In this episode, we are going to celebrate World Malaria Day with our co-host and guests. This year's theme is Time to Deliver Zero Malaria, and it is focused on investing, innovating, and implementing tools that are available today and innovating for future tools.

WHO calls to action include prioritising funding for the most marginalised and hard to reach populations who are less able to access services and are the hardest hit when it comes to becoming ill from malaria. To help us understand more, we have co-host, Dr. Hellen Barsosio, who is a medical Kenyan doctor who has been investigating risk factors, tools, and interventions to prevent adverse birth outcomes, and more recently research on preventing malaria in pregnancy. She is in her final year of her PhD at the Liverpool School of Tropical Medicine under the Department of Clinical Science, where her PhD focuses on new drugs to prevent malaria in pregnancy.

The WHO also calls for stepping up innovation for new vector control approaches, so we have two guests with us today to help us to understand what those are.

We will be speaking to reader and Wolfson Fellow, Dr. Grant Hughes, and reader, Dr. Tony Nolan from the Vector Biology and Tropical Disease Biology Department at the Liverpool School of Tropical Medicine. Tony has led the development of genetic tools to better understand the biology of mosquitoes that transmit malaria, and this has led to the development of genetic approaches to control mosquito populations. This is to decrease the amount of malaria transmission. Tony is also using some of these tools to understand how insecticides work, and in particular, how mosquitoes can evolve resistance to insecticides.

Grant is currently focusing on novel control strategies for arboviruses and malaria, and his overarching goal is to develop approaches which will either reduce mosquito numbers, or stop these mosquitoes transmitting the pathogens that make people ill.

This episode features:

Dr Hellen Barsosio - Clinical Research Scientist and section Head Maternal and New-born Health Studies, Malaria Program, KEMRI-CGHR

Over the past 11 years, Hellen has been investigating risk factors, tools and interventions to prevent adverse birth outcomes, and more recently research on preventing malaria in pregnancy as one of the causes of adverse birth outcomes in malaria endemic areas. She trained in Kenya as a medical doctor, and did her post-graduate studies at the London School of Hygiene and Tropical Medicine and University of Oxford. She is in the final year of her PhD at Liverpool School of Tropical Medicine under the department of Clinical Science where her PhD work focuses on new drugs to prevent malaria in pregnancy.

Dr Tony Nolan - Reader in Insect Genetics and Research Group Leader, Liverpool School of Tropical Medicine

Tony has led the development of genetic tools to better understand the biology of mosquitoes that transmit malaria. This has led to the development of genetic approaches to control mosquito populations, in order to decrease the amount of malaria transmission. Tony is also using some of these genetic tools to understand how insecticides work and, in particular, how mosquitoes can evolve resistance to insecticides.

Dr Grant Hughes - Reader and Royal Society Wolfson Fellow, Liverpool School of Tropical Medicine

Grant has been investigating the use of microbes to control mosquito-borne diseases for over 15 years. After undertaking a PhD at the University of Queensland in Australia looking at microbial control of crop pests, Grant moved to the US to complete a post-doctoral fellowship at Johns Hopkins Bloomberg School of Public Health to examine how a bacteria called Wolbachia infected mosquitoes and interacted with Plasmodium parasites, the parasites that cause Malaria. After further work at Penn State University, working on the same project, Grant moved to the University of Texas Medical Branch in Galveston where his research shifted focus to examine microbes, mosquitoes, and arboviruses. Since moving to the Liverpool School of Tropical Medicine research has focused on novel control strategies for arboviruses and malaria, with the overarching goal to develop approaches which will either reduce mosquito number or stop these mosquitoes transmitting the pathogens that make people sick.

Relevant links:

BBC article ‘UK scientists say they have reached a milestone in the fight against malaria by creating a genetically modified mosquito that is infertile’ https://www.bbc.co.uk/news/health-35024794

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Hello and welcome to the Connecting Citizens to Science Podcast.

A podcast about connecting people and communities to research and science so that we can join forces to catalyse sustainable global change.

In this episode, we are going to celebrate World Malaria Day with our co-host and guests.

This year's theme is 'Time to Deliver Zero Malaria', and it is focused on investing, innovating, and implementing tools that are available today and innovating for future tools.

WHO calls to action include; prioritising funding for the most marginalised and hard to reach populations who are less able to access services

To help us understand more, we have co-host, Dr.

Hellen Barsosio, who is a medical Kenyan doctor who has been investigating risk factors, tools, and interventions to prevent adverse birth

She is in her final year of her PhD at the Liverpool School of Tropical Medicine under the Department of Clinical Science, where her PhD focuses on new drugs to prevent malaria in pregnancy.

The WHO also calls for stepping up innovation for new vector control approaches, so we have two guests with us today to help us to understand what those are.

We will be speaking to reader and Wolfson Fellow, Dr.

Grant Hughes, and reader, Dr.

Tony Nolan from the Vector Biology and Tropical Disease Biology Department at the Liverpool School of Tropical Medicine.

Tony has led the development of genetic tools to better understand the biology of mosquitoes that transmit malaria, and this has led to

This is to decrease the amount of malaria transmission.

Tony is also using some of these tools to understand how insecticides work, and in particular, how mosquitoes can evolve resistance to insecticides.

Grant is currently focusing on novel control strategies for arboviruses and malaria, and his overarching goal is to develop approaches which will either reduce mosquito

So without further ado, let's meet our uh, co-host Hellen Barsosio.

Hellen, welcome to the podcast and thank you for co-hosting.

Tell us a bit about yourself and the work that you've been doing as part of the IMPROVE consortium.

Thank you, Kim.

I'm Hellen.

I work in Kenya as a medical doctor and a clinical research scientist, and I work with pregnant women and newborn babies, and I investigate new drugs to prevent malaria in pregnancy.

Some of the work that we've been doing is finding alternative s for the prevention drugs.

What we've been using are old drugs.

Some of them were invented in the sixties and the seventies, and they're increasingly losing their efficacy.

So we need new, better drugs, and these new better drugs we're looking at are those that can last very long, meaning they can protect a woman for at least a month.

And why that is important is we see women every month at clinic, so once we release them and we see them a month later, we know that they're well protected.

Some of the new drugs we are looking at is we want to see how they fit in within routine health systems.

While you can invent a new drug and a really good drug, sometimes routine health systems might struggle with it.

For instance, if the prescription is too complex and women will struggle to adhere to it.

Some of our research work is looking at how do we help women adhere to the newer complex regiments that we are moving towards.

Hellen, if you could set the scene for us in terms of malaria.

WHO is calling for innovations and to invest more in malaria.

After so many years of research in malaria, why is there still a need to continue, uh, and innovate more?

Looking at what the WHO has been recording, let's look at the 2021 data, a little under 250 million new cases of malaria were reported

And during the Covid Pandemic, we saw an uptake of about 13 million new cases, which means that we've reported new malaria cases and we are not making as much

While we have a couple of tools in our arsenal to be able to prevent malaria, including vector control, such as using insecticide treated nets, and um, IRS, we

But the malaria parasite is quite clever, it mutates quite quickly.

In the case where drugs that you use for treatment are not working as well as they used to, and we're seeing a lot of parasite resistance against these drugs.

And for the mosquito itself, we have vaccines now and one of the vaccine that has now been approved by the WHO, the malaria vaccine RTS,S used in children, is one of the tools that has been added.

It's efficacy, it's about 34%, but I think we could do better.

And we've just seen a new vaccine which has been launched, uh, R 21 in Ghana that has shown a higher efficacy than RTS,S.

So while we can innovate and look for better tools, we really need to keep ahead of the malaria parasite, which mutates quite rapidly.

So it's a very clever parasite and also ahead of the vector, the mosquito, which also mutates quite quickly and stays ahead, um, of our prevention arsenal.

So Grant and Tony, how do we keep ahead of the vector?

As Hellen alluded to, lots of the success we've had in reducing the cases of malaria year on year, has been to do with a combination of approaches.

We're always trying to innovate and have a multitude of approaches because you're targeting either the parasite directly or the mosquito

That's the only way the parasite can get from one human to another.

So there is quite a lot of cost effective benefit in attacking the mosquito.

In 2000, there was about a million deaths per year, and 15 years later that was down to 400,000, which is a significant reduction.

Of course, there's still 400,000 unnecessary deaths, but all of that, or the majority of that reduction was due to control of the mosquito vector.

That isn't always intuitive to people because you might think, you know, just go after the parasite, but as Hellen says, you know, both the parasite and, the vector by, by

So tell us a bit about how you're doing that right now within your lab.

I work on the genetics of mosquitoes, basically.

Just like you and I, the number of genes we have between us will be almost exactly the same.

It's just that we have different flavors of, uh, every gene that we have and mosquitoes are the same.

And you know, mosquitoes can vary in the flavours of certain genes that are actually important in providing protection against some of these interventions that we're trying.

For example, the insecticide treated nets that Hellen mentioned, now they have been very effective in reducing the number of malaria cases

So don't give it a chance to take up a blood meal, but if the mosquito even looks for the human host and it lands on a bed net, if it's impregnated with insecticide, it's likely to die.

That's been very effective, but now insecticide resistance is on the increase in the mosquitoes.

The challenge is trying to find out which genes and certain flavours of those genes are underlying that resistance.

If we can understand that, we can A/ detect it much earlier by using genetic observation methods, but we can also devise new interventions that won't

So that's one approach.

The other approach is trying to understand what genes are essential for mosquito reproduction, or what genes are essential for the mosquito successfully harboring the parasite and trying

Thanks very much.

Could you give us a very simplistic overview of how you interrupt that gene pathway.

Yeah, sure.

for example, if we look in wild mosquitoes and we see certain areas of the genome, which is the, all of their sort of genetic material, and certain flavours seem to

We can prove that in the laboratory by then specifically targeting those genes and disrupting the DNA sequence that makes up those genes.

Then we can see if with those specific disruptions, we get the expected outcome in terms of effects on insecticide resistance or effect on parasite transmission.

The way that we do that is by a technique called genome editing.

It's equivalent to sort of very precise molecular pair of scissors that can recognise any DNA sequence that you specify and cut the

Thank you very much for, for that explanation.

So Grant, can you add to this about the work that you are doing?

Yeah, sure.

We are interested in all the microbes that live within a mosquito.

Just like humans and how we've got a gut microbiome and other microbiomes on our skin and other areas.

So do mosquitoes and these microbiomes can benefit the mosquito.

We're interested in how we could exploit these other microbes that live naturally within the mosquito.

Um, these could be bacterial, they could be fungal, they could be viral, but we're mainly focusing on the bacterial side, mainly because we know the most about these other

These gut microbes have other desirable traits that are advantageous for vector control in that they can be transmitted, or transferred to

So the mother might pass them onto their offspring, for example.

So that's one type of strategy that we're interested in pursuing.

Um, the other one is looking at a particular specific bacteria, and this bacteria's name is Wolbachia and it's been investigated really for a long time, probably

Most of these traits were related to the reproduction of the insect, it did things like feminise insects.

So it would transfer ma males to females, and then those females would then be able to give birth.

It could mean that an insect could have progeny without having sex.

So you could have virgin birth or it would kill all the males.

All of these traits would lead to an advantage, in that the females would have a fitness advantage.

There's another trait that Wolbachia does called CI or cytoplasmic incompatibility, and that lets Wolbachia spread through an insect population.

That's really desirable for control strategies because you could then, for example, release some mosquitoes and then the Wolbachia would spread through that insect population.

So if you can have a desirable trait, you could spread that through the mosquito popul ation.

Thank you very much.

It's really useful to try to understand what happens in the lab environment.

Hellen, I know you're passionate about communities and how these innovations reach them.

Do you have anything to add or any questions?

Yeah.

It was very interesting hearing about your work, and some of the questions I have is are there concerns that you might produce, and forgive my lay question on this, are

Yeah, these are concerns that that come up.

In our case, I didn't go into the mechanism of how we might spread these into a population, but they're basically genetic modifications that can, um, multiply

Um, and the precise changes that we make are, are exactly that.

They're very precise.

We modify specific sequence and we can test that there isn't any adverse effect on its susceptibility to the parasite or other traits such as that.

That can all be tested prior to making it.

How do we communicate such an intervention to a community that we are going to alter the mosquito, and how do we communicate it in a way that

The challenge of explaining this type of technology is there and is real, but sometimes it's a consideration that's only made for this type of technology.

You know, when we use insecticides, we don't expect, villages to understand the mechanism of action of an insecticide or exactly how it's working yet

Um, and effectively changes the population because it selects for resistance.

We don't have the same concern.

So that's an interesting dichotomy, I think, but it is a question that comes up quite a bit.

To hear what they can actually do with Wolbachia, I think it's the same concerns about producing super mosquitoes and how you control them in the

Yeah, certainly these are things that we need to talk about and make sure that, um, everyone has a good understanding, and I think that's what some of

I think one thing that's important to remember about Wolbachia, is this is a bacteria that is naturally in around 50% of insects.

So if you leave your bananas on the shelf and you see some Drosophila coming around them, um, those Drosophila have Wolbachia, and that's

The mosquitoes that are most available, I guess, to control are the ones that don't have Wolbachia.

and by transferring that Drosophila Wolbachia into these uninfected mosquitoes, now they're the mosquitoes that are being used.

These bacteria are already in the environment and they're present, uh, almost everywhere, it's not that we're adding a new bacterium, uh, to the environment, it's

So with, with the work that you're doing, is there long-term intention to replace, um, existing mosquito species with those that have

Yeah, I guess, I guess I can jump onto that question.

So there's two possible strategies that you could use.

So one is to suppress a population, and you can do that in the case of Wolbachia potentially by taking the Wolbachia genes and putting them into the mosquito.

And so they're the genes that cause these reproductive manipulations.

And this is very, it's very much in its infancy, but that's one possible strategy that you could do.

And that's similar to some work that Tony does in Gene Drives.

Um, another, another way you can suppress the population is actually release males that have the bacteria.

And so these males would then go and mate with the females, and those females in the field don't have Wolbachia and that cross would not be viable so you can suppress the population.

Um, It takes a lot of work to do that.

You need to continually release the males.

You need to make big factories where you are producing a lot of mosquitoes, but when you stop doing those releases, those mosquitoes would come back.

Um, and so there's a way that basically you can stop the process and it would revert back to the natural state if you like, but then you'd have

The other way you can do it, and you mentioned this, is to replace the population, and this would be in the case of Wolbachia, where you would release males and females and, given that

And so that's been shown to work very effectively with Aedes mosquitoes that transmit arboviruses, but there's a, a few more challenges to get that working

I can hear the excitement and kind of the anticipation of what's coming next, it's really nice for us to hear that.

Tony, is there anything you'd like to add from this conversation?

Just that different systems pose different challenges.

I think it might be slightly confusing for the listeners to get the difference between Wolbachia and these other genetic control approaches like Gene Drive, but

I think sometimes it's easy to forget the context and that is that what we've been doing in the past, is all about suppression of either the parasite or the, the mosquito vector and it's the

And so, you know, suppression isn't bad in and of itself, we're always suppressing when we use, say, antibiotics for medical intervention or vector control or, or the rest of it.

I had a question for Hellen actually though, if I, may I.

Hellen, um, it's difficult to give, um, drugs or chemotherapy to all patients, so how important is it to target maternal cases of malaria or newborns?

Thank you, Tony, for your question.

So when you look at drugs for chemotherapy in pregnancy, it serves two purposes, really.

One, to prevent malaria in itself and then to treat malaria.

And the drugs that use for prevention are older drugs.

Um, so Sulphadoxine pyrimethamine, uh, these are drugs that have been here since the sixties and the seventies, and are not very effective for treatment, but are still effective for prevention.

Then we have the newer artemisinin combination drugs that we now use, uh, for prevention and why it's important to treat, especially in malaria, is the consequences that

Either the mom would experience a pregnancy loss in the form of a miscarriage or stillbirth, or it creates placental malaria infection in itself creates a hostile environment, and the baby

Small for gestational age or low birth weight, and for this particular conditions, small for gestational age or low birth weight, these

reduces their survival in the first month of life.

So it's very important to prevent malaria, especially in malaria endemic areas, and as well as to treat it as early as possible.

And when you think about chemotherapy or drugs, uh, for malaria, often, when you have that patient in front of you, the first question you want

And why that is important is when they're in first trimester, the baby's still quite small, they're being formed, which means exposure to any chemical would risk how

And some of the work that we are doing in Western Kenya is looking at the safety of these drugs.

Can we prescribe some of the very good anti-malarial combination drugs in first trimester?

The second thing, when they're in second and third trimester, you want to check, are they infected?

No.

And if they're not infected, many, they're not positive for malaria, you want to give them a good drug for prevention.

Where we are heading right now, um, the drugs that we've been using for prevention are not doing as well, so they're not as efficacious as they used to be, and therefore we need to find better drugs.

Some of the work that has been going on for the last 15, 16 years, have been in malaria research, up to six trials or so looking for alternatives to this old set of

And we are looking at products such as injectables that would be long-acting that would last for at least three months, beyond what we currently have,

So that would be excellent if we get a drug like that.

It's really interesting to listen to the work you're doing, within separate disciplines.

How does the work that you're doing, how does that overlap?

Does the prevention and treatment affect the behaviour and modification of mosquitoes in some way?

And do you talk to each other and is that important or not?

That's a really good question.

So, because preventing malaria needs more than one arsenal, we need vector control.

That means that every pregnant woman coming into antenatal clinic leaves with a bed net, at least at their first visit, and an long-acting insecticide treated net.

And we have to catch up with what, um, Tony and Grant are doing and looking at what other entomologists are doing, which means that when WHO releases better nets,

Vector control really is the cornerstone, in addition to that, we also give drugs.

So at clinic, the first time we'll screen you and treat you.

Where screening is not available, it's symptomatic treatment.

So they'd see are you presenting with fever, and that's when they test you before they treat you.

And if you're not sick, meaning that you don't have malaria, then you're given a prevention drug to go home with.

So all of these three activities happen to one patient at the first centre visit.

Then it's repeated every month.

So screen and test.

If you're not positive for malaria, then we give you a prevention drug.

And we keep on doing that until the time when you deliver.

So they would go hand in hand.

Yeah, I think that's a great example.

You know, the bed net that you can pick up at the clinic when you've gone for malaria treatment is, is a good example of joined up thinking.

I think in general there are very few examples where one type of intervention is antagonistic or goes against the other type of intervention.

So there's only really benefit to be had in terms of joining them up.

Of course, if there's only limited resources, then you need to decide which is the best intervention in any one given area, but in general, they're very complimentary, and for

The vector, the parasite, improve living conditions and classic things like removing breeding habitats for the mosquito and things like that.

They all work together.

It is a very good question though, and actually there is some interesting research, it's trying to look at, in mosquito populations, for example, where insecticide

Which is a really important question because if they remaining in relatively high numbers but are not very competent to transmit malaria,

And so these are quite active, active areas of research at the moment.

The other thing I think that's important to point out is, certainly there's no one strategy that's going to be solely effective and responsible.

Tony's pointed out how strategies can work in synergy, but we should also remember that resistance is going to emerge to any strategy.

We're, we're very familiar with insecticide resistance, but we could have resistance to gene drives, we could have resistance to Wolbachia,

But if we deploy all these strategies in unison or together, then we're also likely to, uh, reduce the chances of resistant emerging to one particular strategy.

So I think that's, that's good to think about how we can synergise these both in an effectiveness, but also in mitigating resistance.

Thank you very much.

I have so many questions here, but it's getting more clear how we get from the lab to policies to communities to see impact.

Hellen, a final comment and then we'll get some advice.

My final comment is on a holistic approach to malaria prevention, and I would think about a community health worker, a volunteer who would visit a household and

They live in this particular village where they have tall grass, pools of water that needs to be drained and also a couple of malaria programmes going on.

This is a real example of how malaria control, for instance, is done where LSTM works in Homa Bay County.

When you look at all those populations, first of all, they live in an environment where there's tall grass, and pools that need to be drained.

We have seen programmes that look at larvicidal control, but the most important thing is to clear the bushes around the house and drain

What the public health officers or the community health workers would do, they'd make sure that household has, uh, everyone has a bed net.

You know, they've been quite good at, uh, from what we've seen with the Kenya Demographic Health Survey, is rural populations in malaria endemic areas,

The population that we need to be concerned about are the reservoir.

So these are school-going children.

They'll get malaria.

They've been living there for a very long time.

They've acquired immunity over their childhood, and so they're not symptomatic.

But once the mosquito bites them and transfers to the baby, their under five year old baby and their mom, they're the ones who are at risk of malaria infections,

So we need intervention that also target them.

And for children under the age of five, trying to treat them, but also availing malaria vaccines and you need to catch up and get, uh, malaria vaccines.

So at a household level, at a community health volunteer will look at a book and check off, has a mom started clinic?

Is she on any drugs?

The child under five, have they been vaccinated?

The school going child, are they in any prevention program and how is their household around it?

So this, I think I'd call that the community or the holistic approach to malaria prevention.

Thanks very much.

I think that's really quite crucial in understanding the context and how these interventions work together.

So I think that's an excellent example.

So to finish the podcast, episode, one piece of advice in less than 30 seconds that you would give to anyone who's starting to work in the field of malaria.

Tony, let's start with you.

Well, it's a more of a general message, I think.

I think whenever people are presented with a health problem, they try to intervene to suppress that problem and malaria is a problem largely

So you need to see the urgency about intervening in the context that is not that your everyday context.

Suppressing organisms that harmful to us is something that we've always done as a health intervention measure, and in order to do that, as it's been

So that's my large message.

I guess it's reiterating what Tony said and if someone's interested in to get into the malaria field, to go and do it.

It doesn't particularly matter what area you're going to research.

I think all of them are going to be particularly valid.

We're increasing our tools that we're working with and they might range across a spectrum of technology.

Going to do things like manipulating larval habitats or using insecticides or drugs or looking at different technologies with mosquitoes, but each of them has its own place and

Thanks very much.

And Hellen, take us home with one final message.

We need to carry communities along with us as we invent, um, new interventions.

They need to know why we are doing it, why it costs as much as it does, because research is quite expensive.

And once we have good results, we need to come back and share with them.

If we carry them along with us because, they are our patients, they're our clients, the reason why we do what we do, I think we'll go a lot further

Thank you so much, and at Connecting Citizens to Science, that really is what we're passionate about as well.

So thank you to our guests and my wonderful co-host Hellen, who has been magnificent at a really kind of unpicking the science behind some of the vector control.

So thank you very much and thank you to our listeners.

Please do like rate, share and subscribe so we can continue to bring, uh, amazing stories like this, on innovation in science.