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[Gene drives] are a really powerful tool, but I think in its power lies some of its risk.

And you have then the question, how do you turn it off? Either when you don’t need it any longer, or — as we know with catastrophic risks, in the future something goes wrong and we don’t expect it to — if it does cross over into other insects unintentionally: how do you turn it off?

James Tibenderana

The good news is deaths from malaria have been cut by a third since 2005. The bad news is it still causes 250 million cases and 600,000 deaths a year, mostly among young children in sub-Saharan Africa.

We already have dirt-cheap ways to prevent and treat malaria, and the fraction of the Earth’s surface where the disease exists at all has been halved since 1900. So why is it such a persistent problem in some places, even rebounding 15% since 2019?

That’s one of many questions I put to today’s guest, James Tibenderana — doctor, medical researcher, and technical director at a major global health nonprofit known as Malaria Consortium. James studies the cutting edge of malaria control and treatment in order to optimise how Malaria Consortium spends £100 million a year across countries like Uganda, Nigeria, and Chad.

In sub-Saharan Africa, where 90% of malaria deaths occur, the infection is spread by a few dozen species of mosquito that are ideally suited to the local climatic conditions and have thus been impossible to eliminate so far.

And as James explains, while COVID-19 may have an ‘R’ (reproduction number) of 5, in some situations malaria has a reproduction number in the 1,000s. A single person with malaria can pass the parasite to hundreds of mosquitoes, which themselves each go on to bite dozens of people each, allowing cases to quickly explode.

The nets and antimalarial drugs Malaria Consortium distributes have been highly effective where distributed, but there are tens of millions of young children who are yet to be covered simply due to a lack of funding.

Despite the success of these approaches, given how challenging it will be to create a malaria-free world, there’s enthusiasm to find new approaches to throw at the problem. Two new interventions have recently generated buzz: vaccines and genetic approaches to control the mosquito species that carry malaria.

The RTS,S vaccine is the first-ever vaccine that attacks a protozoa as opposed to a virus or bacteria. Under development for decades, it’s a great scientific achievement. But James points out that even after three doses, it’s still only about 30% effective. Unless future vaccines are substantially more effective, they will remain just a complement to nets and antimalarial drugs, which are cheaper and each cut mortality by more than half.

On the other hand, the latest mosquito-control technologies are almost too effective. It is possible to insert genes into specific mosquito populations that reduce their ability to reproduce. Of course these genes would normally be eliminated by natural selection, but by using a ‘gene drive,’ you can ensure mosquitoes hand these detrimental genes down to 100% of their offspring. If deployed, these genes would spread and ultimately eliminate the mosquitoes that carry malaria at low cost, thereby largely ridding the world of the disease.

Because a single country embracing this method would have global effects, James cautions that it’s important to get buy-in from all the countries involved, and to have a way of reversing the intervention if we realise we’ve made a mistake. Groups like Target Malaria are working on exactly these two issues.

James also emphasises that with thousands of similar mosquito species out there, most of which don’t carry malaria, for better or worse gene drives may not make any difference to the number of mosquitoes out there.

In this comprehensive conversation, Rob and James discuss all of the above, as well as most of what you could reasonably want to know about the state of the art in malaria control today, including:

  • How malaria spreads and the symptoms it causes
  • The use of insecticides and poison baits
  • How big a problem insecticide resistance is
  • How malaria was eliminated in North America and Europe
  • Whether funding is a key bottleneck right now
  • The key strategic choices faced by Malaria Consortium in its efforts to create a malaria-free world
  • And much more

Get this episode by subscribing to our podcast on the world’s most pressing problems and how to solve them: type ‘80,000 Hours’ into your podcasting app. Or read the transcript below.

Producer: Keiran Harris
Audio mastering: Ryan Kessler
Transcriptions: Katy Moore

Highlights

Gene drives

James Tibenderana: Gene drives are a novel intervention that certainly has a lot of potential. There’s still a long way to go. There’s quite a bit of research, especially epidemiological research, that needs to be done to understand the potential impact. But I think the technology itself is very powerful. And I think therein lies some of the risk.

James Tibenderana: It’s really powerful. And of the gene drive systems, there’s sort of low-threshold gene drives and high-threshold gene drives. With high-threshold gene drives, you need a large number of mosquitoes released into the wild to have the impact. And with low-threshold gene drives, you need a few mosquitoes to be released into the wild and really propagate itself. And then within those, you have some gene drives that once introduced will suppress the population of mosquitoes or insects. And then you have some gene drives that will modify elements within the mosquito or the insect, to cause it to not be as efficient or not able to perpetuate a particular attribute.

James Tibenderana: I think in terms of the gene drives for mosquitoes, Anopheles specifically, really it’s a low-threshold type of gene drive, and one that will cause suppression because of the doublesex gene that creates a generation of infertile offspring, and that continues to perpetuate itself until you actually sort of wipe out that particular species. I think the studies that have been done in cages so far suggest that that is possible, so it is certainly a very powerful tool. I guess the question that we will all have — and we see this in nets and we see it in some of the other tools — is what will be the acceptance of national governments or communities to a technology that can be complex to understand?

James Tibenderana: The minute you get into genetically modified technologies, it raises eyebrows. And you have adopters, but you’ll also have the skeptics. I think that’s one thing Target Malaria is conscious of, and they’ve spent a huge amount of time working with communities, and working with members of parliament in some of these countries to understand what the legislative framework is, and what kind of information the decision-makers require for a policy to be adopted in terms of gene drive mosquitoes, or gene drive insects in general.

James Tibenderana: And then communities, how will they perceive these genetically modified mosquitoes? I think they’ve really done some very good community engagement work, some studies, and they’re starting to show that there are ways that one can communicate, with both communities but also decision-makers, that can potentially make this adoptable. That’s one element. Now, with this type of technology, you can’t simply say, “I’m releasing it in one country and it’s not going to spread to the next country.”

Rob Wiblin: It’s probably going to spread everywhere eventually.

James Tibenderana: Exactly. So not only do you need a country adoption, you probably need regional adoption. So if you release it in West Africa, then what is ECOWAS going to think about it? If you release it in Southern Africa, what is SADC going to think about it? So you have all these regional bodies, the African Union, et cetera — what is going to be their perception of gene drive, genetically modified mosquitoes that are released? Because you really need the governance framework and the legislative framework that is regional, rather than just country specific. And that requires you to also be able to engage with all these communities.

James Tibenderana: I’m not saying that this tool isn’t powerful. This is a really powerful tool, but I think in its power lies some of its risk. And you have then the question, how do you turn it off? Either when you don’t need it any longer, or — as we know with catastrophic risks, in the future something goes wrong and we don’t expect it to — if it does cross over into other insects unintentionally: how do you turn it off?

How many people actually use bed nets for fishing?

Rob Wiblin: So quite a few people in the audience were curious about the gap between provision of chemoprevention drugs and provision of nets, and actual use. There’s this kind of mainstream concern that you provide nets, or you provide drugs for free, and then people just don’t use them. I guess there’s this really popular meme that somehow got started that you provide people with nets to protect them from mosquitoes and they use them for fishing — which I think has happened in at least some places, but I suspect is probably substantially overstated because it’s a fun story to tell. Do you want to comment on that?

James Tibenderana: There is an access and use gap for nets and for some of the other interventions. It’s something we pay particular attention to because we would like to close that gap between access and use, because then at least you’re maximizing the impact that you get. It’s important to appreciate that wherever nets are distributed, the majority of the nets are being used. I think WHO tracks that information, we track that information — so all the campaigns will have a component of results measurements that allow us to be able to have a sense in terms of those who have been given the net and those who use the net. And those results measurement systems have improved over time.

James Tibenderana: In the issue of misuse of nets, we’ve got to keep in mind that malaria is a consequence of poverty, and malaria can contribute to inequities. Let’s appreciate that some of these households are really poor, and even the notion that they are actually using these nets for fishing or over their gardens is a sign of the poverty that some of these households are experiencing. I think it is overstated, because even in those households, what we know from all the evidence is that the access to nets is an important driver of use — and so by ensuring this access, you’re actually facilitating the use of them.

James Tibenderana: So yes, from my perspective, I do hear people talking about fishing, et cetera. But when you go into those communities, the majority of people are using those nets, and I think data suggests that the majority of those nets are being used. So sometimes the question is, is it an old net that has been replaced? Is it a new net? I think the fraction of nets that are being misused in that way is probably negligible compared to the nets that are having a positive impact in those communities.

James Tibenderana: And so a question will be, what else is being done in those households that is addressing some of the livelihood issues that they’re experiencing? We know malaria is a consequence, but also the level of poverty itself can contribute to malaria.

Rob Wiblin: I think from memory, the Against Malaria Foundation has some auditing process, where they go and check whether the nets are actually being used. And again, from memory, I think the rates of use were over 90%. So yes, some people don’t end up using them for one reason or another, possibly they use it for something else. But in terms of measuring the cost effectiveness of what they do, they only do that relative to the nets that are being used — they only estimate the impact they’re going to have based on nets that are actually hung up when they go and check, not based on the number of nets that are distributed.

Rob Wiblin: One thing that amuses me about the meme about fishing is, what fraction of all households that are receiving nets are even near a place where they would go fishing or are interested in fishing as a source of food? I think there was one particular case where there was a village that was specifically a fishing village. They all do fishing, that’s how they make their livelihood and they were using the nets for this purpose. But I imagine for the great majority of people receiving nets, fishing is not a key source of income. It’s not the way that they’re getting food in the first place. So it’s hard to believe that this is the first thing that they think of to do, especially if it would involve traveling to somewhere where they can plausibly fish with any meaningful success.

Rob Wiblin: It’s a meme that frustrates me, because I suspect that people are into it in part because it’s a clever story. It’s like, “Oh, you thought that the nets would help them but actually it didn’t.” So it allows you to one-up other people with your level of sophistication and knowledge, even if it’s inaccurate. And also I think it gives people an excuse for not donating, if they can always say, “Well, it’s always the possibility that they’ll use it for something else and then it won’t actually help” — even though 90% of the time it does. I’m not sure whether you share my cynicism.

James Tibenderana: No, I do share it. I do. I do share that cynicism, because really it takes away the message from the positive impact that nets have, and also the majority of people who actually use those nets the way they’re intended. That for me, in itself, is also a signal that is a reminder of the inequities that thrive when malaria is present, and that we should be doing more to ensure that access.

The transmissibility of malaria

James Tibenderana: What I’d like to stress — and I think sometimes people don’t appreciate this — is the transmissibility of malaria. We’ve all seen the COVID pandemic, and there’s something called the “basic reproductive number”: that describes the number of people who are not immune to a disease who will be infected by that disease if one person who is infected is introduced into that population. With COVID, the number can be, let’s say up to five — in some situations, maybe six or eight. With Ebola, it’s up to about 2.5. With measles, it’s up to about 18 individuals who get infected from one infected person. For malaria, it’s more than 3,000.

Rob Wiblin: Sorry, how is that possible?

James Tibenderana: Because of the mosquito.

Rob Wiblin: Because the mosquito will bite so many people? Or because one person is ill and they’re infectious for quite a period of time, and then so many mosquitoes will bite them, and then they’ll go off and bite so many people?

James Tibenderana: Exactly. The mosquito has a multiplier effect. An infected person will be infected for a period of time until they either get treated or, because of the immune system, they’re able to clear the parasites. But more often than not, it’s until they get treated. In that time, they potentially will be transmitting if a female Anopheles mosquito takes a blood meal and picks those gametocytes. So one infected person in a population that is non-immune will have mosquitoes transmitting, and that can multiply. As I said, in some situations where transmission intensity is really high — like a part of Uganda where transmission intensity is really, really high — you can have a large number of people infected, and that can really get up to 3,000.

James Tibenderana: I think where that changes is that quite a number of people are semi-immune or partially immune, but children aren’t, especially children under five. And pregnant women, especially in their first pregnancy, literally are not as immune as they were when they were not pregnant. So that population is really susceptible to malaria.

Rob Wiblin: Yeah, and to spreading it to others.

James Tibenderana: And spreading it to others. So this is a disease of enormous proportions and one that we’ve got to keep in mind that the vector is critical in that transmission cycle. Breaking that cycle requires thinking about the mosquito, thinking about the parasite, and obviously thinking about human behavior.

The heterogeneity of malaria

James Tibenderana: Malaria is heterogeneous. The distribution — especially now, as we’ve seen the last two decades of success — we’ve sort of controlled the malaria that is not embedded within the context. And now we are having to deal with malaria that is context specific, localized, and has variables that are making it more difficult for you to achieve the continued decline. And then we have hard-to-reach areas, or even have behavioral elements.

James Tibenderana: I mentioned treatment seeking in the private sector. You’ve got to be able to reach the private sector. You’re not going to suddenly change and say, “People should all go into the public sector,” because they made a choice, they want to go into the private sector, right? So what are you going to do about the private sector? And then we’ve talked about hard-to-reach areas, and malaria is a disease of poverty. You may say that there are health facilities, but there are households that are not able to access services, because of either geographical distance or the fact that the health facility may be open at a time when they should be looking after their livelihoods, or looking after their gardens. And they won’t have that time.

James Tibenderana: So there’s some of these barriers that are preventing access, and having the capacity to understand those nuances within the context requires data. It’s not insurmountable; it’s just that you have to have the right data. You need to have the data in terms of the people. You need to have data in terms of the mosquitoes — something called entomological surveillance. And you need to understand whether the parasite is continuing to be susceptible to the drugs, or that you are likely to be identifying the parasite itself when you test for it using a malaria rapid diagnostic test. Because even now we have what is called HPR2 deletions, where the malaria parasite is now deleting a gene that the rapid diagnostic tests are supposed to pick up.

Rob Wiblin: Oh wow. That’s savvy. That’s because, I suppose, there’s selective pressure on not being detected, because then you can spread better?

James Tibenderana: Yes, selective pressure. So just having that information that allows you to then make the right choices, and really deploy the tools in the right location, the right intensity. We’ve scaled up everywhere, but we still have gaps. You might find a situation where there is something going on and you need to either react with a better net (for example, a pyrethroid PBO net), or you may have to react with more intense community case management (for example, integrated community case management). You may have seen an upsurge starting and you really want to make sure it’s kept down, or you have a situation where there is genuinely a upsurge taking place and you really want to stop that happening — because the sooner you stomp it down, the less likely you are for mosquitoes to be able to transmit.

Rob Wiblin: I guess we got into this topic because you were saying that this work — where you are tracking where is malaria taking off, and using that information in order to shape your strategy — could be incredibly useful, but it’s maybe harder to convince donors to support, or at least donors who are focused on proven interventions to support it. Because it’s harder to say ahead of time exactly what is the cost effectiveness for this. It’s not just a matter of delivering the same treatment to other people in areas with the same malaria prevalence. It could be that it’s incredibly useful some year, or it could be that some year it doesn’t really help your strategy all that much. It’s a bit more of a speculative spend.

James Tibenderana: Yes it is. But from a personal viewpoint, and I think from an organizational viewpoint, surveillance and response is a critical intervention if we are to achieve malaria elimination. We already see that in Asia, where surveillance and response is playing a very important role in continuing to identify the last case of malaria — where it is and to make sure it’s dealt with. But we’ve not seen that kind of investment in surveillance and response in the control setting where you have higher transmission intensities — I think because the numbers are so large that in some ways, the trends or the spikes get lost out by the noise.

James Tibenderana: But if one was to say, “If you had additional funding, where would you spend it?”, I think surveillance and response for me is one area that can have potential if done properly: having the right data and using it. Because you need to have data and then you need to be able to use it at the subnational level — the districts, the provinces — and then at the national level. Looking ahead, it will be difficult to use machine learning, it will be difficult to use AI, without having data. And if in the next decade, one is to envisage machine learning as contributing to some of the decisions, some of the predictions that allow us to be really more savvy at our choices, we are going to need this data. And if we don’t start collecting that data now, when we have tools to use the data, what will we be doing?

James Tibenderana: You need this long-term data and you need the consistent quality that can allow you to then get into decision support tools, and to really optimize your decision making at the moment we are making decisions. We are bringing on board modeling to help with some of our decision making — so all the cost-effectiveness modeling, some of the modeling work that allows you to identify where to put particular interventions and combinations of interventions. I think in the next 10 years, we should be looking to things like machine learning to be able to support that decision making, so that we’re probably more precise and we are more targeted. And that’s going to require data.

The value of local researchers

James Tibenderana: It’s very important to have local research institutions, and researchers with the capacity to identify research needs. And to participate and really lead on research — whether it’s operational research, or implementation research, clinical trials — a variety of research is really important. And we’ve seen it for seasonal malaria chemoprevention: one of the reasons why the research on the efficacy of seasonal malaria chemoprevention was very quickly adopted in the Sahel was because a lot of those studies were done by national researchers.

James Tibenderana: So as the results were available, they were able to link up with their counterparts in the ministries of health to speed up the process of the adoption, so the adoption process was quite rapid and straightforward. We’ve even seen it with RTS,S. With RTS,S, many of the clinical trials, as well as the malaria vaccine implementation program, were done by local researchers, and some of them with local institutions.

James Tibenderana: One of the things we did in Uganda was we had regular meetings between researchers and ministry officials. In one of these meetings, there was this molecular scientist that was describing the genomics of mosquitoes and insecticide resistance. You had the decision maker in government, who was sitting there and listening. And after this presentation, which was saying, “In these parts of Uganda, the mosquitoes are resistant to this. They have these molecular genetics…”, he looked at the scientist and he said, “So what are you saying? Are you saying that I need to buy an insecticide for that mosquito here? Another insecticide for that mosquito there and there? And yet I have money to buy one insecticide. So can you make me understand how I’m going to be able to achieve my objective with one insecticide?”

James Tibenderana: And you had this conversation between the science and the implementation. And it was a really lively conversation. So you want to be able to have those conversations at a country level. You want to be able to have those conversations, ideally, in a manner that emphasizes trust, in a manner that emphasizes evidence and neutrality.

James Tibenderana: My personal experience working in research in different settings is that having institutions with the capacity to do research in their context is a critical success factor for the adoption of some of these interventions, and maintaining their quality. Because once you’ve introduced, you still need the operational research, the monitoring and evaluation to identify what’s going wrong and what’s going well. And then tweak those in the setting to make sure that you continue to maximize and optimize the impact.

Elimination vs. control

James Tibenderana: As malaria transmission declines, it is expensive, relatively, to continue to maintain the trajectory towards elimination and to sustain it. So the investment in elimination is justified, because we’ve got to continue eliminating so that we are increasing the number of locations that are malaria free.

Rob Wiblin: When a local area is malaria free, does that potentially allow you to ease off on some of the spending, because you say, “Well, it’s largely gone now, so we don’t need the nets right now?” Or is it more that you have to always be doing it?

James Tibenderana: It depends, really. Because what happens is that as you are eliminating, you are reducing the geographical location where there could be potential breeding or viability of transmission. So you can continue to localize your interventions, but you must maintain your surveillance system, such that if anything happens and malaria is triggered in other locations, you can react quite quickly to ensure that you don’t have transmission taking place. One of the criteria for certifying malaria elimination is that you don’t have local transmission taking place. For certification, you need to have met that requirement for three years before WHO can then certify that you’re malaria free. So you need to have that investment taking place.

James Tibenderana: But I think it is also justified to say that there should be a proportional investment in countries with high burdens — the Nigerias, Ugandas, DRCs — countries that if we are not able to demonstrate a sustained decline in the burden of malaria, then it is not possible to talk about a malaria-free world, or to talk about the achievement of the targets for the global technical strategy that WHO has, which says that X number of countries will have reduced their burden by 90% by 2030. That target is not achievable if you can’t deal with malaria in a place like DRC or in a place like Nigeria.

James Tibenderana: I think those numbers are partly driven by population size, population growth. There’s been huge growth in sub-Saharan Africa, sometimes not proportionately met with government investment in the health system. So you have population size, population growth, and I think the population at risk — because even if you have a large population living in urban settings or in settings where there isn’t malaria risk, then your numbers will not be that great. But in Nigeria, in DRC, the majority of the population is at risk of malaria. And so if one is to really be aiming for a malaria-free world, we’ve got to invest proportionally in the countries that have the highest burden.

James Tibenderana: Malaria elimination is a goal. If there’s one change that we need to have in terms of mindset, I think it’s moving away from a control mindset to an elimination mindset. If we can aim for elimination as a goal, then we will see that the investments as well as the effort that is required to really do some of these things effectively will pay off.

James Tibenderana: So I would look at it this way. Before we even talk about elimination, I think in terms of the near term, we have the tools that allow us to reduce the mortality further. Why do we still have 627,000 people dying of malaria? As an immediate need, we do have the tools that can help us, as well as the commitments from governments, Abuja, all these declarations that can allow us to really tackle mortality and disease.

James Tibenderana: Seasonal malaria chemoprevention has 70% reduction in malaria cases, 70% reduction in hospitalizations, right? We should be reaching 40 million kids. When it’s expanded, we should be reaching that group, so that we are, in the near term, reducing the disease and the death impact. And that will also have an economic benefit, because it affects the livelihoods of households as well as the education of children who are not able to achieve their full potential because of some of the neurological sequelae of malaria. So I think that is a goal that is before us and is something that we can achieve, in terms of the immediate need. If I was a household — and I’m only speculating here — and if I was faced with a child who’s going to have malaria up to six times in a year, and you could reduce that to one or even nothing, I would be really happier to have that chance not to have my child or children experience that.

James Tibenderana: While looking at malaria elimination as a next target, and as we’ve seen with some good examples is that if we can sustain this course of bringing down death, bringing down morbidity, then potentially when we have these new tools — whether gene drive or a vaccine, which may not hit 70% or 80% efficacy — then we start to chip away at the transmission intensity and the transmission potential. So I think we have to be looking at it in a long-term vision and add value. Because when you look at cost effectiveness, when you’re looking at costs, it’s difficult to add cost to the value of a long-term goal and add value to that long-term goal, because of the huge benefits that it’s going to have to economies as well.

Articles, books, and other media discussed in the show

James’s and Malaria Consortium’s work:

Ways to get involved:

Current state of malaria in the world:

Seasonal malaria chemoprevention:

Malaria vaccines:

Gene drives and other technologies on the horizon:

Other 80,000 Hours Podcast episodes:

Related episodes

About the show

The 80,000 Hours Podcast features unusually in-depth conversations about the world's most pressing problems and how you can use your career to solve them. We invite guests pursuing a wide range of career paths — from academics and activists to entrepreneurs and policymakers — to analyse the case for and against working on different issues and which approaches are best for solving them.

The 80,000 Hours Podcast is produced and edited by Keiran Harris. Get in touch with feedback or guest suggestions by emailing [email protected].

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