On Mosquito-Borne Diseases and Spatial Repellents—Nicole Achee, Notre Dame

Research professors Neil Lobo (left) and Nicole Achee in the lab
Photo credit: Matt Cashore/University of Notre Dame

Episode Notes

Before the pandemic, we were the show that invited scholars, makers, and professionals out to brunch for informal conversations about their work, and we look forward to being that show again one day. But for now, we’re recording remotely to maintain physical distancing.

It’s still a pretty fantastic job.

Nicole Achee is a research professor of biological sciences at Notre Dame with a joint appointment in the University’s Eck Institute for Global Health. A medical entomologist, she works in the area of infectious and vector-borne diseases. Much of her research focuses on mosquitoes, various species of which are vectors, or transmitters, of illnesses like malaria, dengue, and Zika. 

In 2014, a project led by Nicole and Neil Lobo, also a biologist at Notre Dame, received a grant from the Bill & Melinda Gates Foundation to test the efficacy of what are known as spatial repellents. While the idea underlying spatial repellents is an old one, they could represent an exciting new product class for mosquito control in public health, as they operate in a different manner than existing interventions like spraying and bed nets.

Supported by the Gates Foundation grant—at the time, the second-largest research award in Notre Dame history—and industry partner SC Johnson, Nicole and Neil’s team conducted two large-scale, multiyear clinical trials evaluating spatial repellents, including one in Peru that she says is the first to conclusively show a spatial repellent can protect humans against the types of mosquitoes that transmit dengue and Zika.

Nicole and host Ted Fox started their conversation with some basics about mosquitoes and the impact of mosquito-borne diseases worldwide. She then explained what exactly spatial repellents are and what they do, the specifics of the clinical trials, and next steps on the path toward earning a World Health Organization recommendation for the use of spatial repellents for mosquito-borne disease control—a goal that is one step closer after the recent results in Peru.

Episode Transcript

*Note: We do our best to make these transcripts as accurate as we can. That said, if you want to quote from one of our episodes, particularly the words of our guests, please listen to the audio whenever possible. Thanks.

Ted Fox  0:00  
(voiceover) From the University of Notre Dame, this is With a Side of Knowledge. I'm your host, Ted Fox. Before the pandemic, we were the show that invited scholars, makers, and professionals out to brunch for informal conversations about their work, and we look forward to being that show again one day. But for now, we're recording remotely to maintain physical distancing. If you like what you hear, you can leave us a rating on Apple Podcasts or wherever you're listening. Thanks for stopping by.

Nicole Achee is a research professor of biological sciences at Notre Dame with a joint appointment in the University's Eck Institute for Global Health. A medical entomologist, she works in the area of infectious and vector-borne diseases. Much of her research focuses on mosquitoes, various species of which are vectors, or transmitters, of illnesses like malaria, dengue, and Zika. In 2014, a project led by Nicole and Neil Lobo, also a biologist at Notre Dame, received a grant from the Bill and Melinda Gates Foundation to test the efficacy of what are known as spatial repellents. While the idea underlying spatial repellents is an old one, they could represent an exciting new product class for mosquito control and public health, as they operate in a different manner than existing interventions like spraying and bed nets. Supported by the Gates Foundation grant--at the time the second largest research award in Notre Dame history--and industry partner SC Johnson, Nicole and Neil's team conducted two large-scale, multiyear clinical trials evaluating spatial repellents, including one in Peru that she says is the first to conclusively show a spatial repellent can protect humans against the types of mosquitoes that transmit dengue and Zika.

Nicole and I started our conversation with some basics about mosquitoes and the impact of mosquito-borne diseases worldwide. She then explained what exactly spatial repellents are and what they do, the specifics of the clinical trials, and next steps on the path toward earning a World Health Organization recommendation for the use of spatial repellents for mosquito-borne disease control--a goal that is one step closer after the recent results in Peru. (end voiceover)

Nicole Achee, welcome to With a Side of Knowledge.

Nicole Achee  2:32  
Great, thanks, Ted. Nice to be here.

Ted Fox  2:34  
So I wanted to start with mosquitoes, just generally. I'm sure everyone listening to this remembers the Zika virus outbreak several years ago, and how that was being spread by mosquitoes. But I know not all mosquitoes transmit all types of diseases, certain types go with certain types. So the clinical trials that we're going to be talking about today that your team conducted in Indonesia and Peru, what kinds of mosquitoes and diseases specifically were you focused on?

Nicole Achee  3:06  
Sure. And you're absolutely right, not all mosquitoes are the same. We have different groups. And in the life sciences, those groups are known as genera, or genus. And within each genus, there's different species. And so for our clinical trials in Indonesia and in Peru, we were focusing on two primary vector-borne, mosquito-borne diseases that are quite impactful in terms of mortality and morbidity around the world. In Indonesia, our focus was malaria. And that's a parasitic disease that is transmitted by the Anopheles genus of mosquitoes.

Ted Fox  3:49  
Okay, okay.

Nicole Achee  3:50  
And in Peru, we were focused on dengue and Zika, what we call as Aedes-borne viruses or arboviruses. And those viruses are transmitted by Aedes mosquitoes, in the genus Aedes. And there are several species within Aedes. And there are several species within Anopheles, you know, genera. And so what we do is we try to determine what are the primary vectors, what are the primary mosquito species of those groups. And that's really what we're trying to control is those main, or what we know as primary, vectors, and that would be Aedes aegypti for dengue and Zika in Peru, and there's varied species of Anopheles that are all primary vectors in Indonesia. But one of those would be, for example, Anopheles sundaicus--that would be a, you know, a scientific name of one of our primary vectors for malaria.

Ted Fox  4:50  
And just to give people a sense of the magnitude of these diseases and people who are at risk, I think the World Health Organization has estimated how many people worldwide live in areas where they are particularly susceptible to these types of infections?

Nicole Achee  5:08  
Absolutely. For malaria, the WHO, the Global Malaria Programme, puts out a World Malaria Report every year. And that's a compilation of data that's been reported by countries to WHO, at the national level, for the year before. So for example, we have our WHO World Malaria Report 2020, but it's actually for 2019 data. And at the moment, the estimates are--it ranges between 400- and 600-thousand deaths per year, by malaria. Now, the number of people at risk is much greater. And the number of cases is much greater. It can be, you know, above one to two million cases of malaria. But of those, not everyone will perish. And so we have about 400- to 600-thousand deaths. And that's for malaria worldwide. The majority of those--upwards of 70 to 90 percent-- are in Africa, in the continent of Africa, and primarily in Sub-Saharan Africa in the tropical belt. 

For arboviruses, and specifically dengue, which is predominantly what WHO really focuses on--you know, yellow fever, and there's others, like you mentioned, Zika--but dengue is what we focus on really when we talk about arboviruses. WHO at the moment, you know, reports out over half of the world's population is at risk of dengue infection, and many more other kinds of arboviruses. But for dengue specifically, it's about half of the world's population or a little bit over. We have typically about, you know, at least a couple million cases per year, and for deaths by the severe form of dengue, that ranges. [CDC estimated 20,000 deaths in 2019.]

Ted Fox  6:58  
So we have these diseases that are carried by these mosquitoes as vectors of disease. To date, what kinds of tools have been available to people in countries looking to lessen the spread of mosquito-borne illnesses and diseases?

Nicole Achee  7:12  
Sure. And again, I'll try to conceptualize and compartmentalize this to dengue and also malaria, if you'd like me to.

Ted Fox  7:21  
Sure, sure. 

Nicole Achee  7:21  
So let's go to that urban environment and dengue and Aedes aegypti. We do have strategies that are recommended by the World Health Organization, WHO, that are put out, you know, for countries to consider in their national control programs. And those particular strategies and tools have been evaluated for safety and efficacy, and therefore WHO would recommend them for consideration and implementation. For dengue at the moment, we have ultra-low-volume spraying of chemical. And, you know, you may have seen this already, maybe in pictures; what that is, is you have a truck, or either a handheld sprayer or it can be truck-mounted, and it sprays chemical into the air. Either from the truck--you know, the truck goes up and down the street and it emits, you know, sprays this chemical, and the chemical disperses over some distance through that air--or individuals trained, you know, with the national programs can wear these backpack-type of apparatuses and go into homes and do ultra-low-volume or thermal fogging, you know, spray of chemicals. And those strategies are really meant for an immediate knockdown or immediate kill of Aedes aegypti that might be in the area, and typically they're used for time periods that would be during outbreak, a known outbreak of dengue, or potentially, you know, right before or right after if the programs know when they might be expecting to have an outbreak. But it costs money, of course, so they have to plan pretty strategically.

Some other types of tools and interventions for dengue and Aedes aegypti mosquito control include larval siting, meaning that we would go in and the programs go in with certain types of chemicals. And some of those are natural chemicals, some of them are synthetic. We also have bacteria that are recommended by WHO that you can put into these habitats--you know, tires, or soda bottles and empty cans, anything that might hold water. Well, the national programs go in and they do surveillance in these yards of businesses and homes, and if they see Aedes aegypti larvae--which is quite easy if you're trained to see the movement of that larvae, which is the immature stage of the mosquito, they can treat with these chemicals or natural products in that water, and it'll kill the immature stage of the mosquito so the adults don't emerge. And it's only the adults that would bite.

So larval siting, ULV spraying or fogging, we also have, you know, programs that are community-based. So all vector-borne disease-control strategies include an educational component, which is, of course, to inform, you know, on, What are these diseases, what causes them, how can individuals protect themselves in their households and their family members? One of the strategies for dengue control is community-based, meaning that after the health education campaigns go through, the expectation is that individuals may change their behavior. They would throw their trash into certain areas where, you know, they could be disposed of properly. They may turn over empty jars. For instance, in many of these environments where dengue is endemic, where it occurs all the time, people may hold certain, say, glass bottles for deposit returns, you know, for getting a little bit of money back. Well, the educational and community-based campaigns would, you know, instruct them to turn them upside down, you know, turn those bottles upside down, while you're waiting to compile enough to go turn them in. So clean up your yard, you know, keep things tidy, and so that way, you don't have the standing water in these small containers where Aedes aegypti might breed.

For malaria, we have--these are the standard recommended WHO strategies--we have insecticide-treated bed nets, where they're hung up over sleeping areas on a mattress or wherever that individual might be sleeping, and they put them over the sleeping areas, their beds and such and mattresses, when they go to sleep. And they tuck them in. And the concept there's that there's chemical that's been approved by WHO for safety and efficacy impregnated in the bed net during manufacturing. So if a mosquito were to come and try to take a blood meal at night when that individual is sleeping, it would make contact with the bed net, pick up or absorb some level of insecticide, that chemical, and it would die immediately or some short time later. And again, the type of chemicals that are on those bed nets, most of them are synthetic chemicals of certain chemical classes. But there's also some new, you know, investigation into other types of components that can be put on that bed net.

The other predominant WHO-recommended strategy for malaria control is indoor residual spraying, or IRS. That consists of trained personnel going into homes with a sprayer that's filled with a formulation of chemical--again, that chemical has been approved and evaluated by WHO for safety and efficacy. And they'll go into these houses and they'll spray in a certain technique that's quite standardized, and they have to be trained pretty, you know, rigorously, proficiently, and that spraying puts the chemical on all of the interior wall surfaces. And what happens is the homeowner consents to allow this to happen, and they would normally, and they should, be removing all of their material from inside the house beforehand to allow access to all of the walls and not potentially contaminate items that you do not want chemical to be residing on. And because again, this is residual spraying, which means that those chemicals usually last in efficacy anywhere from, you know, three months to six months, so the strategy is, you know, such that those homeowners would remove their items, and then the campaign officers would spray, and then the items come back in.

So IRS and bednets are the predominant WHO current recommended strategies for malaria control. Those are all for vector control. I mean, I think I'd be remiss not to also make sure that people understand, of course we also have drug therapies for malaria control, right? That, you know, when persons are ill with that parasite, and they're determined to be infected with malaria, they're provided drugs for treatment. And there are some vaccines that are being evaluated, but they're not yet at the full recommendation stage for malaria.

Ted Fox  14:45  
Okay. So we talked--and that's really helpful because we're talking about trying to mitigate and control the mosquitoes before they actually bite someone then and have that blood meal. So we talked about the kinds of mosquitoes, we talked about things that have been available so far towards controlling or trying to mitigate those populations. The research that you've been working on takes a different approach to tackling this problem of mosquito-borne illness and disease mitigation. It's called a spatial repellent. What is a spatial repellent exactly, and how does it work?

Nicole Achee  15:23  
So a spatial repellent represents a class of products. So we can think of a concept where we have a home environment, a house. And the spatial repellent is a device, some product that's put inside of these structures, these houses or homes. And it has chemical that is embedded in this product, these devices, which is released when that product is activated. And all that means by "activated" is either--for our particular case, it's just you open it up, and that automatically activates that product to be exposed to the air inside these houses. And the chemical will then emit or be released into that airspace from the actual product device itself. So what happens is these chemical particles disperse inside the structures or homes, and in dispersing over some time and distance, each of the products have different duration, different lifespans, and how far by distance these chemicals disperse is dependent on the structure of the house, the wind flow within that structure, temperature, humidity--those are all related to how the chemical will behave. But when these chemicals are dispersing over and through that indoor space, and it passes through the walls--because again, we're really thinking of the low- and middle-income country environments, and those structures, the house construction, offers a lot of ways in which the mosquitoes can come in and out. And that means like, you know, cracks between the wooden walls, there's eave gaps, and so this chemical will move in the indoor space and actually through the walls and out of the eave gaps, and that creates conceptually like a bubble around that house.

Ted Fox  17:27  
Mm hmm.

Nicole Achee  17:27  
So we have this spatial type of protection, and the repellent, these chemicals are linked to behavior changes of mosquitoes other than just killing.

Ted Fox  17:39  

Nicole Achee  17:40  
So when I talked about ULV and IRS and bednets, the chemicals that are used in those strategies are developed specifically as insecticides. So you know, we want to achieve 95% mortality within two hours--that's how they're evaluated in the lab. For repellents in spatial repellents, those chemistries are a little bit different because they operate-- they're volatile, they are meant to be able to vaporize quite readily at ambient temperature. Whereas say the chemicals for bed nets and IRS and ULV spraying, they are not designed and their chemical properties are not such--they're not as volatile as what we use in repellents and spatial repellents specifically. So this bubble of protection around the house due to this chemical release of our spatial repellent, when the mosquito makes contact with those chemicals, it can cause a behavior change in causing them to be repelled, to be deterred. So they may not be killed, but they won't enter that space where that bubble is located.

Ted Fox  18:55  

Nicole Achee  18:56  
It's interesting because some of these chemistries, too, may not repel the mosquito upon their exposure to that chemical. But it can interrupt their host attraction, a cue behavior. So they may not--they may be confused. They can't, even if they're not repelled, they can't orient to those humans that may be in ... 

Ted Fox  19:20  
(laughs) What am I doing here?

Nicole Achee  19:21  

Ted Fox  19:21  
Why did I come this way to begin with?

Nicole Achee  19:23  
They're kind of confused. Yeah, they can be confused. And so you may not see a reduction in the number of mosquitoes, but they still won't make that contact with the human inside that bubble, that treated space. The third type of behavior is that even if they can orient to that human and land on them, there's an interruption in their feeding. So they may not feed the way that they normally would, they may not take the blood they normally would, and any one or combination of those--repelling or deterring, confusing or attraction inhibition, and/or interruption of blood feeding--any one of those behaviors will interrupt the ability for that parasite for malaria that may be in a mosquito, if that mosquito's infected, to be passed to that human. And likewise, if a human is infected already, then if that mosquito doesn't make contact with that human, it cannot take up the parasite and therefore potentially transmit it to another. So we interrupt this human-mosquito vector contact through these spatial repellent devices.

And for dengue and Aedes aegypti, it's the same principle. Yeah, we apply the product inside the home. It creates this dispersal of chemical and this protective bubble, if you will. And again, the mosquitoes would either be deterred, confused, or inhibited or unable to feed. And any, like I said, any one of those would still prevent virus, in this case for dengue, to be transmitted to the human or picked up from the human into the mosquito.

Ted Fox  21:05  
And I know with dengue and the Aedes aegypti mosquitoes, they were the focus of your clinical trial in Peru. And so you are a co-principal investigator on that with your colleague and frequent collaborator, Neil Lobo, who's a research professor of medical entomology at Notre Dame. And the study involved--it's a big study--18,000 residents in 2400 households, whom you followed over the course of two years. What did you find in that trial? What were--it was actually what prompted me to reach out to you was some of the results from that were just published very recently.

Nicole Achee  21:41  
Yeah, absolutely. And I will take this opportunity to of course, you know, give acknowledgement to our implementing team, Dr. Amy Morrison and Dr. Tom Scott and all of their team members in Iquitos, Peru. They're both based at UC Davis--University of California, Davis. But certainly, as implementers, you know, they deserve an acknowledgement there. And of course, we also have, you know, Dr. Robert Reiner, Jr., at the University of Washington, who conducted the analysis, statistical analysis. And there's many others that of course I can't mention by name, but certainly--yeah, to your point, it was a very large study. And these clinical trials are just that. I mean, they are built by design to be very large in scale and scope because it's meant to prove or disprove [whether] an intervention is going to be effective. And you need to have very robust and rigorous data to make a conclusive result, a conclusive decision, on efficacy.

So what we found from our clinical trial in Indonesia--I'm sorry, in Iquitos, Peru, was that the spatial repellent products, this intervention, which is experimental, which is what we wanted to see if the concept would prove to reduce dengue infection and/or disease. And what we found is that by following these individuals and taking blood every so often and looking for dengue and Zika virus is that we actually were able to show 34 percent reduction in risk of dengue and/or Zika virus infection in those individuals where their home received the active spatial repellent. So in these trials, you know, we are blinded, meaning that the investigative team, the homeowner, we're blinded as to whether or not we're putting active intervention or placebo intervention in these houses. Placebo is it looks the same as our active spatial repellent; it's just that it doesn't have the active chemical ingredient. And that's very important because again, that adds rigor to the trial. You try to mitigate the bias that you introduce unintentionally just, you know, by understanding if it's an active or placebo. So we found that the persons that were living in houses receiving active ingredient when we were unblinded at the end of the study, and all the data had been collected and locked, was just that. So it did prove conclusively--meaning that through statistical analysis, we showed a significant difference between active and placebo intervention in reducing risk of infection with dengue or Zika--and again, that reduction equated to 34 percent less dengue infection.

Ted Fox  24:42  
That's amazing.

Nicole Achee  24:43  
Yeah, no, we were very, very excited about that for a number of reasons. You know, number one, we have the potential of one of many new strategies that could be introduced, you know, if and when we have more evidence to support a WHO recommendation.

Ted Fox  25:01  
And that was one thing I was gonna ask. So you do something like that, you have a trial, and if I read correctly, you had similar results in Indonesia as well, right? In terms of the efficacy of the spatial repellents, was that right?

Nicole Achee  25:13  
We had about a 27 percent reduction in risk. The one point about the Indonesia trial that's important is that it was not a conclusive result.

Ted Fox  25:23  

Nicole Achee  25:23  
What that means is that we saw a reduction. But when we look at all of our clusters and active and placebo, and we do those comparisons on reduced risk for malaria, we did see that 27 percent reduction, but statistically, it was not significant.

Ted Fox  25:43  

Nicole Achee  25:43  
Yeah. And what that means in clinical trials is that we cannot conclusively state with confidence that that difference was not related to something else. Yeah. That's why we'll have to do more trials for malaria.

Ted Fox  26:02  
So you've done these two trials. What is kind of now the state of play for spatial repellents? Where does that--and I'm sure it's related to work that you're doing as you're going forward and the ideas of, How cost feasible are these compared to other interventions, and things like that. I mean, it was exciting just to read the story about this because of the one thing you talked about with the Iquitos trial afterwards, in Peru, you said, you know, "This is the first clinical trial to conclusively show a spatial repellent can protect against Aedes-borne virus infection in humans," which is a huge deal. So where does it, what are the next steps? Where does it go from here?

Nicole Achee  26:40  
Absolutely. No, that's why, you know, I'm shaking my head even though I know this is gonna be only audio. (both laugh) But we definitely were very excited because of that point. You know, there's many groups that are trying to, we're all working together across the global community in vector-borne disease prevention and control. And certainly, when we have these types of results, you know, it can be quite exciting. But we do understand that it's not sufficient for our our penultimate goal, which is a global health policy recommendation by WHO for the inclusion of spatial repellents in disease-control programs. So what the WHO requires at the moment, because that can change over the years, it can change, operational guidance can be adapted according to lessons learned. At the moment, the bodies that we work with in vector-borne disease control mitigation and prevention at WHO, they require these large-scale clinical epidemiological trials to generate the evidence conclusively on efficacy or not, along with safety, and as you mentioned, with many other things.

Ted Fox  27:56  

Nicole Achee  27:57  
So they require at least two epidemiological trials of the similar scale, in different ecological settings, around the same disease, with the same intervention, to begin to do a formal assessment on whether or not to endorse a policy recommendation. So the process is quite extensive. And it can take anywhere from 10 to 15 years to go from a concept to the epidemiological evidence that we've just been talking about--you know, reduction in human disease or reduction in human infection. That's the epidemiological evidence that is required. It can take 10 to 20 years to build that evidence base for an assessment. And even then, recommendation may not be warranted, depending on how that data unfolds. So we have been able in Peru to demonstrate that spatial repellents are providing, you know, reduction in Aedes-borne virus infection. That's that conclusive result. But we do need at least one more from a different setting to allow WHO and their panels to make a good assessment. For Indonesia, because the trial was showing positive, you know, outcomes, but not statistically significant, such that we can't make conclusive decisions, we'll need at least two more trials on top of that. But this is something I do want to make sure it's also clear maybe to the listeners is that the concept of spatial repellents for mosquito-borne disease control is actually 75 years in the making.

Ted Fox  29:44  
(both laugh) Okay.

Nicole Achee  29:44  
So 75 years ago, close to 100 years ago, there were scientists that had made natural observations, way back when, you know, natural observations were actually pretty much where a lot of information in the life sciences came from. You know, there were some experimental design--you know, data that was generated from experimental dersign--but there was also a lot of natural observations that were feeding into an understanding of the world around us. So there was that concept, almost, like I said, 100 years ago about spatial repellents potentially serving for malaria control specifically. And then there's been through the course of all these years, many different groups looking at laboratory-based studies, semi-field experimental hut, you know, small-scale village trials. And now, of course, we're getting to these clinical trials. So I just, you know, it's definitely not just this small handful of investigators; it's empirical in nature through many, many groups.

But the next steps really will be to conduct the second trial for our dengue prevention evaluation. And as you mentioned, we used one product for the Peru and Indonesia studies. We're allowing now the ability to look at a different spatial repellent product--same chemical, but the duration is longer. So those two trials, the product was two weeks in duration, meaning we had to replace it every two weeks. That's not going to be conducive, in a practical sense, for national programs where there are resource limitations. And our industry partner, you know, definitely understands this. They know that--so they're already designing products, spatial repellent products, that would fit a global health policy recommendation, meaning it has to be deployable and delivered in a way that can be affordable and somewhat easy without, you know, too much rigorous training of individuals. So what we'll be doing next is taking a next-generation spatial repellent product that we used in Peru and Indonesia; it has a longer duration of life. And we're going to be evaluating that, but it's the same chemical. And we've already, of course, spoken with WHO, those bodies. So we've been approved to use this next-generation, and it could still build the database with the other trials. And we will be conducting that through a new program that we've been, you know, funded to perform. It's not myself, that's actually, the lead principal investigator for the new program to continue on with the spatial repellent trials is Dr. John Grieco. He's actually in the Department of Biological Sciences, as well. And he's been, you know, investigating spatial repellents for decades. That's his research track, as well. So he'll be leading that. So we'll have an Aedes-borne virus trial to examine this next-generation spatial repellent in Sri Lanka. And for malaria, our Indonesia study, we require two more trials of similar scale and scope from WHO. And we'll be conducting that also, underneath this larger program led by John; one trial will be in Kenya, and one trial will be in Mali, both in Africa, using the same next-generation spatial repellent product.

We also have faculty members at Notre Dame, Alex Perkins, who's also in the Department of Biological Sciences, who is collaborating with John on this next program. And Alex and his team are going to be evaluating number of cases averted to help us understand, you know, cost effectiveness, and how do we introduce a spatial repellent-- if or when there was a policy recommendation--what would be the requirements to help guide policymakers, those decision-makers at the national level, for whether or not they should consider introducing special repellents into their program, if they were recommended. And those types of policy decisions depend completely usually on cost, not only of the product, but again, cost-benefit to the healthcare system if you prevent infections or deaths. So it gets complicated there, as well. So an economic analysis is required, you know, modeling projections of if you implement a spatial repellent this year, what will that mean for those national bodies in five years from now? You know, will it actually see a benefit to the healthcare system, to the health of their workforce? You know, things that are usually important for the decision-makers in these countries to determine if, say, spatial repellents, should be procured, invested in, and rolled out as compared to, say, some other intervention.

Ted Fox  34:59  
So just as we're wrapping up here, one thing that I think is important for people listening to know is that--and you've alluded to this--that these studies really are a great example of collaboration between universities and industry and philanthropic groups. And just wondering if you could talk a little bit about the partnership with SC Johnson and the Bill and Melinda Gates Foundation, and just how that's been valuable in working on these projects.

Nicole Achee  35:29  
Absolutely. So, of course, you know, we would not have been able to conduct these trials and any of the ones going forward without those types of partnerships, number one, because of the funding. So when we think of funding lines, the Bill and Melinda Gates Foundation is a predominant sponsor for of course most of the research, at least myself and many others included in terms of public health and trying to improve the quality of life of others. And so without that funding opportunity, we could not have conducted this trial. So definitely, they have been an active partner, not only just for funding, though, but they're integrally involved with discussions around, you know, how would we scale this up, and you know, if these policies and recommendations from WHO are afforded, to be thinking for five years ahead, such that when we're conducting the research, you're not just as a medical entomologist, which is myself, I'm not just thinking of medical entomology, I'm actually being forced--but in a very smart and good way--to think about implementation. Even if I'm not the investigator responsible for producing that evidence, I am responsible for the data that I generate in my programs to be helping to guide that type of decision in the future. So the foundation has been wonderful in training me and teaching me how to think like that. 

In terms of the partnerships with industry, SC Johnson is our industry partner for these trials, and without their support financially--and of course, through the design and all of their expertise around the product in terms of manufacturing, quality assurance, disposal, shipment to these locations--without any of that, we would have been severely hindered, if not completely stopped, from being able to be as successful, you know, as we have been in the trials. So, you know, having these types of industry partnerships are also just as critical as the funding from the grant sponsors because they are actually investing financially in producing the products that we evaluate. I think SC Johnson produced nearly eight million of these experimental products.

Ted Fox  37:53  
Oh, wow.

Nicole Achee  37:53  
And that costs money. And you know, of course, going through the quality assurance to give rigor behind the data that we generate, that we know the active was active and the placebo was placebo, and it lasted as long as it should have when we put it in the home. So absolutely, I think it's very important for researchers and investigators to think about how it is broader than just the academic team; it is the funder as well as the industry partner. We've been really lucky, though. We've had some great active partnerships.

Ted Fox  38:25  
Nicole Achee, thank you. I mean, this is--not only is it super interesting just from a science standpoint, it's really important and great work that you and your colleagues are doing. So I appreciate you taking the time to talk to us about it.

Nicole Achee  38:38  
Thanks so much, Ted. I appreciate it.

Ted Fox  38:39  
(voiceover) With a Side of Knowledge is a production of the Office of the Provost at the University of Notre Dame. Our website is withasideofpod.nd.edu.