animals at all. 261 00:12:39,566 --> 00:12:42,933 There are two lineages of circulating influenza B 262 00:12:43,033 --> 00:12:44,500 for the past 20 years, 263 00:12:44,600 --> 00:12:47,533 and those are called Victoria and Yamagata. 264 00:12:51,866 --> 00:12:54,733 So I talked about the viral properties 265 00:12:54,833 --> 00:12:57,533 in regards to hemagglutinin and neuraminidase. 266 00:12:57,633 --> 00:13:01,766 Now, I will go on and change to talk about antigenic drift 267 00:13:01,866 --> 00:13:03,666 and antigenic shift. 268 00:13:03,766 --> 00:13:06,000 So these words sound very similar, 269 00:13:06,100 --> 00:13:07,633 and as a medical student, 270 00:13:07,733 --> 00:13:11,033 and learning all of this, they jumble up in your mind, 271 00:13:11,133 --> 00:13:14,400 so I'll try and make them as different as possible as I can 272 00:13:14,500 --> 00:13:16,933 in using some analogies moving forward. 273 00:13:17,033 --> 00:13:18,933 But really, these are important to understand 274 00:13:19,033 --> 00:13:21,533 why we get outbreaks of influenza 275 00:13:21,633 --> 00:13:25,033 and why we get outbreaks between continents of influenza. 276 00:13:27,600 --> 00:13:29,500 So I'll first start with antigenic drift. 277 00:13:29,600 --> 00:13:32,400 So this is a similar influenza virus that we saw before. 278 00:13:32,500 --> 00:13:35,366 Instead, it's not opened, it's actually closed. 279 00:13:35,466 --> 00:13:37,466 So you have the hemagglutinin and the neuraminidase 280 00:13:37,566 --> 00:13:38,733 on the surface. 281 00:13:41,666 --> 00:13:43,200 So like I had mentioned previously, 282 00:13:43,300 --> 00:13:45,200 influenza is an RNA virus. 283 00:13:45,300 --> 00:13:48,033 With an RNA virus, that virus is at risk 284 00:13:48,133 --> 00:13:50,200 for having certain types of mutations. 285 00:13:50,300 --> 00:13:52,566 It doesn't do a good job of proofreading 286 00:13:53,700 --> 00:13:56,666 through any of the viruses that it makes. 287 00:13:56,766 --> 00:13:59,966 It does not do a great job about it, 288 00:14:00,066 --> 00:14:02,433 and so it can have certain mutations. 289 00:14:02,533 --> 00:14:04,100 It can result in point mutations, 290 00:14:04,200 --> 00:14:05,933 which is just a minor mutation 291 00:14:06,033 --> 00:14:08,366 or a minor change that happens. 292 00:14:08,466 --> 00:14:10,833 So when this happens on those surface proteins, 293 00:14:10,933 --> 00:14:13,733 with hemagglutinin or neuraminidase, 294 00:14:13,833 --> 00:14:17,433 what you get is a virus that is closely related 295 00:14:17,533 --> 00:14:20,566 but not exactly the same as the initial virus. 296 00:14:20,666 --> 00:14:23,100 So as you can see here, the neuraminidase 297 00:14:23,200 --> 00:14:26,333 changed from this circular sort of flower structure 298 00:14:26,433 --> 00:14:29,166 over to these squares overall. 299 00:14:29,266 --> 00:14:33,200 So it's somewhat similar, but definitely has changed. 300 00:14:33,300 --> 00:14:35,366 This can occur with influenza A 301 00:14:35,466 --> 00:14:38,233 and it can occur with influenza B as well. 302 00:14:40,100 --> 00:14:42,666 This is what leads to seasonal epidemics. 303 00:14:42,766 --> 00:14:45,933 So you have your virus, it changes slightly, 304 00:14:46,033 --> 00:14:49,800 but people still have some immunity to it, 305 00:14:49,900 --> 00:14:51,833 then that's when you get your changes 306 00:14:51,933 --> 00:14:54,433 and why the vaccine may not be the best fit 307 00:14:54,533 --> 00:14:57,200 or why certain people are getting sick because of it. 308 00:14:58,700 --> 00:15:01,433 So because it is closely related, like I had mentioned, 309 00:15:01,533 --> 00:15:02,700 there is some immunity 310 00:15:02,800 --> 00:15:06,400 and so people do have some cross-protection. 311 00:15:06,500 --> 00:15:07,833 So there is... 312 00:15:07,933 --> 00:15:09,666 Depending on how big the change is 313 00:15:09,766 --> 00:15:12,766 really depends on how much protection you have circulating. 314 00:15:17,533 --> 00:15:19,933 So we talked about the drift, minor change 315 00:15:20,033 --> 00:15:23,966 leads to seasonal epidemics, occurs with influenza A, 316 00:15:24,066 --> 00:15:26,466 and can occur with influenza B. 317 00:15:26,566 --> 00:15:28,966 Now, we'll move onto antigenic shifts. 318 00:15:29,066 --> 00:15:30,466 So antigenic shifts, 319 00:15:30,566 --> 00:15:32,833 we'll start with the same influenza virus, 320 00:15:32,933 --> 00:15:35,833 but now there's a major change in the virus. 321 00:15:35,933 --> 00:15:38,600 So it's not just a small minor point mutation change, 322 00:15:38,700 --> 00:15:40,233 it's a big change. 323 00:15:40,333 --> 00:15:41,933 So really, you're completely changing 324 00:15:42,033 --> 00:15:43,666 what the virus looks like. 325 00:15:43,766 --> 00:15:46,533 So in this case, the hemagglutinin changes 326 00:15:46,633 --> 00:15:48,633 from that blue color to a yellow color 327 00:15:48,733 --> 00:15:50,966 and it's a completely new virus. 328 00:15:52,666 --> 00:15:55,133 This occurs only with influenza A. 329 00:15:57,500 --> 00:16:00,433 And this is what leads to novel or new viruses 330 00:16:00,533 --> 00:16:02,266 that can cause pandemics. 331 00:16:03,666 --> 00:16:05,833 The other part of this that is important to know 332 00:16:05,933 --> 00:16:08,966 that, in order for these new viruses to cause pandemics, 333 00:16:09,066 --> 00:16:10,433 it has to be really distinct 334 00:16:10,533 --> 00:16:14,100 from any other previously circulating influenza viruses. 335 00:16:14,200 --> 00:16:17,333 So the immunity to this new virus has to be very low 336 00:16:17,433 --> 00:16:20,800 or none at all for it to actually cause a pandemic. 337 00:16:23,933 --> 00:16:26,366 So how exactly does this happen? 338 00:16:26,466 --> 00:16:29,766 How does an antigenic shift or those major changes happen? 339 00:16:29,866 --> 00:16:32,000 There's two ways that have happened, 340 00:16:32,100 --> 00:16:34,533 and I'll go over the history of some of this 341 00:16:34,633 --> 00:16:36,733 and some of the pandemics that we've had in the past, 342 00:16:36,833 --> 00:16:38,733 and which one fits into where. 343 00:16:38,833 --> 00:16:40,600 But as I talked about with influenza A 344 00:16:40,700 --> 00:16:44,000 on the previous slides, influenza A can infect animals 345 00:16:44,100 --> 00:16:46,100 and it can infect humans, 346 00:16:46,200 --> 00:16:48,900 so this is where the shifts become important. 347 00:16:49,000 --> 00:16:52,200 So I'll start off and say I just made up these virus names. 348 00:16:52,300 --> 00:16:55,533 They aren't actual names, but we'll start with the pig. 349 00:16:55,633 --> 00:17:02,666 So he has HpNp, the chicken has HcNc, the duck has HdNd, 350 00:17:02,766 --> 00:17:05,966 and then the human has HhNh. 351 00:17:06,066 --> 00:17:09,733 So what happens is these viruses normally circulate. 352 00:17:09,833 --> 00:17:13,033 Some of the animals may have symptoms, most of them don't, 353 00:17:13,133 --> 00:17:15,833 so no one knows that they actually have these viruses. 354 00:17:15,933 --> 00:17:19,033 And then, somehow there's a change in transmission 355 00:17:19,133 --> 00:17:22,200 and it goes from the animals to the human. 356 00:17:23,800 --> 00:17:26,033 Okay, so this is not like, let's use for an example, 357 00:17:26,133 --> 00:17:28,533 the pig one, so HpNp, is not something 358 00:17:28,633 --> 00:17:31,033 that normally circulates in humans but somehow, 359 00:17:31,133 --> 00:17:33,333 someone was working closely with pigs 360 00:17:33,433 --> 00:17:36,300 or was exposed to the virus when working with pigs 361 00:17:36,400 --> 00:17:39,300 or eating pigs, and then the human gets the virus. 362 00:17:40,433 --> 00:17:42,133 This is something that's called spillover, 363 00:17:42,233 --> 00:17:44,333 so it's spilling over from the animal population 364 00:17:44,433 --> 00:17:46,166 into the human population. 365 00:17:46,266 --> 00:17:48,166 So you may see that word over and over again 366 00:17:48,266 --> 00:17:51,366 when people talk about outbreaks of respiratory viruses. 367 00:17:53,666 --> 00:17:57,133 In order for these viruses to go from the pig 368 00:17:57,233 --> 00:17:59,733 to the human and to actually infect the humans, 369 00:17:59,833 --> 00:18:02,300 there's other things that need to happen 370 00:18:02,400 --> 00:18:04,966 in order for that virus to cause pandemics 371 00:18:05,066 --> 00:18:07,500 or to cause massive outbreaks of them. 372 00:18:08,500 --> 00:18:10,233 The virus itself needs to be able to survive 373 00:18:10,333 --> 00:18:11,633 and replicate in the human. 374 00:18:11,733 --> 00:18:13,533 So it did a really good job about surviving 375 00:18:13,633 --> 00:18:15,233 and replicating in that pig, 376 00:18:15,333 --> 00:18:17,066 but now it's in a completely different host 377 00:18:17,166 --> 00:18:19,533 with completely different receptors for things. 378 00:18:19,633 --> 00:18:22,933 And so that's really important is if that virus can adapt 379 00:18:23,033 --> 00:18:26,533 or change to actually have that survival. 380 00:18:26,633 --> 00:18:28,166 Like I had mentioned previously, 381 00:18:28,266 --> 00:18:32,000 the human has to have no previous or very low immunity 382 00:18:32,100 --> 00:18:35,666 to this virus, otherwise their body would take over 383 00:18:35,766 --> 00:18:38,266 and get protected with antibodies. 384 00:18:38,366 --> 00:18:40,633 And then, in addition, in order for it to pass 385 00:18:40,733 --> 00:18:43,033 from one person to the next, you need to have the virus 386 00:18:43,133 --> 00:18:46,200 be able to be transmitted from humans to humans. 387 00:18:46,300 --> 00:18:48,633 So not only does it have to be a spillover event, 388 00:18:48,733 --> 00:18:50,966 there's all these other factors that need to happen 389 00:18:51,066 --> 00:18:52,700 in order to cause pandemics. 390 00:18:54,633 --> 00:18:57,033 The pig is very unique in this situation 391 00:18:57,133 --> 00:19:00,166 because it has respiratory receptors 392 00:19:00,266 --> 00:19:03,233 for both the avian influenza, so the bird influenza, 393 00:19:03,333 --> 00:19:06,666 as well as the human influenza, 394 00:19:06,766 --> 00:19:09,933 so it really facilitates 395 00:19:10,033 --> 00:19:12,700 some of these interspecies transmissions. 396 00:19:14,033 --> 00:19:17,466 And where that becomes important is this second method 397 00:19:17,566 --> 00:19:20,200 of how antigenic shift can happen. 398 00:19:20,300 --> 00:19:22,400 It's something called reassortment. 399 00:19:22,500 --> 00:19:25,900 So reassortment means, if we look in the middle here, 400 00:19:26,000 --> 00:19:29,766 that the pig was infected with multiple viruses, 401 00:19:29,866 --> 00:19:35,033 so from the human, from a previous pig, from a bird, 402 00:19:36,033 --> 00:19:38,266 and then within the genome of the pig, 403 00:19:38,366 --> 00:19:40,600 it recombines all of these genetic material 404 00:19:40,700 --> 00:19:42,600 and makes a new virus. 405 00:19:43,600 --> 00:19:45,333 Then that new virus can go 406 00:19:45,433 --> 00:19:48,066 and combined again with another virus, 407 00:19:48,166 --> 00:19:50,300 and then create another new virus, 408 00:19:50,400 --> 00:19:53,733 and then it can switch over to humans. 409 00:19:53,833 --> 00:19:57,666 So this example here is what caused the 2009 outbreak 410 00:19:58,800 --> 00:20:01,866 with H1N1, referred to as swine flu, 411 00:20:01,966 --> 00:20:04,033 and so what happened in this situation 412 00:20:04,133 --> 00:20:07,133 is that there were two different swine species 413 00:20:07,233 --> 00:20:09,833 that were involved, so you have the Eurasian swine, 414 00:20:09,933 --> 00:20:12,533 which are located in Europe and Asia, 415 00:20:12,633 --> 00:20:14,233 you have your North American swine, 416 00:20:14,333 --> 00:20:16,000 which are located in North America, 417 00:20:16,100 --> 00:20:18,700 and then you have this previous combination with human 418 00:20:18,800 --> 00:20:20,933 and avian species. 419 00:20:21,033 --> 00:20:24,633 So overall, there were four different species involved 420 00:20:24,733 --> 00:20:29,700 with it that really produced this novel or new H1N1 virus. 421 00:20:31,666 --> 00:20:33,466 So this is called reassortment. 422 00:20:33,566 --> 00:20:34,900 The thing about reassortment 423 00:20:35,000 --> 00:20:37,433 is that it doesn't always lead to pandemics. 424 00:20:37,533 --> 00:20:39,633 So reassortment can happen, we may not know 425 00:20:39,733 --> 00:20:41,400 that it's happening, and as long as people 426 00:20:41,500 --> 00:20:44,233 are not getting sick or not dying from it, 427 00:20:44,333 --> 00:20:45,866 we still wouldn't know. 428 00:20:45,966 --> 00:20:48,266 So a lot of this happens within animals 429 00:20:48,366 --> 00:20:49,966 and we are unaware of it. 430 00:20:54,033 --> 00:20:56,633 So this looks at the different pandemics throughout history. 431 00:20:56,733 --> 00:20:59,533 So we've had four total so far, 432 00:21:01,000 --> 00:21:04,933 the first one starting with the 1918 Spanish influenza. 433 00:21:05,033 --> 00:21:07,933 So what is predicted happened in that situation 434 00:21:08,033 --> 00:21:10,300 was that first method I had talked about. 435 00:21:10,400 --> 00:21:12,766 So all of these are big shifts that happened 436 00:21:12,866 --> 00:21:16,466 that causes the major mutations to cause a new virus 437 00:21:16,566 --> 00:21:18,700 and cause pandemics. 438 00:21:18,800 --> 00:21:21,233 With the 1918 Spanish influenza, what happened 439 00:21:21,333 --> 00:21:25,000 is that there were birds that then transmitted their virus 440 00:21:25,100 --> 00:21:28,266 that humans had never seen before, to humans. 441 00:21:29,466 --> 00:21:32,066 And then, it caused a massive outbreak 442 00:21:32,166 --> 00:21:34,033 where 50 million people died 443 00:21:34,133 --> 00:21:36,266 with the 1918 Spanish influenza. 444 00:21:37,966 --> 00:21:41,200 Then, with the second outbreak in 1957, 445 00:21:41,300 --> 00:21:43,566 referred to as the Asian influenza, 446 00:21:43,666 --> 00:21:45,133 this involved that reassortment, 447 00:21:45,233 --> 00:21:46,966 so that second method I talked about 448 00:21:47,066 --> 00:21:49,300 where there is mixing of the genetic material 449 00:21:49,400 --> 00:21:51,366 to make these new viruses. 450 00:21:51,466 --> 00:21:54,100 But this involved an avian influenza strain 451 00:21:54,200 --> 00:21:56,866 as well as a human influenza strain 452 00:21:56,966 --> 00:21:59,866 to cause H2N2 pandemic. 453 00:22:01,400 --> 00:22:02,866 The third outbreak, here, 454 00:22:02,966 --> 00:22:07,600 is the 1968 Hong Kong influenza pandemic. 455 00:22:07,700 --> 00:22:10,000 And this one also had reassortment 456 00:22:10,100 --> 00:22:12,000 of the avian influenza 457 00:22:12,100 --> 00:22:15,333 and the human influenza that exchanged material, 458 00:22:15,433 --> 00:22:17,533 resulting in H3N2. 459 00:22:19,133 --> 00:22:20,333 The last pandemic, and the reason 460 00:22:20,433 --> 00:22:23,133 why it's not on this particular article 461 00:22:23,233 --> 00:22:25,666 is that this article was written in 2005, 462 00:22:25,766 --> 00:22:29,000 and so the 2009 pandemic was not on that one, 463 00:22:29,100 --> 00:22:30,633 so we had previously talked about that, 464 00:22:30,733 --> 00:22:32,966 that was that quadruple reassortment 465 00:22:33,066 --> 00:22:36,133 with two different swines, an avian, and a human 466 00:22:36,233 --> 00:22:39,066 that then resulted in this new H1N1. 467 00:22:44,366 --> 00:22:47,900 For now, your next question, I assume, is gonna be, 468 00:22:48,000 --> 00:22:49,500 "Okay, well, what does this mean 469 00:22:49,600 --> 00:22:53,133 "and can we predict when the next pandemic is gonna happen?" 470 00:22:54,366 --> 00:22:56,500 There are a lot of experts that are trying to do 471 00:22:56,600 --> 00:22:57,866 that exact same thing, 472 00:22:57,966 --> 00:23:00,733 to try and predict what exactly is gonna happen 473 00:23:00,833 --> 00:23:04,766 and to try and come up with antiviral medications, 474 00:23:04,866 --> 00:23:06,566 to try and come up with vaccines 475 00:23:06,666 --> 00:23:09,400 that can actually protect against some of this. 476 00:23:09,500 --> 00:23:13,000 Overall, experts are really focusing on the avian influenza 477 00:23:13,100 --> 00:23:15,866 and their concern about the avian influenza 478 00:23:15,966 --> 00:23:18,200 actually causing the next pandemic. 479 00:23:18,300 --> 00:23:20,733 And the reason for this has to do with, 480 00:23:20,833 --> 00:23:23,500 there's two current strains of avian influenza 481 00:23:23,600 --> 00:23:27,166 that have actually gone to humans at this point. 482 00:23:27,266 --> 00:23:31,333 The first one is something called H5N1. 483 00:23:31,433 --> 00:23:36,133 So H5N1 started to become present in 1994 484 00:23:36,233 --> 00:23:38,500 when they first noticed that there was a new strain 485 00:23:38,600 --> 00:23:41,466 in humans when someone got very sick, 486 00:23:41,566 --> 00:23:42,866 and they've been tracking it. 487 00:23:42,966 --> 00:23:44,933 It's kind of spread throughout different continents. 488 00:23:45,033 --> 00:23:47,366 It's been present in Europe, it's been present in Asia, 489 00:23:47,466 --> 00:23:49,300 it's been present in North America. 490 00:23:50,766 --> 00:23:54,200 The thing about this one is it causes very severe infection, 491 00:23:54,300 --> 00:23:56,466 and the case fatality rates are quite high. 492 00:23:56,566 --> 00:23:58,566 So the case vitality rates are 53%, 493 00:23:58,666 --> 00:24:02,133 which means 53% of the people that get this infection 494 00:24:02,233 --> 00:24:04,066 are dying from the infection. 495 00:24:05,500 --> 00:24:09,100 So for perspective-wise, the normal seasonal influenza, 496 00:24:09,200 --> 00:24:12,933 it varies a little bit by year, but it's 0.1%. 497 00:24:13,033 --> 00:24:17,933 Okay, coronavirus right now, the novel coronavirus COVID-19, 498 00:24:18,033 --> 00:24:21,500 is predicted to be about 3 to 4%. 499 00:24:21,600 --> 00:24:24,666 So when we're talking about 53% case fatality rate, 500 00:24:24,766 --> 00:24:28,466 that is incredibly high. 501 00:24:28,566 --> 00:24:31,300 The other interesting thing about this H5N1 502 00:24:31,400 --> 00:24:35,200 is that the median age is very young at 20 years of age, 503 00:24:36,466 --> 00:24:37,700 which is something that has happened 504 00:24:37,800 --> 00:24:39,533 with previous pandemics, and I'll go into that 505 00:24:39,633 --> 00:24:41,366 a little bit more when we talk about immunity 506 00:24:41,466 --> 00:24:43,133 moving forward, but it's really hitting 507 00:24:43,233 --> 00:24:46,800 the younger populations with this type of virus. 508 00:24:48,166 --> 00:24:50,233 The thing about this virus, though, is that people 509 00:24:50,333 --> 00:24:53,133 that have been infected, they've been able to track 510 00:24:53,233 --> 00:24:58,466 that they've had exposure to ill poultry 511 00:24:58,566 --> 00:25:01,400 about one week prior to their onset. 512 00:25:01,500 --> 00:25:04,666 So really, the control of this virus has been 513 00:25:04,766 --> 00:25:07,833 monitoring poultry and mass killing of poultry 514 00:25:07,933 --> 00:25:11,233 when they demonstrate any symptoms. 515 00:25:11,333 --> 00:25:13,366 In addition to that, farmers are testing 516 00:25:13,466 --> 00:25:17,766 a lot of their chickens or poultry for this type of virus, 517 00:25:17,866 --> 00:25:22,866 and then will proceed to kill that whole area of chickens. 518 00:25:26,066 --> 00:25:28,633 The second one that also is concerning 519 00:25:28,733 --> 00:25:34,233 is something called H7N9, and this has caused outbreaks 520 00:25:34,333 --> 00:25:35,500 within China. 521 00:25:37,400 --> 00:25:39,333 The case fatality with this one, as well, 522 00:25:39,433 --> 00:25:40,866 is quite high at 30%. 523 00:25:40,966 --> 00:25:44,666 The median age is older, about 60 years of age. 524 00:25:44,766 --> 00:25:47,800 But the reason why this one is such a concern, 525 00:25:47,900 --> 00:25:50,500 in addition to the case fatality rates, 526 00:25:50,600 --> 00:25:54,233 is that it is resistant to Tamiflu. 527 00:25:54,333 --> 00:25:57,966 So Tamiflu is the main antiviral medication 528 00:25:58,066 --> 00:26:02,400 we use to treat and to use as prophylaxis for influenza, 529 00:26:02,500 --> 00:26:04,033 and a lot of the other viruses 530 00:26:04,133 --> 00:26:06,633 have not shown resistance to Tamiflu. 531 00:26:06,733 --> 00:26:08,566 That's why it's so routinely used, 532 00:26:08,666 --> 00:26:10,900 but this one in particular has shown resistance, 533 00:26:11,000 --> 00:26:12,833 which is really concerning 534 00:26:12,933 --> 00:26:14,733 when you don't have a lot of other options 535 00:26:14,833 --> 00:26:17,300 to treat people with for their influenza. 536 00:26:17,400 --> 00:26:21,633 And so the CDC and the WHO have actually labeled this virus 537 00:26:21,733 --> 00:26:25,066 as the highest potential for pandemic risk in the future. 538 00:26:26,266 --> 00:26:29,500 Luckily, this virus has incredibly poor 539 00:26:29,600 --> 00:26:31,800 human to human transmission. 540 00:26:31,900 --> 00:26:36,800 So people can get it from interactions with a poultry 541 00:26:36,900 --> 00:26:41,033 or a chicken that has this type of virus, 542 00:26:41,133 --> 00:26:43,133 but really, it's not transmitting from one person 543 00:26:43,233 --> 00:26:46,800 to the next, so there's no further spread that's happening, 544 00:26:46,900 --> 00:26:48,033 which is really important. 545 00:26:48,133 --> 00:26:50,200 - Attendee: Is that true of H5N1 as well? 546 00:26:50,300 --> 00:26:53,466 - H5N1 has a lower human to human transmission. 547 00:26:53,566 --> 00:26:55,066 It's not as much. 548 00:26:55,166 --> 00:27:00,066 There's about 860 cases total from 2013 to 2018 549 00:27:00,166 --> 00:27:01,400 that have been there, 550 00:27:01,500 --> 00:27:04,033 so it's a pretty poor human to human transmission. 551 00:27:05,766 --> 00:27:08,366 But the concerning thing with these avian influenza 552 00:27:08,466 --> 00:27:10,533 is, like I talked about, if they go through 553 00:27:10,633 --> 00:27:13,600 any major antigenic shifts, 554 00:27:13,700 --> 00:27:16,600 that can increase their transmissibility 555 00:27:16,700 --> 00:27:20,266 or make their transmission from humans to humans better, 556 00:27:20,366 --> 00:27:22,933 then that's where this gets really concerning. 557 00:27:23,033 --> 00:27:26,033 A lot of these patients end up in intensive care units, 558 00:27:26,133 --> 00:27:28,166 have very severe pulmonary problems, 559 00:27:28,266 --> 00:27:30,500 and then the high case fatality rates. 560 00:27:30,600 --> 00:27:33,533 So that's why this is a very concerning area 561 00:27:33,633 --> 00:27:35,033 in regards to influenza. 562 00:27:37,400 --> 00:27:40,066 So I know I told you that these words sound the same 563 00:27:40,166 --> 00:27:43,066 and you may have heard me, and they kind of blur together 564 00:27:43,166 --> 00:27:45,166 when I talk about drift and shift, 565 00:27:46,166 --> 00:27:47,866 so I thought I would give you an example 566 00:27:47,966 --> 00:27:51,066 to take it home to try and really give you a better idea 567 00:27:51,166 --> 00:27:52,566 about remembering these. 568 00:27:52,666 --> 00:27:55,966 So antigenic drift, imagine you're on a lazy river, right? 569 00:27:56,066 --> 00:27:58,200 So you're on the tube, you're just drifting along, 570 00:27:58,300 --> 00:28:00,966 you're drifting along, and then you get stuck on the side 571 00:28:01,066 --> 00:28:03,666 because there's a big bunch of people that are coming by 572 00:28:03,766 --> 00:28:05,966 and you get pushed out of the way. 573 00:28:06,066 --> 00:28:09,600 So your tube goes in a little bit, shifts a little bit, 574 00:28:09,700 --> 00:28:12,133 but in the end, you end up in the same spot, right? 575 00:28:12,233 --> 00:28:14,833 So you have a little bit of a drift, 576 00:28:14,933 --> 00:28:17,866 but you still end up where you wanted to be. 577 00:28:17,966 --> 00:28:20,733 This happens with influenza A, and it happens with B, 578 00:28:20,833 --> 00:28:23,100 and this is what leads to your seasonal epidemics. 579 00:28:23,200 --> 00:28:26,433 So if you think about it, when you got stuck in that area, 580 00:28:26,533 --> 00:28:28,400 you're close to the people that you're around 581 00:28:28,500 --> 00:28:30,066 in that local environment. 582 00:28:30,166 --> 00:28:32,433 You can transmit that virus in that point, 583 00:28:32,533 --> 00:28:34,533 but then you go back to your normal lazy river 584 00:28:34,633 --> 00:28:36,200 once the crowding goes away. 585 00:28:38,533 --> 00:28:41,933 Antigenic shift, you can think about it as a gear shift. 586 00:28:42,033 --> 00:28:43,933 So as you shift the gear, you're ending up 587 00:28:44,033 --> 00:28:45,333 in a different location, 588 00:28:45,433 --> 00:28:47,066 or you're going in a different direction. 589 00:28:47,166 --> 00:28:49,566 So this is a major change from your endpoint 590 00:28:49,666 --> 00:28:50,933 that you initially had, 591 00:28:51,033 --> 00:28:52,633 or your starting point, I should say. 592 00:28:52,733 --> 00:28:54,800 And this occurs with influenza A 593 00:28:54,900 --> 00:28:57,000 and this is what leads to pandemics. 594 00:29:01,066 --> 00:29:04,233 All right, we talked about the viral properties, 595 00:29:04,333 --> 00:29:06,233 the surface antigens, the neuraminidase, 596 00:29:06,333 --> 00:29:07,633 the hemagglutinin. 597 00:29:07,733 --> 00:29:11,033 We talked about the antigenic shift and antigenic drift. 598 00:29:11,133 --> 00:29:12,400 Now, we'll go onto transmission. 599 00:29:12,500 --> 00:29:14,333 So I already previously talked about the animal 600 00:29:14,433 --> 00:29:16,966 to human transmission and why that's important 601 00:29:17,066 --> 00:29:18,933 in regards to influenza, 602 00:29:19,033 --> 00:29:22,466 and now I'll focus on the human to human transmission. 603 00:29:22,566 --> 00:29:25,033 So I'll start with droplets. 604 00:29:26,566 --> 00:29:28,900 So let's say you have your infected person 605 00:29:29,000 --> 00:29:32,066 that has influenza here, and they're coughing, 606 00:29:32,166 --> 00:29:33,866 and they're sneezing, and everything is going 607 00:29:33,966 --> 00:29:36,433 all over the place 'cause they try to control it, 608 00:29:36,533 --> 00:29:39,133 but as you know and you've seen in some of those videos, 609 00:29:39,233 --> 00:29:41,933 the snot goes everywhere, and it's quite disturbing. 610 00:29:43,300 --> 00:29:46,533 And with that, they're carrying influenza virus particles. 611 00:29:46,633 --> 00:29:49,266 So the influenza virus particles get into the air, 612 00:29:49,366 --> 00:29:52,133 and these are all different ways that infectious disease 613 00:29:52,233 --> 00:29:54,033 can be transmitted. 614 00:29:54,133 --> 00:29:58,733 So with influenza itself, it tends to be larger droplets. 615 00:29:58,833 --> 00:30:01,066 So instead of these smaller droplet nuclei 616 00:30:01,166 --> 00:30:04,566 that you can see here, they're really larger droplets. 617 00:30:04,666 --> 00:30:08,000 So what that means is larger droplets can't stay in the air 618 00:30:08,100 --> 00:30:10,900 for a long period of time, so you have to be quite close 619 00:30:11,000 --> 00:30:15,100 to a person in order to actually transmit influenza. 620 00:30:15,200 --> 00:30:17,400 Some of the other things, like tuberculosis, 621 00:30:17,500 --> 00:30:21,133 which is airborne, so these tiny nuclei, 622 00:30:21,233 --> 00:30:23,533 they can stay in the air for a longer period of time 623 00:30:23,633 --> 00:30:25,333 and go further distances. 624 00:30:28,400 --> 00:30:30,600 So let's put these two people in a bubble 625 00:30:30,700 --> 00:30:33,066 and let's say, "Okay, what does that mean, really, 626 00:30:33,166 --> 00:30:34,300 "in real time?" 627 00:30:34,400 --> 00:30:36,666 The infected individual sneezes. 628 00:30:36,766 --> 00:30:39,733 How close does the susceptible individual need to be 629 00:30:39,833 --> 00:30:41,866 in order to actually transmit the virus? 630 00:30:41,966 --> 00:30:44,666 And a lot of studies have been done about this, 631 00:30:44,766 --> 00:30:47,000 and what they have found out 632 00:30:47,100 --> 00:30:49,833 is that it's between three to six feet, 633 00:30:49,933 --> 00:30:51,666 so it has to be quite close. 634 00:30:51,766 --> 00:30:55,833 It's not always super close, but it's a pretty close contact 635 00:30:55,933 --> 00:30:57,433 within that three to six feet. 636 00:30:59,233 --> 00:31:02,133 The other areas that influenza has been shown, 637 00:31:02,233 --> 00:31:05,166 although they're very lower on the list 638 00:31:05,266 --> 00:31:08,300 of being transmitted, is direct contact. 639 00:31:08,400 --> 00:31:11,500 So direct contact means that you have direct contact 640 00:31:11,600 --> 00:31:14,966 with that infectious particle, so if you're sitting close 641 00:31:15,066 --> 00:31:19,466 to that person within that distance, and they sneeze, 642 00:31:19,566 --> 00:31:22,466 and then you grab their Kleenex, and now you have, 643 00:31:22,566 --> 00:31:24,466 I don't know why you would grab their Kleenex but, 644 00:31:24,566 --> 00:31:26,500 [all chuckling] you, 645 00:31:26,600 --> 00:31:28,700 if it's a family member, you don't think about these things, 646 00:31:28,800 --> 00:31:31,766 so you grab their Kleenex, now you have influenza virus, 647 00:31:31,866 --> 00:31:34,566 potentially, on your hand, and then we touch our faces 648 00:31:34,666 --> 00:31:36,833 a lot, I don't know if you guys have ever done 649 00:31:36,933 --> 00:31:39,700 the experiments about how many times you touch your face 650 00:31:39,800 --> 00:31:42,000 within a day or within a short period of time. 651 00:31:42,100 --> 00:31:43,200 It's a lot. 652 00:31:43,300 --> 00:31:45,000 And so, what you would do is you have 653 00:31:45,100 --> 00:31:46,600 those infectious particles on your hand, 654 00:31:46,700 --> 00:31:48,400 you then touch your nose, you touch your mouth, 655 00:31:48,500 --> 00:31:51,300 you touch your eye, and then the virus particles are there. 656 00:31:51,400 --> 00:31:54,700 Again, this is a lower risk of transmission, 657 00:31:54,800 --> 00:31:56,400 but it's still possible. 658 00:31:57,400 --> 00:31:59,166 Indirect contact is what we deal with a lot 659 00:31:59,266 --> 00:32:01,866 in the hospital, so indirect contact has to do 660 00:32:01,966 --> 00:32:06,666 with the person that's infected sneezes on their hand, 661 00:32:06,766 --> 00:32:11,600 they touch an object, they walk away, you would come up, 662 00:32:11,700 --> 00:32:14,866 you touch that object within a shorter time frame, 663 00:32:14,966 --> 00:32:17,433 and you would then have influenza on your hand, 664 00:32:17,533 --> 00:32:19,733 and then touch your nose, or your eye, or your mouth 665 00:32:19,833 --> 00:32:21,000 in those situations. 666 00:32:22,866 --> 00:32:25,200 So these are all important to understand, 667 00:32:25,300 --> 00:32:28,600 and a lot of studies have gone into this 668 00:32:28,700 --> 00:32:31,566 because of hospital situations and precautions 669 00:32:31,666 --> 00:32:34,133 that need to be preventing hospital outbreak. 670 00:32:34,233 --> 00:32:35,766 So I had to show one gross picture 671 00:32:35,866 --> 00:32:37,000 of, [audience chuckling] 672 00:32:37,100 --> 00:32:38,633 there's a lot of 'em on the internet, 673 00:32:38,733 --> 00:32:42,066 but I had to show one gross picture of someone snotty. 674 00:32:42,166 --> 00:32:44,833 So now let's go through, now that we talked about 675 00:32:44,933 --> 00:32:48,600 how you can get transmission, we have these infected people 676 00:32:48,700 --> 00:32:52,633 with influenza, they can transmit influenza virus 677 00:32:52,733 --> 00:32:55,366 anywhere from one day before their symptoms 678 00:32:55,466 --> 00:32:58,600 to seven days after their symptoms, okay? 679 00:32:58,700 --> 00:33:00,866 So the one day before the symptoms is something important 680 00:33:00,966 --> 00:33:04,033 to keep in mind, because they don't know that they're sick 681 00:33:04,133 --> 00:33:06,866 at that point, and so they can transmit it. 682 00:33:06,966 --> 00:33:09,933 The highest transmission rate is really three to four days 683 00:33:10,033 --> 00:33:11,533 after the symptom onset. 684 00:33:13,133 --> 00:33:16,766 So they cough or sneeze and a susceptible individual 685 00:33:16,866 --> 00:33:19,333 is within six feet of that. 686 00:33:19,433 --> 00:33:20,533 So then what happens? 687 00:33:20,633 --> 00:33:22,166 So once it gets coughed and sneeze, 688 00:33:22,266 --> 00:33:25,033 the susceptible individual then gets that viral particle 689 00:33:25,133 --> 00:33:27,900 in their nose, in their mouth, in their eyes, 690 00:33:29,000 --> 00:33:30,166 and then this happens. 691 00:33:30,266 --> 00:33:32,533 So this is a picture of influenza virus, 692 00:33:32,633 --> 00:33:35,233 and you have epithelial cells, which are right here. 693 00:33:35,333 --> 00:33:38,233 Epithelial cells are cells that line your respiratory tract, 694 00:33:38,333 --> 00:33:41,166 so all throughout from your nose to your pharynx, 695 00:33:41,266 --> 00:33:44,400 so your throat, and then into your respiratory system. 696 00:33:44,500 --> 00:33:47,633 So influenza, what it does is it attaches 697 00:33:47,733 --> 00:33:49,200 to these epithelial cells. 698 00:33:49,300 --> 00:33:51,800 So remember that glue I was talking about before? 699 00:33:51,900 --> 00:33:53,266 That's where these become important. 700 00:33:53,366 --> 00:33:56,666 So the hemagglutinin, or that glue, 701 00:33:56,766 --> 00:34:01,733 attaches to the sialic acid receptors that are present 702 00:34:01,833 --> 00:34:03,200 on epithelial cells. 703 00:34:03,300 --> 00:34:05,833 So once it attaches to those, then the virus 704 00:34:05,933 --> 00:34:08,533 can then enter into your system, and then replicate, 705 00:34:08,633 --> 00:34:09,766 and go through the life cycle 706 00:34:09,866 --> 00:34:11,266 that I talked about previously. 707 00:34:14,366 --> 00:34:17,200 So we have these people, the susceptible individual 708 00:34:17,300 --> 00:34:21,033 gets the virus, the virus attaches to the sialic acid, 709 00:34:21,133 --> 00:34:24,500 it goes into the cell, then about one to four days 710 00:34:24,600 --> 00:34:29,166 after being exposed to the virus, they develop symptoms. 711 00:34:29,266 --> 00:34:32,333 So the one to four days is when the virus enters, 712 00:34:32,433 --> 00:34:33,866 and then symptom onset, 713 00:34:33,966 --> 00:34:35,833 and so that's referred to as your incubation period. 714 00:34:35,933 --> 00:34:37,533 So how long it takes for a person 715 00:34:37,633 --> 00:34:39,533 after they've been introduced with the virus 716 00:34:39,633 --> 00:34:41,233 to actually have symptoms. 717 00:34:42,700 --> 00:34:46,466 So relatively to some other viruses, this is quite short, 718 00:34:46,566 --> 00:34:51,000 and so people typically present with symptoms earlier on. 719 00:34:53,766 --> 00:34:55,333 So we talked about droplet, now we'll go 720 00:34:55,433 --> 00:34:58,533 onto some of the environmental things that are important. 721 00:34:59,933 --> 00:35:04,666 So here is a picture of the world, and so what is important 722 00:35:04,766 --> 00:35:08,066 in this picture is that it's a study that was done 723 00:35:08,166 --> 00:35:11,333 that looked at the peak month of influenza, 724 00:35:11,433 --> 00:35:14,666 so when influenza, during the season, their peak month is, 725 00:35:14,766 --> 00:35:17,166 and then how long it lasted for. 726 00:35:17,266 --> 00:35:21,300 So we're very used to having a set period of influenza. 727 00:35:21,400 --> 00:35:23,766 It changes a little bit each year, but most of the time 728 00:35:23,866 --> 00:35:26,633 it'll last from September to about March. 729 00:35:26,733 --> 00:35:28,766 Some years it will last a little bit later 730 00:35:28,866 --> 00:35:31,466 depending on what's circulating and what's going on. 731 00:35:32,633 --> 00:35:34,833 With our peak time, around January or February 732 00:35:34,933 --> 00:35:36,600 in the United States. 733 00:35:36,700 --> 00:35:39,200 But other areas of the world don't have that, 734 00:35:39,300 --> 00:35:43,500 or have different environments that have it peak 735 00:35:43,600 --> 00:35:46,166 at different times of the year. 736 00:35:46,266 --> 00:35:48,466 So when we look at some of these other places, 737 00:35:48,566 --> 00:35:52,666 this is when their influenza epidemics or pandemics peak, 738 00:35:52,766 --> 00:35:56,933 is that in the tropical environments, 739 00:35:57,033 --> 00:35:59,333 they are peaking around June or July, 740 00:35:59,433 --> 00:36:03,733 lasting about the same duration as our influenza season. 741 00:36:03,833 --> 00:36:07,200 But the interesting thing is over here in Asia, 742 00:36:07,300 --> 00:36:09,233 they have these semiannual peaks. 743 00:36:09,333 --> 00:36:11,800 So they have two peaks a year of influenza 744 00:36:11,900 --> 00:36:14,733 instead of having one peak like we do. 745 00:36:15,866 --> 00:36:17,200 That has to do with the environment. 746 00:36:17,300 --> 00:36:19,966 So influenza really likes colder temperatures 747 00:36:20,066 --> 00:36:21,700 and low humidity. 748 00:36:21,800 --> 00:36:24,933 So any time you alter that or change that, 749 00:36:25,033 --> 00:36:27,166 then influenza doesn't do as well 750 00:36:27,266 --> 00:36:29,400 with circulating in the air. 751 00:36:29,500 --> 00:36:33,133 This is from 2013, so it would be interesting to see 752 00:36:33,233 --> 00:36:36,066 how this has changed, and what will change in the future 753 00:36:36,166 --> 00:36:38,333 with some of these climate changes and global warming, 754 00:36:38,433 --> 00:36:41,766 and what that will do for influenza, both the seasons, 755 00:36:41,866 --> 00:36:44,733 the duration of the seasons, and when they actually peak. 756 00:36:48,666 --> 00:36:50,666 So now I'll go onto immunity. 757 00:36:50,766 --> 00:36:54,000 So I'll talk about population immunity and vaccines. 758 00:36:54,100 --> 00:36:56,033 So this is our third concept here. 759 00:36:58,733 --> 00:37:01,266 So we'll start with this diagram here, 760 00:37:01,366 --> 00:37:02,633 and the importance of this diagram 761 00:37:02,733 --> 00:37:04,300 really has to do with immunity, 762 00:37:04,400 --> 00:37:06,833 and what the population immunity is doing, 763 00:37:06,933 --> 00:37:10,366 and how that relates to outbreaks or pandemics. 764 00:37:10,466 --> 00:37:14,933 So we'll start all the way on the left here. 765 00:37:15,033 --> 00:37:17,633 So we have an introduction of a new virus. 766 00:37:17,733 --> 00:37:22,633 So influenza A, HxNx, which we've never seen before. 767 00:37:22,733 --> 00:37:24,333 Okay. 768 00:37:24,433 --> 00:37:26,233 So what happens after that's introduction 769 00:37:26,333 --> 00:37:27,733 is that it leads to a pandemic. 770 00:37:27,833 --> 00:37:29,766 So you see your disease incidence here, 771 00:37:29,866 --> 00:37:34,766 so you get high disease rates, and then those will fall 772 00:37:34,866 --> 00:37:38,666 over time, and as those fall, you see this antibody, 773 00:37:38,766 --> 00:37:41,200 or the immunity to that virus, go up. 774 00:37:42,666 --> 00:37:44,966 And then you get your next season, 775 00:37:45,066 --> 00:37:46,566 which there is some immunity, 776 00:37:46,666 --> 00:37:48,600 so some people have created these antibodies 777 00:37:48,700 --> 00:37:51,333 and can fight off these infections, 778 00:37:51,433 --> 00:37:54,000 and so, then you get lower amounts of incidence. 779 00:37:54,100 --> 00:37:57,566 And then as more of your population is exposed 780 00:37:57,666 --> 00:38:01,466 to this virus, you see that your antibodies go up, 781 00:38:02,900 --> 00:38:06,433 and then you see the rates of disease go down overall. 782 00:38:08,166 --> 00:38:10,233 So this middle range is where we see 783 00:38:10,333 --> 00:38:11,633 some of those drifts happen. 784 00:38:11,733 --> 00:38:13,700 So those are those minor changes 785 00:38:13,800 --> 00:38:16,200 that can affect and still cause disease, 786 00:38:16,300 --> 00:38:18,400 but really, people are protecting themselves 787 00:38:18,500 --> 00:38:21,100 with the antibodies they've had from the previous infection. 788 00:38:22,200 --> 00:38:24,266 So then what happens again is that, 789 00:38:24,366 --> 00:38:26,700 all the way on your right-hand side, 790 00:38:26,800 --> 00:38:28,566 there's an introduction of a new virus. 791 00:38:28,666 --> 00:38:31,766 So now we're introducing HyNy. 792 00:38:33,066 --> 00:38:36,800 So even though we had great immunity to HxNx, 793 00:38:36,900 --> 00:38:39,833 that really doesn't help us for this new virus that comes. 794 00:38:39,933 --> 00:38:41,566 So with this new virus that it comes, 795 00:38:41,666 --> 00:38:45,200 you see a huge peak in your incidence rates of disease, 796 00:38:45,300 --> 00:38:47,166 causing another pandemic. 797 00:38:47,266 --> 00:38:50,366 And then, over time, what you see is the antibodies here 798 00:38:51,366 --> 00:38:53,666 go along and start to go up, 799 00:38:53,766 --> 00:38:55,566 and you see the same sorts of cycles happen 800 00:38:55,666 --> 00:38:57,166 over and over again. 801 00:38:57,266 --> 00:38:59,700 So this is what you see when you look at pandemics 802 00:38:59,800 --> 00:39:03,233 throughout history and that interpandemic era, 803 00:39:03,333 --> 00:39:05,666 where you're seeing little spikes but they're not as big. 804 00:39:05,766 --> 00:39:08,300 It's because the population has developed some immunity 805 00:39:08,400 --> 00:39:09,566 to it. 806 00:39:13,566 --> 00:39:15,733 I'm just gonna show this in a different way 807 00:39:16,900 --> 00:39:19,033 using our history to help follow along. 808 00:39:19,133 --> 00:39:22,933 So first I'll start with the 1918 pandemic, or outbreak, 809 00:39:23,033 --> 00:39:25,033 the Spanish influenza that happened. 810 00:39:26,366 --> 00:39:30,000 So up top you have the circulating influenza viruses. 811 00:39:30,100 --> 00:39:32,200 Down below you have the timeline of pandemics 812 00:39:32,300 --> 00:39:34,700 or important things in influenza history. 813 00:39:35,866 --> 00:39:40,533 So in 1918, you see that H1N1 arises. 814 00:39:40,633 --> 00:39:43,333 It results in about 50 million deaths worldwide, 815 00:39:43,433 --> 00:39:47,066 then H1N1 continues to circulate throughout that time. 816 00:39:47,166 --> 00:39:48,666 So as you follow along the timeline, 817 00:39:48,766 --> 00:39:51,833 you have your 1918 pandemic, and then it circulates 818 00:39:51,933 --> 00:39:54,166 until about 1947. 819 00:39:55,600 --> 00:39:58,000 And then it has a slight drift that makes it 820 00:39:58,100 --> 00:40:01,333 a little bit different, but still protected. 821 00:40:01,433 --> 00:40:03,700 Then we get to 1957. 822 00:40:03,800 --> 00:40:06,133 1957 is when we had our second outbreak, 823 00:40:06,233 --> 00:40:09,766 and that's when you notice that H2N2 arises. 824 00:40:09,866 --> 00:40:13,733 So you have your big peak with no immunity previously, 825 00:40:14,900 --> 00:40:17,933 and then H2N2 circulates for a period of time. 826 00:40:18,033 --> 00:40:20,933 Then you have your 1968 outbreak, 827 00:40:21,033 --> 00:40:24,533 which you notice that H3N2 now arises. 828 00:40:25,966 --> 00:40:29,000 And then we get all the way to 2009, where we notice 829 00:40:29,100 --> 00:40:34,433 that there's this novel H1N1, or the swine flu H1N1, 830 00:40:34,533 --> 00:40:39,433 that came up that resulted in 150,000 to 580,000 deaths 831 00:40:39,533 --> 00:40:40,733 in the world. 832 00:40:42,200 --> 00:40:45,033 What's interesting about the 2009 outbreak 833 00:40:45,133 --> 00:40:48,366 is that it really affected people 834 00:40:48,466 --> 00:40:51,266 that were less than 24 years of age. 835 00:40:51,366 --> 00:40:53,733 And there was a lot of thought when this initially happened, 836 00:40:53,833 --> 00:40:57,733 like, "Why are all these adolescents or college students 837 00:40:57,833 --> 00:41:01,500 "that are healthy, for college students, 838 00:41:01,600 --> 00:41:04,433 "getting really sick and not doing well?" 839 00:41:04,533 --> 00:41:05,933 And what they noticed 840 00:41:06,033 --> 00:41:08,366 is that there actually was some similarity 841 00:41:08,466 --> 00:41:11,200 between the H1N1 that circulated here 842 00:41:11,300 --> 00:41:13,500 and the H1N1 that circulated here. 843 00:41:13,600 --> 00:41:15,066 That's why this arrow is there. 844 00:41:15,166 --> 00:41:18,633 And so it seems like the older adults 845 00:41:18,733 --> 00:41:23,166 actually had partial immunity to the new H1N1 846 00:41:23,266 --> 00:41:26,833 'cause they had previously been exposed to a similar H1N1 847 00:41:26,933 --> 00:41:30,466 that provided cross-protection or cross-immunity. 848 00:41:30,566 --> 00:41:32,833 So with these pandemics, you can see 849 00:41:32,933 --> 00:41:35,600 there's certain age groups that get affected 850 00:41:35,700 --> 00:41:37,866 that aren't the typical age group that you think of 851 00:41:37,966 --> 00:41:40,866 with the highest rates of incidence of influenza. 852 00:41:44,333 --> 00:41:46,033 So we talked about population immunity, 853 00:41:46,133 --> 00:41:48,333 we talked about antibodies circulating, 854 00:41:48,433 --> 00:41:52,466 now we'll go onto influenza vaccine. 855 00:41:54,500 --> 00:41:56,466 So we'll start with our virus here. 856 00:41:58,133 --> 00:42:00,900 What some of you may have noticed on the previous slides 857 00:42:01,000 --> 00:42:04,433 is there are these areas that are called antigenic sites 858 00:42:04,533 --> 00:42:06,733 on this hemagglutinin, and these become important 859 00:42:06,833 --> 00:42:09,700 when we talk about influenza vaccine. 860 00:42:10,766 --> 00:42:12,200 So how does influenza vaccine work? 861 00:42:12,300 --> 00:42:14,833 What it does is your body is exposed 862 00:42:14,933 --> 00:42:18,400 to either a weakened or killed form of the disease, 863 00:42:18,500 --> 00:42:20,633 and then your body creates these antibodies, 864 00:42:20,733 --> 00:42:23,866 which are present here after being exposed to it, 865 00:42:25,233 --> 00:42:29,700 and then these antibodies, let's say you got your flu shot, 866 00:42:29,800 --> 00:42:31,233 you developed your antibodies, 867 00:42:31,333 --> 00:42:34,033 and then you got exposed to influenza, unfortunately. 868 00:42:34,133 --> 00:42:37,400 And what happens is these antibodies 869 00:42:37,500 --> 00:42:41,533 go to these antigenic sites and actually clamp onto them. 870 00:42:41,633 --> 00:42:43,200 So we're talking about these antibodies 871 00:42:43,300 --> 00:42:45,833 that were in your system go to the virus, 872 00:42:45,933 --> 00:42:48,733 the outer portion of the virus, and go on top of them. 873 00:42:49,900 --> 00:42:53,300 And so what that does, is our previous picture, 874 00:42:53,400 --> 00:42:56,733 is it blocks the virus actually being able to attach 875 00:42:56,833 --> 00:42:58,200 to those sites. 876 00:42:58,300 --> 00:43:01,933 So the virus is unable to attach the sites of the cells, 877 00:43:02,033 --> 00:43:04,033 and so they can't enter into the cells, 878 00:43:04,133 --> 00:43:06,433 and then your body mops up this virus 879 00:43:06,533 --> 00:43:08,800 through other immune system cells, 880 00:43:08,900 --> 00:43:11,500 and is able to get rid of it so you don't get sick. 881 00:43:12,833 --> 00:43:15,100 So that's how the influenza virus actually works, 882 00:43:15,200 --> 00:43:17,600 is it really blocks this attachment part. 883 00:43:21,766 --> 00:43:23,466 So the influenza vaccine, 884 00:43:23,566 --> 00:43:27,300 we'll talk about the 2019, 2020 one, 885 00:43:27,400 --> 00:43:28,533 these are the different viruses. 886 00:43:28,633 --> 00:43:30,166 You don't have to read all of them, 887 00:43:30,266 --> 00:43:33,300 just know that there's two influenza A viruses 888 00:43:33,400 --> 00:43:36,500 on there, and there's two influenza B viruses on there. 889 00:43:36,600 --> 00:43:37,766 All of the other stuff 890 00:43:37,866 --> 00:43:40,266 really is just really specific virology names 891 00:43:40,366 --> 00:43:43,166 and what specific virus they put into the influenza. 892 00:43:44,466 --> 00:43:46,633 But you can see here that the first one 893 00:43:46,733 --> 00:43:50,100 was an H1N1-like virus, the second was an H3N2, 894 00:43:50,200 --> 00:43:52,766 and then you have your Victoria and your Yamagata. 895 00:43:54,266 --> 00:43:56,933 The stars next to those first two ones 896 00:43:57,033 --> 00:44:00,700 is what changed from the previous year's vaccines. 897 00:44:00,800 --> 00:44:04,666 So every year, at the end of the influenza season, 898 00:44:04,766 --> 00:44:07,133 a ton of experts get together and try to predict 899 00:44:07,233 --> 00:44:10,666 what they think is gonna be circulating the following year. 900 00:44:10,766 --> 00:44:14,300 And what they predicted for this year are these four. 901 00:44:15,533 --> 00:44:16,800 It's still too early to know 902 00:44:16,900 --> 00:44:19,166 exactly how effective this is. 903 00:44:19,266 --> 00:44:22,766 There's varying rates between the virus strains. 904 00:44:22,866 --> 00:44:26,966 It's probably about 30 to 50% vaccine effectiveness this year, 905 00:44:27,066 --> 00:44:31,200 which is pretty typical of the influenza vaccine. 906 00:44:31,300 --> 00:44:33,466 But these first two are new ones this year. 907 00:44:37,133 --> 00:44:39,033 So the important thing to know and the important thing 908 00:44:39,133 --> 00:44:40,766 that I like to tell patients 909 00:44:40,866 --> 00:44:42,533 when we're talking about influenza vaccine 910 00:44:42,633 --> 00:44:45,766 is you're 50 times less likely to get sick 911 00:44:45,866 --> 00:44:48,033 from influenza compared to someone 912 00:44:48,133 --> 00:44:49,766 who doesn't get the vaccine. 913 00:44:50,933 --> 00:44:52,633 So I feel like this is an important concept 914 00:44:52,733 --> 00:44:54,800 that we don't talk about very much. 915 00:44:56,233 --> 00:44:59,400 And, in addition, not only do you have 50% less likely, 916 00:44:59,500 --> 00:45:01,533 if you do get an influenza strain 917 00:45:01,633 --> 00:45:03,633 that's not one of the ones listed, 918 00:45:03,733 --> 00:45:05,466 there is some cross-protection. 919 00:45:05,566 --> 00:45:08,700 So you can have less severe disease even if you get exposed 920 00:45:08,800 --> 00:45:11,100 to an influenza virus that isn't covered by the vaccine 921 00:45:11,200 --> 00:45:12,366 that year. 922 00:45:18,200 --> 00:45:20,533 So now the vaccine impacts on influenza. 923 00:45:20,633 --> 00:45:24,433 So this is the most recent updated that the CDC has 924 00:45:24,533 --> 00:45:28,933 about what the actual vaccine is helping to prevent. 925 00:45:29,033 --> 00:45:33,933 So in the year of 2017 to 2018 in the United States alone, 926 00:45:34,033 --> 00:45:36,800 it prevented 5,700 deaths. 927 00:45:37,966 --> 00:45:40,700 It prevented 91,000 hospitalizations. 928 00:45:41,866 --> 00:45:43,600 Does anyone what this is, the picture of? 929 00:45:45,666 --> 00:45:47,866 Some stadium, it's Lambeau. 930 00:45:47,966 --> 00:45:50,600 So Lambeau Field can hold about 81,000, 931 00:45:50,700 --> 00:45:54,266 so we're protecting 10,000 more than what Lambeau Field 932 00:45:54,366 --> 00:45:56,533 can hold in hospitalizations. 933 00:45:58,000 --> 00:46:02,033 In addition, we protected 3.2 million medical visits 934 00:46:02,133 --> 00:46:05,433 and 6.2 million illnesses overall. 935 00:46:05,533 --> 00:46:10,766 So we protected over an entire state of Wisconsin population 936 00:46:10,866 --> 00:46:13,033 with illnesses with the vaccine. 937 00:46:14,466 --> 00:46:16,466 So that's quite impressive of something that we can do 938 00:46:16,566 --> 00:46:19,733 and why a lot of medical providers really push 939 00:46:19,833 --> 00:46:21,233 for influenza vaccine. 940 00:46:22,700 --> 00:46:24,966 And this is just in the United States, it's not worldwide. 941 00:46:25,066 --> 00:46:28,033 The rates are much higher when you look at the whole world. 942 00:46:30,666 --> 00:46:32,233 So we talked through these three concepts, 943 00:46:32,333 --> 00:46:34,766 which I think are important in influenza, 944 00:46:34,866 --> 00:46:37,166 and to help you understand some of the other things 945 00:46:37,266 --> 00:46:38,933 that can happen in other respiratory viruses 946 00:46:39,033 --> 00:46:42,133 that are important, why we see these pandemics or outbreaks. 947 00:46:42,233 --> 00:46:44,566 So with influenza, we talked about those viral properties 948 00:46:44,666 --> 00:46:47,000 that are important for the structure of influenza, 949 00:46:47,100 --> 00:46:48,400 how it gets into your cells, 950 00:46:48,500 --> 00:46:51,600 and then why it causes epidemics and pandemics. 951 00:46:51,700 --> 00:46:54,666 And then we talked about the transmission with droplets, 952 00:46:54,766 --> 00:46:57,500 and some other transmission that can happen 953 00:46:57,600 --> 00:46:59,900 as well as the environment and any climate changes 954 00:47:00,000 --> 00:47:01,566 that may affect that. 955 00:47:01,666 --> 00:47:04,233 And then the last concept had to do with immunity, 956 00:47:04,333 --> 00:47:07,633 which is important overall, about your population immunity, 957 00:47:07,733 --> 00:47:09,533 so overall, who's being covered, 958 00:47:09,633 --> 00:47:11,666 and then also the vaccine itself. 959 00:47:14,233 --> 00:47:16,966 So these are the important things to take away, 960 00:47:17,066 --> 00:47:19,766 and why pandemics happen 961 00:47:19,866 --> 00:47:21,966 is a change in each one of these concepts 962 00:47:22,066 --> 00:47:25,100 can really lead to a big outbreak of things. 963 00:47:25,200 --> 00:47:27,933 So viral properties, when we get new virus, 964 00:47:28,033 --> 00:47:32,933 or a novel virus, and then that virus is easily transmitted, 965 00:47:33,033 --> 00:47:36,066 and then the population has no previous immunity, 966 00:47:36,166 --> 00:47:38,900 that's when we get really big outbreaks with viruses. 967 00:47:42,400 --> 00:47:45,500 So I'm gonna talk briefly about my specific research. 968 00:47:45,600 --> 00:47:48,100 I was just giving you a rundown about influenza. 969 00:47:48,200 --> 00:47:50,166 So my research really has to do with the impact 970 00:47:50,266 --> 00:47:52,366 of respiratory infections in children, 971 00:47:53,533 --> 00:47:55,566 and why I care about that, and why I think 972 00:47:55,666 --> 00:47:57,833 that that's important is a lot of these numbers. 973 00:47:57,933 --> 00:48:02,366 So overall, $40 billion is spent per year 974 00:48:02,466 --> 00:48:05,900 on non-influenza respiratory infections in children. 975 00:48:06,000 --> 00:48:07,366 So those rates skyrocket 976 00:48:07,466 --> 00:48:10,800 when you actually include influenza into those accounts. 977 00:48:10,900 --> 00:48:13,600 It also accounts for greater than 45 million missed days 978 00:48:13,700 --> 00:48:15,900 of work and 22 million missed days of school 979 00:48:16,000 --> 00:48:18,466 because of kids being sick, parents needing to leave work, 980 00:48:18,566 --> 00:48:21,300 or parents themselves being sick, adults being sick. 981 00:48:22,466 --> 00:48:24,366 The other interesting thing is down here. 982 00:48:24,466 --> 00:48:28,466 So the $2 billion per year is spent on cold remedies. 983 00:48:28,566 --> 00:48:30,000 So this is out-of-pocket money 984 00:48:30,100 --> 00:48:33,700 that we are spending on cold remedies, overall. 985 00:48:37,033 --> 00:48:38,533 So really where I found this gap 986 00:48:38,633 --> 00:48:40,600 in the respiratory infection research in children 987 00:48:40,700 --> 00:48:42,733 has to do with, we have clinical trials 988 00:48:42,833 --> 00:48:44,966 for some of these symptomatic treatments, 989 00:48:45,066 --> 00:48:46,966 we have clinical trials trying to use 990 00:48:47,066 --> 00:48:48,833 some of these antivirals in certain type 991 00:48:48,933 --> 00:48:51,333 of respiratory viral infections, 992 00:48:51,433 --> 00:48:53,433 but really, the measures that they use 993 00:48:53,533 --> 00:48:55,633 are not consistent between the trials, 994 00:48:55,733 --> 00:48:57,100 and they're not validated. 995 00:48:57,200 --> 00:49:00,300 So they previously haven't been shown to be valid 996 00:49:00,400 --> 00:49:04,266 in pediatric patients with acute respiratory infections. 997 00:49:04,366 --> 00:49:06,400 So what this means is that it's really hard 998 00:49:06,500 --> 00:49:09,600 to compare clinical trials in children 999 00:49:09,700 --> 00:49:11,700 when they're trying to see what helps 1000 00:49:11,800 --> 00:49:13,700 improve their respiratory infections 1001 00:49:13,800 --> 00:49:16,566 or helps to cure their respiratory infections. 1002 00:49:16,666 --> 00:49:19,166 Then, it's also challenging to interpret what this data means 1003 00:49:19,266 --> 00:49:22,000 when they use measures that haven't been validated 1004 00:49:22,100 --> 00:49:24,233 or haven't been researched previously. 1005 00:49:28,500 --> 00:49:31,000 So Wisconsin Upper Respiratory Symptom Survey 1006 00:49:31,100 --> 00:49:33,366 is something that was developed by Dr. Bruce Barrett, 1007 00:49:33,466 --> 00:49:35,600 who is a part of the Department of Family Medicine 1008 00:49:35,700 --> 00:49:37,533 and Community Health. 1009 00:49:37,633 --> 00:49:41,433 He developed it in the 2000s and it was focusing on adults. 1010 00:49:41,533 --> 00:49:44,066 So it's an illness-specific quality of life instrument 1011 00:49:44,166 --> 00:49:46,566 that was used to assess the negative impact 1012 00:49:46,666 --> 00:49:49,466 of acute upper respiratory infections in adults. 1013 00:49:49,566 --> 00:49:52,133 It's been used in various different clinical trials, 1014 00:49:52,233 --> 00:49:55,233 and really, what's happened with it is it's really exploded. 1015 00:49:55,333 --> 00:49:57,333 So 150 institutions around the world 1016 00:49:57,433 --> 00:50:01,633 in 35 different countries use this survey 1017 00:50:01,733 --> 00:50:03,300 to help with their clinical trials, 1018 00:50:03,400 --> 00:50:07,000 their observational trials, and any pharmaceutical companies 1019 00:50:07,100 --> 00:50:08,900 that have picked this up as well. 1020 00:50:09,000 --> 00:50:11,266 It's translated to multiple different languages 1021 00:50:11,366 --> 00:50:13,466 to be used in these different countries. 1022 00:50:16,133 --> 00:50:20,333 So what I am doing right now is taking that framework 1023 00:50:20,433 --> 00:50:23,000 of the Wisconsin Upper Respiratory Symptom Survey 1024 00:50:23,100 --> 00:50:26,333 and trying to validate it in pediatric patients. 1025 00:50:26,433 --> 00:50:30,366 So it was validated and proven to work in adult patients, 1026 00:50:30,466 --> 00:50:32,633 but as we all know, children are very different 1027 00:50:32,733 --> 00:50:35,633 than adults in many different aspects. 1028 00:50:35,733 --> 00:50:37,733 So what I'm trying to do is really assess 1029 00:50:37,833 --> 00:50:39,700 their symptoms and their quality of life, 1030 00:50:39,800 --> 00:50:41,733 and how that impacts their scores overall, 1031 00:50:41,833 --> 00:50:45,266 and what that means with the overarching structure 1032 00:50:45,366 --> 00:50:46,766 of the actual form. 1033 00:50:47,933 --> 00:50:50,166 My goal is to use it in future clinical 1034 00:50:50,266 --> 00:50:52,866 or observational trials focusing on children 1035 00:50:52,966 --> 00:50:55,933 in an outpatient setting with acute respiratory infections. 1036 00:50:56,033 --> 00:50:58,466 There is a lot of research being done about children 1037 00:50:58,566 --> 00:51:01,133 that are hospitalized, children that have asthma, 1038 00:51:01,233 --> 00:51:03,900 or infants with acute respiratory infections, 1039 00:51:04,000 --> 00:51:07,300 but this part with the outpatient setting 1040 00:51:07,400 --> 00:51:08,566 with acute respiratory infections, 1041 00:51:08,666 --> 00:51:10,533 there hasn't been as much research. 1042 00:51:12,433 --> 00:51:14,166 So where I am now with things is 1043 00:51:14,266 --> 00:51:16,600 I completed the administration to all the participants 1044 00:51:16,700 --> 00:51:18,133 in my study. 1045 00:51:18,233 --> 00:51:20,400 The analysis shows that it holds together quite well, 1046 00:51:20,500 --> 00:51:22,333 and it's valid and reliable, 1047 00:51:22,433 --> 00:51:24,700 so now I'm thinking about where do I fit this in 1048 00:51:24,800 --> 00:51:27,533 with different clinical trials and where do I go with this 1049 00:51:27,633 --> 00:51:28,800 at this point? 1050 00:51:30,800 --> 00:51:33,500 These are all of the people I would like to thank. 1051 00:51:33,600 --> 00:51:35,800 So as you know, there's a lot of people involved 1052 00:51:35,900 --> 00:51:37,366 in a lot of this work. 1053 00:51:37,466 --> 00:51:39,500 With the WURSS Kids, these are all the people 1054 00:51:39,600 --> 00:51:41,566 that have helped me get to where I am, 1055 00:51:41,666 --> 00:51:44,066 and then my mentors as well. 1056 00:51:44,166 --> 00:51:45,866 So I'm a part of two different departments 1057 00:51:45,966 --> 00:51:47,033 at the University of Wisconsin, 1058 00:51:47,133 --> 00:51:48,866 so I'd like to thank the University of Wisconsin 1059 00:51:48,966 --> 00:51:50,266 Department of Pediatrics 1060 00:51:50,366 --> 00:51:52,100 and the Department of Family Medicine and Community Health, 1061 00:51:52,200 --> 00:51:53,733 and then the Wisconsin Survey Center 1062 00:51:53,833 --> 00:51:56,333 helped to put together the WURSS Kid Symptom Survey 1063 00:51:56,433 --> 00:51:58,266 that was used and validated. 1064 00:52:00,200 --> 00:52:01,433 So thank you, guys, for listening 1065 00:52:01,533 --> 00:52:03,433 and taking the time out of your night. 1066 00:52:03,533 --> 00:52:05,566 [audience applauding]