Curing mosquitoes of malaria

For decades, insecticide-treated mosquito nets have served as a frontline defence against malaria. But their effectiveness is waning as mosquitoes develop resistance to those insecticides. What if, instead of targeting the mosquito - the disease’s carrier - we targeted the parasite itself? In a groundbreaking new study, researchers have identified compounds that do just that: killing the malaria parasite inside the mosquito within minutes of contact. It’s a bold and innovative approach that could transform how we halt malaria transmission. Alexandra Probst at Harvard University is the brains behind the project…

Alli - We have a couple of different tools that we use to really try and combat malaria, one of which is killing mosquitoes with insecticides, the mosquitoes that transmit malaria to people. Unfortunately, although those tools have been really effective in the past, their really extensive use has led mosquitoes to adapt and develop ways to survive that insecticide exposure. Insecticides are no longer killing mosquitoes, and we need a new way to target the transmission of malaria other than just killing mosquitoes themselves. Our idea was really to target the parasites within those mosquitoes and stop transmission that way.

Chris - So you dose the mosquito and kill the parasite?

Alli - That's right. In humans, of course, we can treat people with anti-malarial drugs, and we wondered if we could basically do the same to mosquitoes and treat them with anti-malarial drugs to cure them of their parasite infection.

Chris - How do you dose a mosquito, though?

Alli - Yeah, no, it's a good question. We obviously can't give them a little pill, but we really do this by treating the surfaces that they land on so that they can take the drugs up through their legs. We've mostly focused on treating bed nets, for example, and that provides both a physical barrier so the mosquitoes can't get to you. But when mosquitoes land on that bed net, they can also come into contact with drugs. So this can be an insecticide that kills the mosquito, or in the context of insecticide resistance where mosquitoes are no longer dying, it can be an anti-malarial drug that treats that mosquito and kills the parasites within it.

Chris - Is that really an efficient way to get drugs in then? Can it go in through the legs to any appreciable amount or degree?

Alli - It's actually a really good question because we did this screen of over 80 anti-malarial drugs to basically try and find compounds that could both kill the parasite and effectively get into the mosquito through its legs. So we were looking at those two key parameters, and we did find some really promising compounds that we were able to show got in really effectively through the sort of waxy cuticle of the mosquito legs.

Chris - How much contact does the mosquito have to have with the bed net then? Is it sort of just a brush pass that's enough or does it got to sit there and dwell for some time for enough of the agent to get in to actually sterilise the mosquito and get rid of the parasites?

Alli - That's a good question. We have primarily in the lab tested this by allowing mosquitoes to land on these treated surfaces for a couple minutes and that sort of approximates the amount of time that they would actually land on a bed net because normally when a mosquito is searching for a blood meal, it will be attracted to the person sleeping under that bed net and then it reaches this barrier and it can't get to that person. So it actually hangs around on the bed net for a long time, sort of moving from place to place, trying to get at that person sleeping underneath. So we think that this couple minutes exposure seems to be just enough time to really get a lot of compound into those mosquitoes.

Chris - And does it sterilise the mosquito as in does it wipe out the parasites on board? Can you prove that?

Alli - Yeah, yeah. So parasite development in a mosquito takes about two weeks. So there's actually a bunch of different stages of the parasite during that timeframe. And what we've shown is that it, yes, it completely sort of sterilises the mosquito in terms of its parasite infection. If you have this exposure and then an infectious blood meal or if you have an infectious blood meal and then shortly thereafter an anti-malarial drug exposure. So it really completely kills those initial stages of infection in the mosquito.

Chris - Why stop at bed nets then? Could not I spray this on because I know mosquitoes will go for my ankles, my elbows. Those are the characteristic sites, aren't they? Can't we spray this on people as well?

Alli - Yeah, that's a good point. We haven't really looked at applications directly for a person, but I think there's no reason to think that that wouldn't work. We've shown now that these compounds can be taken up from a couple of different kinds of treated surfaces. So I expect that would work on a spray for people as well. Another possible application is spraying walls or ceilings inside people's homes. And this is also done currently with insecticides. And the reason for that is that it's a lot more long lasting. So you or I might take a shower at the end of the day and then wash off that anti-malarial drug, whereas it can stay coated on a bed net for many years or on a wall or a ceiling for many months up to a year. So it's much longer lasting that way.

Chris - What's the environmental safety like though? Because we're very worried about things we're put into the environment. DDT taught us a very painful lesson in this respect. I know that's an insecticide, but is this specific just to the mosquitoes? Will it have off target effects? How safe is it effectively?

Alli - That's a great question. Yeah. So that's something that we're actively working on right now. This initial work was basically just to show that it has really good anti-parasitic activity in the mosquito. And now that we've got these really promising hits, we're actually starting to do a lot of this initial safety testing. So far, everything's looking really good. And I think that one of the major benefits of this approach over say other insecticides is that it's actually extremely parasite specific. So we've got a really good therapeutic index for it, which basically means how much drug is needed to kill the parasite versus how much drug could impact people. So we have a really wide range between those two doses, which means the amount that we need to actually kill parasites is most likely not going to have any impact on people. This requires years of safety testing. So we're still doing this, but all signs look really good right now. And because it's parasite specific, we're not going to be having off target effects on other insects. So for example, other insecticides might impact important pollinators, but this approach would not do that.

Chris - There are four or five different types of malaria that hit humans. Will this work on all of them? Or is it specific to just one type?

Alli - Yeah. So far, we think that this should work on all of them. So in this study, we were looking at Plasmodium falciparum, which is one species of human malaria. And this is the parasite that causes over 90% of human cases and deaths worldwide. So we've shown really rigorously that it works against the most important agent of malaria. But we've also begun testing this with partners in some other Plasmodium species. And this was not in the paper that's coming out, but it's also looking really effective there. So the target of the parasite target of these drugs is shared between these different species. So we think that this should be effective against all human malaria.