The Malaria Podcast: Why current interventions are failing

If you’re African, it means that you are very familiar with Malaria. It also means you may have started to notice some differences in your experience of the disease. 

For example, you may have heard people say insecticides that used to work no longer kill mosquitoes, or maybe you know someone who had to go to the hospital because the medicines they used to take did not work? 

How can we explain that? And if that is truly the case, is there anyone working to understand what is going on? 

In this second episode of The Malaria Podcast, Olivia Ndubuisi travels from New York City to Harvard University in Boston and then to Uganda to speak with the scientists racing to understand why current interventions are failing and find solutions to get ahead of what is still one of the world’s oldest diseases.

Transcript

SPEAKER_06 0:08

Everyone I spoke with in episode 1, the ones who aren't scientists or researchers all said the same thing. That they noticed their experience of malaria was changing, but they didn't know if anything was being done about it. Yes, chloroquine stopped being the drug to treat malaria with a long time ago. Yes, there's partial resistance to the drug that is the current treatment in certain parts of the world, including in eight African countries today. Yes, everyone is worried about that. But how much do regular non-science people know about efforts to match that resistance?

SPEAKER_05 0:44

Nobody knows exactly what's been done about the situation. Until the news broke that there's going to be a malaria vaccine for kids aged XYZ, I had no idea anybody was doing any work on that.

SPEAKER_01 0:56

Yeah, I think people need to know that these efforts are happening.

SPEAKER_05 1:01

Welcome to the New Vision Podcast.

SPEAKER_06 1:04

My name is Olivia Ndubisi, and this is the Malaria Podcast, episode 2. How do you solve a problem like malaria? I wondered if there are scientists trying to understand why or how this is happening. And I found them in East Africa. So I got a visa, packed a bag, and travelled from New York City to Enterbury in Uganda to embed with some and find out exactly what is going on. Hello, good morning.

SPEAKER_03 1:42

Good morning, see how are you?

SPEAKER_06 1:44

I'm okay. How's it going? Okay. Alright, I'm on time here.

SPEAKER_03 1:47

Hello?

SPEAKER_06 1:48

Alright. I'm going to see a lot of people today. Yeah, you can. I'm going to also speak with a lot of people today. And I'm looking forward to Hi! How's it going?

SPEAKER_03 2:01

It's good. I like it. You've kept time, eh?

SPEAKER_06 2:03

You like that I kept the time? Yeah.

SPEAKER_03 2:05

So we just need to find a better place where we can do the recording.

SPEAKER_06 2:09

Okay. How do you say hello in Luganda?

SPEAKER_03 2:12

In Luganda. He can't tell it.

SPEAKER_06 2:13

How do you say hello? How do you say hello? How do you say hello in Luganda?

SPEAKER_02 2:18

Oleotia. Yeah.

SPEAKER_06 2:20

Oh, yeah.

SPEAKER_02 2:21

Oleotia.

SPEAKER_06 2:22

Oh no.

SPEAKER_02 2:23

Oleotia. Oleo tia.

SPEAKER_06 2:26

Oleotia. Yeah. Okay. So I'll say Oleotia.

SPEAKER_03 2:30

Oleotia.

SPEAKER_06 2:31

Good morning.

SPEAKER_03 2:33

Yes, gotcha.

SPEAKER_06 2:37

Part of the mandate of the Uganda Virus Research Institute or UVRI is to do surveillance and study mosquito behavior. They do this to see how effective current interventions are. So there are a couple of buildings here. I'm standing in the middle, and there are one, two, three, four, five, six, seven, eight, nine. Nine buildings, and some of them have markings. The one I'm standing in front of says it is the insectory. One of the representatives from Target Malaria who I've been speaking with Moses. He tells me that there are insects being studied in there, and he's asking to see if we're able to come in. Oh, okay. I haven't got the Oclea yet. I did get the Oclea. I met a man, Pizza Nkurunziza. He looks after what's called the insectory, and he gave me a quick lesson on the life cycle of a mosquito in a room where I saw more growing mosquitoes than I'd ever seen anywhere else in my entire life. One of the scientists there told me that you can't fight your enemies if you don't understand them. And by enemies, he was referring to mosquitoes. I spent an afternoon with Martin Lukindu, a postdoctoral researcher, and he explained to me why that study is so significant.

SPEAKER_03 4:04

For example, it is possible that the interventions that we have right now are not super effective because mosquitoes are evading them. Um, because mosquitoes have uh a mechanism of evading some of these uh interventions, and uh, there are about four different ways they can do that. Uh, one can be behaviorally, such that mosquitoes that used to be to bite you, like inside houses when you are sleeping, somehow they get adapted and they no longer bite you.

SPEAKER_06 4:31

Martin referenced a study that came out of Kenya. It was led by researchers from the Kenya Medical Research Institute, and he found that the Anophilis mosquito was now biting school-going children early in the morning when they were at school prep rather than at night when they were protected by mosquito nets. So you're saying that because uh mosquitoes are getting sprayed and because people are sleeping under mosquito nets, the mosquitoes are learning how to evade those things?

SPEAKER_03 4:58

Yes, exactly. I was I was about to give you another mechanism of resistance, what we call metabolic resistance. So mosquitoes are able to toxify the chemicals that you spray with them.

SPEAKER_06 5:08

Martin is saying that any of these reasons could explain why the insecticide usatu bot didn't work. That apart from the mosquitoes behaving differently, like biting in the morning instead of at night, they have learned a way to detoxify the insecticide so that you spray them and they don't die. It's called metabolic resistance. Another way this happens is this insecticides are sometimes made to target a specific part of a mosquito's body. But you spray an insecticide and it doesn't work because the mosquito has changed the form of that part of their body, so they're no longer knocked down by your insecticide. And even more incredibly, there's a third explanation for your sprays not working, where mosquitoes grow thicker body parts so that the insecticides cannot get in.

SPEAKER_03 5:54

Problem is if a mosquito gets some form of resistance, its offsprings are also going to get that form of resistance. Before you know it, the frequency of that form of resistance is going to increase in a population in such a way that each time you apply the same same mechanism to control them, it's not going to be effective at all.

SPEAKER_06 6:16

I had never heard that this was possible, that this contorting by the parasite was possible. But it does explain somewhat about why things that used to work to prevent malaria no longer work as effectively. Martin works within a team of geneticists, entomologists, or working at the same time on different areas of concern. After gaining all this understanding, the knowledge is transferred to the Ugandan government so that they implement the solutions. So if mosquitoes in one area are resistant to a particular insecticide, they say to the government that new ones are needed. If mosquitoes are biting in the morning instead of at night, they advise the government to change their approach as well. The team's work doesn't focus on all mosquitoes, only those that are medically important, which are just three out of about 3,500 species. So far you're saying that the work you're doing and how it connects to the wider goal of eliminating malaria is you're recognizing that the general that the current tools, spraying insecticides, slipping on the nets, and all the all the other ones that we have have done their best, but we need uh we need a new line of defense because the mal the mosquitoes are adapting to the things that we have now. So you're saying that your work is in understanding how that adaptation is working, and and you're then working currently on making new tools to be able to provide that new line of defense. Do I understand that correctly?

SPEAKER_03 7:51

Correctly, Olivia, that's correct. Yeah, we we need the additional tools, and so we need to think outside the box.

SPEAKER_02 8:02

My name is Frank Obi Nade. I am originally from Ghana, and I am a fourth year PhD student in the biological sciences and public health program at Harvard University. I had a lot of episodes of malaria, and my dad, whenever I had malaria, will go for neem leaves and then cook it. It's better, but then he will allow me to drink a portion of it and then also bath with um the remaining. And after some few days, I will feel better, and that that was a genesis of my interest in drug discovery in general. I kept asking myself that what is in this new that is curing malaria.

SPEAKER_06 8:44

The way to think about how Frank's work in the lab ties into the general race to eliminate malaria is this way. For the parasite that causes malaria to develop and survive, there are things that are essential, things it cannot develop without. Many of those things are called proteins. They carry out like essential functions in the parasite. Frank is now studying one of those proteins as potential targets for a brand new anti-malarial in the future. This is important because he's hoping that when successful, it'll be difficult for the parasite to develop resistance against that drug that can be made from his work. Again, this matters because remember from the first episode, resistance eventually catches up with malaria treatments. That's what happened with chloroquine. That's what the WHO has noted is happening with the current drugs, the ACTs. So the goal of the work that scientists like Frank is doing is not just to create new drugs, but to make drugs that stay effective for as long as possible. To do that, he's trying to target parts of the parasite that are very hard to change, parts so essential that if the parasite alters them too much, it simply won't survive. So the point of it is the harder it is for the parasite to work around the drug, the longer that drug can remain useful.

SPEAKER_02 10:04

My research is focused on Plasmodium Farsiparum, which is the parasite or let's say the organism that causes the most dangerous form of malaria. And specifically, what I'm looking at is that so the parasite uses different forms of molecules to cause the disease. One of the proteins or molecules that the parasite use to cause the disease is epigenetic proteins. I don't know how to explain epigenetics, but I'm using these technical words because I don't know how to explain that.

SPEAKER_06 10:40

Epigenetic proteins are part of the system that the parasite uses to control which of its genes are turned on or off at any given time. Think of it like a set of switches. By flipping these switches, the parasite can change how it behaves. For example, it can flip a switch and hide from your immune system, or flip another switch and adapt to a different environment inside your body. Frank's work is focused on understanding exactly how three of those proteins work and how we might be able to disrupt them with a drug. He's chosen to focus on these proteins because they are not fully understood yet, and because they play such an important role in the parasite's very survival. The hope is that by targeting something so essential, it may be harder for the parasite to develop resistance quickly. And that's a key part of the bigger fight against malaria. Finding smarter ways to stay one step ahead of the parasite. Recently, they successfully sequenced the entire human genome for the first time on Nigerian soil.

unknown 12:13

Dr.

SPEAKER_06 12:13

Vera finished her PhD abroad and permanently relocated to Nigeria for her postdoctoral studies there at Redeemers University. Her study is looking at what's happening at the smallest level inside the cells of the parasite to understand why in certain regions of Nigeria one malaria drug kills the parasite and another does nothing.

SPEAKER_01 12:34

We are also interested in understanding diagnostic resistances because we are also using molecular tests in order to diagnose malaria in the hospitals.

SPEAKER_06 12:45

Dr. Vera and her team are trying to understand rapid diagnostic tests better to see if it makes sense to keep using them to find out if they are failing and why. Every day in the lab, she and her team do some complicated work using different methods to read the genetic code of the malaria parasite. And they're looking for a couple of things. They use a small portable device to see if there are markers or clues that the parasite is changing. Some things they're looking for are some specific gene deletions, because when the parasite deletes those genes, they become invisible to certain rapid diagnostic tests, which means that you could have malaria, but the test will say you don't because the parasite has deleted the genes and make the test find them. In very simple terms, generally, Dr. Vera's lab starts with wide searches. Then they zoom in, and if anything looks suspicious, they read the parasite like a book to figure out what exactly is going on.

SPEAKER_01 13:44

We humans sometimes think we're pretty smart and we can develop drugs, but the parasite, as small as it is and as simple as its cell might be, again, by just like a few changes in its genome, we call it point mutation. Just a few changes in its genome can already lead to complete resistance to certain drugs.

SPEAKER_06 14:05

So are you saying that the mutations that you're studying and learning about as a scientist are responsible for what my friends and I are now experiencing out in the real world?

SPEAKER_01 14:18

100%. How scared should we be? I think we should be like medium scared. I think one good thing about it is we know about it and we have the capacity to study it. Like we, for example, when we know that in our area, chloroquine doesn't work anymore. We fortunately still have itemcin and combination therapy that we can use. But no, I still said we should be like medium scared because I told you earlier, we're not looking at a very static or stable system. We're looking at a parasite that keeps changing within its environment, right? We have seen from other regions in the world that it's basically just a matter of time for the parasites to also become resistant to itemissement. I think we should be a little bit alerted. Um, but the good thing is that we know about it. Like we basically know exactly what we are looking at. When a drug doesn't work anymore, we need to switch to another drug. So after hearing this, how scared are you?

SPEAKER_06 15:33

You know, I think I think I became scared when I started to hear about how difficult it is starting to be to get rid of malaria when you have it, because it used to be easier. And so I remember thinking when I heard about people having to go into the hospital more and more, I mean, what are we going to do? If just like chloroquine, the ACC combination therapy stop working, what are we going to do? And from listening to you, and now I'm thinking, does it mean that the way we know to deal with malaria is just to keep making new drugs? Is it sustainable to keep making new drugs? Can countries like Nigeria, where you work, Uganda, where there's also malaria, can they afford to keep making or paying for the process of making new drugs? Because I imagine it's expensive.

SPEAKER_01 16:27

Absolutely. And this is a really valid concern. Because when we look at this, basically what it means is that over time the parasite will also become resistant to artemis in Nigeria, right? I'm still a little bit optimistic because I think there's a few strategies to make sure the drugs last longer. So we can be a little bit more strict in using the drugs. This is number one. So you're 100% right that um if we only rely on anti-malaria, we might not win the fight.

SPEAKER_06 17:08

The plan globally is to eliminate malaria by 2030. This is everybody's plan from the WHO to all kinds of coalitions on the continent. This is 2026, and that target is unlikely to be met. And there are many reasons this is so. One of the reasons is because the malaria parasite itself keeps shifting the goalposts, and that's scary for regular people who are just trying to live their lives, like Osato, who you also heard in episode one.

SPEAKER_04 17:37

I I was trying to buy a kind of insecticide the other day, and I was asking the shop attendant which would work best for me. And you know, they pointed to what I thought was really harsh. And they're like, look, this will get the job done. He didn't get the job done. He didn't get the job done. It's just the ones you think you've killed aren't really dying. And that's scary because mutating, you know, who else knows what's mutating? The plasmolium they're putting into uh bloodstreams, maybe that's also making the manually worse because I don't know, they will cause more harm and thinking about it is really scary. I would get behind anything that would just get that uh as as close to zero as possible.

SPEAKER_06 18:30

There is so much more work going on than we've highlighted, and to be honest, there is a lot of optimism within the research around malaria. And I hope this causes my friends and family to lose some of their worries. However, a few things. To prevent malaria, people are told to sleep under insecticide-treated nets. But the mosquitoes are learning to bite when you are awake. We see to them to use indoor sprays at home, but the mosquitoes are growing new body parts to evade that as well. Then scientists say we can't keep making drug after drug because mosquitoes will eventually develop enough resistance to make the drug stop working. So, what do you do then? How do you get to zero malaria in Nigeria, in Uganda, everywhere? Especially today as funding for science keeps disappearing. And what did Martin mean when he said we needed new tools? Well, he meant the possibility that the mosquitoes themselves can be hacked. Yes, hacked as in scientists could get inside their genes and modify them to stop transmitting malaria entirely. That's in our final episode. The Malaria Podcast was reported, written and presented by me, Olivia Ndubisi. The editor was Alison McAdams. Mixing and sound design by Jamal Roberts. Artwork by Ibukun Shobola. Additional production in Ntebe by Jimmy Luima. Steam music by Premium Beats. Production support in Ntebe by Blanche Musinguzi. Thank you to Chinedum Elua, Camille Aneke, and Annika McGuinness for their help with this episode. The Malaria podcast was made with funding from the John Connor Journalism of Ideas Fellowship.