In Conversation
Don Francis on Ebola in the Sudan, 1976
Don Francis spoke recently to LSF’s Gavin Rynne about his long and distinguished career in public health. In 1971, he joined the Centers for Disease Control (CDC) and helped to eradicate smallpox in Yugoslavia, India, and Bangladesh. In the 1980s, he worked to confront the HIV/AIDS epidemic in the United States. In 1996, he cofounded VaxGen, a spin out from Genentech’s HIV vaccine program. Eight years later, Francis formed a nonprofit organization, Global Solution for Infectious Diseases (GSID), to take over the program after VaxGen abandoned it. Besides work on HIV vaccines, GSID collaborates with international partners on a variety of vaccines and diagnostics for emerging markets.
The portion of the interview published here covers Francis’ work in the late 1970s. While studying virology at Harvard University in 1976, he received an urgent call from the CDC in Atlanta. He was needed immediately in the Sudan. Health officials there were dealing with the spread of a deadly infectious pathogen, something that “looked like Marburg virus…”
Gavin Rynne: The virus in the Sudan belonged to the same family of filoviruses as Marburg, and also caused hemorrhagic fevers. When did the CDC realize that this outbreak wasn’t Marburg?
Donald Francis: The CDC got specimens from a couple of patients, and when they looked at them under the electron microscope, they saw a virus that had the same wormy, very strange morphology as Marburg. Back in the high security lab, they started growing it and playing with it, and they realized it was different.
GR: Was that done before you arrived in Africa, or did it become clear after your team collected samples?
DF: I knew it was a new virus before I got on the plane for Sudan. The larger CDC team went to the Zaire side of the outbreak and collected the first specimens of what became known as Ebola. Ebola is the name of the river in Zaire near where they made the collection. We were kind of irritated that they’d named it in Zaire instead of the Sudan. But, you know, they’d isolated a new virus and so they had the right to name it. Anyway, there we were, out in the bush sending our viruses to London for analysis. Those were the first two known outbreaks of Ebola. What’s interesting is that they weren’t terribly far apart, just a day’s drive. We assumed they were connected, but they weren’t. They were separate outbreaks. At that time, we didn’t know where the virus came from. It took a while to identify the original animal host.
GR: Your WHO team uncovered the origin of the Sudan outbreak to be workers in a cotton factory in Nzara, about eighty miles from Maridi, where you were sent. That wasn’t the point of origin for both outbreaks?
DF: No, they were totally separate. It’s fascinating. You get the first outbreaks of a disease in two nearby places and you think they must be connected. But it is likely that Ebola used to pop up periodically throughout recent history. This was just the first time that someone who could do something about it had a connection to people at CDC and the World Health Organization (WHO). Earlier outbreaks remained small, confined to villages. People essentially ran away from them, and they burned out. But when patients went into hospitals, it was different. It just exploded as transmission was amplified. In the southern Sudan where I was, the hospitals were actually teaching institutions for nurses. So there were all these wonderful nursing students who just hovered over the first cases, and then they got infected, and their fellow nursing students hovered over them, and so there were hundreds of new cases very quickly.
GR: Tell me about arriving in Maridi.
DF: That part of the world has very few people in it, and if you work there for a time, it’s very clear why. It’s just riddled with diseases, malaria and many others. We flew into Juba, the capital of southern Sudan. At that time it was one country, but it has always been divided because the south is Central African, black, and Christian, while the north is Arab, mixed, and Muslim. At that time, very few people lived there. WHO gave us a Land Rover and a truck to transport all of our equipment and supplies. We left in the late afternoon. The road soon turned into muddy tracks. We got to Maridi about two in the morning.
GR: By the time you arrived, the Sudanese had already quarantined the hospital. What did you find when you walked in?
DF: Obviously, the infectious nature of the sickness was pretty clear because so many of the hospital staff had come down with it. The villagers had built an isolation facility. They built two — mud houses with grass roofs, one for males and one for females. Patients went in and many died. But since most of the infected were healthcare workers, the Sudanese officials had the wisdom to take the poor nurses who had survived and put them back to work, even though they had lost 20 percent of their body weight — it’s such a bad disease. Care was basically giving patients fluids and supportive care. There wasn’t much else to do. The mortality rate was about 40 to 50 percent. The Sudanese doctors had done a good job by the time we arrived. A good group of public health people had come from Juba to set up everything. When we arrived we allowed only recovered nurses into the hospital because it was just too dangerous for others.
GR: You went house to house tracking patients?
DF: Much of that was my responsibility. I had a guide with me, a teacher. He was wonderful. We went into houses with patients, little huts. We wore protective respirators. It was very difficult.
GR: The report states that samples and plasma draws were compared with the Marburg virus. At what point did you learn that it was transmitted by blood and fluids?
DF: Well, that was the whole purpose of the investigation. My job as the epidemiologist on the team was to figure out how it was transmitted. Pretty soon, we stopped wearing our respirators because we saw the infections resulted from very close contact. It was not airborne. There would be, for example, a child in a crib, a mother, and a father. The mother or father got sick, and the caring spouse also got the disease, but the child sitting in the bed next to them didn’t get it. Contact was essential to transmission. Sick people had blood oozing out of them that was full of virus and really infectious. Transmission occurred during patient care and the preparation of bodies for funerals.
GR: How did you manage funerals?
DF: Well, it wasn’t our responsibility. Our responsibility was to work up the epidemiology, find the cause, and understand transmission. We had wonderful cooperation. We met every day with the Sudanese public health authorities and it was quickly obvious how the disease was transmitted. Funerals were an important part of it. The Sudanese said, “We’re not going to have funerals anymore. We’re going to bury the bodies.” That was not easy culturally, but the authorities ordered it, and there were no protests. There was unhappiness, but the community was as concerned about the epidemic as the public health authorities. There was never any yelling or screaming at us. The people helped. This was a terrifying outbreak. And, frankly, simple societies control outbreaks like this by fleeing. People understand pretty quickly that it’s transmitted from sick persons to healthy persons — so people run away. The only people who don’t run away are the families of the sick.
GR: The report mentioned plasma that was collected from survivors. Was that just for analysis or for use as an antiserum?
DF: We collected it for use. We didn’t have fancy plasmapheresis machines out there, but recovered patients were very cooperative. They’d lost 30 percent of their body weight and their pants didn’t fit anymore. We hooked them up and took units of blood from them, but we didn’t take the needle out. We wanted only the plasma and because these people were so sick, we didn’t want to rob them of their red blood cells. So we let them sit for half an hour or more and let the blood settle in the bag. We didn’t have a centrifuge anyway, so it didn’t slow us down. While they still had the needles in their veins, we squeezed the clear plasma off the top and into bottles and then squeezed the rest of the blood back into the patients.
Since these people had recovered, the plasma had lots of antibodies in it and was good for treatment. We sent it back to the hot lab at Porton Down near London, so they could take out the immunoglobulin fraction that would be protective for people. Unfortunately, when they looked at it under the microscope, it was full of parasites — malaria and others — because there is so much infectious disease in that area. That plasma is probably still sitting in Porton Down. We had wanted to use it immediately to treat patients, but we decided that the risks outweighed the potential benefits.
GR: Has any antiserum been used?
DF: Yes, the head of the lab at Porton Down, Ernie Bowen, stuck himself with a needle and was infected by Ebola, but he survived and his antibodies have been used ever since. I saw him a year or so later at a conference and I asked him about the illness: “What was it like?” He said he was so sick that he had no memory of it. It is a really bad disease.
GR: Although the source of infection was traced to the cotton factory, the original animal vector was not clear, right?
DF: Those first five or so infections didn’t involve sexual contact or hospital contact. They were workers who had just cleaned the cotton at the factory. So they were very different from the rest of the outbreak. It was clear to us that the virus had gotten aerosolized in factory dust. Urine from some infected animal got on the cotton, which then literally got aerosolized in that work space. That was critical. We did a lot of animal dissections, but didn’t find a host. After we went home, people from Porton Down went to Africa and trapped and dissected animals, which, of course, is very dangerous if the animals are infected. Ultimately, they got a good collection of animals and got the virus out of bats.
GR: Today, pathogens can move around quickly. The recent Ebola outbreak is a case in point. Does that change the practice of public health in any way?
DF: Well, new information always changes practices. If you look at past Ebola outbreaks, all occurred in central Africa, and people there knew how to deal with it. They isolated it. The difference with this latest outbreak was its location. The virus had moved to Liberia and three countries on the southwestern edge of a part of Africa that had rarely seen it, and it was left to burn for perhaps ten to twelve months before people recognized that it was Ebola. By the time that the world really got involved, there were hundreds of cases in three different countries, and it was exported to Nigeria and elsewhere. The difference between this outbreak and the previous ones was that locals saw it as a new thing. They didn’t know what it was. They just let it burn and it got out of control.
GR: In a much more urbanized area.
DF: Ultimately, the same thing happens every time. In the Sudan outbreak, it would have stayed in Nzara, in one little night club, except that the owner of the nightclub became ill by having sex with one of the ladies, and he had money so he was transported to the teaching hospital in Maridi. Otherwise, it would have burned out in Nzara. So the intensity of the outbreak depends on how it’s treated early on, either knowledgably or with the movement of people. In the current case, what happened was probably similar. It was likely that the wealthier people who became infected were referred to a hospital in the next town or next city. Then that hospital was infected and the outbreak became massive in three different countries. If you look at medical history, we find these new bugs all the time. I’m sure Ebola has been in that part of the world for eons. But what’s different now, as you point out, is the movement toward urbanization and hospitalization, the change in the social structures. Urbanization and hospitalization are new amplification systems for epidemics of infectious disease.
Story originally published in the Spring 2015 issue of LSF Magazine
