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  • so welcome back, everyone from what I'm sure was a very enriching afternoon.

  • We're very excited about this final keynote session.

  • It's entitled Preparing for the next Epidemic.

  • Um, we have speakers Dr Jim Needn, Dr Michael Foster home and Dr Sonya Rasmus in I'm an infectious disease of a genealogist.

  • So I'm probably biased, but these are the real heavy hitters in the field.

  • So we're really excited about this panel.

  • These air literally the folks that CDC has on speed dial when they're trying to deal with anti microbial resistance or outbreaks of Zika and Ebola.

  • Um, this session will be moderated by Dr Susan Klein.

  • She is head of the division of our She is in the division of infectious diseases at the School of Medicine and is no less a giant in her field of health care associated infections, particularly in identifying novel devices and practices to prevent these infections.

  • Please join me in welcoming these experts to the stage.

  • Hi, and thank you for the introduction.

  • So I just wanted to tell you a little bit more about myself and then introduce the speakers and tell you what sort of format will be using today.

  • So I am an infectious disease physician at the University of Minnesota Medical School.

  • And I do practice in the medical center in clinic that I'm also the hospital epidemiologist, and I am actually an alumni of this school of public health.

  • I did get the master's in public health and epidemiology, so I use that stuff and, um so today I just wanted to let you know that what we're gonna do is have the three speakers come up individually and give some background.

  • They're gonna be talking about epidemics that we've been dealing with in the recent past and then talking about looking into the future and preparing for future epidemics.

  • And then after they beach had a chance to give some background, we're gonna have some moderated discussion between the speakers, and then we're gonna welcome questions from the audience.

  • So I want you to start thinking about your questions, and there should be some cards on your tables you can write questions on, and they'll be someone coming through the audience to pick up cards.

  • And if you want to ask you questions directly, there will be someone coming through the audience with a microphone and So now I just want to briefly tell you about our three speakers.

  • Jim Needn is, Ah, professor of biostatistics in the School of Public Health here at the University of Minnesota, and he's really an expert in design conduct, an analysis of clinical trials.

  • And he's, um, I've done a lot of really important work related to clinical trials internationally with HIV treatment.

  • And then, most recently, he's been very involved with response to the Ebola outbreaks in Africa, in particular working on vaccine trials.

  • And he can tell you more about that.

  • And then we also have Dr Auster home.

  • Michael Osterholm is the region's professor in the division Environmental Health Sciences, and he has done really, ah lot of work over his career.

  • Initially at the Minnesota Department of Health as state epidemiologist and then since joining the School of Public Health here, he's been very active not only locally, but nationally and internationally, and has served on advisory boards for biosecurity.

  • So he'll be starting off our session, and then our last speaker will be Sonja Rasmussen and Dr Rasmussen is a professor in the Department of Pediatrics and Epidemiology College of Medicine in the school of public health and health professions at the University of Florida.

  • And Dr Rasmussen recently joined the University of Florida faculty after spending 20 years at the Centers for Disease Control and Prevention in Atlanta.

  • And while there she provided significant scientific expertise and leadership dealing with birth defects.

  • Developmental disabilities associate director for science senior scientist.

  • She worked on the 2009 H one n one Pandemic and then most recently worked on the Zika outbreak.

  • So, no, I'm going to ask Dr Auster home to come up to start off the session.

  • Thank you, Sue in good afternoon to all of you.

  • It's a true honor to be here today and celebrating the 75th anniversary.

  • It does give me pause that we're hitting 75.

  • I actually is one of the co chairs, the 50th anniversary celebration 25 years ago, and I don't know where the 25 years went so and this march, my 45th year being at school public health.

  • So it's a wonderful experience to be here today, so my job is to kind of provide a quick overview of what we're talking about today where we're going.

  • Let me just say that my life is a calculus equation, I can tell you that probably more has happened in infectious diseases in the last 10 years and happen in the 1st 35 years of my career, and it's getting faster and faster and fashion to now Try to reflect that because that's the world that we respond to.

  • That's the world that we live in and have to deal with.

  • This slide is one of about 80,000 slides of having electronic slide file, and I've said over and over again, even though it's an older slide.

  • If I had one slide to protect in a slide file fire, this is the one I'd rescue.

  • It basically was come from the 2000 time period, but it gives you a sense of the dynamics of the world today.

  • In 18 50 we had roughly 350,000 people in the face of the earth, 350 million people in the face of the earth, and today we're at 7.8 billion people.

  • That's a remarkable concept to think of how the world has changed in terms of days to circumnavigate the globe with the fast sailing vessels.

  • We sped that up a bit in the 18 fifties, but by 1950 with the jet engine, we change that completely.

  • Now that line looks pretty flat from 1950 on.

  • I will suggest, you know, right now that that's the most incredibly dynamic part of the entire graph, and I'll share with you today.

  • Why that's important with infectious diseases.

  • I might also add in this graph this is public health at its finest.

  • Just remember that in 1900 average life expectancy in this country was 45 years grand.

  • Shoot men not quite as long as women.

  • Today, the average life expectancy is 78 years, a little again and not doing quite as well as women.

  • For every three and 1/2 days we've lived in the last century, we've gained one day of life expectancy.

  • Think about that.

  • It took us from 80,000 generations in the caves to get to 45 years.

  • Think where we've come.

  • That's all.

  • Public health, basically public health.

  • How was the world changing?

  • Well, this is an example.

  • We're gonna hear about this and we talk about Ebola.

  • But today the fastest growing region of the world is not Asia.

  • It's not in many places.

  • Actually central Africa, Kinshasa today, 13.8 million people in for the other cities in the DRC over a 1,000,000.

  • I was in contrast, in 1985 working on HIV.

  • I can tell you at that time in the population was 2.8 million people.

  • Look at the difference shoes since 1985 six 0.5 billion people A 1,000,000 people live in Kinshasa in some of the worst squalor you could imagine in terms of the kind of living conditions.

  • And I'm sure that in a minute a big challenge.

  • The other cities.

  • You can see whether the Legos night in a row, b down the line.

  • All of these, in fact Monrovia, Freetown in Conakry, the three capital cities of West Africa where the Ebola epidemic took off in 2014.

  • 15.

  • Really?

  • If you look at the 4.2 million combined population was just a gas can waiting for Ebola match to hit it Kinshasa's or gas tank waiting for a table, a match to hit it.

  • This is contrasted as we know it today.

  • If you've ever been there, you will never forget it.

  • It's incredible conditions for which lack of sewage, lack of city planning, etcetera is a cold room for the development and the spread of infectious diseases.

  • And if we wanna worry about Ken Bugs move, I've always said a a germ anywhere in the world today could be everywhere tomorrow.

  • Think about this.

  • In 18 2004.1 billion international domestic air passengers flew somewhere between Point A and Point B.

  • Now, some of those flew more than once.

  • That was 39.4 million flights, an average of about 100 and 8000 flights per day, where anyone time, about 4800 planes were in the air, going from somewhere to somewhere.

  • Think how that mixes up all the potential or infectious agents that we could imagine very different than that fast sailing vessel.

  • I showed you where it was at a moment ago.

  • In terms of the U.

  • S.

  • 366 132 million individuals represent about 18.6% of all passengers worldwide, and China was next 550 million.

  • The bottom line is we are a big mixing vessel today, unlike it any time in history that adds complexity to infectious diseases.

  • This slide, which who I took this morning every hour on the hour All 63,000 fast sailing vessels in the world are basic warehouses for all the goods that we use every day report their location and weather conditions.

  • We track this.

  • You can tell where hurricanes are coming typhoons, et cetera.

  • These fans sailing vessels like this one right here are now the new modern warehouse of manufacturing from around the world.

  • Just to give you some sense of the size of these, this particular ship right here can hold one million washing machines on his trip from Seoul to Long Beach, California gives you a sense of the dynamics.

  • Well, this is also a challenge for us today from an infectious disease perspective in particular because you're going to see in a minute we need a lot of things from around the world to deal with our jobs every day.

  • This is an area that I think is by far the one of the biggest crisis is were yet to face.

  • But we will face it.

  • I worry sooner than later.

  • Were now involved with the study supported by the Walton Family Foundation.

  • This has been something near and dear to my heart, and I wrote about in my book several years ago, they published Is the absence of critical acute care drugs when we need them?

  • It turns out that we brought together a group and defined What is the high likelihood that people will die within eight hours out this drug or cannot provide humane care without this drug or an alternative?

  • We identified 100 and 53 drugs across 28 drug categories.

  • It turns out that well over 94% originate from China, either The AP eyes active pharmaceutical ingredient is made in shine and sent to India, or it's actually made in China.

  • Today.

  • China has us literally hostage.

  • If we could not go to war today with China, we would lose immediately because today there are many thousands and thousands of people depended on these drugs every day 690,000 Americans and in stage renal disease or advanced renal disease, all their medications much there, dialysis coming from China.

  • And yet these air drugs, by the way, we're putting terror side.

  • So when one looks at this.

  • You realize anything that would interrupt traitor travel like a pandemic could have collateral damage far beyond anything we could imagine.

  • Our own modeling was suggest more people will die in the 1st 6 months of a severe influenza pandemic from the lack of these drugs will die from influence itself.

  • If you look at the shortage situation that's occurring because of the manufacturing challenges just with making these drugs available regularly not during a crisis you can see here is you look that today the these air, the 100 of 153 drugs.

  • Look at these numbers here and you can get a sense.

  • As of right now, 63 of those 153 drugs on Shorty status in this country, we are constantly acting out to find some way to get an alternative or a different drug.

  • This is just every day.

  • Also, we're gonna be facing water shortages that are going to be remarkable.

  • We've been mining groundwater around the world for decades and decades.

  • I can tell you, I was a location.

  • Hyderabad, India, 40 years ago, almost 40 years ago in which they were drilling in finding water 12 to 15 feet below the surface today, the wells were abandoned at 700 feet because they become too salty, they've run out of water.

  • Well, you can see from this map all the serious water shortages around the world.

  • Yet this is the internal solvent for public health.

  • How do we run our sewer system?

  • How do we grow food?

  • How do we have safe and clean water when you don't have water?

  • And climate change is only going to continue to influence that because the runoff is going to often be massive events due to high high volume, short term rainfall that we're seeing already.

  • So this is gonna be a challenge for public health, and then this one probably is the one that really is the most concerning.

  • In many ways, this is a map showing the fragile state status of 178 countries in the world.

  • And anything here from warning on which you see there the yellow is actually a country that is literally on the potential edge of destabilization or not able to govern its population.

  • When you look at that may up, just know that 75 of the 178.

  • Excuse me, 95 178 countries up here right now or in warning or more severe, That's 80% of the world's population live in a government were country where basically it's relatively unstable.

  • Try to do public health in those kinds of conditions.

  • Two years ago I published a book, and I'm not here to try to sell it, only to say it's the framework for which I look at this deadliest enemy Marv organs killer germs.

  • And frankly, it was a love letter from my perspective, to my kids and grandkids.

  • What do I have left to give them?

  • What can we do with this world that we live in now for the future?

  • And in that I came up with nine priority areas, The 1st 2 really are the only two that I consider a pandemic potential.

  • An epidemic of worldwide proportions.

  • Influenza will come back over and over again, and Amoco be resistance.

  • Why?

  • It's not one book kind of situation.

  • It is a truly a pandemic in terms of all the collective resistance were seen.

  • And then we get into the disease of critical regional importance that can have major impact in a region like Ebola, like Zika mosquitoes.

  • Clearly important bioterrorism.

  • All of these areas are ones we have to address.

  • But let me today concentrate really on those top ones to give you a sense of the challenges we have.

  • And I know that Sonya and Jim will be following up in similar fashion with these diseases.

  • This is an op ed piece.

  • I wrote a New York Times several years ago saying, You know, the real threat to national security is deadly disease.

  • Let me just say, if we had a severe pandemic today and we basically couldn't bring those drugs from trying to hear because manufacturing was shut down, transportation was shut down.

  • This would make a war seem kind of not so bad.

  • That's a pretty hard thought to think about.

  • So, in fact, we have to begin looking at national security.

  • And these infectious diseases asked the developing world countries, low income countries of the world that have had a bowl outbreaks that have had severe cholera outbreaks what this means to them?

  • This is a report that was done by the world health organ.

  • Um, the United Nations, right after the 2013 15 Ebola outbreak in West African, which they basically concluded.

  • My God, public health is really in dire straits globally.

  • We're not well prepared to deal with many of the crisis we have today and the panel chair actually wrote the following following the extensive consultation of panel knows that the high risk of major health crisis is is widely underestimated.

  • The world's preparedness and capacity respond is woefully insufficient.

  • Future epidemics could far exceed the scale of devastation in West Africa.

  • Bowl outbreak The panel is very concerned to learn the emergence of a highly pathogenic influenza virus, which could readily a rapidly result in millions of deaths and caused major social, economic and political disruption is not an unlikely scenario.

  • Was not just flew.

  • Flew is clearly the leader.

  • I don't think we quite get.

  • The fact that was many steps is we've taken forward in public health and infectious diseases the last 20 to 30 years.

  • We've taken many, many steps backwards.

  • Ebola is an example going to hear more about that from our speakers coming, but again, it's a wildlife disease in parts of Africa, for which, when that spills over into humans, of course, we see this type of hemorrhagic disease.

  • This was the night the 2013 15 epidemic in the three Western African countries that redefined Ebola.

  • When you think about it, what happened?

  • Well, if you can read in the third paragraph up there, it says, you know what happened to the virus change?

  • No, it didn't Africa changed and the urbanization of Africa's.

  • We see the organization.

  • Much of the world has fundamentally changed how infectious diseases happened.

  • What happens in this paper that we published our group with a number of international experts.

  • At the same time of the 2013 14 outbreak, we reviewed all the previous 24 Ebola epidemics that occurred between 1976 and 2013.

  • Only 2400 cases in all those 24 outbreaks, and they were easily contained today.

  • Why is it that we're still fighting a second Ebola outbreak that is challenging us immensely after West Africa again?

  • Africa's changed as so has the world.

  • This is the epidemiologic curve for the current epidemic that's in the DRC, one that has had 3313 deaths as of this morning, 2250 cases, 2215 deaths.

  • And it looks good in the sense.

  • Oh my gosh, it looks like it's ending And we were hopeful that we're bringing it to an end after all the social unrest that occurred and made it difficult to contain.

  • But look at what's happened here.

  • If you follow this, you can actually see as we report out by date from CID Rap News this one.

  • In November, Ebola cases hit 3085.

  • His transmission rate slows.

  • People were getting optimistic.

  • We're down to 21 case a day.

  • But then all of a sudden, the violence erupted again.

  • You can see here in November or December what happened where New via violence suspends Ebola response in a key hot spot area again.

  • We had more security.

  • We're so close, but we're beginning to lose it because we're shutting down our operations.

  • More violence Continues to stall Ebola response in DRC Hot spot says of just very recently here and then even more so we actually had two pulls complete staff out because they were being targeted.

  • Last last two weeks, six Ebola workers were targeted and killed trying to do their work.

  • And here it is, right here in the two attacks.

  • And so the challenges right now, we don't know what's happening today.

  • There were five new cases reported.

  • The problem is, we don't have good reporting right now because everything has been shutting down.

  • We were that close.

  • I don't know which way this is going to go in the next two weeks, With the violence as it is, we could see a re occurrence of the major Ebola epidemic.

  • Maybe not.

  • This isn't about vaccines, guys.

  • This isn't about public health response.

  • This is about security and what it is to do.

  • Public health in a world like this, A report earlier this week again more snags for the Ebola situation.

  • So this is the world we live in now.

  • Flu influenza is the one that I mentioned earlier.

  • Clearly is a major challenge for us and influenza is at a point in human and animal history, unlike any time it ever, ever has been.

  • We all know that the primary reservoir for influenza viruses that then make their way to humans is avian species, primarily poultry today.

  • And we know that when those viruses eventually change and get into a pig population where they change a little bit more or they get into humans.

  • That's when they like looking for a new pandemic strength or a strain that humans can be infected by and spread.

  • But in fact, we don't have protection.

  • Well, just look at these numbers here.

  • This is remarkable.

  • Today we live in a chicken world.

  • There are more chickens, any other mammal or avian species on the planet.

  • Why?

  • Because we need protein.

  • Today, the conversion of energy is most effectively done.

  • You know, chicken 25 to 35 days out that chickens harvested and that chicken breast is on your plate.

  • So today you can see up there.

  • We're talking about 22 billion chickens in the earth.

  • The next highest bird species has only 1.5 billion to feed Shanghai to feed the world.

  • We now have us.

  • And if you want to breed avian influenza viruses, just do this.

  • Just watch what happened?

  • It's remarkable.

  • So we're sitting in the cost of what could be one of the most dynamic periods of avian virus maturation and transmission to humans imaginable.

  • And we can't forget what happened in 1918.

  • I know this is of some debate with some.

  • It's not among many of us.

  • Let me remind you that in 1918 just like we saw in 2009 but fortunately in a much lower level would killed people, was what killed them young and what killed them young was not bacterial infections.

  • It was a sight, a kind storm.

  • It was a condition that, frankly, we don't do hell.

  • What better today in 2020 that we did in 1918?

  • And so we're not.

  • If we have another one, those events and I might add, just to give you a sense, The average age of doubts in two in 2009 with H one N one was actually younger when adjusted for life expectancy.

  • The 1918.

  • I think about that h one n one strain what it does.

  • So we are prime potentially form or large and very, very disruptive and potentially very consequential pandemics.

  • We have reviewed the 1918 pandemic, and we warn that it's a global threat.

  • You've got to take this seriously, and yet most of the world has had very little preparation for this We published a paper in 2011 that almost I thought was going to get me burned at the stake.

  • My name was thrown out there at the time with the the dear gentleman who gave us measles and autism, which we challenged, how well flu vaccines worked and it had not baby intentionally misrepresented him.

  • They didn't understand how to measure outcome for flu.

  • They're using serology, which turned out it didn't work well and we found that you know what, That 70 90 percents not true.

  • If you get 50% that's a good year and many years you'll get zero.

  • Just like last year with H three, n two h one n 11 of them gave us 48% protection.

  • Ellen gave a zero.

  • Now it's still the best we have.

  • I've been vaccinated.

  • I get my vaccine.

  • But don't count on it being the answer.

  • And more importantly, don't count on the world having access to it in every one of the pandemics to date.

  • It's always arrived after the second scene.

  • Big wave.

  • I don't see how that's going to change much in the future, so until we change that, that's gonna be a big, huge problem.

  • The good news is, Is there now finally a lot of work going on trying to move this forward?

  • This is a piece in today's New England Journal of Medicine preparing for the next pandemic.

  • Adobe issue of Global Influence Wins Wins a Strategy I'd like to say my colleagues at A W H O.

  • Thank you for this, but it's not very meaningful.

  • Industry is really where the action's at.

  • An industry can only produce probably 400,000 400 million doses of vaccine for the seven point seven billion people in the 1st 6 to 12 months, with a pandemic lottery hit been got.

  • So we need to work on this area.

  • It's a huge area of of importance.

  • One area I also just want to mention brief is an amicable resistance.

  • This paper is, to me, one of the most fascinating pieces in all of science.

  • This is a study that a group did in the far far reaches of calls Bad Cavern, where they went in over back, where no human had been in three million years and the culture the walls a skeptically to see what they could find for microbes, and they found a lot of and they found that they resisted up to 14 of the current commercially available antibiotics.

  • You said, Well, how can that be?

  • They had no access to him.

  • Well, microbes been fighting for space and food since the beginning of time.

  • And each time a mutation which frequently occurs in their reproduction of stages means that something bad happens to him and they die or something good happens.

  • And they beat out the guy next to him.

  • Because now my cell wall isn't affected by that chemical you put out.

  • And in fact, the chemical I would hood out now is gonna kill you.

  • That's animal covered resistance.

  • And it turns out that we, before we ever made the first antibody, already had a challenge.

  • Antibiotic resistance is global global evolution at its finest.

  • So please don't think that we can outsmart the bugs this way.

  • We're living in an era where we're just borrowing time with the antibiotics we have developed and used.

  • This is a report that was published by the A M R Group in England two and 1/2 years ago.

  • Sir Jim O'Neill lead this effort by commissioned by the British government, supported by the Wellcome Trust, it was by far the most comprehensive review of an improper resistance anywhere it's ever been done.

  • And in this particular report they laid out very clearly all the different organisms that we need to be concerned about and some of them they didn't even have on there at the time.

  • That today, for example, is a fungus, too, today that we worry greatly about this resistant.

  • But what was also telling is to give some perspective to this.

  • They predicted it by 2050.

  • There'll be more detrimental code resistance, as you can see then cancer and diabetes combined worldwide, adjusted for age.

  • I think about that.

  • We've been all time or chronic diseases, which are really important, but we are losing the power of antibiotics that gave us those 45 to 78 year life expectancy changes.

  • In part, this report was reviewed two months ago at a meeting at Chatham House in London, and to say everyone was disappointed by the world's response was an understatement.

  • And look at the last sentence up there.

  • The animal profit resistance by 2050 could result in 10 million people dying with a economic impact of $100 trillion.

  • And you know what?

  • It's like climate change today, which, while they're activists and their groups, we're losing the battle of climate change.

  • You know, we've got greenhouse gas levels now we haven't seen in three million years, and we are taking this seriously.

  • Well, what does that mean?

  • I don't know if I'll go here yet to say that the post antibiotic era is here, but we're getting closer and closer every day.

  • The easy antibiotics were gone today Commercially.

  • Nobody wants to make an antibiotic if you're a pharmaceutical company, because we tell you, don't use it unless you absolutely need to, which does not a lot of things for your sales.

  • It's like trying to, you know, sell a car that is the best running, just looking safest.

  • Most fuel efficient car, which only driving on Sunday from 9 to 9:30 a.m. Nobody buys it, so today we can't get the industry interested in these antibiotics.

  • This is one huge.

  • When we have to deal with, let me just say a couple of comments about mosquitoes, the absolutely most dangerous creature on earth in terms of human and animal health.

  • This is probably the saddest commentary on the fluid nature of public health preparedness.

  • If I were to ask you this question, I'm sure most of you might not think this is the answer.

  • But the very first country in the world to eliminate malaria from his populous regions was Venezuela.

  • They beat the United States in 1964.

  • They beat the United States.

  • Today, Venezuela isn't such freefall.

  • Doctors, nurses, architects don't have work.

  • So what do they do?

  • They end up going out into the illegal gold mines in the jungles where they do pick up malaria.

  • They bring it back to the major metropolitan areas.

  • Today we have the largest outbreaks of urbanized malaria in the history of the world in Venezuela.

  • How can we go from eliminating it to now the worst in the world?

  • That shows you the importance of maintaining public health preparedness.

  • This is by far the most dangerous of mosquitoes, you might say in terms of the number of the newer diseases we talk about.

  • When I came into the building was in 1975 of the universe here.

  • I was told by many Why the hell are you going into infectious diseases?

  • It's the course and buggy stuff.

  • Well, if you look at that map, you can see where eighties Egypt I was located the 19 thirties and what Pa Ho and the Rockefeller Foundation had done by 1970.

  • This is a mosquito that won't fly across the city street or an open field.

  • It's a mosquito that's a daytime biter.

  • Bites in the back of the neck, back of the oboe, back of the knees.

  • You don't feel it.

  • And it loves to live in dark oyster areas and little bodies of water, like what might be in a water vessel or a piece of plastic that holds a little bit of water.

  • That's it.

  • Look what happened by 2015.

  • Look at where eighties Egypt I is today.

  • And not only is it there, but it's in population levels anywhere from 100 to 500 times what it was even in the 19 thirties.

  • Is this public health progress?

  • We only talk about diseases like yellow fever and dengue and Zika chicken gun.

  • You're you know, you start to think about what does this all mean?

  • And it's these kinds of environments today for the couple of you in the room.

  • Old enough.

  • Remember the Graduate?

  • Would we tell Benjamin to go into plastics?

  • Well, it's not the water.

  • The picture in its all that tire and plastics back there.

  • It's the plastics on one of the most popular beaches for the Olympics several years ago.

  • It's the plastics that are in every urbanized area in many rural areas, and that's where we have to think about it.

  • Think about what we're looking for for the future.

  • Let me just close off with clearly the issue of where we're going today, with the whole area of vaccine hesitancy, there can be no greater again immediate failure that we can imagine.

  • Then what's happened with measles?

  • I grew up in a world of measles before the first measles vaccine and what we had kids my age die.

  • But many of you in this room have not ever had to worry about that well today because of vaccine hesitancy, one of the top 10 priorities the W H O has launched for this year, we're now seeing major major challenges with measles.

  • This is the worldwide mutual's epidemic that by the way.

  • It's in the down phase, right on the far right side.

  • But no, that's a season when it seasonally adjusted.

  • And when you look Gordon over 440,000 cases of measles for this year and by the time world reporting catches up and we know many don't get reportedly much higher later today, that will be a show tomorrow Friday.

  • Their time are going to be announcing that they have now concluded that last year alone, over 140,000 individuals in the world died from measles, died from measles, something no one should die from.

  • And yet look how far we've slipped back.

  • More importantly, don't forget.

  • And I tried to detail this in my book.

  • What kills us versus what hurts us versus what concerns us.

  • What scares the hell out of us all very different.

  • Many times 2200 people have died from Ebola.

  • Over the course of this Ebola outbreak in DRC, 4400 or now 4500 kids have died from measles in the same area at the same time.

  • Juror B.

  • By dying from measles there we all talked about Ebola, but the infrastructure doesn't exist.

  • And so these kids were dying of measles.

  • Six nations now report polio cases.

  • This past week, 18 different countries have reported polio.

  • This past year, we thought, we're gonna eliminate eradicated out of everywhere.

  • Today it's at the highest level.

  • It's been in years again.

  • Why?

  • Well, 110 Pakistani polio eradicate er's well been assassinated in the last two years trying to deliver polio vaccine in box.

  • Think about that.

  • It's a whole new world order.

  • Let me gives conclude by saying a situation, Churchill once said.

  • It's no use saying we're doing our best.

  • You've got to succeed in doing what is necessary.

  • If any of you want to get in the fight against infections using public health, now is the time if there's ever been a need for a renaissance, if there's ever been a need to re establish our ability to respond to infectious diseases, it's now it's gonna be very different than I first knew, and I got into the business a lot of additional challenges.

  • But I'm telling you, as a CZ I've shared with you throughout.

  • We will deal with infectious diseases for the decades to come, and if mutton.

  • How public health response to that will determine a lot about how that love letter to my kids and grandkids plays out.

  • Thank you.

  • So now that now that Mike is scared, you all kind of death, I'm gonna kind of change change it a little bit here.

  • So I've, uh, as Susan said for the last 30 years have been largely doing research and infectious diseases for the most part, HIV.

  • But I want to talk to you about doing research during an Ebola epidemic.

  • And I guess the thing I want you to think about is the only way that we're gonna understand the efficacy and safety of, say, vaccines and treatments for infectious diseases like Ebola is to do research in the epidemic on.

  • So people have kind of you may have heard HIV is touted because in a very short period of time, you know, from the eighties to the mid nineties, where HIV was a death, since people are now living much longer how fast that occurred.

  • And so you don't have much time during a bold epidemic to do the research.

  • So a CZ mike mentioned a Ebola's an interesting infection.

  • You can trace it back to a number of outbreaks between 1976 and 2008.

  • Among these outbreaks the largest involved quarter and 25 infections and 225 dust.

  • They were largely contained then what happened was the West African 2014 15 outbreak.

  • Over 28,000 infections overall hit 11,000 deaths.

  • And there's a reason for that.

  • Be apparent from my next slide, if not already.

  • From what might talked about, kind of where this epidemic hit in the populations in the large cities in this area, we're now experiencing kind of another kind of epidemic of Ebola and kind of what's interesting to me.

  • And, you know, I mention it again when I talk about one of the trials that we have done is that this may be a disease where you know you, you don't complete the research in one epidemic and you just hold off to the next one.

  • And we definitely tried to weigh that issue in 2015 and actually stopped a trial before we had conclusive answers, thinking this isn't gonna happen again for a while.

  • Well, it it did not too long later and I put a star here because this outbreak is is Mike indicated it's uncertain when it's gonna so.

  • The 2014 15 outbreak occurred in a small town, a young girl that could be traced back to December 2013 that was confirmed in a report later in March on What I wanted to point out from this slide is that it occurred right on the border between three countries Sierra Leone, Guinea and Liberia and the borders.

  • There are very fluid.

  • People would walk back and forth and you know you didn't know which country you were young on.

  • Ultimately, this infection hit all three capitals.

  • Conakry, Freetown, in Monrovia on that's where the devastation kind of was paramount, so that in September of 2014 we at the University of Minnesota were asked to kind of provide support for the design and the conduct of trials on Ebola in Liberia.

  • There's been a long standing relationship between Liberia, United States.

  • In August, the Ministry of Health sent our secretary of human health and Human Service is a request for support in doing research in a TSH responded in September on dhe.

  • I went over with a group of people from an H in 2014 and this was the situation.

  • Very little infrastructure remained after the civil wars.

  • There wasn't much there to begin with.

  • I have not been to Can ASHA.

  • But two of my colleagues have been Mike and they basically have said that Can ASHA is incredibly great better than Monrovia on also Freetown in Conakry.

  • This is an extremely poor area of the world.

  • In October, when I was there, there were already 3000 people infected wth e World Health Organization hadn't declared a public health emergency until August.

  • And so that a lot had happened between the confirmation of this girl young girl with having the case of Ebola in December to kind of August that largely went unnoticed by most of the world.

  • But we were well into the epidemic already in all three countries and there were 3000 infections in Liberia.

  • There were Ebola treatment units around the capital and there were 250 people there.

  • During this epidemic, roughly 50 to 60% of the people that went into an Ebola treatment unit did not survive.

  • It was a state of emergency schools were closed.

  • And another important point that I wanted to highlight is that we were in a stage when we began this work.

  • There were no license treatments for either.

  • The prevention of Ebola are the kind of treatment of Ebola so that we need the kind of plan well, in advance of when these epidemics begin for the drug developing the vaccine development.

  • And as you might expect in a country like this, there were many misconceptions and doubts and about the disease as well as are we gonna be, what kind of investigation of treatments might you be using?

  • So this collaboration, which a month or two later, after October, when we had developed the protocols, became known as Prevail the Partnership for Research on Ebola Virus in Liberia, we set we established three priorities.

  • Get a vaccine trial going as rapidly as possible, followed immediately with the treatment trial and plan a cohort study of the survivors of Ebola toe, understand the long term complications of the infection research really, which not had not been done in the smaller previous epidemics and actually has proved to be very useful because there's some understanding now how even survivors of a bola may transmit the infection two others and basically start another kind of epidemics.

  • So I put the kinds of things that were were considered these air the kind of the logical things to think about when you're doing any kind of study of investigational agents.

  • But I put them here because the goal and considering them, is to get reliable evidence is rapidly as possible so that you can basically inform, practice and guide future kind of future treatment.

  • Prevention of the disease.

  • Random ization.

  • Which treatment and control group is Can you blind the study?

  • What's your target population?

  • I'll come back to that because I know So you may talk about that a little bit.

  • Her presentation, How much data can you collect and how?

  • How should you monitor the data in the trial as soon as possible?

  • So in this epidemic there were five treatment trials and of the five treatment trials, one was randomized.

  • This is the one we did.

  • There were three vaccine trials one in Sierra Leone, one in Guinea in one in Liberia and there was not a good collaboration among the groups doing the vaccine trials.

  • And so that they and they were designed differently.

  • The vaccine trials all had an element of random ization, innit?

  • One was a placebo controlled the one I'll show you.

  • The others were not so that the vaccine trial that we designed was a phase 23 trial of defined that in just a moment.

  • But it included two vaccines, one for Merck and one from G S K.

  • Without going into the long names for you.

  • What versus a common placebo group on this began on February 2nd.

  • So I won't keep keep that timeline in mine.

  • We met for the first time near Halloween in October, and we began on February 2nd, a trial with to experimental vaccines.

  • There were limited safety data available.

  • There were none from a West African population.

  • As a matter of fact, if you read the background section of the proposed A CO for the vaccine trial way, we sight Phase One studies which had not been completed in which have not even been I'm blinded.

  • So we knew there were no serious adverse events among the 24 patients in the Phase one trial.

  • But we didn't know in terms of the immunologist t that what the results were by treatment group or how they adverse events that were obsolescent severity buried by treatment group, we decided after a lot of discussion.

  • When you look at eligibility criteria in large part, it's a balancing of risk versus benefit.

  • So here the risk, even though in the middle of an epidemic of acquiring Ebola, was relatively low on for that reason because of the absence of of safety data except in adults largely seen in the U.

  • S.

  • And in Europe, we restricted the trial two adults, men and women, but not Children and women who were pregnant or repressed city.

  • This was, ah, long discussion about this and one that we still have about doing vaccine trials, which you may hear more from Sonia and her presentation Now.

  • On the other hand, when we designed the treatment trial, there was no license therapy and rather than placebo, are doing it blinded, we basically defined.

  • The control group is optimized standard of care, and the major reason for that was that this was an injectable drug called Z map, and the injection itself put staff clinical staff a risk on kind of taking care of people with Ebola, which is transmitted through bodily fluids.

  • Again, there was very limited safety data, uh, kind of human safety data on this vaccine.

  • There was anecdotal information from eight patients have been treated by compassionate use.

  • There was a phase one study that had just been ongoing, but there was a limited supply of the drug.

  • I mean, those were all considerations.

  • I think that led us to do a randomized trial with a standard of control, control arm and essentially to take all comers.

  • So we in this trial the risk benefit clearly, because the death rate was 50 to 60% clearly favored putting everybody.

  • And even though the data was not there for Children are for pregnant women or other kind of individuals that that potentially were at higher risk.

  • And so all the participants, all the potentially eligible participants with Ebola were eligible for random ization.

  • This trial, because of ah waning epidemic in Liberia, got moved to Sierra Leone and light and Guinea, but just want to point out the trial protocol was actually open in the United States.

  • The very first patient randomized was in the United States, and the 2nd 1 was in Liberia.

  • We began the trial, so these were kind of design issues, which I think it went surprisingly well in our discussions with people at the Ministry of Health in Liberia.

  • In other settings on you may have read about it.

  • Absolutely no random ization.

  • Absolutely no placebo.

  • Uh, you know, And so here we had a group of people who basically very quickly a re agreed at 40,000 feet.

  • You might say that what the overall trial design should be both randomized trials, one kind of double blind and the other not.

  • And then the focus here became kind of implementation.

  • And I just wanted to mention a few of these because it highlights the importance of preparedness on DDE what we had to do in terms of getting doing these trials in beginning a trial in essentially three months following initial discussions with the Liberian Ministry of Health.

  • So one question might be is how do you prepare syringes without clean rooms or freezers and provide them to sites within a few hours.

  • So much like the safety data which didn't exist?

  • Stability information of the vaccine, once you had filled the syringe also was lacking.

  • So both companies, Merkin G s K.

  • Felt that to be safe, vaccine should be used within three or four hours.

  • So what we did?

  • Well, we went to the embassy.

  • We had an incredible ambassador who was very kind of helpful.

  • She gave us a new old building on what they call the old embassy grounds.

  • We quickly renovated it.

  • We bought hoods.

  • We bought freezers on the vaccine, arrived one week prior to starting the study on Guy mentioned that because even if we had moved faster in terms of the design and they kind of renovation and the work preparing to begin, it would not been possible to start because the vaccines weren't ready to be shown.

  • And so the picture on the right eyes a picture of six Liberian pharmacist that were trained by a pharmacist from an agent, a pharmacist from the FDA.

  • Every morning they showed up at six o'clock.

  • They prepared the syringe is to provide for the vaccine for the random ization of the vaccination on.

  • They were delivered to the vaccination side.

  • So how do you conduct a phase 23 trial with had a clinical laboratory and examining rooms So I failed to mention earlier that in turn, what I mean by phase 23 is that there was no way we could felt like we could vaccinate 30 to 40,000 people, was what we had estimated was gonna be required without doing a run in safety study to make certain that the vaccines were safe.

  • And so the face to part of it was to include 600 people.

  • You understand the safety of the vaccines before we kind of did them on a more widespread basis.

  • So we chose to do the face to study at Redemption Hospital on Redemption Hospital.

  • Actually turned out was the a place where most health care workers in life in Monrovia lost their lives on dhe.

  • The people who ran that hospital is the free hospital.

  • The typical kind of number of people you might see in a day there in that hospital is over 1000 people.

  • It's spread out.

  • It looks small, but it's actually a spread out in environment.

  • When we visited in October, there was no one there, actually, that there were 45 clinical staff and they were watching TV.

  • Basically, most all of the health care facilities in Monrovia had closed down and people were afraid to go there because that's where people died on.

  • That's actually where a number of health care workers died.

  • So we, in order to do this study, we built a lab in December, brought in the equipment, got it running so we could do the laboratory screening that was necessary for the vaccine on remodeled the space, showing the vaccination room there.

  • So how do you obtain informed consent from a population that may never be able to read a consent form?

  • So they actually had an ingenious idea.

  • The Liberians we're gonna have a group session led by Liberians were gonna put pictures on the wall to show what's gonna happen at each stage of the trial.

  • And we're gonna explain the trial to the group, and they would bring in, like, 20 or 25 people at a time.

  • And if you've met people from Liberia and many of them live here in the Twin Cities area, they like to talk.

  • They like to argue, and they'd have me.

  • So if you ask, you stop and pause and say, Does anybody have any questions?

  • If there's 20 people in the audience, 15 of them hands would go up, and so they actually would spend roughly an hour in these information sessions asking questions.

  • After that, they went into a private room for individuals informed consent on.

  • I've mentioned to several people I don't think I've ever seen such good informed consent where there was actually lots of discussion about the trial and what they were getting into.

  • How do you randomize people with no access to the Internet?

  • Sometimes you even have electricity.

  • In October, almost all the meetings I went to with the ministry were in the dark.

  • Electricity would go off for hours at a time.

  • So we did.

  • You know, the important things in terms of random ization.

  • You know, you've heard a blinded random ization.

  • Potentially, you don't want to have people know what the next assignments going to be.

  • And so what was done by the pharmacist in the upper left hand corner?

  • There is.

  • They prepared syringes and put a bar coded label according to a random ization role of labels that was prepared here in Minnesota.

  • They then kind of filled the syringes, but before that, they filled the syringe is.

  • Then they put them into a kind of ah basket for transport to Redemption Hospital.

  • And when I got to Redemption Hospital, we randomly pulled a syringe out of a bag and vaccinate.

  • Somebody had that really desirable feature because we use blocks of 12 and they would typically see 24 to 30 people a day that if you looked at the paper that we published in this trial, there's almost a precise with his exact allocation that we have desired.

  • There's 500 on GSK's vaccine, 500 armored and 500 on placebo.

  • And this was the case when you got randomized, you were vaccinated.

  • So there's nobody that got randomized that wasn't vaccinated.

  • And the linkage that was put on by the person in the vaccination room with a case report form was with a patient identifying information.

  • And so nobody knew with that code correspondent to accept statisticians back here at Minnesota.

  • But the linkage with the patient was established there on the form so one could produce the summa

so welcome back, everyone from what I'm sure was a very enriching afternoon.

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次の流行に備えて|健康未来サミット (Preparing for the Next Epidemic | Healthy Futures Summit)

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    林宜悉 に公開 2021 年 01 月 14 日
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