University Place

Hello, I'm Emily Auerbach, and

you today as part of Eloquence and Eminence

Emeritus Faculty Lectures. This is a series that we started 21 years ago to showcase UW professors who have retired but are known for their teaching excellence and scholarly expertise. We're sponsored by the Division of Continuing Studies, the Institute on Aging, and an anonymous committee. We're grateful to Wisconsin Public Television for broadcasting this talk to a statewide audience in the best spirit of the Wisconsin Idea, a phrase that I hope is never deleted from the university's mission. (applause) It gives me great pleasure to introduce today's speaker, Dr. Dennis Maki. Dr. Maki is the Ovid O Meyer Professor of Medicine in the Divisions of Infectious Diseases and Pulmonary Critical Care Medicine at the UW Madison School of Medicine and Public Health. He's an attending physician in the UW Hospital Center for Trauma and Life Support and eICU and the former head of the Division of Infectious Diseases from 1979 through 2007. He has many, many awards, publications, his research has been cited more than 16,000 times by other colleagues, he has been a past consultant at the CDC, NIH, and many other places, he's been listed in every edition of the Best Doctors in America since 1982, and received numerous awards for teaching, research, and service at the UW, nationally, and internationally. In 2000, he was a master at the American College of Physicians and was cited by the Infectious Disease Society of America for lifetime achievements in the field of infectious disease. If I told you about all his awards, we'd be here all day, and instead I know we want to hear his presentation. So please join me in welcoming Dr. Dennis Maki for emerging infectious disease in the 21st century. (applause) Thank you very much, Emily. I apologize for being delayed. I'd like to just tell you a little bit about myself because I'm a child of Wisconsin. I was born and raised in a very small town of 500 people in north central Wisconsin, and had a wonderful childhood and adolescence and was planning to go to a small college to play basketball. And my father said you're going to UW Madison, and there was no further discussion. And I'll be ever grateful to my father's wisdom because it was an extraordinary education, and the opportunity when I completed my training at Harvard to come back and join the faculty 41 years ago. It has been an incredible academic ride. I love Wisconsin, and the university has been an extraordinary experience. I really appreciate the chance to talk about the subject today because it's a relatively new field of inquiry, only about 25 years old. I have no conflicts of interest to report, and that's important. It's mandatory in modern day continuing medical education. I have no conflicts of interest. And I'm going to try and cover six areas very quickly. I'm going to basically give two talks. I'm going to talk about emerging infectious diseases, and then I'm going to talk about Ebola as the most recent and extraordinary example of an emerging infectious disease and the challenges it poses to global health. The whole concept of infectious disease and emerging infectious disease really goes back a long time because infectious diseases, long before we knew about microorganisms or germs, were recognized as being contagious. They were transmissible, that was known 3,000 years ago with Hippocrates. And contagious diseases were written about in medical history. Literally, they're in the papyrus's of the Egyptian dynasties. This is a woodcut from the Middle Ages that shows the four horsemen of the apocalypse, a revelation, war, death, famine and pestilence, or contagious disease. This man changed the world. He is probably the greatest biologic scientist of the last 500 years. This is the great Louis Pasteur. He not only showed that microorganisms that people could see microscopically for several hundred years were the cause of infectious disease syndromes, but he was the father of immunology. He actually developed the first targeted vaccine, rabies vaccine. After Pasteur's epical work in the mid-19th century, there was an explosion of research across the world, and hundreds of different microorganisms were identified and characterized that caused the whole wide panoply of human infectious diseases. If Pasteur were here today, he'd be astonished at all of the vaccines that have been developed following his initial nascent rabies vaccine. And all of the antibiotics and antivirals and antifungals that we have for treating most infectious disease syndromes. It's been extraordinary. And we can take great pride in the progress that's been made on treatment and control of infectious diseases in all aspects of medicine. In fact, as long ago as 1970, one of our most esteemed Surgeon Generals, William Stewart, who commissioned the first Surgeon General's report on smoking, was quoted as having said, We've made so much progress, "we're about to close the book on infectious "diseases as a public health threat. Well, infections didn't go away. They remained a huge problem worldwide. More people die due to an infectious disease around the world every day than die due to cancer or heart disease combined. The field of infectious diseases, however, seemed to be stagnating by the mid-1970s. There had been no new microorganisms could understand a little bit where Stewart was coming from. And in 1976 the field of emerging infectious diseases had its outset. A whole bunch of Legionnaires' went to a big convention in Philadelphia, and about the time they were going home, many of them were getting sick, coughing, getting short of breath, and they had pneumonia. It was severe pneumonia. One out of five died who got this pneumonia. And the CDC spent a huge amount of effort to try and find the cause, and their initial efforts struck out. In fact, they were criticized severely by our congress because they hadn't found the cause of legionnaires' disease. The cause was found, and it was found by CDC six months later by researchers working in the middle of the night. I think it was on Christmas Eve, showing with a special stain, tissues from the victims. It looked like there was a strange bacterium in it. All the bacteria had been identified. They quickly developed a very enriched media, and they quickly found an entirely new pathogen, the legionella organism, Legionnaires' disease. Within weeks, it was clear that this organism was in our domestic water supplies and rivers and streams as the major cause of community acquired pneumonia, hospital acquired pneumonia. And CDC did a look back, there were at least five epidemics of pneumonia that had been unidentified. They were caused by legionella organism. I can tell you this really shook up the infectious disease community. This organism, under our noses that we did not recognize. Within several years, young women, healthy young women, pre-menopausal women were being admitted to hospitals in profound shock. They all were very (mumbles). They looked very pink, almost red. And they were in profound shock, and this was caused by a hyper-absorbent tampon. The toxic shock syndrome caused by staph aureus. 15,000 women got infected with this. Almost 15% of them died because we didn't know the cause right away, didn't know how to treat it, and once we understood that, nobody should die of toxic shock syndrome due to tampons, It's so easily treated. Within another year, we had this strange report of opportunistic infections occurring in healthy, young, gay men or intravenous drug users, the first episodes of AIDS. The acquired immune deficiency syndrome that over the past 40 years has spread across the world, and, in fact, that epidemic is far from being played out. The good news is the progress has been made and control of AIDS has been a little short of extraordinary. We have over 40 drugs for treating this virus. And as you can see here, on this slide, death rates due to AIDS have dropped precipitously, and with HIV infection takes their medication, they ought to be able to live a long, long time with a good quality of life. Well, about 15 years ago, new microorganisms, new disease syndromes were being identified so rapidly that the National Institute of Medicine of the American Academy of Science commissioned a blue ribbon panel to make recommendations on the control of emerging infectious diseases. And the first thing we had to do is what is an emerging infectious disease? Define it. And they defined an emerging infectious disease as an entirely new microorganism that was causing significant numbers of human disease or the reemergence of an infection that had been totally controlled, or antibiotic resistance on a major scale. And we could talk all day about antibiotic resistance, that's another time. But the point is emerging infectious diseases are a big deal. This is from an editorial I wrote about six to seven years ago in the Mayo Clinic proceedings. I listed the major emerging infectious diseases of this 30 year period of time. Every single one of the infections on this list has been identified since 1975. If I stopped reading when I finished medical school in the late 1960s, I wouldn't know very much. These are common infections, many of these are very common infections we deal with on a daily basis, and they're very important pathogens and they've had a huge impact on human health. Now, I'm sure many of you are thinking in your mind, why have these emerging infectious diseases emerged? And that's a very interesting story. It's a story of humanity. There are many reasons that emerging infectious diseases appear. A very important one is when you have disruption of society. War, death, excuse me, war, famine, massive flooding, when that happens we start to see children dying in large numbers of diarrhea, typhoid, measles, tuberculosis. What are children dying of in Sub-Saharan Africa in these huge camps? They're dying of TB, chicken pox, measles, diseases that shouldn't be killing people. Changes in healthcare. In my lifetime, the changes in healthcare are a little short of extraordinary. I do critical care medicine on a major scale, and the progress that's been made in this field is just almost breathtaking. If you get to the hospital alive, we've got a very good chance we can save your life. We can support almost any type of organ failure for an extended period of time until you heal and repair and survive. But all the things we have to do, these invasive procedures and putting on a breathing machine and giving you intravenous fluids and catheters and big operations, there's a risk of hospital acquired infections. This has been one of the major emerging infections of the last 30 years. Antibiotic resistant hospital acquired infections. The good news is rates are dropping precipitously. They've dropped by more than a half in the last 10 years alone. Look at advances in healthcare. Implanted medical devices, I'd be willing to bet there's one or two people here who have a pacemaker. I bet you there's a half a dozen who have an artificial joint, or who have artificial lenses, who have an artificial heart valve. Those implanted devices can become infected, and they're devastating infections. The good news is we know now how to prevent them, and they're rare. We know how to treat them. The bad news is an infection of most of these devices mandates explanting the device, intensive antibiotic therapy, and then we put a new one in. But they have been a major, these devices have improved health immensely, but emerging infectious disease are the risk of infection that is associated. Changes in food production. We have 400 million people to feed in North America. The industrial production of food is a fact of life. We aren't going to change that. There's no way in the world we can go back to a little 100 acre farms and raise organic food and feed 400 million people. The reality of life is food is going to have to be produced on a huge scale or we'll have international famine. The downside of this is the risk of food-borne disease. When you have enormous numbers of food animals in very close proximity, there's a risk that they can become infected and carry germs that infect human beings. And food-borne disease is one of the downsides of industrial production of food. The risks of food-borne disease have doubled in our lifetime. Fortunately, with the enormous amount of food that's produced, the vast majority of it is quite safe, but it's very important to be informed how to prepare your food to protect you and your family from food-borne disease. Changes in human behavior. That's part and parcel of our society evolving. The sexual revolution of the 1960's was a very extraordinary time. The offshoot of that is sexually acquired infections. We have epidemic antibiotic resistant gonorrhea, rampant syphilis. Syphilis used to be rare prior to the 1960s. It was so rare, I never saw a case as a medical student. I never saw a case as an early resident. But now it's a relatively common infection. I treated two patients last week for syphilis, one for neurosyphilis. Herpes, 50 million in this country have genital herpes infection. Genital warts is the epidemic that nobody wants to talk about because it's very likely going to translate to an epidemic of cervical cancer. This is an oncogenic virus. Environmental changes. We all want to live out in the country. The au naturel life. However, there's scads of microorganisms that are out in the country. Exposure to tick borne diseases, which have gone up markedly in the last 15 to 20 years, and zoonoses such as West Nile infection. These are the consequences of environmental change. This is the gorgeous Brazilian tropical rain forest which is being cut down and burned at a frightening rate. And the consequences of that with human disease and global warming I don't like to think about. Changes in the public health infrastructure. We don't really realize the thin veneer of protection that public health provides in a developed country such as the United States. We do have, I think, the best public health system in the world. Let me show you what happens when public health starts to erode. Many of us here are old enough to remember Gorbachev and Glasnost, 1989. And there was rapprochement between the US and the Soviet Union. And the Soviet Union made the decision they were going to become a free enterprise society, and they were going to sell off their inefficient state-owned industries, which, interestingly, were bought by the same people who were running the country and became oligarchs and many billionaires, but for about 10 years their economy imploded. People didn't pay taxes. They stopped sending pension checks out, and they stopped immunizing their children. As recently as 1988, were probably less than a hundred cases of pharyngeal diphtheria in this huge country in eight time zones. When the economy imploded and they stopped immunizing children, within three years they had 50,000 cases of diphtheria in children. That's probably a vast underestimate of the true number of cases. If we move fast forward to today, we have a resurgence of measles because many people don't believe in vaccines and immunizing their children. And the price paid is the resurgence of these infections of childhood that should be easily controlled. Let me tell you, measles is not trivial cute little disease where they get a rash. One out of a thousand children gets encephalitis and may be severally impaired for life, and it is not a trivial disease. It's a very serious disease, and every effort should be made to control it. And if we look at the great achievements of public health of the last thousand years, vaccines are number one on the list. Vaccines have saved more lives than almost any other single thing that we've ever done in medicine. And microorganisms adapt. Why does a toxigenic strain of staph appear and start to spread? Why do we have new virulent pathogens appear? That's a subject for research and another day. So, I hope I've defined for you emerging infectious diseases are part and parcel of all of our daily lives, and it's a very rapidly moving dynamic field. One of the most terrible days in our history was 9/11. And everybody can remember where they were on 9/11. If that wasn't bad enough, in the weeks following 9/11, somebody started sending weaponized anthrax through the US mail. And thousands and thousands of postal workers and others were exposed on the east coast. This was a black time. I remember I had to go to Cornell to do grand rounds two weeks after 9/11. The planes had started flying again. I was the only person on the plane to Detroit. I stood in the Detroit airport, this very long airport, I could have shot a deer rifle down the middle of it and I wouldn't have hit anybody. There was nobody there. It was a terrible time. But there's a very famous old English

aphorism

it's an ill wind that blows no good. And the terrible events of 9/11 and the weaponized anthrax had an upside. It made us realize, starkly, how vulnerable we were as a country. We had no preparation to speak of, for terrorism let alone bio-terrorism, and preparation for bio-terrorism is preparation for emerging infectious diseases. And the good news is that in the five years that followed 9/11 we made more progress in preparation for bio-terrorism and emerging infectious diseases. Public health got a huge injection of resources for the first time in probably 30 years, and all of our public health sector came out of this much stronger and we can do a much better job in terms of protecting people from disease. Preparation for bio-terrorism, as I said, is preparation for emerging infectious disease threats, and it starts with a greatly strengthened national, state, and local network, and these people have to talk to each other. I remember serving on local state committees in preparation for bio-terrorism and emerging infectious diseases. The computer system locally didn't talk to the state system, didn't talk to the CDC. It was terrible. They were silos that didn't communicate with each other. That's all over. There's a very smooth communication at health in this country, which as been a huge benefit in terms of protecting the public. It's absolutely essential that primary care providers, family practitioners, pediatricians, internists, emergency physicians, urgent care physicians can recognize these bio-terrorist illnesses, that they can recognize emerging infectious diseases because being able to recognize them early is fundamental to implementing control measures early that will be effective. Having an adequate stock pile of critical vaccines and anti-infectives. We now have what's called the national stockpile. We have essential vaccines, antibiotics, medications that could be needed for bio-terrorism or emerging infectious threats dispersed across the country. If we needed to give small pox vaccine because small pox was introduced in Madison, Wisconsin, and we had 41 cases, I can tell you we would immunize the entire state in three days, and we'd have vaccine available within six hours from Chicago. That wasn't possible only 15 years ago. And, obviously, research to develop better vaccines, technologies to detect infection have absolutely boomed. So, that's emerging infectious diseases. Let's talk about Ebola, which is the most recent of all of the emerging infectious diseases and which you've heard so much in the media. It's always appropriate to review the history of a disease because you know where you've come from and it charts the direction where you're going to go and what you need to do. Ebola virus is one of the hemorrhagic fever viruses. There's actually about seven or eight distinct viruses that fall in this category where they're called the hemorrhagic fever viruses. 99% of these infections occur in tropical areas of the world. And they're called hemorrhagic fever viruses because they cause hemorrhage into the skin, into the tissues, into the gastrointestinal tract, sometimes into the lungs, and about 15% to 20% of the people who get infected with these viruses have these hemorrhagic manifestations. Mortality of these viruses has been high. It's been in the range of 25% to 75%. These are very serious infections. The only one of these viruses that we have in the United States is the last one, US Hantavirus. That was only identified about 15 years ago in the southwest. And this virus, fortunately, it's not very common. It's a very devastating infection, but we manage it, and there are very, very few cases, fortunately. The whole story of Ebola actually started back in 1976. They had an outbreak of hemorrhagic fever Sudan, northern Zaire area of north central Africa. And in this fairly large regional hospital there were almost 300 cases of hemorrhagic fever, and 53% of these people died. What was even more astonishing, of 230 nurses, doctors, pharmacists, and others who worked in this hospital, 76 of them acquired infection from patients, and more than half of them died. They thought that this was Marburg virus, which had been characterized probably 10 to 15 years earlier, but teams came in from WHO from the UK, and they took specimens from victims, and when they took it home and did special testing, they discovered something quite striking. It was a new Filovirus. Very distinct from any other known hemorrhagic fever virus. They named it Ebola because they thought it would be a terrible thing to name it after the village where this hospital was. And the village was located near the Ebola River, which is on the major tributaries of the Congo. And so they called it Ebola virus infection or Ebola infection. Since that time, we have learned that Ebola is a big deal in Africa. There have been 19 outbreaks between 1976 and 2013. Some of these as small as a handful of cases, some of these hundreds of cases, like the first outbreak. They have been mainly in north central Africa, the Sudan, Zaire, Congo, Gabon, Uganda, with a handful of cases that were introduced (mumbling) infections in developed countries. A lot of people don't realize there actually was an Ebola virus outbreak in the United States, if you read The Hot Zone. It turns out that by federal law primates that are brought into the United States for research purposes or zoos have to be quarantined for one month before they're allowed to be sent to their ultimate destination because of fear of hemorrhagic fever virus because almost all of the hemorrhagic fever viruses can infect primates. And there was a large primate holding area that had thousands and thousands of mainly monkeys, chimpanzees, right outside of Washington, DC, in Reston, Virginia. And they had about 160 animal handlers who worked in this facility. And one day they noticed the monkeys were looking droopy, many of them, and then some of them started to die, and they got very alarmed. They called in researchers from the US Army Infectious Disease Institute in Fort Detrick, Maryland. They came in, did testing, and within a very short period of time they said this is Ebola. Ebola? In a suburb of Washington, DC? Well, to make a long story short, this strain of Ebola had never been seen before, and these monkeys that bought it in came from the Philippines. They called it Ebola Reston. And Ebola Reston can infect humans, but it doesn't make them sick. Six of the animal handlers got sick, they had antibodies, didn't get sick but rather had antibody. They'd gotten infected, but they had almost no clinical illness. The researchers who've gone to the Philippines then had found that this is endemic in the Philippines and that it commonly infects pigs and kills large numbers of domestic pigs. It also kills primates. But we escaped a serious Ebola outbreak. The 2014 outbreak that we're going to discuss hereafter now actually started in Guinea. And Guinea is on the west coast of Africa, had never had Ebola virus. And this first case was only identified in retrospect, and I'll tell you how they identified it afterwards. But there was a cluster of cases from this first case. A little boy got sick, a witch doctor came in to treat him. All of his family members got sick. I think just about all of them died. He died. The witch doctor went to other villages and spread Ebola, which quickly spread not only from Guinea but spread to the two contiguous countries, Liberia and Sierra Leone. These three countries are three of the poorest countries in the world. They have very nascent public health systems at best. This outbreak has gone gangbusters. From a handful of cases in late 2014, in early 2014, we've now have thousands and thousands of cases, and each one of those circles represents a cluster of cases. The larger circles can be as many as a thousand or more cases. As you can see in these three countries, they've been absolutely devastated by Ebola As the most recent data in the WHO website is of April 19th, 26,000 proven cases and almost 11,000 deaths. This is a 40% mortality. The true number of cases is probably many times higher. So this is not a trivial outbreak. It makes all the previous Ebola virus outbreaks pale in comparison. What's been most striking about this outbreak, over 600 healthcare workers have become infected, and more than half of them have died as a consequence. This is the most recent data from the WHO website. You can see Guinea, Liberia, and Sierra Leone have had just thousands and thousands of cases. The largest number of cases in Sierra Leone and in Liberia. There have been a handful of cases in Mali and in Nigeria and Senegal, but they have not spread, and we're extremely grateful, obviously. There's been an interesting feature here. The number of cases has risen strikingly, but the number of deaths may be starting to taper off for reasons we're going to talk about shortly. And the epidemic looks like it's starting to burn itself out, or, I'd like to believe, all of the efforts that have been made to control it by the local health authorities and a lot of help coming from the outside, from the United States, from WHO and European countries has had an impact. Interestingly, relatively early in the outbreak Nigeria had the introduced case, and by the time they realized what had happened, they had 13 secondary cases, and everybody thought now we're really in for it. Nigeria is the biggest country in Africa. It has between two and 300 million people and has enormous numbers of people in Lagos who are living in extremely close, crowded quarters, and if it starts to spread in Nigeria, it's going to make what's happening in West Africa look like nothing. The Nigerians did an extraordinary job. They have a much more developed public health system. They did cutting edge shoe leather epidemiology. Tracked down every exposed person, put in mandatory quarantine, and contained spread very successfully. It was very admirable. The US had two endogenous cases in nurses in Dallas, which we'll talk about shortly, but there was no further spread from those two cases. There's an important side on this outbreak, and that is that during this outbreak that's been going on now for almost 18 months there's been an unrelated outbreak of Ebola virus Zaire infection in the Congo, which appears to have wound down, burn itself out, had a 74% mortality. There's a little difference in mortality between the different strains. So let's talk about Ebola virus. As I said, this is one of the hemorrhagic fever viruses. It's a Filovirus. Filo, the root, means thread. Most viruses occur, they package their DNA or their RNA in an elliptical or spherical configuration. Ebola virus and Marburg virus, which are the Filoviruses, the RNA is in a long, linear structure, and the end of it attaches to the cell, injects the RNA, co-ops the machinery of the cell, totally takes over the cell, turns off the normal cellular mechanisms, and forces the cell to do nothing but make more virus. And it bursts out and kills the cell and leaves. It's like an alien brain floating around looking for a body to take over, and that's what viral infection really is all about. Viruses are almost mystical infectious agents in many ways. There have been five clearly defined species of Ebola virus. The vast majority of infections have been with two of them, Ebola virus Zaire and Sudan, which have caused almost all of the disease in north central Africa. The question I'm sure that's in many of your minds, how did people get diseased in such large numbers? How does it spread? The question is, what is the epidemiology of the disease? Epidemiology is the field of inquiry that identifies the source of an infection and the mechanisms of transmission. So, how does Ebola virus, where does Ebola virus live? A big mystery for almost 30 years was where did Marburg virus and Ebola virus hide out between outbreaks? Because it's very clear if you get Ebola virus, you're going to either live or die. If you die, they'll bury you. If you live, you'll clear the virus, and nobody has chronic Ebola virus infection. And so when the outbreak is contained, there's nobody sick. There's nobody carrying it around who's going to spread it. So, where does it come from? Is it in the soil? Is it in food? Where does Ebola virus hang out between outbreaks? Only in the last four or five years have we learned that these Filoviruses appear to hang out in bats. This is a very important reservoir because this SARS epidemic of 10 years ago was discovered to hang out in bats. And it turns out the new Middle East Respiratory Disease Syndrome looks like it hangs out in bats between outbreaks. The bats don't get sick. They carry the virus and in fairly large amounts and it's in their entire body and when they defecate there's a lot of virus in their feces. What now becomes pretty clear is that the virus initially gets to somebody who eats a food that has Ebola virus in it. It may be a vegetable that has some bat dropping on it. More likely, it's vegetative matter that is eaten by a primate or a duiker, which is a deer-like creature because in Africa, as in most parts of the developing world, protein is precious. It's expensive, and you never waste protein. And if you go to a fairly large food market in Africa, you'll find the bush meat area. And they sell all types of animals that had been killed and they're going to be eaten. On the left, you see what's called bat stew. And they just basically take a bat that's been caught, and it gets boiled and they make a meat. They eat the meat of the bat, and they drink the liquid. It's most likely that the virus got into humans by eating either vegetative matter that was contaminated or eating an infected animal. There have been instances where families have discovered an animal that had died, look like it just died. Well, protein is precious. They basically cooked it up and ate it, and the whole family came down with Ebola and died. Once it gets into even one or two people, it is very, very transmissible, and it spreads person to person. And person to person spread is a major transmission of Ebola virus. In western Africa, it is part of the culture that when somebody dies the family members want to personally wash the body and touch the body before the body is buried. That is part of the culture. And that is a very high risk thing to do if the person died of Ebola. They may have a lawn of Ebola virus on their body surface, and there's quite a bit of evidence that this has promoted the spread of Ebola. What about the little boy? How do we know this little boy is the source? Well, the extraordinary advances in molecular biology in our lifetime, we now can sequence the entire genome of a viral strain in hours. So they take strains of Ebola virus that they've identified from throughout the outbreak, and by looking at the number of mutations, they can actually trace the virus. Is this an old or early infection? And the earliest case they could find appears to have been in that area of where this child got sick and the family got sick and the witch doctor went to other villages. That appears to have been the source. And that little tree you see is hollow where bats live is where this little boy was playing in the days before he got sick and died. Now, I'm sure many of you are asking here you've told me about 19 outbreaks of Ebola between '76 and 2013. They all burned out. Why has this outbreak not burned out? Why has it spread in uncontrolled fashion? Why has it killed enormous numbers of people? I'm a child of the 1950's, and I used to love to go to the Tarzan movies with Johnny Weissmuller. And my childhood picture of Africa is what you see here. A very pastoral society. These little peaceful villages. People raise their crops. In North Africa, they raise cattle. Didn't have much contact with each other. It's a very pastoral thing. And that's probably pretty accurate. That is not the Africa of today. This is the Africa of the 21st century. The urbanization of Africa has been striking in our lifetime. If we look at rates of urbanization, the highest rates of urbanization in the entire world are occurring right now in Africa and parts of Asia. By 2050, there will likely be at least 10 cities in Africa that have over 10 million people. This is 21st century Africa, and the fact that people that may live in rural areas go to the big city to get a job, for their children to get educated, to get medical treatment, the tremendous communication that's occurred in our lifetime is why this Ebola outbreak has spread in a uncontrolled manner. A second issue is that this outbreak occurred in three of the poorest countries in Africa that had probably the least resources in terms of public health. What is Ebola virus like clinically? Well, a lot of people know, what's the incubation period? If I'm exposed, how long does it take before I get sick? These data were very, very carefully collected. And what they show is that the median incubation period is about five days. If you're exposed to Ebola, most people will start to get sick by about the fifth day. There have been a handful of cases out to two to even pushing three weeks, but they're very, very, very few. Which is why this 21-day quarantine period, is where this number comes from. Ebola virus infection starts off looking like a flu. Feel a little achy, little headache, feel a little weak. You're nauseous. You probably start to have a little diarrhea. You may vomit a little bit, but it's very nonspecific. And if I live in Africa, that could be early typhoid or malaria or dengue, hepatitis, typhus, meningococcemia, measles. The last thing we'd think about would be Ebola. However, once you've become symptomatic, virtually nobody gets better with the mild illness. Almost everybody gets sick, gets seriously sick with a high fever, with profound diarrhea and vomiting, and 10% to 15% will show massive hemorrhage and people often are in coma because they're in such profound shock. Why does Ebola virus kill people? That's a very interesting story. Why is it such a virulent virus? Well, we've learned a great deal about why infectious diseases make people sick and why they kill. And the very common notion is that this virus or this bacterium is nibbling away at our vital structures and causing damage to our organs. But that isn't really what happens most of the time. There's a very small number of infections where that does occur. In the vast majority of infections we get sick because of our immune and inflammatory response. When our body detects microorganisms, it triggers a tremendous inflammatory response. We start pouring out white cells. We start pouring out molecules that enhance and amplify the inflammatory response called cytokines, or biologic mediators. It turns out that that is what makes you sick. A person who gets a serious infection is being consumed by the flames of their own immune and And there's been a huge amount of research in the last two decades of how can we modulate this response in serious infections, septic shock, to improve survival. And progress is being made here. There's just no question about it. Well, it turns out Ebola virus probably triggers as much inflammation as any virus known. It triggers a huge amount of inflammation. But if that isn't enough, it actually turns off your immune system for about 10 days to two weeks. You stop making antibody, your cellular immunity goes to hell in a hand basket, and you are basically probably genetically predisposed that you're going to survive or not survive if you don't get really good supportive therapy. If you get good supportive therapies, there's a much better chance you're going to survive. These are predictive factors. Most of us in this room are really over the hill as far as Ebola is concerned. Over the age of 45, the mortality in Africa is about 90% to 95%. Very few people survive. Over 60, forget it. And people who have hemorrhaged or are in shock or in coma, the vast majority of them have died in Africa. How do we manage Ebola virus in proven Ebola virus disease? Well, you have to start off by realizing if you can't protect the healthcare workers, who's going to take care of the sick patients? You have to protect the healthcare workers. So that means you need well trained healthcare workers who have adequate protective apparel. This is what we use for MRSA or other contagious diseases in the hospital. This won't cut it for Ebola. For Ebola, we need rigorous training in how to put on all the apparel. We need to cover every body surface. Here I'm prepared to do battle with Ebola. I have a PAP, or a positive airway device, that is blowing air under pressure into the suit so that there's no way air can get in through any leaks, and there's not an area exposed. There's double gloves on. There's extra garb covering the shoes, and you have a buddy that monitors you putting it on and taking it off because it's very easy to contaminate It's adequate to have appropriate isolation rooms. They need to be separate air isolation rooms. A room where the air does not recirculate. The air we're breathing is probably recirculated through 20 rooms in this module. In the isolation for rest or isolation, the only air, the outlet air goes directly to the roof line where it's diluted in the infinite amount of air, or it's filtered when it goes out. A lot of people have said, well, Ebola has such a terrible prognosis, if they come in in shock and they're dying, they look awful, we shouldn't even treat them. We shouldn't intubate them, shouldn't put them on a vent. They're going to die anyhow, and it puts the healthcare works at risk. That is a bad, bad idea because it's become very clear that patients with Ebola virus can be on death's door and with modern day critical care, very sophisticated care, dialyzing for their kidney failure, ventilating them on a breathing machine when they're in respiratory failure, if need be for two or three weeks, can save their life and they'll walk out of the hospital. It's very clear. It is a privilege to be a healthcare worker. Is there a risk? Yes. Is it a big risk? No. If people are well trained, have adequate protective apparel, the risk is very low, and we should never have qualms about treating anybody who needs to be treated because of fear of disease. Now, this is a very important issue. Treating dehydration, electrolyte If my blood potassium or sodium is real low, replace it with IV fluids, electrolytes. There's been a raging debate for much of the Ebola outbreak because Doctors Without Borders, the very admirable French society, volunteer healthcare workers, who I have enormous admiration for them, did not want to put IV catheters in patients. Did not want to give IV fluids. They were afraid there was too much risk of a needle stick. So their treatment centers were basically triage centers where you came, they'll feed you, they'll treat your pain, but you're going to live or die on your own. Well, it turns out that if you get modern day healthcare, you're much more likely to do well. There have been 10 people with Ebola virus treated in the United States as of a couple months ago. Only two of them died, and both of them were moribund, at the end of the road, by the time they got into our system. This report, just came out in the New England Journal, I think is profound. This is a Ebola treatment center founded by several Americans, and they decided anybody who came into their center with probable Ebola would get an IV catheter put in, they'd start giving them IV fluids, they'd re-hydrate them because they're all dehydrated, and aggressively hydrate them. Give them antimalarial prophylaxis. Feed them, if need be with a feeding tube or IV. To make a long story short, mortality in their center dropped from a baseline of 75% to 23%. It's very clear that simple things will make a big difference. There's a whole bunch of experimental therapies that have been tested and are being tested in experimental animals that are just about going into trials in Africa. This is the most recent. This isn't even published yet. I just got it offline today. It is an interesting vaccine that appears to protect primates against Ebola virus infection. These new therapies that they're studying are extremely expensive. If we did nothing more than set up 200 centers throughout all of western Africa that could do timely electrolyte measurements and re-hydrate critical ill victims with sterile solutions, we'd save more lives than anything else we do. I don't think there's any question. Protecting healthcare workers, I want to show you a study, and it's a very important study in understanding how Ebola spreads. This is a study done in an earlier Ebola outbreak. They had 27 households where one member of the household got Ebola infection. Unequivocal, they had Ebola virus infection. What happened to the other people in the household? And they tracked down 173 household members who were exposed in the next case. Now, 16% of those family members became secondarily infected. Every single one had direct hands-on contact with the index case. Nobody who didn't touch the person got sick, got infected. So this tells us that airborne spread is probably very, very rare, and the vast majority of transmissions are by person to person spread by contact. Our director of CDC made this statement about six months ago. I'm sure he's regretted it many times since. (laughter) Because Dallas Methodist Hospital had a patient come in who had Ebola virus infection. He said he just arrived from West Africa. He'd been in West Africa. That information somehow never got transmitted to the emergency room physician who saw him. He got sent out, thought he had the flu. He came back several days later in desperate condition, profound shock, was admitted to the ICU, and he died within days. Two nurses that took care of those individuals became infected, but, fortunately, our quickly identified all of their contacts, put them in quarantine, and there was never any further spread. It was very, very effective. When that occurred, we sort of came to our senses. We realized not every hospital can treat Ebola virus infection. The hospitals have treated it, it cost literally more than a million dollars a case. Atlanta has probably treated more than anybody because they have a federally funded bio-containment separate unit. They treated, I think, four or five people. They had over 50 people working full-time taking care of these patients. A huge semi would back up once or twice a week and be filled with trash and all of the liquid waste. They thought they could put the liquid waste into the sewers and flush it down the toilet because that's what we do for other things. The city of Atlanta said you do that, we're turning your water off. And so that means they had to take all the liquid waste that came from these patients, and it involved washing them, etc, and dispose of it separately. It is unrealistic to think that the average smaller hospital could begin to take care of Ebola patients. Thirty-five US hospitals have been designated as centers that have a lot of resources, have strong infection control. We have a emerging infectious disease unit at University Hospitals. We have up to 30 beds totally sealed off from the rest of the hospital, separate air. Totally, we could take care of a huge H5N1 flu outbreak if we needed to and protect the rest of the patients. And these other 35 hospitals have similar facilities. Let me close about saying about protecting, controlling Ebola in Africa. Adequate protective personnel, bleach disinfection, quarantining the exposed, identifying them, prompt burial and cremation of the dead, disinfecting a home, discouraging the eating of dead animals, cooking bush meat well, trying to limit travel. They thought they could quarantine villages. If nobody brings in food, what are people supposed to do? That was never realistic. And if we had a good vaccine, we could stop Ebola virus in its tracks quickly. And maybe we have a promising vaccine. There are a number of experimental vaccines in trials. Hopefully we'll get some information yet before the epidemic winds down. I would simply reemphasize centers that can treat dehydration would save a lot of lives. So, what does the future hold? There's a lot of big ifs. If the developed countries and WHO provide much greater on-site aid and food delivery to minimize travel and Ebola doesn't get to Nigeria or, god forbid, Ethiopia or Somalia, which are public health basket-cases. They have very little public health resources. They have huge numbers of people in camps. There's tremendous social disruption, and Ebola would spread like wildfire if it got there. And if we could get an effective vaccine, vaccines are so effective, we really need an Ebola vaccine. If none of these occur, I'm very concerned that the epidemic could spread beyond West Africa. If it gets beyond West Africa, then we've got serious problems. I don't think it's likely to get beyond Africa because most of the rest of the world has adequate public health to contain that. I don't think it'll ever be a true major health threat to the developed countries, but the cost of protecting our citizens and healthcare workers could certainly become prohibitive. So, what can we do as US citizens to control Ebola? We can support public health initiatives and major US aid to the affiliated countries. I think we have a moral obligation to do that and do that in a huge scale. We are ready and we can never do enough. WHO really blackened their eye because they took the outbreak way too lightly, and they took a long, long time before they brought their substantial resources to bear to contain its spread. Donate to Doctors Without Borders. I truly admire that group, notwithstanding their position on IV. It's a wonderful group of people. Before I close, I want to tell you that Ebola is not the only threat. I don't lose a lot of sleep worrying about Ebola causing world pandemic day, but I do think about this. A lot of people don't realize there's been a huge outbreak of bird flu in Asia. And there have been literally close to a billion food birds that have had to be destroyed, burned, and buried because they got this highly contagious bird flu. This strain has been now in 22 countries, and there have been almost 800 cases of H5N1 bird flu in humans. The average age of the victim is 13. The mortality has been 60%, this is transmitted by the air. Person to person as well as by airborne route. If this virus had a mutation of one or two genes so it could spread efficiently person to person, we would have pandemic disease that would make 1918 look like a picnic. I do think about this when it's dark at night. It's also important to realize that there's a new viral infection that's going on in the Middle East called Middle East Respiratory Syndrome, a virus very similar to the SARS virus. There have been over 400 cases. The mortality is 40%. And what they have found, bats are the reservoir. They get to camels and the problem with camels is people eat camel meat, they drink camel milk is how individuals get infected in these countries. In closing, this is a picture of the father of modern day medicine. This is the great William Osler, who was professor of medicine at Johns Hopkins, at Oxford, and he wrote the first textbook of internal medicine. There he's sitting working on his textbook about 1900. He was a very, very wise man and advanced modern day medicine enormously. He made a few very pithy statements. The one I love most was, "Look wise, say nothing, "and grunt; speech was given to conceal thought. (laughing) So, William Osler made this statement before he died. Humanity

has but three great enemies

fever, famine, "and war; and of these by far the greatest, by far the "most terrible, is fever or infectious diseases. Thank you very much. (applause)