Laurens Liesenborghs: If something goes wrong, it can go wrong quickly and, and very badly.
Narrator: This is Transmission, the podcast of the Institute of Tropical Medicine in Antwerp. In this podcast, we will uncover the mysteries of diseases that impact us all and delve into the cutting edge science of keeping people healthy. We invite you to look over the shoulders of the experts who make it their life's mission to improve global health. In our first episode, we met professor Jean-Jacques Muyembe, one of the scientists who first discovered Ebola and researched how this infectious disease was being transmitted. In this second episode of Transmission, we delve deeper into the complex riddles pathogens throw on our path and the intriguing research that is being done to stop them. Transmission, your front row seat to the world of health, science and beyond.
Narrator: Laurens Liesenborghs and Placide Mbala-Kingebeni are experts in infectious diseases. They travel the world to unravel the mystery of monkeypox or Mpox as it is officially called. They go far and wide always on the move but right now their four-by-four is stuck in the mud.
Laurens Liesenborghs: Yeah well, the Congolese have a very nice word in French, it is ‘embourbé’. The word means when a, when a vehicle gets stuck in the mud euh, literally, euh, which is, one of the most euh, often used words that you experience on such a trip.
Narrator: The car is leaning precariously, and everyone is trying to get the vehicle back on track. It is 2022, we are in the DRC, short for the Democratic Republic of the Congo. And we are on the road to a remote village in the rainforest. But as Laurens explains…
Laurens Liesenborghs: Yeah, unfortunately, once you get out of the capital the roads become really, really bad.
Narrator: And when it rains, everything floods.
Narrator: Placide and Laurens can finally get back in the car. But there is still a long way to go.
Laurens Liesenborghs: It’s a real hassle to get anywhere, especially in rainy seasons. They are completely cut off from the outside world and they are completely self sufficient as well.
Narrator: Laurens, Placide and the rest of the team are researching an outbreak of Mpox. A disease that starts with small blisters that often spread all over the body. After a while, these blisters become large bumps filled with pus. Overtime they disappear but they leave large scars and wounds that often inflame.
Laurens Liesenborghs: Often they also go to the eyes, so we saw a lot of people with blindness as a consequence of an Mpox infection.
Narrator: In the DRC, between 1 and 10% of Mpox patients die. And this is why Laurens and his colleagues go to the hotbed of the disease to study it.
Laurens Liesenborghs: It’s a disease that we find really in the heart of the rainforest in, in the Democratic Republic of the Congo.
Narrator: Laurens and Placide were studying one of the largest outbreaks ever recorded in the country. And getting to the heart of the rainforest was not easy. First they had to take internal flights, then they drove two days by car. When that became impossible, they transferred to a motorcycle. And of course also…
Laurens Liesenborghs: Wading through the rivers and so we were waist high in the water searching for these Mpox cases.
Narrator: After all those challenges and setbacks they arrived at the village. Laurens took time to talk to the villagers, get to know how they live with the disease and get a better understanding of the whole spectrum of Mpox transmission. From animal to human and from human to human.
Laurens Liesenborghs: We returned to the provincial capital where finally we had some internet connection.
Narrator: But when they opened their computers…
Spreker: Er is een eerste geval van het apenpokkenvirus opgedoken in…
Translation: A first case of Mpox has surfaced in Belgium, so the virus has also reached our country. And we have a few questions for Isabel Brosius of the Institute of Tropical Medicine in Antwerp: you and your team have been researching the Mpox virus?
Isabel: Ja, dat klopt, ….
Translation: Euh, yeah, that’s right. The patient presented himself at the Institute of Tropical Medicine here in Antwerp. With symptoms for which the necessary samples were taken to be able to confirm the infection.
Laurens Liesenborghs: All of a sudden we found out that there, hey, there’s already been five cases of Mpox at the Institute of Tropical Medicine in Antwerp.
Narrator: The variant of the virus that spread in Europe was much less dangerous. Still, infectious disease specialist Isabel Brosius found herself at the center of what was happening in Belgium.
Isabel Brosius: I work very closely with euh, with Laurens and I, normally would have gone together on this euhm, field trip euh, but I, I was pregnant at the time, so I, I was forced a bit to observe from the side but then while they were there, I, I mean, how big the coincidence can it be, there is a certain moment where, yeah, we had the news via all sorts of scientific networks of cases om Mpox that were suddenly euh, being reported, UK, some in the US, some in Spain, euhm, so already we had the sense like, okay, this is out of the ordinary, euh, we should start preparing and then only two days afterwards, euh, we had our first case. There was this whole media storm that actually broke loose a bit and, and at that time, I, I was, well one of the few people then still at ITM that was actively involved already in, in, in research on the topic.
Laurens Liesenborghs: So we, we were completely surprised of course, euh, we expected, we, we knew about the epidemic potential, euh, about this disease, but then, going really to the far end of the world to look for Mpox cases and all of a sudden you come back and there are Mpox cases at your doorstep. So that was quite euh, quite strange indeed, and unexpected.
Narrator: You could start to wonder what drives such a disease. What is the reason a virus like Mpox suddenly appears in a population? It might start with someone eating a sick animal but why is it transmitted from human to human?
Laurens Liesenborghs: What are the important mechanisms? Is it through the respiratory road? Is it euh, because people get into close physical contact? Is it through euh, contaminating objects like a plate, or a spoon that is shared or clothes that are shared? To really understand these mechanisms behind euh, the transmission. And, because of course, that will enable us to stop these epidemics.
Narrator: So if we don’t map out our answers clearly in advance, before there is a crisis, we will steer blind during the outbreak itself. We would have no idea what measures to take. So it is of the utmost importance to research smaller outbreaks to collect data about the disease as soon as possible. But as the Ebola outbreak of 2014 made abundantly clear, researching an outbreak isn’t easy.
Dr. Mandjeku: Before we enter the Ebola ward, we pray.
Narrator: This is what Doctor Mandjeku tells us before we enter the ward.
Dr. Mandjeku: We put on scrabs, boots, a pair of gloves, foot covers, a full body Tyvek suit, a second pair of gloves, a respirator mask, a second hood, goggles, a third pair of gloves and a heavy yellow apron, not a spec of skin will be exposed to the air. After just 5 minutes you are saturated in sweat.
Narrator: Walking into an Ebola ward is a strange experience.
Johan van Griensven: The first time it’s a bit horrifying.
Narrator: This is Johan van Griensven, from ITM. Together with Alex Delamou, who studied at ITM and was doing his PhD in 2014, he was researching Ebola.
Johan van Griensven: You see people very sick dying, bleeding, euh, confused, you, to some extent have to keep distance. You feel a bit helpless, because also what you can do medically in such a facility. It has changed now, but at that point in time, it was basically about isolating them, euh, and giving some fluids and there was not a lot beyond that that you could do. Situations happened where Ebola patients would start running around and trying to escape and, and, yeah…
Narrator: Quite a challenge. And you are overwhelmed. On the other hand…
Johan van Griensven: You have to still think very clear, it’s very hot, you are sweating, you are dehydrating but you have to stick to the precautions. You might see someone vomiting, you might wanting to help, but then if the person is confused pulls your mask, you might actually get exposed yourself, so it’s finding a balance between keeping your head cool, but still yeah, they are still patients.
Narrator: And the only thing those patients see from Johan and Alex is them walking around in some kind of space suit. You have to admire the health care workers who do this day in and day out.
Johan van Griensven: I think they are, it’s where most of my respect goes.
Narrator: It’s a very high-risk job and if they get sick, they will just end up with the other patients.
Johan van Griensven: They are remarkable people.
Narrator: No matter how complex the situation in such an Ebola ward is, the reason why Johan and Alex are there is simple. They want to better understand the disease and this is by no means self-evident. An outbreak is always unexpected.
Laurens Liesenborghs: Of course this means that you need to drop everything and, and go there often without funding.
Narrator: Laurens again. This is one of the reasons why the Institute of Tropical Medicine has set up an outbreak research team. A multidisciplinary group with an anthropologist, a virologist, a clinical scientist, a lab expert, an epidemiologist and so on. They tried to be ready to study a disease as soon as there is a new outbreak. Alex Delamou dropped everything.
Alex Delamou: The Ebola outbreak started in my country, Guinea, I decided to go back and help with euh, Ebola control.
Narrator: Johan and the rest of his team wanted to go to Guinea as well as test a new treatment with plasma from blood of Ebola survivors. But they were not sure and had to decide which action to take.
Johan van Griensven: A dramatic outbreak can lead to political unrest. There was already violence, so unpredictable, even risk for the people involved. Are we up to it? Will we take the risk? Is everyone willing to take it?
Narrator: Eventually, they thought about it for three precious days.
Johan van Griensven: We called each other every day, over the weekend and on Monday we decided, we will proceed.
Narrator: This time, Johan and Alex arrived in time but the team had to be quick. Ebola pops up, kills a lot of people and it is very plausible that the virus will retreat back into the forest before they can get their studies up and running. Or before they can get to the remote places where the disease rages. It could be years before Ebola returns to humans, attacks and retreats before it can be studied. And there is another reason the team had to be quick. When an outbreak starts…
Laurens Liesenborghs: Well, then everyone yeah, wants to stop the outbreak as, as soon as possible.
Narrator: But that makes research challenging. Because once the outbreak is over, there will no longer be people to participate in their studies. Everyone is either cured or deceased.
Laurens Liesenborghs: But okay, that’s, that’s part of the game and, and that’s one of the things that makes outbreak research so, so difficult.
Narrator: The outbreak research team does not go out there to actually help people or stop a specific outbreak. They are there to research it. To understand how the disease works.
Laurens Liesenborghs : This is a bit frown upon upon by humanitarian organizations, because the response, that’s what is important and an outbreak you need to control it, euh, you need to take care of patients and that’s all 100% true, but the big thing that’s also very important to also do research.
Narrator: Research is crucial, to learn lessons from outbreaks and in the future support the humanitarian organizations and response teams.
Jean-Jacques Muyembe: An outbreak is always something that is accompanied by euh, panic and also remorse. And most, most of the time we are not prepared for that. It is like a surprise.
Narrator: This is Jean-Jacques Muyembe, the microbiologist and professor who we met in our first episode.
Jean-Jacques Muyembe: You can take euh, the good measures,or the, the bad measures. Euh, most of the time, it’s the bad measures we will take at the beginning. Yes. So, an outbreak, euh, it is like a, in a class, we are, we are learning. We are learning during the outbreak. To find medicine, to find vaccines, and also to change the behaviour.
Narrator: Johan and Alex knew they had to be quick. Reports of the Ebola outbreak were all over the news.
Reporter 1: There is a fear that the virus will spread rapidly.
Reporter 2: This is the deadliest outbreak of Ebola on record.
Reporter 3: Any communicable or infectious disease can go anywhere in the world within 24 hours.
Narrator: Johan didn’t know this at the time, but it would eventually become the largest Ebola outbreak ever recorded and would cost the lives of more than 11,000 people.
Alex Delamou: I must say that it was really a shock.
Narrator: Alex again.
Alex Delamou: We quickly realized that the country itself would not be able to respond, euh, because of the rapidity euh of this spread of the outbreak, euh, it started in one town and then, euh, in four, in four, five months it was already in the capital city. Euh, which is located about 1.000 kilometres from the place where the first cases started.
Narrator: And once Johan and Alex’s team had set up, nothing went as planned. They might have mapped out a strategy, but every day they realized their approach was not working as intended. Or that there was resistance. Problems stacked onto more problems.
Johan van Griensven: So it’s frightening and, and also yeah, stressful, definitely stressful. There is also very, a lot of pressure also, expectations locally, also politicians or ministries of health that support you. Euh, they, they want to help the community, they also want to show to the community things are being done. So you have to deliver.
Alex Delamou: But also you are doing it within an epidemic period. So you have to protect yourself and also you have to protect euh, your family and your, your close relatives you know. So it’s like euh, very, very risky area. So, you have to be euh, 100% euh, focus because small mistakes can break anything.
Narrator: Or as Laurens puts it when he was in the DRC…
Laurens Liesenborghs: If something goes wrong, it can go wrong quickly and, and very badly.
Narrator: Evacuation options are limited.
Laurens Liesenborghs: One night and there was a, a territorial dispute, euh, 20 kilometres from, from the village where we were remaining, so a territorial dispute between two villages.
Narrator: Rumors suddenly started to spread. An attack on the village was imminent. And what was more, in a recent unrest, one soldier was killed and one went missing. The weapons of those soldiers, two AK47s, were still in circulation.
Laurens Liesenborghs: So there were guns in, in the village and so, then all of a sudden things can get tense quite often.
Narrator: Then, you had to work as a team.
Laurens Liesenborghs: Being able to rely on each other is, is crucially important and so, so then I was very happy to be there with, with my Congolese friends, euh, which did an amazing job also to, to negotiate.
Narrator: The team got away safely. But it does indicate that outbreak research is not necessarily safe. Not for ITM researchers, nor for their local partners. Or as Johan summarises this Ebola project:
Johan van Griensven: I think, yeah, the most stressful moment, period of my life, I wouldn’t recommend it to my enemy. You live every second euh, you live for this project.
Narrator: But as a researcher, Alex says:
Alex Delamou: You have to take a responsibility to do your part of the job.
Narrator: An outbreak research team standing by to jump into action when there is an outbreak is crucial to prepare us for future cases. Because beyond the search for treatments and drivers of the disease, everyone wants to know where the virus comes from and where it could retreat to once it has run its course. In other words, where does the disease hide when it is not infecting humans?
Narrator: David is ten years old. He’s playing football with his friends. They hear the car before they see it. David forgets about the ball, drops everything and runs to the vehicle, it’s a 4 by 4. Some white people get out. Some Congolese as well. He doesn’t know they’re Mpox researchers, but he has heard some people will arrive in the village today. What are they up to? He keeps on watching them from a safe distance. The Congolese people speak the local language and talk to George, the father of one of his friends. After a while, George points them in the direction of the house of the chief. The visitors enter the building. David keeps on looking. But everything is quiet and nothing seems to be happening. David goes back to his football.
Laurens Liesenborghs: Generally, the reception is quite well, but of course, you don’t just arrive there…
Narrator: A visit to a village involves a lot of homework. Laurens and the team of Mpox researchers could upset the whole political and social balance in the village and that is the last thing they want to do.
Laurens Liesenborghs: Always work together and through local organisations.
Narrator: But also with governments or the chief of the village.
Laurens Liesenborghs: To make sure that, that you are welcome and to make sure and to inform people what the intention is and, and to also listen to what they expect.
Narrator: This is crucially important.
Laurens Liesenborghs: And that takes a lot of time.
Narrator: Laurens stays in the village for three weeks. He then returns to Belgium. His Congolese colleagues will stay longer. During those weeks, they will map out how Mpox is transmitted and they will be looking for the animal reservoir of the disease. A virus can only survive if it has a place where it can live happily and undisturbed. It must be able to reside in an animal that doesn’t die from the virus itself. Because when the animal dies, the virus also dies. Mpox for example indiscriminately infects monkeys, rats, mise, squirrels and rabbits. There is a good chance that the virus will withdraw into one of these animals when it is not infecting humans. But it could just as well be an animal that is not yet on our watchlist. Once Laurens and his colleagues know which animal is the reservoir for the virus, they can give advice on how to avoid contact with the animal and greatly diminish the chance for a new outbreak. Sounds deceptively simple but the search for the reservoir is not obvious.
Laurens Liesenborghs: It is like looking for a needle in a haystack. That is actually mainly by off the record research that you cannot do in a questionnaire, by really talking to people and knowing their hunting habits, that you understand yeah which species might be the culprit and so for example we have a lot of indications that it’s mainly squirrels that transmit the disease. But these hunting habits and these balances are, are quite complex.
Narrator: Once they have an idea of which animal is a contender, the team has to locate the suspect in that endless jungle, catch it and take blood samples.
Kevin Ariën: There is a lot of guidelines and regulations on this, you can not just go out and, and catch euhm, hundreds of bats and kill them off.
Narrator: This is Kevin Ariën, virologist at ITM, discussing the challenges of looking for the reservoir of Ebola.
Kevin Ariën: This has to be done in the least invasive possible way, euhm, with rodents, it’s a bit different but nevertheless, I mean, there is never the intention to just kill and slaughter these animals, it’s, it’s catching them, euh, taking a small blood drop and then releasing them again.
Narrator: The field researchers then send the samples to the lab where the virologist tests the blood to look for the virus. If the animal has the virus without getting sick from it: reservoir found. Or at least one of the possible reservoirs. Now researchers can write extra guidelines on how the disease is transmitted, and how to avoid contact with the animal. Sounds great, but it remains a big haystack and a small needle. Professor Jean-Jacques Muyembe is still looking for the reservoir of Ebola, almost 50 years after he first came across the disease.
Jean-Jacques Muyembe: We are studying also the reservoir of the virus of Ebola, but it is very difficult for the moment to have the proof, the scientific evidences, euh, to isolate the virus from the reservoir. But until now, we process more than euh, 10.000 samples at my institute, but we didn’t euh, isolate the, the virus.
Narrator: The challenge is that most of the time, samples aren’t collected during the outbreak itself.
Jean-Jacques Muyembe: So it is very difficult to isolate the virus, but we know that the first outbreak of Ebola Sudan, the patients were infected in a cotton factory. And euh, the roof of the factory was plenty with bats.
Narrator: And we also know that the reservoir of the Marburg virus, the cousin of Ebola, is a bat.
Jean-Jacques Muyembe: But until now, we have no confirmation for Ebola.
Narrator: We keep looking. Looking for some kind of pattern that can help us.
Narrator: A woman sits under a large and beautiful mango tree.
Kathy Kreppel: Usually on a little chair, under a big tree, hopefully it’s not gonna rain too much.
Narrator: The woman under the tree is Kathy Kreppel and she’s waiting. Kathy is an epidemiologist at ITM. She is here to talk, to talk to people and to find patterns. Kathy loves patterns. She recently found a special pattern that links the rainy season to the plague in Madagascar and it has something to do with traps and rodents.
Kathy Kreppel: I already found out that they have certain times when the kids are preparing for the rodent season and making all sorts of elaborate traps, it’s a bit like a competition, who has the best trap.
Narrator: And when rodent season starts, all the children enthusiastically start catching rodents and then they get sick.
Kathy Kreppel: Knowing that they do that at certain times of the year, to me indicates that there must be a seasonality. And seasonality is always linked to climate.
Narrator: If Kathy can find the right link between something as large as the seasons and something as small as a rat catching competition in Madagascar, she will finally understand which factors play a role in spreading the disease. Kathy knows she can’t ask people in the village why they start catching rodents at this time of year.
Kathy Kreppel: For them it’s very, it’s totally clear. They are like ‘well, this is when the rodents are out.’
Narrator: But why are the rodents out? She has to find the bigger link herself. Eventually Kathy realized it had to do with the end of the rainy season.
Kathy Kreppel: It’s when the rain stopped, so you have a lot of rodents because they have just had a lot of food, a lot of grass, and a lot of insects and so to eat. But now the rain stopped so you can start lighting fires and you can strategically set the fire, so it pushes the rodents that run away from the fire into your specially prepared traps. But of course depending on the climate, the rain will take longer or will not come at all or the dry season is very sudden.
Narrator: And all of that has an effect on the start of the trap making competition and on the timing of the spread of the disease. It also tells you who is at risk of contracting it.
Kathy Kreppel: It is not the grannies that are sitting at home, it’s the kids that are in touch with the rodents and catch them and kill them and get scratched and bitten.
Narrator: How do you beat an infectious disease? A good question. You can start with medicines, vaccines or lockdowns, you can take it apart in a lab to understand how it works or look for a treatment. Kathy chooses a different route. She tackles the disease with questionnaires, conversations and big data that link the big picture to the minuscule details. And that is why we now see her sitting on a small chair under a large mango tree, waiting for the village elders to tell her stories about how they live.
Kathy Kreppel: I love being in the communities and just having these aha-moments.
Narrator: By talking to the people, she can uncover little details that she would never ever think of on her own and that she can only see when she is in the village. She can then link these little stories to huge datasets, like linking the rats to the rainy season. But she also discovered that the outbreak of the plague in Madagascar is often linked to the El Niño Southern Oscillation, a climate phenomenon in the Pacific Ocean. Wait, stop. A natural phenomenon somewhere in South America has an effect on the outbreak of plague in Madagascar, an island that last time we checked, was off the coast of Mozambique? Yes, correct. In Madagascar.
Kathy Kreppel: There is a tradition to remember the dead every seven years and they actually take the shrouded, so they, they, they wrap their dead in shrouds, lay them to rest and after seven years, they take them back out. They are not in deep graves, they are more in like, a bit like a crypt, euhm, but above ground. So they take the shrouded euhm, dead out and they spend days just singing about their achievements and their lives to remember the dead. Euhm, it’s a really big traditional, very important festival.
Narrator: Unfortunately there’s evidence that while they do so, they also become infected with the plague, which comes from fleas from the rats that live in the crypts. And since the El Niño Southern Oscillation affects the weather and the weather affects how many fleas there will be on the rats, El Niño has a clear effect on the likelihood of a plague outbreak in Madagascar.
Kathy Kreppel: Things are interconnected, there is no black and white, there are many factors affecting things, especially diseases, it’s a complex system.
Narrator: During the outbreak itself, you can no longer find Kathy in the field or on a chair under a tree. During an outbreak she no longer concerns herself with individual cases. At that moment she remains at ITM in Belgium and mainly wants to be fed with data. Lots and lots of data.
Kathy Kreppel: So we would like to know what’s the climate data, what was the climate data in the last year. How many cases are there, what are the conditions right now? Was there anything special? It’s not about dropping everything, going there and seeing a patient. Because actually, the exact symptoms that a patient has is for me not very meaningful. That doesn’t, doesn’t play a role. What plays a role for me is how do the families react, how does the country react, euhm, what is the normal behaviour, the day-to-day behaviour of a person that got infected.
Narrator: In this way Kathy tries to get a clear picture of how the pathogen reacts in people and how people react to the disease. She says to other researchers and health professionals: give me the pieces of the puzzle. She then tries to put together everything we know and tell us what that picture looks like, for instance the picture of avian flu. At that moment, the outbreak itself has already started.
Kathy Kreppel: You can’t stop it from causing the first cases, it’s already happened. But you can prevent it spreading. With avian influenza you need to know where the birds are. You need to know where the poultry farms are. You need to know what the regulations in the country are. And so on.
Narrator: And so she tries to answer the question…
Kathy Kreppel: Who is gonna be next for example. What is gonna happen next?
Narrator: Whether you are Laurens stuck in the mud, Kevin peering through his microscope, Johan trying to set up a project or Kathy trying to solve the puzzle, it is very difficult to collect answers and puzzle pieces during the chaos of an outbreak.
Laurens Liesenborghs: It is crucially important to prepare well in what we call peace time, and this is also for research.
Narrator: Much better to collect your answers in advance so that you know how a disease will behave when it breaks out. Nowadays we have the solutions to cure a lot of infectious diseases. We often know how the disease is transmitted and how we should stop the outbreak. We sometimes even have vaccines. But there is one giant challenge. We can get all the biomedical proof we want, but if people don’t want to take a leap of faith, it’s useless. We need to know how people think and react in times of uncertainty. We may already find it difficult just to understand our partners or our best friends at times, so how can we expect to ever understand what drives people from other cultures or people with opposing opinions. That is what we will figure out in the next episode.
Charlotte Gryseels: The only thing standing in the way of malaria elimination is really the human factor.
Kathy Kreppel: There are many, many things that we do every day where we know that is not healthy, but we do it anyway.
Narrator: Thanks for listening. Join us next time and find out the importance of the human factor in combating infectious diseases. For more information on the Institute of Tropical Medicine in Antwerp, please go to ITG.be/podcast.