I want to welcome you to this course entitled Ebola, An Evolving Epidemic. In this course we will explore the Ebola epidemic, addressing many topics, including biomedical, ethical, and sociocultural issues. We are honored to have as our guest speaker today Dr. Anthony Fauci, who's giving the introductory lecture to the course. Doctor Fauci is the Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in the United States, and has served in his role since 1984. As Director of the institute, Doctor Fauci oversees an extensive research portfolio of basic and applied research to prevent, diagnose, and treat infectious diseases. He's well known for having made some of the most important contributions in the field of HIV AIDS. Most recently, Dr. Fauci has led the NIH efforts in addressing the Ebola epidemic. And has been a voice of reason addressing the public fears and anxieties that the Ebola epidemic has caused. We welcome Dr. Fauci to our course. >> Hello. My name is Tony Fauci, and I'm the Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. And I'm very pleased to to give this open introductory talk for the Coursera course sponsored by Emory University. The title of my talk is the Ebola Outbreak of 2014-15. And I entitle it A Perfect Storm. And I hope it will become clear to you in a few minutes why I chose that title. I'm going to break my talk down up into four major areas. And I'll give a brief description of each starting off with some background on Ebola. I'm sure this audience has a certain degree of knowledge about it, but just very briefly, Ebola is a member of the filovirus family of viruses. There are five separate species. The ones we're dealing with right now is the Zaire specie. As you see, next to each of the species is a number. With Zaire, it's 50 to 90%. That was the reported fatality, case fatality prior to our now more in depth understanding of the role that intensive care can play in diminishing the mortality. And so 90% is likely not a reflection of the viral pathology itself, but more a reflection of a lack of ability to get intensive care to people. And when people go into intensive care, as you'll see, the morbidity and mortality is considerably less. The transmission cycle is one of an enzootic cycle involving fruit bats as well as non human primates, antelopes, and others. Although we know it's in fruit bats as the putative reservoir, conclusive evidence is not at forth hand here. We know when it jumps species and goes into a human that the spread from human to human is through transmission of direct contact with bodily fluids such as vomit, diarrhea, blood, and respiratory secretions. Particularly in the in extremis part of the clinical course. Also fomites, or objects, particularly equipment, when it's taken off, personal protective equipment that might be contaminated by body fluids. And as I mentioned also, direct contact with animals. In fact, the first case that triggered the current outbreak very likely was a young boy who came into contact with a fruit bat in December of 2013. Who then led to the smoldering of cases, which then became recognized as an outbreak in March of 2014. The typical Ebola clinical course is now very well established, since the initial descriptions in 1976 are very much in tune and in line with what we're seeing now in the current outbreak. An incubation period of 2 to 21 days, but heavy concentration on the appearance of symptoms within 8 to 10 days. Symptoms begin and have 1 to 3 days of flu-like illness, weakness, fever, malaise, which then goes in day four to seven, into what we, some have called the wet phase. Or vomiting, diarrhea, some bleeding, not as much as we thought in the previous outbreaks, leading to a hypovolemic shock, multiple organ system failure, and either death or recovery if one can maintain the patient, mostly with replenishment of fluid and electrolytes. The current outbreak in West Africa, as I mentioned, started in Guinea, with a single case in a young boy, which then, by March of 2014, was recognized as a bona fide outbreak. This is a map in March of 2014 showing the cases in Guinea. And I note for those not familiar with the geography of this region, how Guinea wraps itself around Sierra Leone and Liberia. And over a period of several months if one looks at the right-hand side of the slide, the total cases which began in Guinea. Now, when you get to one year later, the red coloring are in districts or prefectures in which there have been cases. As you can see now, we have virtually all parts of Sierra Leone, Guinea, and Liberia involved and infected with about 25,000 cases and 10,000 deaths. When one compares this to previous outbreaks, as you know, the first outbreak was reported in 1976 almost simultaneously in Zaire and Sudan. There were 24 outbreaks. I can't delineate each on this slide because some were so small as to have two or three people involved in the outbreak. The bottom line is that the total number of cumulative cases of all the outbreaks are many fold less than the total number that we're seeing in this current outbreak, which really is truly a historic unprecedented outbreak. What are the factors that facilitated spread that had me give the title A Perfect Storm? You have poor nations with limited instru, infrastructure who had no experience previously with Ebola, a dreadfully few health professionals per population that has multiple health threats. Such as malaria and other infectious diseases. Frequent travel across porous borders. Limited cooperation among neighboring governments. A history of regional conflicts and distrust in authority. And the local customs, such as burial practices which put people into very close, prolonged contact with contaminated bodies, has led to a great facilitation of spread. The responses have been rather significant, particularly in countries early on like Liberia and now in Sierra Leone, and to some extent in Guinea. With increasing in education, giving of hygienic practices that have now been trained for the people. Case identification, isolation, contact tracing, the use of proper personal protective equipment, aggressive supportive care, and safe but respectful burials. The United States government got involved. And it was very important that the military, that, who did not take care of patients, came in to supply command and control, construction of Ebola units, a 25-bed facility of a, a Monrovia medical unit for healthcare facilities. As well as an unprecedented effort by the CDC and the USAID. This has led to a dramatic diminution now where there are very few cases in Liberia, yet there are still some smoldering cases in Sierra Leone and Guinea. We'll get back to that in a moment. Let's take a quick look at Ebola in the United States. Which can be broken into three separate buckets. The deliberate, safe, and controlled air evacuation to the United States of patients effected with Ebola in Africa. The inadvertent importation, a rare event. One traveler and one health care worker, namely Thomas Duncan, and Craig Spencer, the health care provider who came to New York. In addition, healthcare workers who were infected with the Ebola virus. There were two of them. We, in the United States had the privilege of taking care of these two individuals, one at Emery, Amber Vincent, and the one that we took care of at the NIH, Nina Pham. How did all that happen? First, let's take a look at the Thomas Duncan issue. He was infected in Monrovia, did not know he was infected, flew through Brussels to Dallas, was asymptomatic for four days, in society, living in an apartment with family, including his girlfriend. Presented to the emergency room after now two days of symptoms on the 24th to the 26th. Was not diagnosed to have Ebola, was sent home and then two days later was dreadfully ill, came into the hospital. And then during that period of care by the intensive care nurses, he in fact was able to transmit, very likely in the heathcare setting, almost certainly to the two nurses in question. Now, as I mentioned we had the opportunity to take care of one of those, Nina Pham. We brought her into our facility, which is one of the three facilities in the country that have now been able to be certified as being able to deliver care in a contained facility for the protection of the healthcare workers. One is Emory, one is Nebraska, and one is the NIH. And this is us. That happens to be me in my personal protective equipment getting ready to go into the room to take care of Nina Pham. And here is Nina getting discharged free of Ebola from the NIH clinical center. And on the right, we show the nurses who are highly skilled, very similar to the kind of care that she would have gotten at Emory and Nebraska. This however, this coming through of a patient inadvertently without being detected led to somewhat of a firestorm of suggestions of banning travel from West Africa, which none of us felt was a good idea. However, airport screening was involved in looking at individuals before they leave an involved country and upon entry. We refer to that as exit and entry screening into the United States. The individuals are screened for fever, symptoms, contact with an Ebola patient. If any of those occur, they're refused exit, or they're detained upon entry. This however, was not enough because when an individual, in this case a healthcare worker, Craig Spencer. Who was infected in West Africa, got to the United States, was in society for about 24 hours. When he got a fever, he did the correct thing. He reported himself, was admitted to Bellevue hospital, and no one got infected. He was given good care and did well. However, this triggered an outcry of quarantining all medical workers, which many of you who are watching this know I was very much against. Because I felt if you do the balance of the risk to the American public to the unintended consequence of dis-incentivizing medical workers, healthcare workers from getting involved in Ebola care. We would soon run out of people to care for patients if you had to quarantine for 21 days any healthcare worker who came into contact with an Ebola patient. So we put together, we being the CDC and myself here at NIH, a graded stratification of risk balanced against the stratification of the degree of monitoring and the degree of restriction of activity. And so if you did not have a high risk, there would be a judgment call, even though everyone would be directly and actively monitored by a temperature and symptom check by a separate individual. There would be a judgement call in some cases as to whether or not movement would be restricted. And so these individuals could continue to take care of patients. Finally, let me close on a quick review of the role of research and development in diagnostics, vaccines, and therapeutics, focusing particularly on vaccines. There are a number of candidates shown on this slide. The two that have now gone into a phase two, three trial in Liberia is the NIAID/GSK chimp adeno vector expressing an Ebola-like protein gene. And the NewLink/Merck VSV candidate that is also part of that trial. As I mentioned, it started on February 2nd, ultimately, with the hope of getting 27,000 volunteers following the end of phase two, which would be 600 individuals. With regard to the therapeutics of Ebola, there are a number of candidates in the pipeline. I want to first point out to the audience that none of these, although there are anecdotal reports have been shown to be effective against Ebola, or even safe against Ebola. And because of that, we have taken one of these, ZMapp, which is a cocktail of three monoclonal antibodies against the glycoprotein of Ebola. And have started now a trial of comparing the standard of care, replenishment of fluid, versus standard of care plus ZMapp. In a trial that has started in Liberia and will be done in the United States for any cases that we import here, as well as making it a regional effort, hopefully in other of the West African countries. Looking ahead, we must remember, despite all of the attention placed on the few cases of Ebola in the United States. We must continue to focus on West Africa. We must prepare for future outbreaks. There's a global health security agenda which increases the surveillance and the infrastructure to be able to identify and prepare for epidemics. As well as moving towards something which was really part of the perfect storm that led to this, is the health disparities in the care infrastructure in the developing world. And then finally as Jim Kim has often said, although we've made major progress in curtailing the epidemic and containing it, we will not have been successful unless we reach zero cases. Because even one or two cases can be the seed of a rebound of the outbreak. And so once again, I want to thank you for giving me the opportunity to give this introductory lecture. I wish you a very successful course. Thank you very much.
