Currently there is an Ebola outbreak in Uganda. As of this writing there have been 39 confirmed and probable deaths due to the Sudan ebolavirus. Here is a Nature news story on this situation. This podcast series focuses on COVID-19 but its main theme applies to infectious disease research more generally in the Global South.
Across the Global South researchers deploy much creative grit to deal with COVID-19. I wrote a story about what some of these researchers did and do to jump to the frontlines to address a public health emergency, how they organize supplies, how they network. The story travels to Cambodia, Cameroon, Kenya, Nigeria and Uganda, among other countries. The story, published in Nature Methods is Lessons from the Global South's Fight against COVID-19 .
Creative Grit is a podcast series that presents conversations with some of the scientists in this story.
Episode 1 is with Dr. Marycelin Baba of the University of Maidugiri, in Maidugiri, Nigeria.
Episode 2 is with Dr. Leo Poon, who co-directs the Hong Kong University Pasteur Research Pole. He and his team have helped colleagues all over the world on COVID-19. I asked him if he has a fleet of private jets. He does not. But he wishes he did.
He and his team developed a diagnostic assay quite soon after the genome sequence of SARS-CoV-2, the virus that causes COVID-19, became known. His is the lab that detected and identified SARS, the outbreak in 2003. And many other viruses.
Here is episode 3, a chat with Dr. Thomas Egwang, director general of Med Biotech Laboratories, a research lab in Kampala, Uganda.
In Nature Immunology, he and his colleagues published a letter: COVID-19 vaccine trials must include helminth-infected cohorts. But they don't. At least not yet. Here is the chat with Dr. Egwang about the "quarter of humanity" that deserve consideration in this context.
Note: These podcasts are produced to be heard. If you can, please tune in. Transcripts are generated using speech recognition software and there’s a human editor. But a transcript may contain errors. Please check the corresponding audio before quoting.
Transcript of the podcast with some audio excerpts.
When the vaccines came, the whole idea was to fast-track clinical trials, get the results as soon as possible. But I think, in that haste, to trial the vaccines, one population nobody thought about were people and they constitute about a quarter of humanity. You have about 2 billion people who carry helminth parasites.
Two billion people, a quarter of humanity, Dr. Thomas Egwang just said. He is director general of Med Biotech Laboratories, a research lab in Kampala Uganda that was founded in 1995. You will hear more from Dr. Egwang and about the importance of that quarter of humanity, in a moment. Hi and welcome to conversations with scientists, I’m Vivien Marx.
Like most science journalists, I also report on COVID-19 and I had been wondering about researchers in the Global South. I did a piece for Nature Methods, there is a link in the show notes to the story and the show notes also have a transcript of this podcast.
As usual in doing this story, so much fell on the cutting room-floor. That is why I do podcasts to share more of what I hear as I do stories. https://www.nature.com/articles/s41592-022-01439-w
Thus far there have multiple podcasts in this series on COVID-19 research in the Global South. This is the third podcast. You can listen to them in any sequence.
As I spoke with researchers in different countries about COVID-19, I felt they were all sharing how they were innovating and finding the stamina and creativity to keep going in most difficult circumstances. That’s why I felt these episodes should be called Creative grit.
Many of these researchers were called to the front-lines to help their country build capacity and to train others. As is the case in Uganda. Med Biotech Laboratories has been building capacity for a while, not just starting with COVID-19.
Thomas Egwang, director general of Med Biotech Laboratories and his team have been helping to build research infrastructure in Uganda focused on infectious disease and they are involved in training people at the graduate and PhD level. Here’s Dr Egwang
We've been doing most research and capacity building, training people at the master’s and PhD levels. Some of our people have been trained even in the United States, UK, Japan and stuff like that.
Med Biotech Laboratories has a history of capacity building and training. It is a non-governmental organization.
Thomas Egwang [2:30]
Over the years, we have trained people. Somebody comes in, yes, he has maybe a diploma degree and they register for a Bachelor of Science degree. And I have somebody who actually went through from a diploma to BSc, Bachelor of Science to Master of Science. I have others who come in with Bachelor of Science right up to the doctorate. Capacity building. It’s a bit dicey, especially for a private organization like Med Biotech Laboratories, because we are not part of government. Independent, and all our funding almost, I would say 99% come from outside.
Of course, nobody was ready for COVID but at Med Biotech Laboratories , they were relatively ready to the jump to the front lines when COVID-19, a public health emergency, hit. Thomas Egwang spends his time managing the institute and its personnel, its supplies, its funding. And he knows supply chain challenges, which of course didn’t just start with COVID-19.
Thomas Egwang [3:20]
Well, there was a time when I used to do gene cloning when I first came back to Uganda. Some of my projects I would want to clone malaria genes. And yes, I used to import ethanol from abroad. I didn’t trust any ethanol that I could get locally that would be served with my DNA.
COVID-19 brought on its own specific supply chain issues, which are still ongoing, everywhere. Key for many labs in the Global North and the Global South was and is collaboration and networks. That was how you could organize and get what you need.
Thomas Egwang [4:20]
I didn't jump right into COVID research from the beginning, but I know that my colleagues here in Kampala had to get consumables right through their network, collaborative networks from the States and so on. I myself have tried to search, for example, diagnostic kits, and it's been impossible. You write to a company, and they give you a lot of runaround, but they don't eventually get to you. So it's been hard. But when you have a network of collaborators and whether it's for RT-PCR or for sequencing, you can get access to these reagents. Personally, I've not experienced it, but I know of my colleagues at the university who managed to get some work done through those collaborative linkages.
Collaborative linkages, networking those are factors that have played big roles in COVID-19. It’s a global public health emergency and without collaboration you just can’t take on a virus like this.
Vaccines have been developed and for COVID-19 they have been developed quickly, building on a lot of basic research. But before vaccines go into many arms in the general population, vaccine candidates are tested in animals and then in people, in clinical trials.
Thomas Egwang and colleagues published a letter in Nature Immunology https://www.nature.com/articles/s41590-021-01116-8 about an issue that was missed about COVID-19 in the rush to clinical trials. His letter co-authors are Margaret Kemigsha from Kiruddu Referral Hospital in Kampala and Tonny Jimmy Owalla who is at Med Biotech Laboratories.
Thomas Egwang [6:10]
Tonny is actually a research associate of mine. We've been working together for quite a while, and he’s got a master's degree and most likely he might come to the States for a PhD. Margaret is a physician. She's a doctor in a hospital, which is near my laboratory.
In their letter the scientists point out that COVID-19 vaccination is being rolled out around the world, also in the Global South, also across Africa. But this unfolds more slowly than in the Global North. The issue is as many as 2 billion people in lower and middle income countries, which is around one quarter of the population on this planet, these two billion people, that’s billion with a b, harbor helminth parasites, which can change the human immune response to vaccines. Here’s Thomas Egwang:
Thomas Egwang [7:00]
First, like you said, we live in an environment where we have a lot of parasitic diseases and there are different parasitic diseases. For example, you have helminths, the subject of my letter, there are helminths. And even amongst the helminths, you have different species of helminths that do different things. And then you have malaria. And I think there are already two papers out there in the literature, which shows that malaria, for example, having malaria or having had malaria may protect you against severe COVID. Actually, that study was done here in Uganda.
What these diseases do is that they polarize immune response in one way or other or in one direction or other. Take worms, for example, which is the subject of my letter. Worms polarize the immune response towards what we call the TH2 immunity, type of immunity. This is characterized by increased in IgE antibodies, increased the numbers of eosinophils, increase in mast cells or basophils. And then you also have molecules called cytokines that are unique for helminths infections like interleukin-4, interleukin-5, interleukin-13.
The immune system can become biased in one direction or another. It’s more ready to defend in one way or another due to this bias. So helminth infections bias toward TH-2 immunity. But what one needs to battle SARS-CoV-2 is TH-1 immunity. Thomas Egwang explains what it means if one’s immune system has been biased toward TH-2 immunity due to infection with helminths.
Thomas Egwang [ 9:00]
Now, in that kind of environment where you have had a prior infection with helminths and your immune system is biased towards the TH-2, automatically, you may not be able to mount a potent and robust immune response against, for example, bacterial infections, which require a TH-1 kind of immunity. COVID, with SARS CoV-2, it's quite established that you need a TH-1 type of response, whereas helminth infection polarizes immunity towards TH-2. So already you see that the polarization. Actually, right now I'm writing, resubmitting an NIH grant where I want to look at the effect of helminths on COVID-19 severity.
One scientific question he wants to explore more in his research is: if you have had a helminth infection it might bias the immune response for some time, it might affect COVID-19 severity and might also affect how well vaccines work.
Thomas Egwang [10:15]
That's one of the things that my research is going to try to find out. You have people who have active helminth infections and they have this TH-2 immunity. But you also have people who might have been treated six months ago and they cleared the helminths.
However, we don't know whether having had a prior helminth infection, still you maintain the TH-2 profile. My own thinking is that people with past helminth infections are mixed. You have those with recent infections probably still have TH-2 responses, and those who might have been treated one year ago, they probably have lost the TH-2 kind of immunity. But we don't know; that's something that we would need to find out. So the bottom line is that the fact that helminths polarize immune response towards TH-2 immunity, this compromises actually immune responses to other pathogens and to other vaccines.
And that’s the subject of my letter. Because none of the clinical trials involving COVID-19 vaccines have involved people with worms. And we know I wouldn’t say a donze, but at least I could think of about a dozen number of papers out there that shows that whether you're talking about the cholera vaccine or the hepatitis B or even some experimental malaria vaccines, measles, helminth infections have impaired immunity. That's basically why we wrote that story. So it was like a call to action.
This issue matters also as in some countries and regions, authorities are fractionating vaccine doses, splitting vaccine doses, because there is too little vaccine to go around.
Thomas Egwang [12:25]
Okay, so whether you give somebody a full dose, we still don't know how that full dose will work for people with helminths. It's like, if you like, I'm sure you have heard about the performance of the COVID-19 vaccines in immunocompromised people like HIV, like people with organ transplants, who have to receive massive doses of gene expression drugs, and therefore that impairs their ability to respond to the vaccine.
So in the same way helminth infections do that. And so the question is, what happens if they receive a full dose? Do they get impaired responses, are antibodies short-lived? Do you need to boost them the way you are boosting other people, maybe with cancers or organ transplants, et cetera.
So the issue is placing people who are infected with helminths into the same category as the immunocompromised individuals who need booster doses. If you have to give booster doses. And then if you want to spread the vaccine, people are thinking very much of using, let's say, a fraction of the dose, will that fractional dose, will it work in somebody with helminths? Will the same fractional dose work with somebody with helminths? That's basically the conclusion statement, the call to action, that whether you are testing full, fractional or booster doses, we need to have data in people who have been infected with helminths.
In the rush to get vaccines ready, this kind of aspect was indeed not front and center. The Global North has some biases.
Thomas Egwang [14:20]
I think in all fairness to the North. COVID is an emergency situation. So when the vaccines came, the whole idea was to fast track clinical trials, get the results as soon as possible. But I think in that haste to trial the vaccines, one population nobody thought about were people and they constitute about a quarter of humanity. You have about 2 billion people who carry helminth parasites.
Wait, hold on. A quarter of the population. Oh, my God. You are blowing my mind. Whoa.
If you put that into perspective, you have at least about 2 billion people in lower and middle income countries that carry helminth, parasites. So that constitutes about one quarter of the global population. That's a huge number.
My gosh, yes.
So what we don't know is whether some of the few millions of Africans who have been vaccinated against COVID and they have helminths--and I know some places where one out of two or one out of three people--have helminths. We don't know whether their immunity is not as robust as those who don't have helminths and that's the whole idea why it's an important subject.
An important subject indeed. That was Conversations with scientists, and this is an episode in the series Creative grit. Today’s episode was with Dr. Thomas Egwang, director general of Med Biotech Laboratory in Kampala, Uganda. And the music was Africa
And I just wanted to say, because there is confusion about these things sometimes, Med Biotech Laboratories did not pay to be in this podcast. This is independent journalism that I produce in my living room. I’m Vivien Marx. Thanks for listening.
The following music was used for this media project: Music: Africa by Rafael Krux Free download: https://filmmusic.io/song/5489-africa License (CC BY 4.0): https://filmmusic.io/standard-license Artist website: https://www.orchestralis.net
This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19. It was isolated from a patient in the U.S. Virus particles are emerging from the surface of cells cultured in the lab. Credit: NIAID-RML