- Welcome everyone to Wednesday Nite @ the Lab. I'm Tom Zinnen, I work here at the UW-Madison Biotechnology Center. I also work for UW-Extension, Cooperative Extension, and on behalf of those folks and our other co-organizers, Wisconsin Public Television, Wisconsin Alumni Association, and the UW-Madison Science Alliance. Thanks again for coming to Wednesday Night @ the Lab. We do this every Wednesday night, 50 times a year. Tonight, it's my pleasure to introduce to you Pete Shult and Tom Haupt from the Wisconsin State Laboratory of Hygiene. Tom was born in Manitowoc, Wisconsin. And graduated from Manitowoc Lincoln High School. Then he went to UW-Parkside, which is celebrating it's 50th Anniversary this year.

There in the wonderful Petrifying Springs Park where we used to go to for our family reunions back in the late 60's. 

At UW-Parkside, Tom studied Public Environmental Health and then got his master's degree in Health Care Administration from Cardinal Stritch college. He started with the state in 1985 and then has been with the Department of Health since about 1995. Pete Shult was born in East Lansing, Michigan. And grew up in Oconomo, how do you say that? Oconomowoc, Wisconsin. 
(laughing)

 I could tell that I was long enough in Wisconsin that I could pronounce Oconomowoc. He went to UW-Madison for all three of his degrees. All three of them were in Med Micro at the undergraduate, master's, and PhD level. And then he spent two years as a post doc in Christchurch, New Zealand.

And he came back, which is pretty amazing, and he's been with the Wisconsin State Laboratory of Hygiene since 1988. Tonight, he's going to talk with us about influ-- They're both going to talk with us about influenza. It's not just about pandemics. I hope you've all got your flu shots.- 
[Audience Member]

 I did.

- It's a pretty amazing thing. 88,000 people died from flu last year. Let's see if we can drop that number a little bit this year. Pete's going to go first, so please join me in welcoming both Tom Haupt and Pete Schultz on Wednesday Nite @ the Lab. 
(clapping)

- Thank you all and thanks to Tom and the Wednesday Nite @ the Lab crew. This is my second time here. I really enjoy doing this, so.

Going to talk about influenza and the title's not exactly along the lines of pandemic, but that'll become obvious why we're kind of taking this tack as we go through the talk. I want to begin with this slide. The reason we're having this trilogy of presentations on flu is I think everybody now realize this is the centennial of the great influenza pandemic of 1918-1919 which, really in human history ranks as one of the biggest and arguably most impactful of global health crisis in human history. CDC is also recognizing the centennial and they put together just a tremendous website if you want more information on the science, on the historical aspects, the societal impacts, this is a great website to go to.

I'd recommend everybody do that if you have interest in the topic. And just to get started, we're going to stray from pandemic influenza in fairly short order. 

But I just want to highlight some of the facts, and I think again, a lot of people know about this. They're lot of somewhat unique attributes to this pandemic. Very notable things.

This slide illustrates that actually the pandemic event occurred as three distinct waves over about a one-year period. With the two, the second and the third wave, being the most devastating of the two. When all was said and done, estimates of 50 to 100 million people died worldwide, over 650 thousand in the US.

Couple of other really amazing facts, the case fatality rate was in excess of 2 1/2%. Which in the worst pandemic since then and the worst season since then we're around 0.1 % So really remarkable there. And during this period, during the three waves, it was estimated that a third of the entire global population, well over 500 million people, suffered clinical illness of varying degrees. And then there's been a lot of comparisons over time, comparing to the impact of the pandemic in World War I.

And one other kind of interesting thing, on this lower curve, for a couple of year period, this pandemic actually lowered the average life expectancy by 12 years. Which is, when you think of it, really quite remarkable, that's in the United States.

Some elements of the disease were also very notable. Most of the cases were like typical albeit on the severe end, influenza. But what's really highlighted are the 15 or 20% of cases that developed a pneumonia. And it was a very characteristic pneumonia. It should be quotes around that italicized part, "unlike anything that had been seen."

And basically, it was mentioned last week, there was excellent presentation by the three scientists from UW, gave a little of the scientific background on this. And it was pointed out that the direct cause of many of that, of those cases of pneumonia was in fact, bacterial. And there's very good evidence to support that. 

But in fact, it was very much a one, two punch. The virus hit first and actually did considerable damage throughout the respiratory tree and just sort of opened the doorway to the bacteria that normally inhabit our upper-respiratory tract to go down there, get established. And it was primarily the bacteria then that was the result of the end stage for a number of these patients. And then the second really remarkable thing, we'll mention it probably later, but it's pretty characteristic that influenza has it's most severe impacts now at the age extremes, the very young, in particularly, those greater than 65 years of age. And that's highlighted by that dotted, dashed line. And this just shows seasons before and after 1918, as a pattern we've seen consistently ever since. What made 1918-1919 a bit remarkable was the W-shaped curve that a substantial part of the mortality and very severe illness occurred in otherwise healthy adolescents, young adults, into middle age. Which made this even more devastating, the impact this would have in communities, since this is the most active vital part of the community. And this is something that is not seen-- It's been seen certainly to this extent, with any other pandemic. So originally, I think Tom alluded to this last week. 

The original topic was really going to discuss the impacts of the great pandemic, both back then, and what are some of the lessons that we have learned that are applicable today. And in thinking about this, I decided that might not be the best use of this hour. I show these different books and magazines, and I already referenced the CDC website. You can find if you go to these, excellent scientific descriptions, descriptions of the disease, the public health impact, the societal impact of this pandemic. And I'd encourage if you're really interested in this to pursue some of these. These are really tough books to put down. You are just in awe of the impact that this pandemic had. Rather what we decided to do is fast forward to what happened last year.

Of course in public health, we worry about pandemics, but something we're going to tell you through the course of today, we deal with influenza epidemics on a year-to-year basis and last year was really an eye opener. So, why did we do that? 

Why did we choose to focus on that? Well I show up, just kind of little collage of some headlines from last year. There's been a tremendous amount of press devoted to last influenza season. The most recent of which and it kind of culminated last week when the CDC came out with a report documenting that last year over 80,000 people died, 900 thousand hospitalizations, and a particularly severe impact on young children. Which in their estimation, makes this easily the most severe epidemic we've had in over 40 years.

And in addition, as you followed the news throughout the year, we heard of school closures, ER's and urgent care throughout the country being overrun. Hospitals had to divert patients 'cause they couldn't take any more. There were shortages of medical supplies, saline, some antibiotics, antivirals, laboratory supplies in certain areas, particularly associated with influenza diagnosis. Anyway, what made this even more remarkable, it's not something we knew was going to happen, even as we hit the typical part of the influenza season when we know it's going to be taking off. There were no indications from flu, the summer before where flu is active in the southern hemisphere, that there was going to be this severe a year. 

And even a couple of weeks into the season, there was nothing that made this seem it was going to be anything unusual in the virology. The information we had about the viruses we'd expect. There was nothing remarkable. The season hit, and it truly became a historic event. So, what I'm going to do is talk to you a little about influenza and make the distinction of virologically the differences between pandemic influenza and seasonal influenza. There's distinct mechanisms that allow the viruses that cause either pandemic or seasonal influenza to arise. And I just want to review that. Keep it not too scientifically detailed. I'll turn it over to Tom and he's going to focus on last year and past flu seasons.

Talk a little about the clinical, the public health impact, and perhaps the most important part of his message moving forward, is review what you can do to help yourself as we're coming in to the next influenza season. 

So, we'll be talking about the antivirals available and the vaccine. And then it's going to come back to me given the severity of influenza we can take some solace, even though we don't know what's going to happen on a day-to -day, year-to-year basis until we're in the middle of it. We have an incredible surveillance system, global surveillance system. And I just want to review the highlights. Throughout the course of a year, you can access those information and kind of be more informed on how the influenza season is progressing. So, quick virology lesson here. And I put this up kind of you see cartoons about influenza a lot. We saw one last week. But I just want to highlight a couple of the features. And this is done in the context that the real hallmark of influenza is its changeability. 

It's ability to mutate. And there's a couple of major ways this does, it does this. I'm going to go over each of those. One of the mechanisms leads to pandemic influenza. The other much more subtle mechanism leads to the seasonal epidemics that we experience each year. And I just wanted to lay that groundwork, so you understand the difference between the two and be sure as bad as last season was, it definitely was not a pandemic, both on virological grounds and also in how the rest of the globe was involved. So the things to know: we'll be talking throughout the talk about Influenza A and B. There's two types of influenza of public health significance. Of the two, Influenza A is the only one of the types capable of causing pandemics, and in general, causes more severe disease and bigger epidemics. That said, as Tom can attest, we see in the laboratory, Influenza B in its own right in certain years can contribute to significant morbidity and mortality. 

So I don't want to minimize it, but in the context of today's talk, it's really about Influenza A. Couple of features of the virus are very instrumental. In how this virus changes those two different ways. One of these is, it's genome. It's genetic material that allows itself to replicate itself, is RNA based, and any microorganism that's RNA based has that really nasty habit of mutating all the time. Influenza is the greatest example of it. HIV is another excellent example of it.

It's also segmented. So, the genome has discreet segments. Each segment serves as a gene. 

And I'll talk about the consequences of that in a second. And then, the other feature that is relevant to both types of mutation, the two features, the proteins are on the surface. The Hemagglutinin, abbreviated as 
(H)

. The Neuraminidase, abbreviated as 
(N)

. That's how we determine the subtype of Influenza A. H3N2 is one of the subtypes of Hemagglutinin and Neuraminidase. 

H1N1 which is the other subtype currently circulating these days, another similar example of that. These two proteins are instrumental in this virus creating the infection in your body that leads to the illness. It allows it to attach to the cells, infect the cells, move on to new cells, cause illness, and ultimately leave the body and go on to infect other individuals.

Of equal importance, it's against these proteins that our immune response is directed, okay.

And the unfortunate thing is, they're also two of the most changeable proteins. Or the genes that govern those proteins, are the two of the most changeable genes in the virus. You can surmise this is a bad combination. The two key proteins that are most changeable are the ones we happen to mount our immune response to. Which means in short, our immune response, on a population basis, is always playing from behind. We're always a step behind. 

And that's what makes influenza such a very successful pathogen. So, the two ways in which it changes antigenically, one of these is called antigenic shift. And I've defined it when there's a novice subtype, a new subtype that humans have not seen of Hemagglutinin and Neuraminidase. And this can only influence-- antigenic shift only occurs with Influenza A. When this virus emerges in a human population, it's one of the necessary precursors for a pandemic. And the mechanism that does this, and I'll go, only briefly mention this, 'cause it was talked about last week. Mechanistically this occurs because of that segmented genome. And if you get two unrelated Influenza A viruses infecting the same host at the same time, they start selecting and picking and choosing those genetic components. And if a new virus that we show down here comes up and ends up with a new set of Hemagglutinin and Neuraminidase, that are novel to humans, then we're being set up and there's a potential for pandemic influenza. And the process by which this occurs is called reassortment. 

How this and where this occurs in nature, again was talked about last week. Influenza actually, the primary host of influenza are migratory water fowl throughout the world. They carry the entiner genetic repertoire of Influenza A viruses. 16 HA types, or 16 Hemagglutinin types, 9 are Neuraminidase. There's a couple of others that have been found in bats. We don't know what role they play in human illness at this point. But these human, or these migratory water fowl, are reassorting these viruses all the time. And occasionally, these get into other hosts. A variety of mammalian hosts, other birds, domestic poultry. The problem arises when they get in, in establishing those animals, such as swine and poultry, that puts them in closer contact to humans. 

Who in many other areas, because of their agricultural practices, humans live in close proximity to swine and poultry. So this gives a real opportunity for these novel subtypes to get into humans, which again raises the possibility of a pandemic.

This model has been shown to now retrospectively looking back at all the pandemics we've suffered since and including 1918. 1918, it's well acknowledged that it was probably set off by an avian virus. But that virus was created because of reassortment going on in other avian species. That lead to the H1N1 pandemic and that virus was with us for many decades until it combined with another avian virus. And the new virus picked up different components from that new avian virus and we ended up with the H2N2 virus, the cause of the Asian flu in 1957. Similar event occurred in 1968 when the H2N2 reassorted with another avian virus and we ended up with the H3N2. And progeny of that H3N2 are the ones that are affecting us today by the other change mechanism that I'll talk about. And finally, in 2009, H1N1 2009, arose. 

If you were at last week's talk, a really good explanation. Extraordinary complex series of reassortments involving pigs in different parts of the world, multiple avian species and humans. And when it all was said and done, the dust settled, we ended up with the pandemic strain that caused 2009 pandemic. And the consequences of this is pandemic flu. In the interest of time, I'll let you read about this. Basically pandemic flu is a global epidemic that has these characteristics: very rapid spread, occurs pretty much around the world at the same time, often with severe disease; and because of all that there's a lot of other significant social impacts. Impacts on infrastructure and so on.

Now these novel influenza viruses are generating all the time. And we've seen in the last five to 10 years a strong uptake in the number of these novel viruses that are being identified. And when I talk a little about the surveillance, I'll show how this is being picked up globally. 

But we're seeing a number of these and a number of these have infected humans. And to a certain extent, in a very serious way. We heard about the H5N1 virus, the H7N9, which have been with us in the former case for almost 20 years now. And the H7N9 over in China, the last five years. Capable of causing human disease with mortality rates in excess of 50%. But what hasn't occurred with those, leaves this final slide about pandemic flu, there's a recipe for a pandemic. You need the emergence of a novel subtype, you need infection and illness to occur in humans, but you need efficient and sustained human-to-human transmission. That has occurred with our past pandemics. This has not occurred with those other novel subtypes yet, but the number of mutations to make that leap are not large. So it's something we have to be concerned of. 

So with that, I want to briefly tell you the second mechanism of antigenic change is called antigenic drift. Much more subtle, always occurring as influenza circulates around the globe, and the impact of antigenic drift is seasonal influenza. What happens, the Hemagglutinin a Neuraminidase acquires mutations that keep it a step ahead of our immune response. It causes an epidemic, everywhere in the world, every year. Different times depending where you live in the world. And it's the reason we have to essentially reengineer our vaccine each and every year to try to keep up with the virus. The consequences of that is our annual flu epidemic. I show that at the bottom. These are data from the state lab and the considerable public health impact that influenza has each and every year. And I'll leave you to read the number of cases that occur every year in the typical year, number of hospitalizations, and number of deaths. 

And you can see how this impacts us globally as well. You can see why last year compared to what the mean has been essentially for the last 20 years, why last year is considered a historic year. So, with that, I'm going to turn this over to Tom and he's going to pick up with what happened to us last year and what's been the impact, and what can you do about it.- Thanks Pete, appreciate it. Welcome to Wednesday @ the Lab, this is my first time here. Very proud to be here. I do want to add a couple of things to my bio very quickly, to what Tom said earlier. Back in 1997, the CDC actually made the first designation of having state influenza surveillance coordinators. Our jobs were to kind of pull together laboratory outpatient, mortality, hospitalizations, all together, so all saying the same thing. And I'm proud to say that I'm one of the two remaining original influenza surveilors in the country. 

So, thank you very much. 
(clapping)

I will also share that with my colleague from Connecticut, on that, so.

So influenzic activity in the United States, we were actually in with the Department of Health Services, very blessed to have a great relationship with the State Laboratory of Hygiene. Not a lot of other states have what we have. Some people, some of the Department of Healths, do not even know who their laboratorian, or laboratory people are. It really is kind of scary how some of these things happen, but we've developed a relationship over my 24 years here to really talk to each other, get on the same page. Hey, we have disagreements, we all do. But again, it's something that we have been very blessed with, and in Wisconsin to have one of the best relationships between Department of Health and the State Laboratory of Hygiene. One of the main ways I wanted to show you some information both federal, United States wise, and also I'm going to Winsconize it a little bit. 

But this first slide, the top portion is the severity, and you see this on like the Weather Channel, and some of those other stations will show this. Obviously, the more red, closer to the red, the more severe, the more intense influenza is. And this is influenza like illness which is defined as a fever, with cough, and sore throat. Fever with cough and sore throat, and nothing more than that. But this top picture shows that all but six states were in the red high range back in the third week of February, around February 3rd actually, the first week of February. This has never happened before. It's never been more like 15 to 20 states. We had 44 of our states actually in the red at the same time. The bottom one is geographic spread. And never have we had all 48 states plus the Alaska, or 49 out of our 50 states, to actually be at widespread activity. 

Now widespread activity is something that I'm responsible for. I am looking at outbreaks. I'm looking at influenza activity through laboratory surveillance, putting all this together through a formula they have. We report on a weekly basis down at the CDC, but these two maps show you things that have never happened since we started this surveillance back in 1997.

Influenza activity in Wisconsin over the past few years. You notice the highest is actually in the 2014-15 season. If you recall, the 2014-15 season was the year that the vaccine and the viruses did not match at all. But this past year, which is shown in the red right here, while it was lower, it was a much, much, longer year. And the past two years have been, and this is actually, the influenza, the influenza B viruses. The influenza B viruses really extended our seasons, the last two years significantly. 

It also hit the elderly population. I'm going to say the older population. I know sometimes they say elderly, people don't like that. Slightly older population. 
(laughing)

 Somebody told me at work to say seasoned. I don't know if that cuts it or not. I don't know. You tell me if you like that word or not. But again, it hits the slightly older population harder than it does the younger population and that was very significant this year, because many of the people over 65 years old, had the Fluzone high dose or the Adjuvanted vaccine and that did not cover the influenza B virus that was circulating. 

So they were hit very hard towards the end, making it a much more extended season over the past few years.

The mortality: these two graphs are from what we call FluView, which CDC puts out every week. And you can see how higher mortality was. This was nationwide by the way. This is United States. We had some of the highest numbers, highest percentages, over the past five, six years. Also our number of deaths. The number of pediatric deaths; we all heard that was 80,000 deaths estimated this past year. We had 180 children, 80% of which were not vaccinated or the family members. That is the highest we've ever had. 

Well, it was very close to what we had in pandemic. The pandemic I think we had maybe at 200, but in a non-pandemic year, this is again, a record we're not proud of breaking.

Influenza and Pneumonia in Wisconsin, thought you might be interested in that, and again it shows very, very clearly the number of flu cases in Wisconsin, this past year, where they actually diagnosed and caused-- It was caused by influenza, was 379. The next highest was it been 2014 at 267. You can really see that the H3 years are much more powerful, much more powerful and much more deadly to people who are not vaccinated. And even to those people who are vaccinated who have underlying illnesses. Vaccine you depend on, but you also depend on those people around you to get vaccinated. To make sure that they get the proper protection. But this is also influenza and pneumonia. And this is something we're going to be tracking very closely this year in our weekly report, perhaps some of you have seen it. 

We're going to be putting the numbers in. We're going to have 'em by age group. This is an eye catcher. We want people to know how deadly influenza is. And this is going to be part of our weekly report. We also hope that the media gets a hold of this, 'cause we want to have every opportunity to get our message out to the media much faster and much more accurate than what happened last year. If you happen to remember last year, they had this early season total of the vaccine efficacy being about 10% and even public health people who shied away from the vaccine at first, it was really very, very poorly done. We want to get ahead of the game with the media. We want them to call us. We want to explain the situation. 

We want to encourage vaccine until there's no more vaccine available or it has expired. But again, you notice the difference between like the 2014-15 season, which is right here. Very thin, very small, as far as going up and down, very quickly, much wider. Much longer season in 2016-2017.

Flu hospitalizations: this is a graph of influenza incidence by age group. You can see how very, very large the incidences overall...

compared to other ones. And this is not only overall influenzas, it's also the over 65 range, over 65 people of adult by age group. So again, it was a year that the hit the over 65 population much, much harder than anybody else. We had multiple nursing home and long-term care outbreaks. 

We had probably close to 500. And that's over the season. And you think it's not hard to follow up on them. I mean, did I do my job? I did the best I could, but you know I depend on the local health departments to help them out, to make sure they know the guidelines, the precautions to take. Know when to use the antivirals, what antivirals to use. But again, it was this very, very, overwhelming year for all of us at the Department of Health Services and the State Laboratory of Hygiene. This is flu hospitalizations in the last five years in Wisconsin. And I have last years in red. We had 7,530 hospitalizations. 

The next highest we had was 2014-15, where we had 4,700, so we practically doubled. What I have thought was going to be one of the worst years, 2014-15, that we had in decades, turns out this year really over shadowed that and made 2014-15 look pretty mild. But again, 66% of all of hospitalizations are people over 65 years old. Hospitals were overwhelmed. They did diverting, as Pete had mentioned earlier. None-- We didn't have to-- There was nothing like making it in California, and Atlanta, and some of those places. They actually had to build tents in order to keep pace, to get patients their treatment. It didn't get quite that far, but there were a lot of hospitals that had absolutely no place to put people. It was a situation you would probably see in a pandemic, but again it wasn't as bad in 2009 when we actually did have the pandemic. But this year over-passed the 2009 in just about every single category. 

And if you look at influenza hospitalizations, you always want to look too at the adverse effects. Now, we're looking at ICU admissions, people who are put on mechanical ventilation, almost a thousand people wound up on ICU last year. And of that, like 273 people were required to get mechanical ventilation. Very serious year. Much higher numbers in every category. Broke every record. And not a record we wanted to break.

So why, why was the past season so severe? When you think about it, it was the same vaccine and the same virus that was going through on the 2016-17 season. I didn't think it was going to be as bad. 

I thought we'd have a lot of immunity, because we had the same vaccine and there was the same viruses. The viruses pretty well matched too. But there was vaccine efficacy issues. And I went so far as to do a media interview and say I don't think it's going to be quite so bad this year. I hope that has been erased. I hope it's no longer on YouTube or any place like that. If it is, apologize, 'cause I really put my foot in my mouth at that my particular time and I have learned my lesson. So, why was it so bad? One of the things I wanted to show you and thy put together a model at CDC, and it's based on outpatient influenza-like illness, hospitalization rates, and pneumonia and influenza mortality. And this past year was the first time since they went back to 2004 that all the age categories were in the high category. 

As demonstrated by the circle on this chart. Other years like 2014-15, it really hit the elderly population very hard, but not so much the younger people. It was a bad year, but it wasn't a year where they, CDC, actually went so far as to say, "It's very severe." It's always been moderately severe, or mild to moderate, that's been their terminology for years, but this again, is a record we didn't want to set, but this is a new model they have. We're going to be watching this very closely. This was done at CDC but again, they work with us through influenza coordinators and through the state laboratories, public health laboratories to share this information. We do a lot of talking. We do a lot of talking and a lot of listening on both parts, so that's probably the best thing that we have done, is to just listen to each other and talk to each other, make sure we're all on the same page.

Influenza prevention and treatment. Again, we're looking at vaccination, antivirals, as two of the main ways of preventing and treating influenza. 

We can get into some details. Seasonal influenza antivirals. Years ago, I don't think it's been before 2009, they actually used Adamantanes, which is Amantadine and Rimantadine. Those were never effective against anything except influenza A, so there was no effect on influenza B. Also, the specimens, or excuse me, the viruses that are circulating today, the pdm H1N1 and H3 are susceptible to Neuraminidase inhibitors, but there's a resistance to the antivirals. They're the antiviral Adamantanes. Adamantanes also have a very adverse effect on the older populations, especially nursing homes. There's increased falling because of the Amantadine and Rimantadine. Neuraminidase inhibitors, as Pete was mentioning earlier, Tamiflu, or its generic equivalent, is probably the main antiviral people use. It's done orally. 

It can actually be preventive solution for small children. People did not use Zanamivir very often. It's also called Relenza. It's an inhalant, that people who have respiratory disease do not want to use as it's some kind of inhalant, a powder. Peramivir is I.V. and that's for people who are hospitalized who can not take an oral antiviral. For people who maybe are not-- Maybe are in a coma or something because of their illness, very much used pretty much as a last resort. Not used for prophylaxis, where Tamiflu or also Tamivir, is a Zanamivir, which can be used for both treatment and for prophylaxis.

Again, as I mentioned earlier pdm H1N1 and H3N2 are very susceptible to Neuraminidase inhibitors. Now one thing I wanted to mention too. There's a new antiviral coming out, it's called Baloxivir. 

Maybe some of you have read about it. It was really-- the media made a big mistake and they said, it's the new drug that will kill the influenza virus in one day. Not the case. What Baloxavir does is the same thing as a Neuraminidase inhibitors, but a Neuraminidase is one protein, the Baloxavir stops the duplication of a different protein. Difference is, it's a one-time thing, one pill, where as with Tamiflu, it's twice a day for five days. So it's in process of being okayed by FDA, possibly by, sometime this season, but I don't think it's going to be very available. So I'm looking forward to it more in the 2019-2020 season.

Vaccine strategies to reduce influenza infections. They are safe and effective. And we're going to talk about vaccine efficacy shortly. 

And the vaccine efficacy is different than a match. and I think people talk about this a little bit later, but a match means it's genetically the same thing, but the vaccine efficacy is something totally different. The two options we have are inactivated vaccine, which is a trivalent. It covers both influenza A H1 and A H3, and but it only covers one out of the two B's. And the quadrivalent vaccine covers both influenza B's. Both the Victoria lineage and the Yamagata lineage. As I mentioned earlier, the last two years, the trivalent vaccine did not cover the correct influenza B that was circulating. And a lot of people over 65 who had that flu zone, or the agivent type of thing which actually help increases, it gives you better immunity to the top three, H3, H1, and one of the influenza B viruses. It completely missed the B viruses leading to a extended season, leading to more and more mortality. This year coming back is also the live-attenuated virus. 

That's the mist, for people up to 49 years old. It was dismissed because it was thought to be ineffective. Ineffectivity to the H1 virus over the past few years. There's still some controversy out there. You know the people in Canada, the doctors, the clinicians in Canada swear by it, there's some reluctance with doctors around here. And because it was only okayed in February, a lot of places were not able to order it. So, it's not the easiest thing to find. It is out there if you look hard enough. If you have children who will not get a shot, it is a good alternative to use. Again, it's very safe, but it is a live virus, so you always have to be a little bit careful of those particular things. 

Now vaccine effectiveness. Hopefully, I can explain this. This is the overall vaccine effectiveness for the last five years. And you can see, they thought that we were going to have like a 10% vaccine efficacy, like they did in Australia. It did not turn out. It was about the same as what we had the previous year, 2016-2017 year. Both about 40% overall. You're always in the H1 years, you always seem to have better vaccine efficacy, up to 48% in 2015-16 season, and well over 52% in 2013-14. Part of this has to do with the H3 virus and how it's actually made in eggs and how they actually inoculate the eggs with the virus, but what they're putting into the egg is not what's coming out. It's called an egg adaptation. 

Something in that egg is happening where it really changes the structure, changes the whole efficacy of the H3 vaccine. And that's something, because we have such an archaic system using eggs, we really would love the manufacturers to start looking at perhaps at cell-based cultures. I think that is in the long run, but vaccine, influenza vaccine is not a moneymaker too. We have to realize that. There's only a short amount of time that you can give it. It's a new product every year. I think there's only two or three manufacturers who make it where years ago we had five or six, maybe even seven. So breaking this down real quickly again. This is the influenza vaccine by the actual virus.

And again 40% for all, overall. 

It was only 24% effective against the H3 virus which is by far the predominant virus in the 2017-2018 season. The A
(H1N1)

, 65%. That's really good. I mean you're never going to get a 100%, but where you have to get over 60%, that's really good. And the B Yamagata's again were about 50%. There weren't enough of the B Victoria strains around to really do a vaccine efficacy study on that. And I want to break it down one more time with the H3, and I want to show you something. Again 24% for all ages. 

Six months to eight years is 37%. Thank goodness for that age group, 'cause otherwise this would probably have been significantly lower. Why is it higher in the six-month to the eight-year-old group? More likely, a lot of these kids were getting their vaccine for the first time which means they get their second shot, their second vaccination one month later. Probably gave them some better protection. Nine- to 17-year-olds, 10%. And look at the long line. That's the confidence interval. I mean it really are not sure about some of these numbers. It's not as black and white as where we'd like it to be, but 10% efficacy for that age group and the 18-49 years old, a little bit better in the 50-64-year-olds, and again, way down for the over 65-year-olds. 

This is vaccine efficacy. Again, the match was not that bad. The vaccine working was not that good. We're hoping that the two changes that we made this year in both the H3 virus and one of the influenza B's will improve this significantly. We are going to be very optimistic like we are every year. We are encouraging people to not shy away from the vaccine. But to really keep going and get vaccinated not only for yourself, but to protect those people who are around you. What was expected again, was largely what we got. It was not a bad match last year. But again, some of the vaccination rates, and I have some numbers from Wisconsin that I thought you might be interested in. 

If I could find mine quickly. I thought I had this right page on here and I apologize for that. But significantly in Wisconsin, 35% of the people got vaccinated. That's not good. Our 2020 health goal is 70% and I don't think we're going to get it. You may think otherwise and I hope you're right. But again, 35%, and that was even better than we had the year before; that was like 33%. But the highest numbers, it's about 50% in children zero to four years old. Only 25 to 30% in those five to 49 and it really was pretty good over 65. It was about 60%. 

Once you get into the five-year-olds to the 49-year-olds, the vaccine rates are horrible. I don't know why this is. Maybe we need to do a better job of selling the vaccine and making sure people know what it's all about. That its main purpose is not to prevent, but it's to prevent complications, and to protect those people around you. Maybe the message needs to be changed.

Seasonal influenza vaccine, why isn't everybody getting vaccinated?

"It's a trivial disease, why bother?" I don't get it. You get this all the time and unfortunately I hear it from my own colleagues. "It's not safe during pregnancy." 

It's proven time and time again, it is. You can get it in any of the three trimesters and it is the best protection for that child who is about to be born during that first six months when they cannot be vaccinated. "Not another vaccine for my children." Well, that why the internasal vaccine is now back. It's for those children specifically who do not want to get another poke in the arm. There's a lot of 'em, we know that, so it is an option now, again, to have that internasal to come back. "I got the flu shot and I still got the flu." Well, if you've been exposed to it shortly before you got the flu shot, you can get the flu. But it's not caused by the shot. It's a dead virus. 

The shot is a dead virus. You cannot get the flu from an influenza shot. "There's thimerosol in it." There's like a small mercury of compound, but there are many vaccines that are thimerosol free. So, it's a preservative and it's usually in the multi-dose syringes, than the single syringes, do not have thimerosol. For the very most part. "And costs too much." It's really not that much. I've heard people say, yeah, I've had to pay $200 for it. Well somebody's making a big profit on that for no reason. 

That's just ridiculous. It shouldn't be costing more than 35, $40 tops, maybe at like a Walgreens or a CVS. And "it's not as effective as the government says." Well you know we never said it's been 100%. We try to explain what vaccine efficacy is. Some protection is always better than no protection. Think of yourself going outside in 10 below degrees weather. You have a light jacket or something to go out and get your mail or do whatever you have to do outside, go to the car, it gives you a little bit of warmth. You won't freeze. It's like same way with the vaccine. 

You need some protection. It's a very, very rough disease. It's a very severe disease. We obviously had thousands of people die last year. I think the estimate was like 80,000 last year. It's something that we have to take much more serious than what we are in the past. And again, that's partially my job at the state, to work with our immunization program to do that.

Could there be problems with the vaccines? It may not, as I said, it may not be perfect, but it does give a substantial people the best we have and that's a CDC source. So again, I will encourage you, if you haven't got your vaccine, to get it as soon as possible. 

Do not worry about waiting. It should last, if you get it now, it should definitely last you through the season. There's been a lot of talk that you lose the vaccine efficacy of 10% or more every month. That's still not totally proven. There's a lot of studies that are out there. There's some studies that says it will definitely get you through the season. But we're dealing with such a severe virus. I really hope that it's a much better year than what we had in the past, especially after last year. No predictions this year. I don't want to put my foot in my mouth again, I won't do that. 

But, I'm confident that it's going to be a much better season. With that Pete, I'll let you finish up. 
(clapping)

- Thanks Tom. In the time remaining, as I said at the outset, I want to kind of reassure you. It's a bad bug. We don't have the optimal way to prevent it, but I reinforce what Tom, the public health party line is: it is the best we have and it's way more effective than a lot of people give it credit for. You've got to get that vaccine. All ages need to get it. Despite the limitations, despite the severity of the disease, over the last 20 years, largely because of the concerns in, with pandemic flu, we have developed an incredible influenza surveillance system that is now global. 

I'm going to quickly tell you what goes on globally and then get down to the US. Because within the world, the United States really has the most robust of model for flu surveillance. And we're constantly exporting that to other countries and helping them get to that same level. And then I'll second Tom, Wisconsin is second to no other state in the country for state level surveillance that actually advises our national surveillance. I'd say in general, there is no other infectious disease period in the world, in the United States that is surveyed and followed and monitored as closely as influenza. There's not even really a close second here. It's really quite impressive a system.

First there's global surveillance happening in humans. And when you're looking at the map, and in the United States, CDC is the lead agency and in fact they're a lead public health agency for the world. Being one of the primary response agencies in collaboration with the World Health Organization. 

And each year, more and more countries are developing their own influenza surveillance centers that are going into this global network. And they're being tasked with setting up surveillance models within their country that look within their country and then advise the greater global surveillance. And the number of countries able to do that and the degree that their able to do that is growing each and every year. Largely through the efforts of the US and some of the other wealthier countries that are helping the rest of the world catch up with their surveillance.

Moving on, there's also very extensive animal surveillance. And the purpose of this surveillance is to be detecting those novel subtypes. Those viruses that have the potential to get into the human host and lead to a pandemic.

They're looking in bird populations, migratory as well as domestic bird. There's also swine surveillance in different countries around the world. And these are just a list of the different novel subtypes that each and every year are being detected. 

They then, have very extensive surveillance looking, particularly for outbreaks in domestic poultry or in migratory waterfowl, which may indicate there's been a fundamental change in that virus that could then portend that maybe similar change could happen in humans. And then what the CDC with World Health Organization does, is they look at all these novel flu detections, and the monitoring that's being done, and they apply a number of criteria to each new novel subtype that is seen. And try to estimate, what is the potential this could emerge in the human population, and it if it does, what is the likely public health impact. They have a very extensive algorithm that they apply. And basically, they rank these and right now I made passing reference to two novel subtypes. They've been on our radar for a while, H5N1, H7N9 and those easily sit at the top of the heap of those novel subtypes that bear special attention because of their potential to trigger the next influenza pandemic. And again, the number of mutations necessary for that sustained human to human spread. Partly through study that's been done on this campus, have been found to be relatively few. So it is very important that this type of surveillance continue.

You then get to the US surveillance system. 

And it's broken up into basically three categories. There's virologic surveillance, I'll come to that in a second. It's what my lab participates in. Morbidity surveillance, where we're looking at influenza-like illness and it's the magnitude, the extent it's occurring, and it's spread throughout the country. We're looking at hospitalizations which is obviously on the more severe end of the spectrum as far as influenza disease. And then mortality surveillance. National Center for Health Statistics keeps statistics for the whole country on deaths due to pneumonia and influenza and that help populate that curve, those curves that Tom showed you about mortality each influenza season. Childhood influenza is now a reportable condition. I believe nationwide. All states are doing it. 

And I'm telling you the first thing you hear 80,000 people die of the flu but only 180 children.

These were unvaccinated children and each one of those-- And we get involved with these cases in Wisconsin, they are absolute tragedies. In most cases, in many cases, those are otherwise healthy kids who just bad luck gets a severe unremitting illness and they die. Often unexpectedly. It doesn't matter where there's only one of 'em, they are way more tragic than a lot of the other illnesses that we see, and it's really heart rending when you see this. Now, all of these data then are accumulated at the national level and then are sent back out to the states, to Tom, and his counterparts throughout the country. And also you can access these at the CDC by going to their website, www.cdc.gov/flu.

And go to FluView, 'cause it gives a very good, and understandable synopsis on what's happening with influenza on week to week basis in the United States.

And this, just a compilation of the data. Tom showed you this. 

These are the types of data then that they show you as the season progresses.

Viralogic surveillance. Public health laboratories are tasked with working with CDC that pay special attention to those viruses circulating in the United States. We work with our clinical laboratories throughout the state who do a lot of their own influenza testing. They gather their data of how many tests are they running and are they seeing influenza A or B. Those isolates then come to my laboratory and we look for the subtype, we look for whether, and confirm whether it's influenza A or B, look at the subtype for influenza A and determine which lineage of influenza B. It's with these data we know that each of the last two years the trivalent vaccine missed on that flu B that was circulating. We knew that very early on 'cause we were doing the characterization of the viruses. We're also always looking for novel and reassortent viruses throughout the year. We do our surveillance year-round now, because we have these cases that come up that are swine origin or avian origin. 

The work we do then is shared with CDC, along with the specimens we've worked on. We give 'em to them by the middle of the flu season, right around January, and then they make a selection of all the different isolates and viruses we've worked on throughout the country that determine which are the ones most likely to be circulating next year and they begin the development of their vaccine, which is a six- to seven-month process. So we're heavily involved in determining what viruses are going to show up in that vaccine and we also detect and monitor antiviral resistance. This is just a shout out. We've got 50 clinical labs or 132 total laboratories in the state, hospital-based laboratories. 50 of them are now active doing state of the art molecular influenza diagnosis. And we get data and specimens from each and every one of them. We really are a model for our states. We're working hard with other states, so they can kind of develop similar networks within their states. And all these data and all these isolates go to the CDC for further characterization.

So with that, that's a synopsis of surveillance. I want to just leave you then kind of wrap up one final slide. A parting message. First of all, hopefully even before this talk, you've recognized the clinical importance of influenza and the public health importance. Not only pandemic. It would have been real easy to talk about pandemic influenza and wow you with what really what bad things it does. We thought it'd be more appropriate to let you know what confronts you each and every year. This is something you need to deal with for sure. Pandemics may happen next year. It may not happen for 30 years. 

But be assured you're going to have another epidemic next year and we're going to have to deal with that. And respect it. And a lot of people do not. This is a serious illness. I'm in the same age group as many of you. We sit at the top in terms of being a risk group here and that's got my attention and it should have all of our attention. Protect yourselves. Vaccine isn't perfect, but it does protect some people absolutely and it protects a whole lot of people to the extent that it lessens the hospitalization rate and reduces the mortality across the age spectrum. And that ain't bad. And we need to recognize that.

And when you feel like you might have influenza and Tom gets a lot of press. He's in front of us on a week to week basis. You have these reports. If you think you have flu, the number one recommendation is call your healthcare provider, tell 'em, they can order up an antiviral, which if you get in that first one- or two-day window, absolutely will reduce the severity and also incidentally will keep you out of the hospital and keep you alive, so, it's a good thing. You need to proactively reach out to your healthcare then.

And protect yourselves by being aware of what's going around in the community, in the state, and nationally. And finally, protect others. Tom shouted out one thing here. Any vaccine isn't just about the recipient of the vaccine, there's herd immunity. We owe it to each other to get vaccinated to help protect those who need further protection. 

Those of us who are in risks groups. Cover coughs, wash your hands, all the hygiene things we hear all the time, and the parents in the audience, you need to keep your sick kids out of daycare and out of the school. And those of us who drag ourselves into work faithfully, we're only sharing the joy that our kids brought home to us. And we have to be a lot better of realizing when we're fairly sick, we're serving nobody, plus we're not really that much worth at work, by going there and spreading them, spreading the disease amongst them. And it's very important we all take that to heart. So with that final message, thank you for your attention and any time remaining, I'll be glad to answer any questions we can. 
(clapping)