We Were There – Ebola

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We Were There – Ebola

[ Music ] >> Good afternoon thank you so much for joining us for We Were There It’s my pleasure this The series was series was created so that the original investigators can share their stories and insights and inspire us to continue their work Without further ado, it is my pleasure to introduce Dr. Anne Schuchat, Principal Deputy Director of CDC >> Well thanks so much Phoebe and welcome everybody to our We Were There session In the midst of the 2019 Ebola outbreak, today’s We Were There presentation takes us back to our very first experience with the deadly virus, in a remote part of the DRC then known as Zaire Today’s Ebola outbreak occurs in the midst of multiple other challenging CDC responses The opioid overdose epidemic, the effort to end HIV transmission in America, investigations into severe lung injury occurring in association with vaping And in 1976 the deadly Ebola outbreak was relegated to the back pages of US newspapers Because that February, a cluster of severe respiratory illness in soldiers in Fort Dix seemed to herald a new flu pandemic, with echoes of 1918 In July of 1976, just a month before the first reports of Ebola in Yambuku, it seemed the pandemic had arrived, as dozens of men and women who attended the American Legion Convention in Philadelphia developed severe pneumonia By August, shortly before the WHO reported a second Ebola outbreak in Sudan, hundreds of legionnaires fell ill and many died Influenza was ruled out quickly, but it would take until Christmas for CDC to discover the bacterial cause of that outbreak When we faced the unprecedented urban Ebola epidemic in West Africa in 2014, and authorities raced to develop a vaccine against the virus, a leader from Sierra Leone wondered how serious this race could be if this virus had been known for 40 years Today we’ll hear about that initial sprint to understand and stop a deadly Ebola outbreak Today we know that Ebola is not the only challenge the Congo leaders are battling, nor the only public health response that CDC is tackling Some of the roots of today’s outbreak were also at play back in 1976 And then hearing from those who were there, as well as those who’ve been returning to DRC since then, I hope we’ll discover some insights to the way forward Thank you [ Applause ] >> Thank you Dr. Schuchat And now it’s my pleasure to introduce today’s speakers Dr. James Lang, Dr. Joel Freeman and Dr. Jonathan Towner if you’ll please come to the stage Thank you >> Good afternoon Welcome all I will relate to you a little bit of experience that I had through my involvement in the initial discovery of what came to be known as the Ebola virus, although we didn’t learn that right away, it — it took some time But the — the primary theme of this is that we were there And so I will try to show you where there was and what the basis is for saying that we have had 50 years

of high containment laboratories on this campus I tried and tried to find pictures of this first facility that was put in to operation in 1969 The best I could do is a schematic that consisted of a trailer I’ve heard two descriptions of it, one being similar to an Airstream trailer and another being the trailer that you see on the highways in the tractor trailer tandem Whether — which one is correct, I do not know but this — this gives you a little bit of a layout where people entered, exited and the showered out of this facility The reason it was placed here was because of the initial discovery of a virus called Marburg virus which involves outbreaks in three different European cities, one of which was Marburg, Germany And that’s where the — the namesake, wound up in the literature and — and approved by all of nomenclature committees So this 1969 facility is the basis for our saying we’ve had containment facilities on this campus for 50 years The second iteration of a high containment lab was when I first arrived called Building 5A, and then 7A, and finally after another nomenclature scramble, Building 8 And that’s what we call it to this day, Building 8 It consisted of two levels, the red level that you see contained an inner laboratory, the bio-containment concepts were being applied even then, a box in a box in a box This outer shell was simply to protect the inner shell from the elements because it didn’t function as a — a barrier per se, but the inner hallways and then the room itself that were contained therein were negatively pressurized so that nothing in the air moved away or outside the facility It was commissioned in 1972 I want to give you an idea of what it was like to work in It was strictly a class three glove box line, consisting of stainless steel and Plexiglas under very high negative pressure I forgot to point out that the — the brick portion of this contained the support systems for the upper level laboratory And the most important part of which was an incinerator that incinerated all of the exhaust air out of the glove boxes to a temperature of 1500 degrees This is where anyone who worked in the lab started their day through this double door autoclave, a confounding and limiting factor working in such facilities as it you have to plan down to almost the minutest detail so that you bring in all of your materials that you’ll be needing on that given work day through this double door autoclave Once you put — place it in from the outside it closed the door That outer door can’t open until this one is opened and then run, so that you can safely open the outer door, that — that’s at the end of the workday when you shove all the contaminated materials back in it, so that you can start the process This is a photograph of typical workstations It doesn’t show the stools we used to sit on Working in them was cumbersome but not totally uncomfortable The gloves themselves consisted of neoprene 32 inch long lengths of either 30 thousandths of an inch or 15 thousandths of an inch The 30,000 were at the transfer point so that when you were handling potentially sharper or edgy materials that you would be safe handling those And of course when you worked in the lab you worked in a laboratory supplied gown or jumpsuit along with a pair of gloves inside these neoprene gloves But these functioned quite well We could do almost anything other than molecular — ultracentrifugation, you know we had — we had standard incubators, standard laboratories, centrifuges, microscopes, refrigerators, freezers, and they — they all did the job for us as over the years that we operated this facility

Up at the top, you can see magma helix, that were telling us what level the negative pressure was inside each and every cabinet And — and they did vary from one to another depending on the type of work The animal corridors were the ones that — that had the strongest negative pressure I’ve labeled these to show that we had both a standard light microscope on the side that — that this picture shows you as well as incubator cabinets We had separate incubators so that we could vary temperatures depending upon our needs On the other side of the — this microscope cabinet, we installed a fluorescence microscope after I arrived So that gave us a little bit better capability I do want to highlight the fact that this facility, when it was commissioned was largely the responsibility of the Office of Biosafety, and the Division of virology This is a photograph of Dr. Robert Huffaker He’s a veterinarian who was the boss of Biosafety He not only put it in motion, but he kept — helped us keep it in motion He gave us excellent support, assign one of his permanent personnel to us to work strictly with us and — and to take care of any needs that we have And — and anytime you have mechanical things such as centrifuges, refrigerators, freezers, you — you have breakdowns and we had lots of good support anytime we needed it, thanks to Bob Huffaker This is a picture of Bill Gary, Dr. Bill Gary was the in charge person of laboratory operations when I arrived in 1974 He did my left seat, right seat briefing to take me through all the functional systems, to tell me how things were supposed to work And to explain to me how to make sure we operated things safely One of the ironies when we first started is everything that we did, no matter whether it was from a lab operation standpoint, or just a logistical standpoint, was not in writing So we had to — we had to start from scratch and put all of this into a written form and produce an operations manual for this particular lab And the person who I worked most closely with on that is Lee Alderman He was invited here, but could not make it today And he — he was an Office of Biosafety employee But I show you this in particular to highlight the fact that the room itself had an autoclave And this little box here was an ultraviolet light box that we would pass things in and out of the lab if we happened to forget something that could be used outside And it is the UV box that I passed through a centrifuge to with a suspension of virus infected cells, suspended in power formaldehyde that I handed to Fred Murphy on the other side And this is the Squawk Box This is a good little communications device that you pressed the talk and you released to listen And on the day that we did the work, that’s what we use to communicate What was — what was known that given time This is not an — an ideal slide, but it shows what tissue culture cells is supposed to look like when nothing’s happening to them, nothing is going wrong It’s a confluent monolayer fibroblast that are slightly out of focus, I apologize for that But I wanted to show you that in 1976 when the — the initial Ebola response began my branch chief, Carl Johnson, went to head up the International Commission in Zaire And my immediate supervisor, Patricia Web, who I’ll describe in detail in — in a minute, took out the — the shipment that we had received and there were sister shipments sent to laboratories in — in England, in France and in Belgium So four facilities received specimens I — I assumed that they were split among the four of us We looked through the manifest, we looked at the specimen, we made sure what they said was there was there and then we begin the task of deciding which one we would pick to inoculate into a confluent monolayer of African green monkey kidney cells, which — which I did myself Forty-eight hours later, about 24, I checked them, they look okay, 48 hours later they look sick What do sick cells look like? They start looking pyknotic They disperse

They form giant cells They don’t look the same as that previous slide They’re not healthy So at 48 hours I was jumping on my high horse and asking Patricia if I could go ahead and do the harvest And Patricia said no, let’s wait 24 hours So she being the boss, I said aye aye And next waited another 24 hours, did the harvest, went through a whole series of standard protocol measures, saving lots of stuff back in the freezer, passing some to another passage of vero cells And most importantly from our perspective, making slides of that material that you put into what we call a Teflon coated slide that had punch holes in them that served as literally a well that would hold liquid in them Place those on there, dry them, fix them And you can do lots of things with that after you have them Made a — a box of slides like that Now when I did that, while they were — were drying and we — we talked about what else we were going to do The first thing we did was take that — a preparation of that suspension that I explained that I passed through the — the glove box to Fred Murphy And less than 30 minutes after that Fred was on that little Squawk Box saying it’s loaded with Marburg So when we heard Fred say that, that got us very excited We thought we had solved the riddle We were the first ones to discover the causative agent of the outbreak in northern Zaire Patricia wasn’t a high five or anything like that So we — we just had a mutually comfortable and — and giddy feeling about it So once — once we — once we knew what we had, I took one of those slides and then went into the freezer and pulled out some of the referenced antisera against Marburg that the previous two years I had been working on building up a stockpile of And I did what’s called an indirect immunosuppressant’s test on the slide, on a slide, along with controls, of course And after the — the proper procedure took a look under the fluorescence microscope on the other side of the cabinet I showed you, and didn’t see anything It was negative And so I looked at Patricia and said, oh no, am I so stupid, I can’t do a simple IFA test? So the two of us and shoulder to shoulder did another IFA tests on replicant slide And it turned out to be negative And we said, oh man what have we got going on here? It looks like Marburg but antigenically it’s not So that’s when we were put on to the right pathway, once Fred said Marburg, we looked for Marburg, confirmed not Marber And I’ll give you an idea of what that process looked like Now this is the one that Fred published and is seen thousands of time over the years But what he described to us on his screen on the electron microscope was literally a bird’s nest of filoviruses Not this particular one He said there was virus in between cells, attached to cells, everywhere once we got to talk to him afterward And interestingly, 35 years later, I road in an elevator with David Center and introduced myself and said, you were my first boss and I’ve worked for Fred Murphy, when I started and Carl Johnson, he said yeah — yeah I remember Fred ran into my office telling me they had Marburg virus, going on in northern Zaire So I said yup, that we heard — we heard it before you though [ Laughter ] This is what a slide should look like if there’s nothing going on immunologically that is no fluorescence Oops. And a juxtapose one here to show you the green lights that are fluorescent, that indicate there’s an antigen antibody reaction along with a reaction with the tag of FITC, fluorescein isothiocyanate, that is used to detect what works, what reacts with a given antibody or antigen I — I do want to make sure I recognize Dr. Webb She was a — a very good mentor She took excellent care of those of us who worked for her If you worked as — in her supervisory chain,

she could make life miserable for you because she was constantly asking and — and trying to get more resources for our group and fighting the bureaucrats too She — she was a good bureaucratic infighter She — she’s an interesting and she’s British to the core Her father sent her here during the Blitz in 1941, when she was a teenager She wound up at Agnes Scott College at age 16, graduating in three and a half years Was the only female in her medical class at Tulane Medical School And let us — she explained to me that many of the male counterparts let her know that she was stealing a seat from a fully qualified male But if you knew Patricia, she gave as good as she got But she’s a terrific supervisor to work for and I — I do want to highlight the fact And the other thing I want to bring up that’s — that’s not known to other than a very few of us is that after this initial discovery, Patricia worried about my welfare, and decided that she would do all of the remaining work herself But she was too chicken to tell me, which if you knew her, you would understand So she got Bill Fagin to tell me, which — which is hilarious when you think about it And we both laughed about this years later But Patricia then went — went back to the original manifest and looked at the very limited clinical information that was available And I — I did participate now because it was noninfectious work And we — we found one serum from a patient that had survived, my memory says to day 11 in the hopes that IGM antibodies would have started showing up And so she did the subsequent tests, using that pa — a drip of that patient’s serum that she squeezed out of a — a blood clot, of course, mechanically not with her fingers And it lit up those slides that I had made And so that’s — that’s when we had immunologic confirmation that we had a new agent that looked like Marburg, but wasn’t Marburg And then my recollection is that Carl used as a — a CIA map, we used to have a — a whole library of CIA books on country — countries And some of them came with good maps And he pulled out a map trying to pick out a — a location that would not be associated with either Zaire or that part of the country, and found a very small tributary of the Congo River called the Ebola River And that’s how, my understanding is the virus got its name The next iteration of high containment laboratory came as Building Nine It was purchased from the National Cancer Institute, came down in modules CDC can — well contractors through CDC constructed again the outer shell, which is the metal upper part and then the — the red brick lower supporting part This particular laboratory came to us as what was called a virus tissue processing lab It consisted of a glove box line, and offices, and all that you see around the glove box cabinet line, rectangular laboratory, was retrofitted over an excruciatingly long three year period by engineering services here at CDC and some contractors into a suit laboratory And of course when it came in, said ’75 Carl Johnson asked, how soon can we have it, and I had no idea He wanted it next week As the years went on, it drove him to distraction But we finally put it into operation and ’78, and it — it operated quite well, having been completely retrofitted from office space to suit lab space, which is quite remarkable in and of itself Now everyone has seen these, this is where we stored our suit’s The chemical shower was just to the left of here Each person of course had their own suit’s We were a small group, there were only nine of us in the branch And that ended my association with that I — I went on to do other things, after 14 years in Biosafety And toward the end of my career, I was given the opportunity to do ploy to West Africa to participate

in the 2014 Liberia outbreak in support of an EPI in Bong County and then 2015 and ’16, while working for Jane Seaward in the immunogenicity sub-study of the Ebola vaccine trial And this is the facility we worked at upstairs where another lab was retrofitted to suit our needs And that is it I always pay honor to my spouse of 50 years now and our first grandchild [ Applause ] >> So EIS officer is in an autopsy room in Detroit during the 1976 swine flu campaign that Ann introduced us to — to see whether the patient, the person who died, had swine flu or had a complication following swine flu vaccination So he walks out of the room and says there’s a phone call from Atlanta for you And Lyle Conrad’s on the end of the line, who is chief of Field Services, and said, Joel, I was that EIS officer, there’s a terrible epidemic going on in northwest at that time in Zaire And we don’t know what’s going on The calls come in to the embassy and then to CDC, and the government has asked CDC to participate in this And I said, wait a minute Lyle, what — what’s going on He said, well we know very little information, only 100% of the villages are infected, 100% of the people in the villages are sick and all those people have died He said, do you want to go for just a few days [ Laughter ] That’s how CDC operates, for those of you who don’t know, just a few days to find out And I said, well you know I’ve lived in Africa He said, we know you did, that’s why we’re calling you, you speak French And we’d like you to go with someone from the laboratory And — and by the way, there is a concurrent epidemic in South Sudan, we don’t know what’s going on So a glutton for adventure, I go home, talk with my wife and two small kids They couldn’t talk much then But my wife said, I know you’re a glutton for you like adventure, you know I said, also I have never been to Zaire Oh anyway I call all around to find out what could be going on And they said, well you’re going, first of all they say you’re going with Pat Webb, from the laboratory who — who I had been introduced to So I had two or three conversations with Pat And then I called all around, a number of people said what could be going on in Africa at that time, CDC didn’t know much about Africa at that time in the ’70s, other than those of us who had worked on smallpox eradication And so they said, well the visas have come through, you’re ready to roll And just before I left I get a call from one Carl Johnson, who I had never met And we met at JFK in New York He said, I’m going because Dr Sensor has concluded this is so hot in growing, because messages that come in, and there’s a great amount of disorder in the capital of Kinshasa that we want to send the chief of the lab to go with you So Carl, at JFK, shows me this virus, which you’ve seen A very important photo micrograph that Fred Murphy had taken And I said, well nothing kills 100%, maybe rabies, but you know not so many people as had been reported But even though there had been one survivor from rabies So anyway, we’re on the airplane with 17 packages and —

and we arrive in Kinshasa, picked up by the US Embassy And immediately taken to Fometro, which is the Belgian Center for Medical Activities They had been there over 100 years in the former Congo And sitting around the table where people from a variety of countries, and from WHO And we were told the city is in turmoil because now two nuns had come in to Kinshasa from the epidemic area Both of them had died And a Zarian nurse who had taken care of one of the nuns herself is sick and in the hospital And the Minister of Health, Dr. [inaudible] says around to the table, the airplane is ready to take the team out to the epidemic area, and to tell us more about what’s going on So Carl, who doesn’t — still doesn’t speak any French but was following this, I’m translating as best I can I said, Carl these people are really organized here A team is going out, we’re going to learn, go to the hospital, see the patient Everyone’s looking at Carl and me We were the people to go out to the field And by the way, leave your 17 cartons of scientific equipment here So simultaneously Carl and I said no way we — we’ve got to find out what’s going on The Embassy, ours and others are hollering And then the Minister says something has to be done Now on the airplane coming in to Kinshasa from actually Geneva, was one Bill Close Anyone hear of Bill Close? No Bill Close Several people Bill Close had come to Zaire in 1961 Anyway and ultimately became president of Mobutu’s personal physician Ran Mama Yemo Hospital Had been a mentor to Dr. Ken Kella, the Minister of Health And Bill on the airplane sat with us and said I will help during the event He was now director of the largest hospital at that time in Africa So we said we had met the right guy and was precious Anyway, the Minister said, you got to do something The next day I’m on an airplane with [inaudible] from France, Peter [inaudible], first mission to Africa, from Belgium Andy Cook from Zaire and John Frances Lepone [assumed spelling] from Belgium who ran this mission, the Belgian mission with 400 Belgian doctors around the country John Frances Lepone had been born there, spoke the languages He was on the airplane with us And here we are In — flying over the Congo River going, within 24 hours I’m now on an airplane going off to the area What were we supposed to do there? We’re just supposed to, again, go for just a few days to do find out actually how far this epidemic, whatever it was comprised of in signs and symptoms, how far it had spread up from this rural mission hospital To find out if there were active cases Three, if there were people who recovered, and four, to find out if we could equip this rural mission hospital of 120 beds with adequate facilities to bring forward a treatment team, a surveillance epidemiology team, a laboratory team To find out what’s going on out there And so then the airplane was supposed to come back and pick us up So having had some exposure to epidemiology and CDC, the — everyone said, yeah that’s good, now what do we do? Well I said well we’d go, you know, finally they’re talking to me They had known I had worked on smallpox and had some experience with field experience And Carl quickly became the scientific director because he was renowned for discovering Venezuelan

and Bolivian, Argentinian hemorrhagic fevers And so he quickly became our scientific director Now here we are coming into the Boma zone The villages spread along these tropical roads Navigation is not easy, and there is the mission, empty, barren, because everyone in that hospital, if they were still alive, had run away Seventeen staff at the hospital of those 13, had gotten the illness and 11 had died And obviously it was hospital centered because several of the patients who were there for other things now started getting this, what they call it a hemorrhagic syndrome There were three nuns and one priest left there, but five of the religious order had died And they had a picture, the nuns showed us this picture on the right, here are four sisters and a father who had died of this disease, two of them in Kinshasa having been evacuated, and then one father there And there are their graves in the lower left So Sister Marcella, in front of all the beds, because they didn’t know what it was, they exterminated the empty hospital, brought out all the mattresses to burn And that was — they were very glum So our initial plan designed on the run was for each four teams of us as I described, to go north, south, east and west with a sister who spoke Lingala and some Botza [assumed spelling], with us And so forth three days in a driving rain, under the conditions that you’ve seen, went from village to village And I was struck early on in talking to some folks who said, some well people had come to the hospital or come from a village had received an injection And the injection was for whatever it was, aches and pains, particularly prenatal care And then a week later this syndrome had begun and they died Well that was unusual I said, well tell me about the needles and syringes They said well, you know 120 bed hospital, several hundred people a day we have five needles and syringes used in the outpatient, glass and metal And you know, we just kept using the same one for each patient And I said well sterilization? They said, well we have soapy water in the pan at night Unbelievable So this, you know, the hair in the back of my neck raised And then when we started going to the villages, the nuns had gone giving prenatal care out to the villages and the same story They got injection with calcium, vitamins, antibiotics in those days and even now injections are favored So my first — this is the second day I was out in the field And here’s a patient, first patient with Ebola I said, you know, we had defined what a probable case was, what a possible case was, and of course a confirmed case would be one with immunofluorescence antibodies because that was all that equipment was with us So this is a 25 year old gentleman was complaining of belly pain, pharyngitis, he had conjunctivitis and he had some bleeding from his rectum and around his gums But he — and abdominal pain was very severe So I talked to him and of course we carried, not of course, but after a while we were carrying with us paracetamol Tylenol, chloroquine and quinine, tetracycline things that could cause this fever, headache, and unusual syndrome There is [inaudible] in the personal protection equipment of the time, paper, mask and gloves, but oppressively hot and humid, very hard even to wear this stuff And so this gentleman died the next day Now we — they knew about smallpox and about isolating sick people, and several other people

who had some of the villages isolated the patients in that way Quarantine-able disease was an unknown here So we moved on And then we went back to Boma where we were to give our report, we did an inventory The plane didn’t come The plane didn’t come for, two or three days So by that time Joe McCormick had flown in from Sierra Leone to help with the epidemic And he got through, Joe knew his way around Africa And when — and another mission came to us We were at the Catholic mission waiting for the plane Who would say, we’re from the mission We said, well we’re at the mission They said we’re at the Protestant mission Protestant, Catholic missions, weren’t in good communication He — he said, what’s going on? So we gave him our preliminary information And at that time, a plane came everyone had, you know a lot of people had run away because they were afraid And the pilot said runaway President Mobutu had sent his family with a couple of planes to Europe So it was tough to get an airplane and pilot Finally the plane came, after about almost a week, and the pilot said do not come anywhere near the cabin, sit in the back And then we went back with our information Now when we came back we were loaded with sand fly bites and a — and a rash on our sleeves, on our arms and elsewhere And of course it was black humor all the time Eleven by Primus the medicine, the beer of the place And if you look carefully there’s a bottle or two of Jack Daniels That we always had to have And so here is Marguerite Isaacson from South Africa who had experienced treating Marburg in 1975 She came with two units of convalescent Marburg serum And that didn’t work other than land you in the hospital And there is Bill Close, director of the hospital and so he is now part of the team And that’s a thermometer in my mouth, not a cigarette [ Laughter ] Bill was a chain smoker, but anyway The — the guidance that each person on the team and you’ll hear more about that, take their temperature twice a day, and if they were sick tell the chief of their team Well what are the teams? We quickly formed into clinical team, logistics and equipment That was Bill, board certified Harvard Columbia trained surgeon, who said I’ll do the logistics communication John Frances Lepone was the chief of the Belgian medical mission, said I will do communications because every embassy, every business, every society person was clamoring, do we leave Kinshasa? Some did or not? John Frances handled that Ito Vandenberg handled the immunofluorescence, that Pat Webb and team were now sending him [inaudible] fixed slides And we did those right out in the field Could we go back, we told the sisters who so many — over so many years that mission have been there 19, since ’35 They — and so people had gone out there and never come back, often is the case is rural health facilities and issues And we said we will be back in ten days, I said I’ll be back And I told the minister I was going back because we needed to do surveillance far and wide And the other team, the scientific backup team also had to come up to do the things I mentioned And no one wanted to go, except a few others But Dr. [inaudible] ordered now some great clinicians from the hospital We got the smallpox, the monkey pox, the vaccination, the public health A few people came out to do mainly the surveillance work because we had to now go to many villages So here’s Dr. M. Mbuyi, an immunologist in training, and nurse Cocteau, who had recovered, and his serum had come And that’s one of the ones that Pat Webb had that — his serum cross-reacted with the new virus and didn’t react

with Marburg which the CDC hot lab had archived from, not only from ’75 in South Africa, but from ’67 in Yugoslavia, and Germany And so [inaudible] was a convalescent And here we are going from village to village One of our six surveillance teams going over these ten routes that I show — showed you before And asking people with our paper forms, village form, individual patient form, epidemiologic forms, history, signs, symptoms And this gentleman has a shaved head, that was a sign — is a sign — will be a sign of mourning in these villages So we could identify people who had recently had a death in the family And they’re very, very cooperative during our visit’s So in — after, we were there from mid-October, to the end of January Now our whole team wasn’t there, we had a — a major part of our team left in December, but then David Heiman came and continued the Plasmapheresis program We’ll talk more about that And the Sudan team couldn’t get in there because civil war was going on in the south, it was a WHO mission And Don Francis from CDC was part of that team But when they finally got in they did some case counting And it was curious, it was a different center, it was about 50% case fatality rate, a lot of pulmonary signs and symptoms And then it turned out the virus is a different strain So here is our epidemic curve, I don’t know if I’ve got a — here we go This on it So you see the green here are those that had received the injection at the hospital And early in the epidemic, the majority of patients had received that was it, feeling well or had come in for malaria, fever dropped and the they developed this terrible syndrome, a lot of them with severe bleeding But classic systemic signs and symptoms And then as we went on it was person to person mainly in the villages Of course we came in now in October, but we didn’t know that You know that when you come into an epidemic, you think you’re here, but you want to come in when you’re here at the end of the epidemic also try and do that it’s safer But — [ Laughter ] But we didn’t know where we were So that’s why we were now moving through and gathering information, really ensuring it as we got it So let’s move here to the incubation period And again the villagers were very cooperative, saying yes, the woman or man got their injection on such and such a date And then — or they had contact with the patient that you describe And so the mean incubation period we found with 6.3 days or so And for person to person was over nine days However, we counted, we used the first contact with the patient, they could have gotten the infection at a later date and had a shorter incubation period, similar to that of injection So this is important Note that the last incubation period we calculated was, we’re told was 21 days, that’s still used today isn’t it? Incubation 21 Like lifting quarantine 42, three periods This hasn’t changed guys So this information still used Now okay you can see better over there Symptoms, I’m still using my clinical background, symptoms, what you feel, signs are what you see So what I described with that patient is clear, fever, headache, sore throat, all classic, a few had

Now the nuns had this rash that I mentioned On black folks, you sort of a more [inaudible] rash you can’t see But the signs were as I described with vomiting and diarrhea Diarrhea very important because we’re looking, and then bleeding RO lesions, and of course many of them had a lot of other things Now epidemiology I was told every village had cases, every case died That wasn’t the case We went around to 550 villages, several times over this several month period, and we found that a third of the villages only had one case and over 90% had less than 20 cases, and only two had more than 30 patients So it wasn’t so explosive in the way that we were told Next, age and sex Well females here were over 60, were close to 60% And newborns died if the woman — pregnant woman picked up the disease So but particularly in the young childbearing age they were heavily infected Why is that? Of course young women, women of any age, are caregiving Now risk factors So we spent a fair amount of time trying to find out and these are very tight communities socially In the family everyone’s involved with touching, caring, sleeping in the same room, preparing the cadaver, attending the funeral, you could say even those in the village who weren’t in the family, everyone was at the funeral And aiding in the delivery that was very high risk there But the other factors, and there were many more risk factors that we have listed, animal, food and the rest, nothing spun up So this is maybe the most important epidemiologic slide I consider from this first outbreak And that is the term that I’ve used a lot The secondary attack rate can be used for R zero, your basic reproduction But Ebola is not a highly transmissible disease I will stamp my foot from our first outbreak on that, that if you’re an injection, we spent quite a bit of time trying to find out how many contacts there were for these patients And the attack rate for injection was less than 10% And that the few transmission chains that we tracked down before the epidemic withered was overall 5.6 But each generation, the secondary attack rate was very low, except if you delivered as a midwife or were the caregiving spouse, you had a much higher chance of getting the disease Now here’s one of our volunteers Dell Conn, a Peace Corps volunteer, a laboratory technician, who was collecting blood On the right Danny Courtois and Marguerite Isaacson taking — doing Plasmapheresis from nurse [inaudible] Don’t do this at home or in the field, wear gloves Of course we didn’t know everything there is to know Because you can get fever and chills and headache when you’re working in these conditions And Dell Conn did That may have been the saddest day for many of us out in the field when Dell got sick We gave him a unit of convalescent and we did have a plan for evacuation, A and B. Of course we didn’t know exactly how that plan would work But Dell was — got into a transport isolator in the back of a Land Rover, evacuated to Kinshasa and then to Johannesburg He did not have anything that they could find, certainly didn’t have Ebola Marburg We never did find out But for those of you who have been in the field, you know,

or even here in the US, young, you know, there are 3% or 4% of children will have fever in a community all the time Out in the tropics it’s maybe eight or 10% Fevers are out there mainly arboviruses So where did this begin, this outbreak? Well my hypothesis was that it came from the Sudan We’ll talk more about that But we looked through the outpatient in the — well the inpatient registry, there was a page from an inpatient register at the hospital All of the outpatient records, thousands of them had been burned or thrown away But here in the inpatient we looked through for the past year is a patient [inaudible], from Yondong, who had a nosebleed and diarrhea, and fever, who came in at the end of August And we went to the village found out, tried to find where that contacts of that patient And we couldn’t go any further back We had some other history of people moving around, but no village reported earlier epidemic Now Joe McCormick, we airlifted Joe to North East Zaire to find out if there were outbreaks occurring along the frontier Between — and that was the hypothesis, that there would be smoldering disease connecting Joe found nothing He actually penetrated into Pinjara and Marabe [assumed spelling], Pinjara in particular Was there before the WHO team And Joe came back and was very tough, but he could find no connection So that hypothesis, even before we knew Sudan was a separate outbreak, was very helpful to us And Simon Van Nevenhoof [assumed spelling] went on the North East border with actually South Sudan, but also down into Ivo, Iturbi, seems familiar to you all So here are the major findings what I’ve talked about from the first outbreak, summarizing the manifestations, the incubation Clinically we collected over 200 units of serum On the epidemiology we defined the geographic extent having covered these 550 villages We found 55 of which were infected We defined if that person’s at risk the mode of transmission, transmissibility A couple of teams that had been there before we had had recommended that the commissar de zoom, the county chief put the area in quarantine, this was very helpful They were isolating patients They also had rapid burial, which we reinforced And with the medicines, we would rule out other diseases, if anyone had this fever In the laboratory we did basic tests right there in the hospital We did IFA In one patient we did serial viral culture, nurse [inaudible] from France did — collected mosquitoes, a few rodents We didn’t turn anything up then So in ’76, we left not knowing anything about the animal transmission to humans We had no treatments Although we had some plasma, no vaccine We didn’t know the extent even within the DR Congo or elsewhere Although we were getting now calls from all over the country, and Peter Piot and others would go out, carbon monoxide poisoning, a bleeding ulcer, you know, sleeping sickness, so many things that people in the — malaria, malaria, malaria in these villages So here’s a slide, one of the slides of our team out there, and I — I want to show you, you haven’t seen Dr. Johnson yet Maybe you saw him in — in the laboratory But he sends his greetings I just talked to him two days ago, couldn’t travel But I do want to show you Dr. Miatudila here, who was a clinician, a microbiologist, who was part of our team taking care of patients at the hospital that we immediately tried to open, because we needed confidence in our team in — in the hospital to take care of —

and somebody to take care of malaria, diarrhea, the usual things that folks in these rural communities suffer, including obstructed labor That was important One of our doctors had done a, on the door out in the opening, fracture of a simplest pubis to deliver a new baby from a woman who was in dire condition I don’t — the names are down below, young Peter Piot above me So what are the lessons here? You’ve seen scientific Each person had a task and a group of people under her or him to work, clearly defined during this several month period On the equally important, at times more important, the what I call delivery component of science, of public health programs We had leadership, we had organization, the communications, transparency, partnerships, all the groups that were at the original table contributed, coordination, supplies, transport, selective quarantine, isolation And then we took care of the people, the few survivors because we wanted them to cooperate for Plasmapheresis, but also to learn more from them Now here is Johnson with not a CIA map, but with a map used for human monkey pox, which was also in that area And when we went through Geneva on our way to Zaire, we stopped by the smallpox office on the weekend in [inaudible] Henderson were there — they gave us this map which we used and here’s Carl looking at the circuit that Joe McCormick used And then one day when things were calmer, we took an excursion on the Ebola river It was really sort of an effluent of the Congo And here it is Now, so I’m going to summarize all this with a slide I’ve used before, relating emotion in activity So there was terror in — everywhere People didn’t know There was fear, there was confusion, leaving the country, what should I do, to inactivity And there are some, many people who left chaos running around without focus And local investigations There had been some people who had gone up there and collected specimens particularly the local doctor, who was honest in saying, we had all these signs and symptoms, and I don’t know what it is Another person went up and said, it’s typhoid and brought typhoid vaccine and start giving shots in the usual way So these local vaccinations even before we arrived, and the specimens collected and sent to identify, were key So we didn’t have much information Then as time went on, there was even more uncertainty, anger of all the deaths, sorrow, shock, then isolation quarantine The virus was identified Our international commission was formed And by that time anxiety was being modified with understanding, trust, focus And then we did the rapid and then the more detailed investigations And confidence was being developed Partnerships and trust and, you know, our band of brothers and sisters was really forming And at the end, we had a huge celebration because there hadn’t been cases now for a couple of months And it continued afterwards and the epidemic was over Now in 1996 NIH in Antwerp is through tropical medicine, had a conference in Antwerp because 1995 we had Kittaka, second big outbreak in DR Congo, it was huge And a year after that outbreak we had a symposium Some of you were there And now Dr. Muyembe who worked with us initially came and he, again another one of the heroes,

and he is leading the Congolese effort today And I do want to show at that ceremony, Pat, who was already getting sick, Pat Webb, who is the discoverer of Ebola virus, I’ll define that, as the person who sees something new and knows that it’s new Everyone else saw what they called Marburg virus and called it Marburg virus But Pat knew something new by the indirect fluorescence test And here’s Peter So let me dedicate this part of the talk to all of those who participated First and foremost are the people who suffered up in northwest Ecuador province, and then the six countries who are our collaborators, including the World Health Organization So thank you all very much This is dedicated to over 100 people [ Applause ] >> Okay so for the record, in 1976, I was not there [ Laughter ] I was ten years old and trying to figure out what I was going to do as I was starting fifth grade So I think my — my job is to — to bring you up to present day So and a lot has — has changed from 1976 One you can see from — from this slide here showing Ebola outbreaks, that Ebola’s reemerged in different forms, quite a number of times since — since 1976 And I say that because if you look at here, the current nomenclature, I mean there — there’s a lot more known species of Ebola In 1976, we knew about Marburg virus, as we just heard Ebola in Sudan, although we didn’t know there were two different viruses at that time But since then, we’ve discovered Ravn virus, Reston virus of hot zone fame in ’89 which Tom Kazakh and [inaudible] were quite heavily involved in, and read at the time Tai Forest virus When the Bundibugyo virus, the newest Ebola known to be pathogenic in humans, and just last year, Bombali virus which was found in bats, for which there hasn’t been any known association with — with human disease So I came to the branch, special pathogens branch, in 1997 to develop a genetic system for studying Ebola virus to try and pick apart genetic determinants of virulence Inspired by the finding a couple years before by Carl Klaus Conzelman, where we’re finally, after many years of looking, or of — of trying to develop a — a genetic system for a negative strand already virus he was successful with rabies So I toiled with that for a couple of years And then in 2000 it was one of those instances where your life is taking a left turn but you don’t know it yet And Ebola emerged in Gulu in — in northern Uganda And overall the — the outbreak was — was large, 425 cases that up until the 2014 outbreak was the largest Ebola outbreak on record Was — this was Ebola Sudan I went there with five other folks, with Tony Sanchez, who is here in the audience Scott Doyle, Scott Harper and — and Dan Bausch And the, I’m not going to tell you — I’m — I’m a lab guy so I can give you this from the laboratory perspective And so one of the main things we wanted to do was to set up the diagnostics right there at the site of the outbreak and we knew from previous work that they, you know, the serology their engine capture to ask me that Tom Kaziak had developed, as well as him and [inaudible] were — were field Ebola, we weren’t sure about PCR And so as a molecular dude, that was my job to set up the — the PCR based diagnostics And of course, at that time there wasn’t real time PCR, this was submarine gels and sort of old school PCR So we set up shop in the diagnostic, or in the laboratory wing of St. Mary’s Lacor Hospital in — in Gulu

You can see in the corner — circle there in the red, picked out room that had a good open window and there was a sort of a non-functioning biosafety cabinet, the light went on but I don’t think there’s all that much airflow So — and you see in the upper part there, there’s Pierre and Tony, who do most of — do all the hot lab work, doing engine capture, IDG and IGM handling all the — the material And they will pass it out to me, I’d stick to samples in TriPure which worked great for all of you on the LSRP board, TriPure works just fine And do the PCR across the hall to do the RNA extraction and then at the top part, let’s see if I can get this thing to go here Up here, we do the product analysis, this is summary and gels we want to keep this stuff as — as separate as possible And in all toll we tested over 1,000 specimens We were the first of — of three teams to — to show up And in the subsequent study of the specimens, once the outbreak was over, one of the things we learned and the reason why I mentioned this now is because it’s pertinent to how we’re evaluating some of the therapeutics for the ongoing outbreak And that is that the fatal cases would have much higher viral loads than nonfatal cases And this is evident very early on the orders of two or more logs higher in fatal versus nonfatal cases So moving on it — a couple years later, Marburg virus emerged in Angola, and this was in 2005, 252 cases and a 90% case fatality And this emerged in — in [inaudible] the northern part of — of Angola And so the difference here in terms of fielding diagnostic assays was that in addition to the — the Eliza based methods, now real time PCR was involved, and we had developed high throughput platforms for real time PCR A lot of that actually was developed as a result of the anthrax outbreaks where we needed to develop high throughput capacity for select agents And so this we set up in the — the bottom floor of the — of the Public Health Institute there in Luanda, Angola I should mention that Health Canada at the time also was doing some diagnostic work in [inaudible] in the northern part And so we set up in the bottom floor at what was then the Global AIDS Program, diagnostic lab that was run by Amocar Tierney And so in that space there was a — a functioning biosafety cabinet which we then piped out the — the window to generate some — some negative airflow And somewhere along the lines, I guess someone realized that the INSP wasn’t paying the electrical bill, so they cut the cord, so we had no power And fortunately, Tom Kaziak got on the phone, because Chevron, Shell, BP all have a financial stake in Angola because there’s lots of oil there So Chevron produced 100 KVA diesel generator and 2,000 liters of diesel fuel within about 24 hours So we are eternally grateful to them So in the end, I think we tested a little over 500 samples of various sorts And they said this was the first time we sort of set up sort of a higher throughput real time PCR And also it was the first widespread use of oral swabs as a — as a diagnostic specimen This comes with some limitations, obviously, a lot less things you can do with oral swabs, but this is — this is when it started Moving forward into, there were a couple of years of what we call banner years of field virus activity Starting in 2007 with the Marburg virus emerged in a small mine in — in Western Uganda, this small outbreak too only three cases And this — the small size of that allowed us to engage in an ecological investigation which proved to be very fruitful which I’ll talk a little bit about later And then a couple of months later a second minor went in surreptitiously got infected with Rabin virus So the other Marburg virus And about the same time in the Weibo [assumed spelling] in the middle of DRC, Ebola had — had emerged And this is a fairly large outbreak, a little over 264 cases And our — their branch CDC effort led by Tom Kaziak, there on the motorbike, assisted by Stuart Nickel riding on the back of the motorbike There’s no helmet laws And so anyway they — they lead the — the CDC effort there in — in Weibo And as we’re always in a situation we’re trying

to improve upon the situation, the — there was a fan that was set up in the window to try and create some rudimentary negative airflow, where the — the hot samples were — were run And then at the end of the year, another Ebola virus outbreak emerged And this was a brand new species of Ebola called, that we then later named, Bundibugyo virus And this was a — the newest to date species of human pathogenic Ebola virus discovered And it’s also notable because it was the first time the NGS, or Next Generation Sequencing, which is very commonplace now, then it was 454 and alumina based, was used to characterize a — a new phenyl virus 2008 it didn’t get much of a break In July, Marburg reemerged in a nearby place called Python Cave, not too far from Kittaka which I just talked about previously And in fact, there were two cases independent, one was a, see the first one was from a woman from the Netherlands The second one was a woman from Colorado, that actually had been — been infected six months prior And then it was later on that year, we discovered, along with our colleagues at USDA in Plum Island, that swine would serve as a very good host for Reston Ebola virus And so I, you know, that went on Today there’s still no known pathogenicity in humans with — with Reston Interestingly, in 2014, at the time that many of us in this room were buried in the West Africa outbreak, there is a report in archives of orology that the Chinese had detecting — detected Reston virus circulation in pigs in 2011 in Shanghai, China They were screening those pigs for PRRS Virus or Porcine Reproductive Respiratory Virus, which actually was how the samples ended up at the USDA in the first place So I guess if you go to Shanghai next, beware of the pig meat And then Ebola reemerged in the Weibo, again, about a year later So there were a couple years off And then in 2012, we — we had another banner year where Ebola Sudan, this time in Jabaal and sort of the middle, sort of northern part of — of Uganda emerged was a small case, we’re able to do some — some ecological studies Ebola Bundibugyo emerged for the second time, this time in North Eastern DRC actually about 200 miles north of where the current outbreak is now And so this was the Bundibugyo variety You can see Christina there being taught by Brian Bird how to fuel a — a generator And then just to cap it off, Marburg emerged in — in Umbanda [assumed spelling] which is the town that services the Kittaka mine, that had appeared seven years prior And then Ebola Sudan reemerged in Luararo [assumed spelling] again And so a lot of activity going on And what you may have noticed, at least in those Uganda episodes, that — that the overall number of cases was — was quite small and this is not by accident It is in large part due to the fact that starting in 2010 we had — our branch had invested majorly in establishing the VHF surveillance program at Uganda Virus Research Institute in Entebbe there in — in Uganda not too far from — from the Red Star there in Kampala And as evidence of this effectiveness, you can see in this slide here on — on the left sort of outside of the shading area are the — shows a couple of outbreaks, where you can see in the blue are the number of probable confirmed cases are quite large And the — on the — on the — the bottom part of in — in the pink is the time it takes to detect that — that outbreak And you can see that once the VHF surveillance got established, both of those become much, much smaller And again proof in the pudding that if you put in the — the effort here as — as we did and — and have maintained, it’s very effective at being able to detect these outbreaks quite quickly, which obviously minimizes the — the public health impact So moving on to — to West Africa, and obviously, this — this changed everything, at least from the diagnostic challenges in response It was a — it was a major effort I think as most of us in the room here are aware that it started, at least it was first detected, came to our consciousness in — in March of — of 2014 But we think it probably started back in December of 2013 And from the lab — the standpoint, this turned into a United Nations of — of labs In the end, over I guess 27 different field labs were established and operated all over West Africa

These labs were provided by multiple countries besides the United States The US agencies involved, besides CDC included National Institutes of Health And — and [inaudible] So for the CDC lab we operated two labs One was at Ella in — in Liberia, we helped run that along with the NIH guys at Rocky Mountain Labs But probably most of the effort was devoted to the Bough lab in the central part of Sierra Leone And you can see in the — in the center there our hot lab was about as rudimentary as you could ask for It was four posts and a tarp and a corrugated roof and natural ventilation But it proved to be very effective And they — the — the PPE or the — the protection, we just used pappers, and the — it worked quite well and had a very high throughput And you know, this lab was embedded in the NSF ETU there in — in Bough, this is a shot from the — from the helicopter And so how we set this up, so I showed you the hot lab and then the rest of the — of the laboratory for the RNA extraction and the — the PCR part, and all the paperwork and — and specimen sectioning That was all done in a nearby two bedroom house that we essentially repurposed, the bedrooms and the — the main living area So the clean room was a bedroom, there you can see some of the before and the after You have your unmade bed and then on the right turned into the clean area And then the other bedroom, you can see the bed there on the left and this turned into the RNA extraction room And this is a — a slide showing that at least in the — in the middle part, at least through January of 2015, the — the Bough lab tested over 7,000 cases And so a relative contribution of the other labs, it was quite significant So there were a lot of samples that — that went through this lab This is one of my favorite slides So the specimens came in multiple types There’s lots of confusion and so lots of different ideas about how to send a specimen Some of them came in a plastic jar, some of them came in a coffee urn, plastic bottles The — getting the paperwork there in the upper right was always a challenge because sometimes there was a little bit of a reddish smear and you weren’t quite sure what that was So we always disinfected the paperwork that came with it Some things came in Falcon tubes and some tubes were shoved in the — in gloves or other bags of various sorts Sample transport was a challenge and — and had to be scaled up dramatically They came on motorbikes, ambulances And at one point we had a — a helicopter circuit running by [inaudible] of — of either the Russian illusion helicopters or these Bell helicopters So in the end the — the accomplishments for the — of the Bough lab were over 27,000 samples tested The lab remained operational for over 400 days without a day off And the agency can be pretty proud of itself In — in the end there were 28 teams of personnel pulled from 17 different branches that were all trained in special pathogens, and were deployed in — in series to operate the Bough lab So it was a major agency effort So I thought I have next kind of series of slides here just a commemorate — commemoration of the 50th anniversary of — of HCO activity here So we just learned about the Ebola Zaire in — in ’76 And showing here is a picture of — of Carl Johnson working here at — at CDC And this is kind of from the — the midpoint on, starting in 1993 with identification and isolation of Sonomry [assumed spelling] virus, which is the four corners virus Here’s the Hanna virus, caused a lot of panic at that period Since then many Hanna viruses have since been discovered and Stuart Nicole was in the — in the lead with that one, NEPA virus, which was a — it’s a bat born paramyxovirus that emerged in — in pigs We now know it comes from bats, and if that sounds a little bit familiar, that’s because this sort of scenario was the inspiration for the movie Contagion SARS virus was identified here with an — in — in VSPB and also with IBPD, and I should say with many of these virus discoveries the infectious disease pathology branch was working hand in hand with VSPB in terms of in identifying many of these agents Bundibugyo Ebola virus that we already mentioned, Ludgovirus [assumed spelling] first discovered is South African arena virus that killed four

out of five people that were infected In 2012, Heartland virus, now you see quite a few cases of that every year Some of them are — are fatal So supravirus is a — a bat born paramyxovirus discovered in 2014 And I’m sensing to — to move forward [ Laughter ] All right >> We have two minutes >> Two minutes Great. All right So vaccines, do you want me to finish or no? >> Sure >> All right The first vaccine established was operated in — in Building 15 This is now the — the J&J vaccine, the current vaccine going on it’s being used, it’s looking quite promising over 200,000 doses given, 97% efficacy There’s a couple of — of therapeutics that are looking promising this — they’re both monoclonal antibody based And a few slides about where does Ebola come from bringing So bringing you up — fully up to date And a couple bats, that’s the prevailing theory We don’t, at this point still don’t know what the reservoir is A couple of bats tested positive, but we still — that data hasn’t been reproduced since then, in 2005 However, there was a story at least the — the Zaire or the outbreak in West Africa started in Guinea, at this tree that a two year old kid played in [Inaudible] bats inhabited that tree They all tested negative however, that’s the same species that turns out looks like it hosts Bombali virus A finding that’s been confirmed in Kenya and also nearby Guinea And then I’ll just finish with saying however, we do know a lot about Marburg virus So it’s the — the close sister to Ebola where we’ve identified the Egyptian Rosetta bat as the natural reservoir for — for Marburg virus And this was started with studies carried out by Botswana [inaudible] in Rumba in a Rumba mine in eastern DRC and then followed up And first isolated by us here in Building 15 in 2007 And this is a discovery that we’ve now confirmed again in Sierra Leone So it turns out [inaudible] bats in Sierra Leone, they too carry Marburg virus So in two minutes, I’ll stop there and say that there’s a — a lot of lessons learned that we can apply to Ebola And we’re — we’re working on it now I mean, it’s — it’s going to be a long effort One of the main lessons is just that the percentage of animals are actively infected is low Which means that you could combine that with the fact that there’s over 250 different bat species throughout Africa, that’s a lot of bats that — that need to be tested, if in fact bats are the reservoir for — for Ebola virus And so I think with that, I’m going to stop I sense Phoebe next me, and we’re going to move into the questions >> Yes well — [ Applause ] It and thank you so much for joining us And I would like to again thank the speakers for their excellent presentations It — it is 2:00 p.m., and I’m sorry that we do not have time for question and answer now but you are free to stay in the room for a few minutes and — and come up and talk to the speakers And then there is something again at 3:00 p.m., if you want to talk there’s room outside too Thank you again so much for joining us Appreciate it