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your concerns and actions. What's on your mind? What are you actively doing to build a better future?

Include links. If you include a scholarly link, please note that.

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anything else you think we should all consider/address. What else do we need to keep in mind as we build a better future? Include links. If you include a scholarly link, please note that.

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anything pertaining to the 7th generation principle, Buddhism, and other philosophies/religions/mindsets. Is MacAskill trying to take credit for something new when the 7th generation principle has existed for thousands of years already? What is the link? How can they work together? Is this moral philosophy of longtermism only going to appeal to a certain group of people? Do we focus on the immediate concerns or a distant future that is hard to predict?

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the original view of moral philosopher William MacAskill that we should be doing much more to protect future generations.

Your posts (questions and answers) will cover the most-discussed book of 2022, What We Owe the Future, and his NYT opinion piece we read. Dig deep.

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Who is trying to make a difference on the future planet/people? What groups are already seeing success? Who is emphasized? Who is ignored? Is our money better spent fixing actual needs now or preserving humanity?

Include links. Have fun with this. If you include a scholarly link, please note that.

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helping people/the planet now (neartermism) v. in the future (longtermism). What is effective altruism? What is going on in this movement?

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images that pertain to the matter at hand and offer insight. State how they fit this issue.

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Treating Malaria: What are the implications of near-term and long-term goals and how do they work against each other versus how they can be changed to work together?

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Treating Malaria: What are the implications of near-term and long-term goals and how do they work against each other versus how they can be changed to work together?

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This article looks at the bigger implications of the short-term eradication of malaria versus the long-term goals and processes that need buy-in from entire regions and populations. There is no easy fix, but if we don't approach eradicating malaria differently, the problem will continue to exist.

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Transcript

Rob's intro [00:00:00]

Rob Wiblin: Hi listeners, this is The 80,000 Hours Podcast, where we have unusually in-depth conversations about the world's most pressing problems, what you can do to solve them, and whether people are still using bed nets for fishing even when they don't live near a body of water. I'm Rob Wiblin, Head of Research at 80,000 Hours.

It's about damn time we got to doing an episode on malaria. Malaria is not something I have to think about often in the UK, but globally there are still something like 250 million cases of the disease a year and it causes 600,000 deaths, mostly in young children.

The crazy thing about this, and the reason it has attracted so much attention from people focused on effective charity over the years, is that we know full well how to put an end to this - and on paper the necessary equipment looks like it costs peanuts.

Today's guest came strongly recommended and has helped us produce a seriously comprehensive episode.

James Tibenderana is a triple threat: medical doctor, academic medical researcher, and expert with decades of experience designing and delivering medical interventions in the developing world.

Malaria isn't one of the pressing global problems I know the most about, so as you're about to hear I was learning a tonne as we went.

Many of you will have heard of the charity evaluator GiveWell, which seeks out nonprofits that have strong evidence of effectiveness, that can save or improve lives the most per dollar, and that have room to effectively spend more money and grow.

They've long recommended giving to groups like Against Malaria Foundation and Malaria Consortium - where James works - because they are leading mass deployment of insecticide-treated bed nets, as well as seasonal malaria chemoprevention.

James and I talk plenty about the pros and cons of each of those two approaches.

But we actually open the episode by talking about emerging ways to eliminate malaria - including a recently approved vaccine and genetically assisted mosquito elimination.

James is cautiously optimistic about both strategies. I personally came out very hopeful about the latter and wonder if it shouldn't be getting much more attention than it is.

Later on we discuss how it is that malaria is still so prevalent, what's unusual about malaria as a disease, the key strategic choices faced by Malaria Consortium, what upcoming research we can look forward to, and plenty more.

All right, without further ado, I bring you James Tibenderana.

The interview begins [00:02:06]

Rob Wiblin: Today, I'm speaking with Dr. James Tibenderana. James is the Global Technical Director at Malaria Consortium, a nonprofit with an annual budget of around £100 million a year. Malaria Consortium's seasonal malaria chemoprevention programme is top-rated by GiveWell, where they estimate that the programme can protect a child from malaria for a year for about $6.50, and save a life for each $4,500 that it spends. As a result of GiveWell's recommendation, Malaria Consortium receives philanthropic funding which enabled them to reach 20 million children with SMC in 2021, with plans to expand the programme further in 2022.

Rob Wiblin: James trained as a medical doctor at Makerere University in Uganda, and then as an epidemiologist at the University of Cambridge and the London School of Hygiene and Tropical Medicine, where he is now an honorary associate professor. He joined Malaria Consortium in 2005, just a few years after it was founded, and worked as Africa Technical Director and Development Director before becoming Global Technical Director. During the last 20 years in the field, he helped study parasite-based diagnosis for malaria before treatment, changed Uganda's antimalarial treatment policy to artemisinin-based combination therapy, and spearheaded the establishment of a national research center for malaria in Uganda. Thanks for coming on the podcast, James.

James Tibenderana: Thank you, Rob. It's a pleasure to be here to speak about my work; my experience; importantly, a disease that is really personal to me; as well as an organization that I've worked for for over 15 years and value its mission, as well as the impact that it has.

Rob Wiblin: I hope we'll get to talk about progress on malaria vaccines and why Malaria Consortium focuses on the interventions and places that it does. But first, what are you working on at the moment, and why do you think it's important?

James Tibenderana: I'm working on an intervention called intermittent preventive treatment of infants. It's an intervention that was recommended by WHO in 2010, whereby a child in the infant age group (that's under one) should receive a complete dose of a drug called sulfadoxine-pyrimethamine either three times or more through the expanded program for immunization. That way, it can protect the child in the first year of life from malaria.

James Tibenderana: Since 2010, this intervention has only been scaled up in one country: Sierra Leone. Currently, we have funding from the Bill and Melinda Gates Foundation to carry out a study in Nigeria to study the effectiveness of IPTI - that's the acronym - and provide evidence to the government so that it can potentially think about adopting it as an additional tool. This is important because, as WHO has been saying, we have stalled in our progress towards achieving malaria elimination. And what implementers like ourselves, as well as researchers, are trying to do is to find the additional interventions that can be added to the current strategies and maximize the impact that we're achieving.

Rob Wiblin: You mentioned that things have slightly stalled lately on malaria prevention. I noticed in some of the graphs, things were kind of turning around in 2020. I assume that was probably COVID related. Is that a big part of the explanation?

James Tibenderana: It actually started before COVID. I would say roughly around 2017, the substantial progress that had been made sort of started to plateau off. And I think since that point, we've not seen the dramatic declines that we've had in the last two decades. That, I think, is a combination of factors, of which certainly COVID has caused some disruptions.

James Tibenderana: But you have other risks. Things like insecticide resistance, you have the fact that we don't have the optimal funding that is required. WHO, on average, estimates that we need something like 6.8 billion US dollars per annum to really achieve the global technical strategy targets - and on average, we're about 3 billion per annum. So there's a huge funding gap that does not allow us to implement and deploy all the interventions that could be appropriate in particular geographical locations.

James Tibenderana: Malaria is a complex disease, and I think over the last two decades, we have been successful because that's the relatively easy part. We've been scaling up interventions, trying to achieve high coverage with our interventions, and I think we've potentially reached the maximum impact that we can achieve with the current methods. I don't mean changing interventions, but I think what we now need to be doing is really targeting better, optimizing the field - so where we have 50% coverage of some interventions, really finding out what we can do to increase that to about 80% or even 90% in some locations. And then you have behavior change: working very closely with communities to really get to understand what they feel are their priorities, but how they can engage with these interventions and really take them up as they're designed.

Rob Wiblin: Fantastic. Well, that is basically an agenda for the rest of the conversation, or at least a lot of it.

Malaria basics [00:06:56]

Rob Wiblin: OK, before we go on, a lot of listeners are going to have some idea about malaria, and a few of them are going to be incredible experts at malaria as well, but let's very quickly give everyone a brief refresher. How is malaria spread?

James Tibenderana: Malaria is spread by a vector called a mosquito, and primarily the Anopheles mosquito. It's usually the female Anopheles mosquito that spreads malaria, and of about 400 different species of mosquitoes, there are about 40 Anopheles that are responsible for spreading malaria.

Rob Wiblin: So the female bites one person, and picks up this tiny single-cell parasite? I'm just trying to remember back to my high school biology here.

James Tibenderana: Yeah.

Rob Wiblin: It picks up this parasite and then it goes and bites someone else and passes it into their blood as well.

James Tibenderana: Yeah. The lifecycle of, I would say the parasite, combines a presence in the mosquito as well as in the host, a human being. What happens is that a mosquito will pick up a sexual stage of the parasite from a person who is infected. And that sexual stage, called a gametocyte, gets into the mosquito and goes through a process of development and turns into something called sporozoites that are in the salivary gland of the mosquito. The next time that female mosquito is feeding, it will introduce those sporozoites into the skin of the next person that it bites, and the sporozoites go through a process where they move into the bloodstream and establish themselves in the liver of the individual - it could be a child, it could be a pregnant person, a woman, it could be an adult male.

James Tibenderana: In the liver, depending on what type of parasite it is - for example, plasmodium falciparum - it can then convert into other cells which are called merozoites that then attack the red blood cells. Plasmodium vivax can stay in the liver by forming what are called hypnozoites, and those can stay in the liver for several years without exposing themselves. That's why vivax malaria is complicated: it has a potential to propagate itself even without symptoms, but also without mosquito bites.

Rob Wiblin: Oh, right.

James Tibenderana: So with falciparum, the merozoites are then present in the red blood cells and destroy the red blood cells, and continue that cycle of destroying the red blood cells. They also make the red blood cells less able to carry oxygen, and therefore, one of the symptoms that is caused by the parasite infecting the red blood cells is that the individual may not have enough oxygen-carrying capacity. Then those merozoites, some of them will be converted into gametocytes, and then you have the cycle again repeating itself.

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.

Malaria vaccines [00:12:37]

Rob Wiblin: OK so with that little primer on malaria out of the way I'd like to turn to the various approaches we are taking or could take to reduce the damage malaria does around the world.

Rob Wiblin: Later in the interview we'll come back to Malaria Consortium's core existing programs, but when I asked around, listeners were particularly keen to hear about some new possible ways of reducing the damage that malaria does. One of those is malaria vaccines, in which there's been ongoing research for many decades. And there have been some kind of recent announcements about progress that have, I think, really caught people's attention and made it kind of a hot topic. What's the state of the art in malaria vaccination today?

James Tibenderana: When I was training to be a malariologist, I did not expect in my lifetime to see a WHO recommendation for a malaria vaccine, because the development of a vaccine is quite complex.

Rob Wiblin: Right. So because the pathogen here is a tiny organism rather than a virus or a bacteria, it's quite a different beast to try to tackle with a vaccine - not something that we've really had vaccines against in the past.

James Tibenderana: Precisely. It's a protozoa.

Rob Wiblin: Protozoa. OK, yeah.

James Tibenderana: It's a protozoa and it's got various stages within its host. So the first stages are sporozoite that gets into the skin and into the bloodstream and then goes into the liver. That stage is called the pre-erythrocytic stage - that's the stage that occurs before it gets into the red blood cell. Then it gets into the red blood cell and has merozoites and then causes some of the damage that is seen as symptoms in either complicated malaria or severe malaria. That's an asexual stage, so it's merozoite and then it continues to propagate. Then you have a couple of those that then form gametocytes, creating a sexual stage that can be transmitted by a mosquito that picks it up during a meal. So those stages have different proteins and antigens.

Rob Wiblin: Right. So you can't target it at every stage. You've kind of got to pick one.

James Tibenderana: Yes.

Rob Wiblin: And it's only going to be at that stage for so long.

James Tibenderana: Exactly. So you have questions: which stage do you pick and then which antigen? Or which protein in that stage will be similar across the potential different subtypes of strains that a child will face or a host will face in that particular context?

James Tibenderana: So RTS,S - which is the malaria vaccine that WHO recommended in October 2021, which was really a milestone and historic - is a pre-erythrocytic vaccine. It prevents the infection of the red blood cells by the parasite that is released from the liver. So RTS,S is the malaria vaccine that WHO recommended in October 2021, which is a historical watershed moment for us, because it, for the first time, introduces a malaria vaccine into the toolkit. But I think it also sends a positive message to manufacturers and researchers who are working on creating a malaria vaccine that is highly efficacious.

James Tibenderana: R21 is a pre-erythrocytic vaccine that is currently going through phase 1 and 2 trials. It has a potential to either be as effective as RTS,S, or potentially even more effective, but we still have to wait for the phase 3 trials. But hopefully in the next five years, we should have an alternative to RTS,S in the shape of R21.

Rob Wiblin: I guess we should say that the effectiveness of RTS,S is unfortunately only about 30% in the trials, in terms of saving children's lives from malaria. They have to get multiple shots, I think, and even then it's only 30% effective. So it's certainly not a silver bullet, regrettably.

James Tibenderana: Yes, RTS,S isn't a silver bullet in the malaria vaccine implementation project. The pooled data showed a 29% reduction in hospitalizations due to severe malaria, but that's an effect size that we cannot ignore.

Rob Wiblin: I would definitely rather have it than not have it.

James Tibenderana: Yes. That's an effect size that we cannot ignore. And we have seen in the past, in the research around nets, initially the trials showed a 45% reduction in clinical episodes of malaria, but I think something like an 18% reduction in all-cause mortality. With SMC, we've seen a 70% reduction in clinical episodes and a similar 70% reduction in hospitalizations due to severe malaria.

James Tibenderana: So we've got to think about the complementarity that these tools provide, because no tool is absolutely effective. We are not able to rely on one tool alone. And by putting these tools in the right combination, one is able to then achieve a higher impact. So, in the malaria vaccine implementation project, the combination of RTS,S and nets meant that 90% of the children who were vaccinated were actually protected from malaria, because there were some children who were not being protected by nets who got protected by RTS,S. And achieving a 90% coverage of protection for children is impressive.

Rob Wiblin: Absolutely. Yeah. So I'm immediately starting to think about this in terms of cost effectiveness, given that we unfortunately have a limited budget here, and can't provide even the basic things that we would really want to to everyone who's vulnerable to malaria. So with seasonal malaria chemoprevention, we're talking $6 per child per year. And I think with nets, we're talking only like $5 or $6 to deliver a net, which then protects potentially multiple children for multiple years. How much does it cost per vaccine delivery? Because from memory, I think it was three shots delivered over the course of a year.

James Tibenderana: So three initial shots, the primer doses, and then you have a fourth shot 18 months after the third dose. And then a group used a seasonal approach to vaccination, where they then gave an annual dose before the rainy season. So you could say on average four doses. I think the modeled estimates have used a cost of $5 per dose, so roughly we are talking about $20 to $25 to have a child covered with RTS,S.

Rob Wiblin: So it's going to be somewhat less cost effective than these other options, in terms of lives saved per dollar, probably most of the time. But it's still going to look very good in the broader scheme of liberal health interventions. Is that kind of the bottom line?

James Tibenderana: Yes. I think that would probably be the bottom line. But I think this study that the London School and their partners did in the seasonal use of RTS,S achieved really impressive results when they combined RTS,S with seasonal malaria chemoprevention. They were able to achieve a 70% reduction in hospitalizations due to severe malaria, and a 73% reduction in deaths associated with malaria. So the gain that one can make, if RTS,S is introduced appropriately in the right context, could be substantial and could justify the potential increasing cost of delivery.

Rob Wiblin: My initial thought was that if you already have the nets and the SMC, then that would reduce the lives saved per dollar of the vaccine, because you have reduced already the number of deaths by 80 or 90% or something like that, if you have reasonably high distribution of both of those.

Rob Wiblin: I suppose a different take on it, that might be familiar to people now because of COVID, is this idea of herd immunity. That if you can get all of these different layers of protection that stop people from getting sick and therefore from passing it on to others, you might almost be able to get local elimination of malaria from an area that would then have spillover benefits to all kinds of people - even those who aren't using the nets or the SMC. With the way that malaria spreads, is there the possibility of eliminating the disease locally through a herd immunity effect?

James Tibenderana: It is plausible. It is plausible.

Rob Wiblin: But hard.

James Tibenderana: But hard.

Rob Wiblin: Yeah. Just because of that R being so high.

James Tibenderana: Yeah. It is plausible, but rather difficult. What we've seen with nets is that if you do achieve high coverage with nets, there is a benefit to those who may not have a net. And it could be similar for some of the other tools. But I think the interface of the mosquito and the fact that achieving herd immunity does require being exposed repeatedly to different xenophily: plasmodium falciparum and the substrains within plasmodium falciparum. So I think herd immunity comes at a cost. And that cost is you've got to have repeated episodes, and those episodes have to be consistent. It also depends at what age you're exposed. With children, their immune systems are not fully developed, so the immune system has to develop. It's very different from an adult. So a child has got to have its immune system grow and mature. And during that time, they will experience episodes of malaria.

James Tibenderana: So it's a combination of things. I think relying on potential herd immunity will have a cost that I would say most households would want to avoid, if they had the option to have access to interventions that could be potentially effective. None of these tools is absolute because we're not dealing with a virus where you can give a vaccination and achieve high efficacy or effectiveness. So even with nets, even with seasonal malaria chemoprevention, even with indoor residual spraying, even with RTS,S (the malaria vaccine), there will be some exposure to parasites that will give the opportunity or the risk for people to get exposed to malaria.

James Tibenderana: I think bringing these tools together so that you have even more effective prevention, so that kids or pregnant women are not getting ill. Or if they do get ill, they have the right tests and the right treatments so that it doesn't progress into severe disease, but also it shortens the amount of time that the parasites are present for a mosquito to then pass that on to someone else. Being able to shorten that time will have an overall benefit of reducing transmission intensity, but also in us aiming for a malaria elimination target that I think most people now want to achieve. So it's no longer just about controlling, but that we are really looking at a vision for a malaria-free world.

Rob Wiblin: Yeah. This kind of layered defense will be - again, because of COVID - quite familiar to people. Because we found even with the vaccines, even with the boosters, it's not really enough with the latest strains. So we have to do that, and then on top of that, for people who do get really sick, we have to have these drugs that then on top of that, again, reduce the mortality rate by 50% or 75%. And even that's not perfect. So COVID's still a problem, but in combination, we've managed to bring down mortality by 95% or something like that - by layering on both the vaccines and the better treatments.

Rob Wiblin: Is malaria vaccine research a neglected target for additional funding, or is it the kind of thing that already has quite a few people working on it?

James Tibenderana: Malaria vaccine development is neglected. It's taken over 30 years for RTS,S, but we know it's been complex because there's so much that goes into developing a vaccine: identifying the antigens, testing the antigens, finding the right dose, the right delivery strategies. There's lots of R&D that's involved and investment. Presently on average, there are about 10 clinical trials that are registered on clinicaltrials.gov - where most of the clinical trials, whether it's a vaccine or a drug, are registered - per year. Ten trials for a disease that causes so much.

Rob Wiblin: Yeah. 200 million cases a year.

James Tibenderana: I think that number needs to go up.

Rob Wiblin: The ratio is not great.

James Tibenderana: The ratio is not great. And currently I think in the pipeline, there's something like 18 or 20 different vaccine candidates that are going through testing. Some targeting the sporozoite to really reduce the capacity of the sporozoite to cause disease by infecting the red blood cell. Then you have some vaccines that are blood-stage vaccines that really are trying to ensure that the merozoites don't get established in the red blood cells, but the red blood cells themselves do not get destroyed in a manner that we know happens when you have malaria. And then you have transmission-blocking vaccines that prevent the gametocyte from being taken up by the mosquito - or if it is taken up by the mosquito, it's not able to establish itself in the mosquito and then form a sporozoite, which then continues the cycle. So with those various stages, you have on average something like five to six different types of candidates that are being looked at.

James Tibenderana: Then some of those vaccines use a subunit of an antigen: the circumsporozoite protein that is within the sporozoite. RTS,S uses a subunit of that. And then you have some vaccines that use the sporozoite, and attenuate it or inactivate it. So that when that is given, it generates an immune response that the body can then remember for the next time a viable sporozoite appears.

James Tibenderana: So with this variety of antigens, with these different types of vaccines... For example, if one wants to eliminate, you probably need a transmission-blocking vaccine. That is probably the most neglected aspect of vaccine development, because it's very complex. And then blood-stage vaccines, we don't have any that are close to phase 3 - they're largely phase 1 trials - so we still probably have another 10 years before we see a viable candidate that's within the blood-stage group.

James Tibenderana: There is one that is being tested for malaria in pregnancy. What happens is that the parasite causes the red blood cells to stay within the placenta, the connection between the fetus and the mother. And so there is a vaccine that is actually now being trialed that can prevent those cells from going into the placenta and sequestering and preventing oxygen as well as energy from being transmitted from the uterus to the child.

James Tibenderana: But vaccine development is neglected, and for a malaria-free future, we do need a healthy pipeline of vaccines. And we do need to shorten the period from the actual identification of the antigen all the way up to the use of that or the recommendation by WHO and its use. From all the efforts that have gone to developing the vaccine against COVID, we've seen some spinoffs for malaria vaccine development. So there is now some effort on the RNA technology being used, including the DNA technology being used to identify a vaccine for malaria. And companies like BioNTech that were instrumental in developing the RNA vaccines against COVID have committed to doing that work.

Rob Wiblin: Yeah. Possibly this is a result of underfunding. The RTS,S vaccine - the best and I guess only approved one that we have at the moment - was first developed, I think, in the late '80s or early '90s. And then a proper clinical trial wasn't finished until 2015. And it's still kind of in this pilot phase, where it's not being scaled up on a huge level. It's being tested on populations to see what impact it has on a large scale, but it's not a product that one can easily go and buy, something being commercialized on a mass scale.

Rob Wiblin: For a long time with COVID-19, I was up in arms about the vaccines getting delayed by regulatory caution by like weeks or months. And here we're talking about a 30-year period going from the very early development phase to figuring out whether it's good. It feels slow. Am I understanding this right? I don't want to criticize the people in this area, but it's like, what's going on?

James Tibenderana: We can't criticize because I think they really did make the effort - and they could have given up, but they didn't. So I think they have to be acknowledged, the scientists. But also the funding from the Bill & Melinda Gates Foundation that was really instrumental in ensuring that this moved forward, as well as the research that GSK did initially, and organizations like PATH who continue to work with GSK on its development. The work has been complex.

Rob Wiblin: Yeah. Scientifically difficult.

James Tibenderana: Scientifically difficult. Just getting the right antigen, and just understanding the dosing: what dose is required for you to be able to achieve the right immune response? And then there's also the markers of the immune response. What's your marker, right?

Rob Wiblin: You want to be able to check whether someone's developed immunity?

James Tibenderana: Yes. You want to check, but also if you have this antigen, what is the likely response in the immune system that then translates into an efficacious or an effective tool. So the science has been complex. And then you have the research, which goes through ethical approval. Then you have the regulatory aspects that also take time. But I think it's a lesson, and I hope a lesson that we have learned from, and that the next generation of malaria vaccines will take a shorter period of time.

James Tibenderana: I think R21, for example, is probably going to take a shorter period of time because of some of the lessons that have been learned from RTS,S: really trying to not only do the research, but also to think about the potential manufacture, so that you don't have delays once you have approvals from either the drug authorities or any of the regulatory bodies. You can really go straight into the manufacture and then scale that up. So I think with RTS,S, there's been some lessons and we've seen R21 is benefiting from those. But I think all of us hope that what we have seen from the COVID pandemic is that you can -

Rob Wiblin: Turn things around fast.

James Tibenderana: Turn things around fast, and sometimes, for these major emergencies, some of the research needs to be done concurrently.

Getting rid of mosquitoes [00:32:20]

Rob Wiblin: Let's push on from vaccines and talk for a bit about different methods of vector control, which is to say, getting rid of the damn mosquitoes that carry malaria. As I understand it, 70 or maybe 80 years ago, people were getting malaria in the American South, but that has largely been ended. I think 200 years ago, people were getting malaria in East Asia, in Europe as well. Even in England, I think 300 years ago, malaria was endemic. And I think the primary way that's been dealt with is getting rid of the mosquitoes - primarily it was vector control that largely eliminated malaria. I think about a quarter of the world used to have malaria and now basically doesn't. Why can't we just use those same methods that have worked for a quarter of the Earth's surface on the remaining quarter where malaria is still quite common?

James Tibenderana: The distribution of mosquitoes around the world differs. In sub-Saharan Africa, the Anopheles gambiae complex is the most efficient transmitter of malaria. It's far more efficient than the mosquitoes that were in Asia, that were in the UK or Europe, or in the Americas. It is so efficient that you just need a couple of mosquitoes to establish transmission in a setting.

Rob Wiblin: I see.

James Tibenderana: And they don't need a lot of breeding sites. They need very few breeding sites in which to establish themselves.

Rob Wiblin: So it's basically this difference in the species of mosquitoes. What was possible in England is not at all possible in Congo.

James Tibenderana: Yes. And then you have other variables. Temperature: below 16 degrees centigrade, the parasite's development in the mosquito is slower than at 25 or 30 degrees centigrade, where the parasite in the mosquito will really develop quite rapidly and have a shorter period in which it then can be transmitted through the mosquito's salivary glands. So there are environmental variables as well: temperature, rainfall, the amount of rain.

James Tibenderana: I think what has been a consequence of economic development in those locations is that people have then been able to put in place good drainage, build up cities, and get rid of the breeding sites. And much of Africa and some parts of Asia are still quite rural, where you do have a large proportion of the population in rural settings or semi-urban settings, and there's breeding sites and they're close together. During the transmission season, the mosquitoes can very rapidly establish transmission in those settings.

James Tibenderana: And then from an epidemiological perspective, there's something called "transmission potential." Transmission potential is the ability for malaria to be reestablished in a setting where it has been reduced. So even in sub-Saharan Africa, as one is reducing the burden of disease, for example, the number of children who are dying is coming down, the number of people who are exposed, the potential for malaria to resurface continues to exist for quite a long while.

Rob Wiblin: I see.

James Tibenderana: So if anything interrupts the control - it could be like suddenly you have floods, you have displacements, or -

Rob Wiblin: Defunding.

James Tibenderana: - defunding, you don't do your indoor residual spraying on time - then quite rapidly -

Rob Wiblin: Comes all back.

James Tibenderana: - it comes all back. And that transmission potential differs in location. And also because it's driven by the type of mosquito, it's driven by the vulnerability of the individuals in that setting - children under five, pregnant women. You also have the receptibility of the environment, as I mentioned, temperature. Those variables all come together to sort of create either high transmission potential or low transmission potential.

Rob Wiblin: Yeah. I think it might be worth talking about this a little bit more, because I think I've carried around this misconception that the US managed to get rid of malaria in Florida. And I guess I was thinking it was partly they just urbanized more: they put down more concrete, people moved into urban areas. So probably as Uganda becomes richer and urbanized, they'll just get rid of malaria in the same way.

Rob Wiblin: It sounds like that will have some effect, but it's not going to eliminate malaria in the same way that it has elsewhere, because the mosquitoes are different and it's just not so easy to get rid of these ones. There's also these specific mosquitoes now that are spreading malaria in cities, right? I imagine that they've maybe evolved over time to become even more effective at living in urban environments and more resilient to people trying to change the environment to get rid of water and so on, and that could present an ongoing impediment to vector control.

James Tibenderana: Yes. I can't remember the author, but they've really modeled the potential impact that economic development as well as urbanization could have on malaria elimination. And with their models, their findings were that it's not likely that you can eliminate malaria in sub-Saharan Africa by simply urbanizing and building up, partly because of these variables I said: the vector capacity of the mosquito, the climate, all these variables. So urbanization and economic development will have a contribution and an important contribution, but I think the reliance on effective interventions that are used consistently over time and that continue to remain effective has to be emphasized.

Gene drives [00:38:06]

Rob Wiblin: OK. So if we're not going to be able to get rid of mosquitoes that way, just in the national course of events, what do you think of the idea of using gene drives to eliminate the specific species of mosquitoes that carry the malaria parasite? I think there's an organization called Target Malaria that is working on research to figure out where this might be possible and whether it's a good idea.

Rob Wiblin: Basically the idea here is you release a bunch of mosquitoes that have been genetically engineered such that whenever they mate with a partner, all of the children could either be infertile, or they could all be males or all be females, or something like that. That means that if that happens every generation, then after a series of replication cycles, they all die out because there's no females or no males left, and so largely the species will go extinct locally. This does have the implication that if you release some of these mosquitoes and they don't evolve to break this gene drive technology, that this could spread globally and eliminate that species of mosquito completely, which has proven slightly controversial with some people. Do you want to talk about gene drives and Target Malaria?

James Tibenderana: Yeah. 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.

Rob Wiblin: It's almost too powerful.

James Tibenderana: Yeah. 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?

Rob Wiblin: Yeah, I see.

James Tibenderana: The minute you get into genetically modified technologies -

Rob Wiblin: It raises eyebrows.

James Tibenderana: 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.

Rob Wiblin: Yeah, totally.

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?

Rob Wiblin: Right.

James Tibenderana: So there's the technology, but I think we also need the cross-country collaboration and governance. And we do need a good understanding as to what will happen if we have unintended consequences and we need to turn this technology off.

Rob Wiblin: Yeah. I think there is a way of turning it off as I understand. Unfortunately I didn't look into this, but I think basically you would release new mosquitoes with a gene drive that cuts out and deactivates the other gene drive, basically. So there is an option, but it's a challenge. Or it's something we haven't done before.

James Tibenderana: Exactly. So you need the two happening almost concurrently. I mean, let's see what happens when it goes into larger-scale trials in different locations. But it certainly has potential, and it could be an important game changer maybe in the next 10 or 20 years. But I think you do need the investment in understanding how to mitigate some of the risks of the technology, so that we are able to describe both the technology as well as the mitigation of those risks to communities and governments who need to be on board for this to be introduced and have the impact that it could achieve.

Rob Wiblin: Yeah. A lot of people worry about unintended consequences here, or they're nervous about this technology. I think that's understandable. I'm a bit more of a risk taker maybe. I just want to say, to be frank, we're talking about driving very specific species of mosquitoes extinct globally. We're trying to get rid of them because, unfortunately, they're the ones that carry this parasite. However, we would in the process save 600,000 children's lives every year, and prevent 200 million cases of this very unpleasant illness. It could be something that really does end malaria, or at least dramatically reduce malaria. So the benefits we're talking about here are very large.

Rob Wiblin: And I think some people hear this and they're like, "You're getting rid of all mosquitoes." To be honest, I'm not sure that I would be that against getting rid of mosquitoes. Maybe there'd be other insects that could fill that niche that aren't as annoying as mosquitoes. However, that's not actually what's being suggested, because there's tons of other species of mosquitoes that don't carry the malaria parasite and so don't have this problem. And likely, given that they are an extremely similar insect, they would probably just colonize the same niche in the environment that the Anopheles mosquitoes and so on are currently filling.

Rob Wiblin: So to me, it does just seem like the benefits greatly outweigh the costs on their face. So I would like to see maybe a bit more hustle about figuring out how we can do this. To some extent, it surprises me that there hasn't been one country that's been like, "We want to get rid of malaria and we're just going to do this." And then that does have effects on other countries, and maybe they don't like it. But it's something where a single actor can potentially do this for the whole world if they're willing to be unilateralist about it. It's kind of interesting that that hasn't happened, or that there's no proposal, or that it doesn't seem like that's likely to happen anytime soon.

James Tibenderana: Yeah. I mean, Rob, there's like 3,500 species of mosquitoes. So getting rid of 40 specific species, as you know with gene drives, you have to go species by species, right? There's four billion people at risk of malaria. I think if we ask those four billion people about how they would feel getting rid of these vectors, I suspect they will be keen not to be at risk of malaria.

James Tibenderana: So there are benefits certainly - in the short term and probably in the long term - because of the value of a malaria-free world. Remember it's not just the disease, but it's also the economic benefits that will be had if we are able to achieve a malaria-free world. So I think there's huge benefits, and like you, I would certainly be a proponent of the risks. But that's you and me. We've still got to recognize that national governments - and I suspect they will see the urgency, they will see the need - but at the same time, we have to recognize that they have to go through their own legislative process. It's not just going to be a ministry of health policy; this is about potential -

Rob Wiblin: It's a big deal.

James Tibenderana: This is a big deal. We have to recognize that countries will have to understand both the benefits and understand the risks. And providing the right evidence, and at least a sense of what the potential mitigations are for the risks, would really go a long way in the fast adoption of the technology. So that we don't have a technology that we've shown we've proven, and then we spend another five years trying to get it adopted. I think what we all want is that by the time this technology is available, countries are really just -

Rob Wiblin: Everyone is on board.

James Tibenderana: Everyone is on board, engaged communities, they're ready, and the potential can be achieved. I mean, the history of malaria seems to be that you take 15 years from a WHO recommendation to a potential scaleup of a tool. It happened with nets. We've struggled with IPTi, we've struggled with IPTp. We've been fortunate with SMC, with a 2012 recommendation made. In 2022, 2021, we're almost 20. In 2020, we've got 31 million kids out of 40 million. So there's this long period between a recommendation and scaleup. We don't want that to happen with the next generation of tools that are so powerful, especially one like gene drive.

Rob Wiblin: Yeah. Zooming out, I'm kind of impressed and glad that we've managed to coordinate so much as to not use this technology before we're confident that it's a good idea and we've found a way to undo it if we decide that it's a mistake. It's impressive that we're sufficiently cautious about a new technology that could be used for harm I suppose, or could accidentally cause a lot of harm. I suspect that in this specific case, it is a mistake and that when we do end up using it, people will question why we didn't do it earlier - because I suspect that it will go fine, and a lot of lives will be saved and it'll be great. But I hope that we could do that groundwork as soon as possible of persuading people, and talking to regulators, and getting governments on board, and getting the scientific community on board.

Rob Wiblin: It seems like the most likely scenario is that in 50 years' time, probably malaria will be largely gone because of these gene drives, or at least more likely than not. Possibly in 30 years, we could be there. It seems like that maybe should affect Malaria Consortium's strategy, if there's the possibility of elimination using this other technology at some point. It slightly shortens the time horizon that we're thinking about. Like how long do we have to use the chemoprevention? How long do we have to use the nets? It maybe increases the desire to deliver things immediately now, and maybe less investment in very long-term R&D projects that may not pay off until gene drives perhaps have already been implemented. Is that a possibility?

James Tibenderana: I would look at it from the short term and the longer term - the neartermism and the longtermism. Even with gene drives, with some of the other tools, the horizon is probably 10 or 20 years out before we potentially could see a recommendation and adoption in some countries. The tools that we currently have, we should be maximally achieving their potential, such that the addition of these new technologies will take a shorter period for us to achieve the goal of malaria elimination and potentially malaria eradication.

James Tibenderana: And keep in mind that there is falciparum and there is vivax malaria - there's two. Potentially with gene drives you could be targeting both with that technology. Whereas I think with some of the other technologies, you're looking at a situation where you still have the hypnozoites that, as I mentioned with vivax, will remain in the liver. And then six months later they could pop out, one year later they can pop out. I think you can even get to something like two to three years later.

James Tibenderana: So in the short term, I think our approach needs to be to really maximize and achieve the potential so that we are bringing the burden of disease down. Because what you want is more locations with less malaria expanding, or more locations with lots of malaria coming down. So you either bring high transmission down, or you have malaria-free locations and you're expanding those. I tend to look at it from, you have a high transmission intensity and you want to bring it down - such that when you have these new tools, you are at a transmission intensity and a transmission potential that these new tools are more likely to then achieve malaria elimination or eradication in a shorter period of time.

Rob Wiblin: Yeah. OK, that makes sense. This might not be something that you've looked at, but do you know how long it might take if a country decides that it's going to implement gene drives to try to eliminate specific species of mosquitoes? How long until it is gone in that country and then potentially gone across all of Africa, if it spreads widely enough? We could probably do some maths on how fast is the replication cycle and how long does it take to spread.

James Tibenderana: Yeah, you need to do some maths.

Rob Wiblin: Probably it would take a little while.

James Tibenderana: It will take a little while. But I think the recent work that a group looked at was, when they released in this large cage, within a 12-month period, they were actually able to see a complete suppression of that population. But I think when you take these things out into the wild, it's different. We haven't done that modeling. I haven't seen that modeling done, but you could envisage a situation where if the specific drives are able to maintain themselves, you could see a rapid decline in the mosquito population.

Rob Wiblin: OK, we'll stick up some links to more stuff about gene drives and targeting malaria for people who are keen to learn more.

Rob Wiblin: Changing topic, how promising do you think attractive toxic sugar baits are? This is a question from the audience. So this is an alternative means of getting rid of mosquitoes, which is, I guess, having a combination of a poison for mosquitoes with some sugar basically, that they go and eat and then they die. And you can hang this up in a house. I think I've actually been somewhere that had one of these, but I think it was for flies rather than mosquitoes. What do you think?

James Tibenderana: There's still quite a bit of research that's needed on attractive toxic sugar baits before you can start to do that comparison between that and nets, or that and some of the other tools. There still needs to be epidemiological studies that happen. From a malaria epidemiology view or perspective it has potential, but I think we have to wait for the data. There's still got to be some epidemiological studies before we can start to draw those comparisons and those conclusions. I often have to think about tools and their risks so that I don't get surprised. And one of the things that has to be contemplated is -

Rob Wiblin: They'd kill other insects, right?

James Tibenderana: Potentially, but there is an effort to reduce the potential for other insects. But then once you need to dispose of the baits, what happens? What's the disposal? Could some of the toxic ingredients affect other insects, again, as an unintended consequence? So how do you deploy, create acceptance, and then when you no longer need those tools, what happens and how does it affect communities? How does it affect the environment?

James Tibenderana: Those are some of the questions that as an implementer I would want some answers to, because that helps with the adoption. What we want to avoid is situations where we have tools that have potential waiting for scaleup. We really want to have a situation where a tool is proven to work, a recommendation is made, and we can rapidly go into scaleup - a similar story that we've had with seasonal malaria chemoprevention.

Rob Wiblin: You mentioned earlier this other approach of vector control, which is spraying a house with insecticide, such that if the mosquitoes land on the wall, then they pick up this certain insecticide and they die. As I understand it, that's not something that Malaria Consortium promotes in particular. Is that because it's just not a good fit for the organization, or because it's maybe not the most cost-effective way of preventing malaria?

James Tibenderana: Indoor residual spraying is highly effective, and does have a very important role to play within a comprehensive malaria program. In the organization at present, it isn't a good fit, because it really requires a logistic delivery platform working obviously very closely with governments. You need to have sprayers. So we've attempted it in the past, we've done it in the past. But it's not been part of our approach or strategy currently.

James Tibenderana: We are, however, involved in advising governments on the kinds of insecticides to use in the IRS programs. So one of the programs we work on with President's Malaria Initiative US government funding - led by Act Associates, one of our partners - is that we provide technical assistance to the programs. We look at the evidence, we work with them to develop their integrated vector management plans, their insecticide resistance management plans, that allow them to make choices as to which insecticide to use in which location. So on the technical side, in terms of advice, we are heavily involved. But in terms of the delivery we aren't.

Rob Wiblin: Yeah. It doesn't have a lot of complementarity with delivering pills, I guess.

James Tibenderana: No, it's very different. It's really different. We have the capacity to do so if we wanted, but we don't feel it's a good fit. But it certainly is a cost-effective and valuable tool within the toolbox.

Symptoms [00:58:00]

Rob Wiblin: Alright so we've now spoken a bunch about two emerging ways of tackling malaria, that is vaccines and new forms of vector control. I'd like to come back and learn more about malaria and its treatments because there's a fair bit of fundamental stuff I don't know.

Rob Wiblin: So if I got malaria now, I think the classic symptoms are kind of nausea and vomiting and really bad fever, right?

James Tibenderana: Yes.

Rob Wiblin: Are there any other important symptoms that people should have in mind? I guess you feel like total rubbish, from what I've heard.

James Tibenderana: Yeah. So you get fever, you have vomiting, nausea, some people get muscle aches, joint pains, you could have sort of drowsiness. It can then become more severe where you actually start to lose consciousness, you're very weak. Some children can't even sit up. The vomiting, if it's persistent, you really lose energy. And then really very severe malaria, you start to get pale and that requires real rapid reaction.

Rob Wiblin: I see, yeah. I guess people are familiar now with long COVID, these long-lasting effects for weeks, months, possibly years. You can have these enduring effects where you just aren't as energetic and able to do things as you were before. That's an issue with malaria as well, right, this ongoing lethargy?

James Tibenderana: Yes. There are some sequelae that can happen, especially with severe malaria. There's some neurological sequelae where cognitive function is impaired, even memory can be impaired, as a result of a combination of the disease. And sometimes previously, when we were using quinine as the treatment, you could even get a type of blindness called cortical blindness. Even motor function in children and adults can be compromised. And then you have cognitive function. Children can return back to school and not be as sharp and functional as they were before the episode of severe malaria. There is a trend that sometimes kids who've had severe malaria have an increased risk of getting it again. Multiple episodes of that can really be devastating to a child's cognitive function.

Rob Wiblin: I think you've had malaria, right? So you could speak to this from personal experience.

James Tibenderana: Yes. I can speak to it from personal experience, but I think what I must stress is that I'm one of the lucky ones. Yes, I have had malaria. I probably could have died from malaria, if not for the fact that my parents were quite vigilant. But I want to stress that I'm a lucky person. There's so many others who've had malaria and have not lived to see their fifth birthdays. WHO estimates that about 627,000 deaths occurred of malaria in 2020. So for one of me, I want us to keep in mind the 627,000 who have not been able to survive and sit here.

James Tibenderana: And so yes, malaria is personal because I've had it, but I have also seen mothers, parents struggle with the loss of their children. I've literally looked at children in front of me die because of the consequences of malaria. So it's a personal thing, not because I've had it, but because of those who don't survive and those who have the neurological sequelae of this disease. I think that, for me, is where I would stress the issues, rather than myself who was very fortunate to survive it.

James Tibenderana: In terms of numbers, I would just refer back to the World Malaria Report, which points out that about 241 million cases of malaria occurred in 2020. I've mentioned 627,000 deaths from malaria: 90% of that is in sub-Saharan Africa, and largely children under five, as well as pregnant women. It's important to remember that malaria also impacts the survival of the fetus - you can have stillbirths and low-birthweight children - so it's a disease that really is really devastating. WHO has also estimated, I think, since 2000, in the last two decades, about 1.6 billion cases of malaria have been averted.

Rob Wiblin: By...?

James Tibenderana: With all the interventions that we've used: nets, SMC, treatment, diagnostics. The variety of things that we've been able to deploy since the year 2000. And about 10.6 million deaths have been averted. You can imagine just those numbers for a disease that, as I've stressed, is really a huge burden on the health of individuals, but also on the economies. On average, malaria endemic countries gross lower by about 1.3% per annum.

Rob Wiblin: Why is that?

James Tibenderana: I think malaria is a consequence of poverty, but malaria itself can contribute to poverty.

Rob Wiblin: I guess it's just how you were saying it destroys people's red blood cells, and then I guess they're not as fit and energetic as they would've been otherwise, which makes it harder to just get anything done.

James Tibenderana: Yes, productivity is affected in terms of adults, but also the time that households spend looking after sick children. If a child is sick and needs to go to hospital, the mother will have to spend time. Literally, she should be on the farm or she should be tending livestock, but can't do that. If the child gets severe malaria, the child may end up spending anywhere between five to seven days in the health facility, so there's time taken away from livelihoods.

James Tibenderana: There's also a cost: the cost of treatment, the cost of diagnosis. On average, a child in sub-Saharan Africa will experience anywhere up to about six episodes of malaria per annum - I think on average, it's about three. Each of those episodes is a cost that often is borne by the household: either because they go to the private sector, or even if they're accessing public-sector services that may be free, there's the transportation costs, so the numbers start to add up.

James Tibenderana: And if that child gets severe malaria, then the costs almost quadruple. You're talking something of the order of about $20, even up to about $30 per episode, because of the variety of things that they need to be able to either add to what is provided in the public sector, or if they're in the private sector, those are the additional things that they're going to need to buy.

Rob Wiblin: That's something like 5% of annual household income in some of these places, right?

James Tibenderana: Yes.

Rob Wiblin: So we're talking the equivalent of many thousands of pounds, basically.

James Tibenderana: Exactly. It really is a catastrophic cost. Oftentimes, they may not actually have that money and have to borrow it or sell livestock to generate that income. It also causes delays when households don't have that money. Severe malaria is one of those diseases that you're really running against time, so you really have to get that child into a suitable health facility that can manage severe disease as quickly as possible. And if you don't do that because you're waiting to sell a goat or a cow, or wait for a decision on how you can spend the last few dollars in the household, that really causes delays.

James Tibenderana: So you find that some of these kids come to the health facility when they're really very sick. A child could be in a coma or a child could be very anemic, meaning that their red blood cells are not sufficient and don't have the capacity to carry the amount of oxygen that they require.

Rob Wiblin: To grow healthily.

James Tibenderana: To grow healthily and operate physiologically. And so, children show up and they're really very ill and the clock really is ticking.

Preventing the spread [01:06:00]

Rob Wiblin: What are the options for preventing the spread of malaria?

James Tibenderana: Malaria prevention currently relies heavily on insecticide-treated nets. Insecticide-treated nets are basically a barrier that is put over a bed that provides a physical barrier to the mosquito, but also has a chemical that is within the lining of the net that can either repel the mosquito, or when the mosquito comes in contact, kill the mosquito. So that's one of the tools.

James Tibenderana: Then you have drug-based tools like seasonal malaria chemoprevention, where a medicine is given to a child, and that medicine creates a therapeutic barrier. For example, when a mosquito introduces sporozoites, those sporozoites will not be able to be established in the child. Or if that child has parasites when they're given the medicine, then it will clear those parasites.

James Tibenderana: And then you have indoor residual spraying, which is the use of an insecticide that is put on the wall indoors that, again, has the ability to repel the mosquito, but it also has the ability to kill the mosquito if it comes in contact.

Rob Wiblin: If it lands on that surface.

James Tibenderana: If it lands on that surface. So we've relied heavily, I would say, on insecticide-treated nets, on indoor residual spraying, and these drug-based tools.

Rob Wiblin: What about getting rid of still water where mosquitoes can breed? Is that an option as well?

James Tibenderana: Larval source management is an option as well. Yes, getting rid of breeding sites. But it depends on the context. An example is Anopheles gambiae in Africa just needs a footprint of rain water to establish itself. It doesn't need a lot of water; it just has to be a puddle, a pool of fresh water where it can breed and it can establish itself. So it's very difficult in some locations to try to get rid of the breeding sites. But then there are some locations where the breeding sites may be well defined and you can use larval source management, where you put a larvicide that can get rid of the larvae or constrain the larvae's development.

James Tibenderana: I've seen a lot of documents talking about clearing bushes, but that really doesn't impact malaria. But you have situations where you do want households to avoid having empty containers, tyres where there could be puddles, things like that that can contribute to the number of breeding sites.

Rob Wiblin: That makes sense. Sounds like there's some species where it's easier to get rid of them by draining the sources of water, because maybe they need larger bodies of water for a longer period of time. But you're saying there's particular ones that spread malaria that really don't require very much water and they don't require it to be there for very long. So the idea of just draining all the lakes is not going to fix the problem.

James Tibenderana: Anopheles gambiae doesn't need a lot of water. And I think there are different species - there's Anopheles gambiae, there's Anopheles funestus, there's Anopheles arabiensis - and they tend to have slightly different breeding sites, but they also coexist. So you have situations where during the rainy season, Anopheles gambiae may be prevalent. And then during the drier season where you have less water available, you have species like Anopheles funestus or Anopheles arabiensis that could establish itself. And so with those combinations, you can have yearlong transmission, because you have these mosquitoes that are able to breed in different conditions.

Rob Wiblin: I see.

James Tibenderana: As I've mentioned, I think the distribution of mosquitoes does contribute to the transmissibility of malaria.

Rob Wiblin: When someone has malaria, what are the treatment options, and how effective are they?

James Tibenderana: Malaria presents itself in different ways. Uncomplicated malaria - some call it "simple malaria," but there's no malaria that's simple - usually presents itself with a fever, and children may have vomiting, they may have diarrhea, they may have other mild features. And when tested with a malaria test - it could be a rapid malaria test, or it could be microscopy - when they're positive, they are given a treatment called artemisinin-based combination therapy. It's a combination of artemisinin and another antimalarial that when given together are more effective.

James Tibenderana: In Asia and some other parts of the world, chloroquine is used for the treatment of vivax malaria. And so between artemisinin-based combinations and chloroquine, one is able to treat falciparum and vivax malaria - that's for what we term "uncomplicated malaria."

Rob Wiblin: So if I got malaria tomorrow, and then as soon as I had symptoms I started taking one of these therapies, how much is that going to reduce my symptoms or my risk of death?

James Tibenderana: They're very effective. Artemisinin-based combination therapies are highly effective. There are studies that go on to monitor their effectiveness. And I'm sure your listeners have heard of artemisinin resistance, which we know is establishing itself. But on average, artemisinin-based combination therapies are highly effective.

James Tibenderana: Complicated malaria can present as a child in coma, or an adult who is not immune in a coma, a child who is anemic and not able to carry enough oxygen that they require. They often are very, very pale and will sometimes require a blood transfusion. So for severe malaria, one has to use an injectable form of artesunate, and that is either given intravenously or it is given as an injection in the muscle. It is more effective when it is given intravenously, because it is very rapid acting. And within a couple of days, a child who was literally in coma could be up sitting and breastfeeding or interacting with their environment.

James Tibenderana: In addition to that, it's important that the referral of a child to the health facility is fast enough for that child to really get the benefits of being in a health facility. Rectal artesunate is a tool that is used at the community level. It's a suppository of artesunate that can be given by a community health worker to a child who has danger signs, signs that I've said: a child who is very drowsy, a child who has a very high temperature, a child who is in coma, or, as I have mentioned, a child who's really pale. The community health worker can give a rectal suppository that can start to initiate the treatment to buy time for that child to get to the health facility.

Rob Wiblin: Before they've deteriorated too far.

James Tibenderana: Before they've deteriorated too far. And then as I mentioned, artesunate is given in the health facility and there may be situations where blood transfusion is required because some of these children really are very pale, very anemic, and they need a blood transfusion to save their life.

Rob Wiblin: So the seasonal malaria chemoprevention protocol, I didn't know this, but it's basically for four months or so of the year when malaria is most common. Basically a healthcare worker comes to a house, I guess possibly a school, and every 30 days or so, they'll give the child two tablets on the first day, and then leave them three more tablets, I think, to take on days two, three, four. And you have to do this on a monthly cycle, every 30 days coming back. Basically there's one tablet you have to take once a month and then another drug that you're taking for four days out of the month, and you have to do it on a fairly rigorous schedule. Is there anything to add to that?

James Tibenderana: Yeah, there are various approaches. What we've found in terms of equity is a door-to-door approach gives you equitable distribution. But you also have a fixed-point approach whereby you can identify a fixed location - it could be a health facility, it could be a school - a location that is pretty safe and accessible for households to bring their children and then get treated. And as you've rightly said, we do directly observed therapy for the first dose when the seasonal malaria chemoprevention medicine, sulfadoxine-pyrimethamine and amodiaquine, are given on the first day and then for the next two days, the caregiver is given the additional tablets (which are amodiaquine) that they then take on day two and day three.

Rob Wiblin: Got it. Nice.

Why we haven't gotten rid of malaria yet [01:15:07]

Rob Wiblin: Just to reiterate something I said in the intro, GiveWell estimates that it costs about $6 or so to provide seasonal malaria chemoprevention to an extra kid for a year through Malaria Consortium, and that's including all of the costs that are involved. And they expect Malaria Consortium to save an extra life for each incremental $4,500 that gets spent.

Rob Wiblin: A 2021 paper from just last year that Malaria Consortium contributed to estimated that the cost of death averted ranged from $533 in Niger to $2,256 in The Gambia. That's like a couple of fold lower costs. I guess GiveWell tends to be a bit more pessimistic. They do all of these adjustments to consider all of the ways that things could go wrong and all of the incidental negative effects, which tends to drive up the cost per life spared.

Rob Wiblin: But the basic story is we have all of these different ways of preventing the spread of malaria: we've got the nets, we've got the insecticides, we've got chemoprevention. We've got these treatments that people can take once they have malaria. And they're all pretty cheap. They're not that difficult to distribute.

Rob Wiblin: I asked for audience questions as I usually do on Twitter, and one audience member asked, "How is it that we have all of these options for preventing the spread of malaria? And it's not as if people don't know about malaria - The Global Fund, the Bill & Melinda Gates Foundation - there's lots of different groups that are interested in this, as are governments around the world. Why is it that malaria is one of the remaining top contagious diseases that does an enormous amount of damage, yet is so preventable? Why haven't we gotten rid of it?"

Rob Wiblin: Sorry, this sounds a little bit accusatory, but it's just interesting to think. I guess there's always going to be some disease that's the next one that's ready to be gotten rid of.

James Tibenderana: It is a valid question. We ask ourselves that question oftentimes - especially, I think, more recently. But malaria is complex, and the dynamic between the vector, the parasite, and the human host is complex. And we constantly have to keep referring back to that dynamic, but also the transmissibility of malaria.

Rob Wiblin: So you could flip this on its head and say, "Given that one person can infect 3,000, how is it that we've made any progress against this, given that it can be phenomenally contagious?"

James Tibenderana: Exactly. Exactly. I think we do have to appreciate the success that we've made. But we could do more. I think what you will see from many of the figures is that the coverage gap still exists. So for some of the interventions, for example, intermittent preventive treatment for malaria in pregnancy, the coverage of that is pretty low and we've not been able to achieve the high coverage that we've seen with seasonal malaria chemoprevention or that we've seen with nets in those tools.

Rob Wiblin: And the key issue is funding there, primarily?

James Tibenderana: Yeah. I mean, even with nets, we still have a huge access-use gap: even then we still have a gap in terms of those who could benefit from nets. So I think one is, there's a financial gap: the funding needs are still far greater than the funding that exists. And that means that we're not able to either achieve coverage because of numbers, or that we're not able to put the appropriate systems around the tools - for example, the surveillance or the monitoring as well as getting the commodities in at the right time to really maximize the value of the tools that we are deploying. So I think there's a financial gap.

James Tibenderana: Then there is a use gap. Engaging communities requires substantial effort, but also a relationship that is able to be based on trust and to be based on ownership. Sometimes one can make an assumption that you get nets and just take them to the community and they will use them. That may not be the case if you've not done the engagement right, and if you've not really appreciated some of the barriers that the households could be facing. For example, hanging a net requires string and nails.

Rob Wiblin: Which people may not have on hand.

James Tibenderana: People may not have that on hand. Hanging a net sometimes presupposes that you have a bed to sleep on. There are situations where people will not have sleeping surfaces, but obviously you can tuck the net below a mat. And then there are situations where even the household is smaller than a net. So there are these barriers that are context specific that require you to really tailor the deployment of your intervention to that context. And without the resources, that tailoring sometimes is missed, because we end up standardizing - you have a standard net, standard size, standard color, and that's distributed - or you have a situation where we're not able to engage the private sector.

James Tibenderana: So for example, the diagnostics and the treatment, we will work with governments to introduce that in the public sector. But then in a country like Nigeria, 60% of the population seek treatment in the private sector, and you're not doing anything with the private sector. And so the quality of diagnosis and treatment in the private sector may not be similar to what is happening in the public sector, and yet you have a huge proportion of people who are being treated in the private sector. And you see that in many countries, where the private sector is a main source of treatment as well as advice that's given to families who have malaria.

James Tibenderana: So there's a funding gap, and there's the issue of how to engage the communities, as well as how to engage the private sector, to really tailor those tools to fit the context. And then I think there is a potential gap in the enablers that we need: social behavior change, the behavior change that's required to really get these tools adopted and used consistently. So you could have situations where during the rainy season or when the density of mosquitoes is high, bed net use may be higher. And then during the dry season or during the very hot season or situations where the mosquito densities are very low, then the use may not be as consistent.

Rob Wiblin: Sounds like how I would behave.

James Tibenderana: Exactly. Exactly. So we need behavior change in a consistent manner that continues to engage communities with the tools that we are deploying with governments.

James Tibenderana: And then surveillance and response: the data that's required to understand what's going on, the data that's required to identify where there may be inequities or where there may be populations that are currently not either engaging in the public health sector, or may not be accessing either prevention or treatment services. And you need that data at the right time to be able to make decisions, to ensure that those communities are able to provide access.

James Tibenderana: Then the response side to surveillance is that when things are going wrong, you need the data to be able to identify what's going wrong and to be able to react. Oftentimes those data are not readily available and we tend to be reactive and we don't have the capacity to really move into a more anticipatory or even a more predictive mode that allows us to be able to anticipate changes or risks that are happening in that context and reacting. So that is one element that I think we could do better when I speak about enablers.

James Tibenderana: And then I think the last thing I would say is that our existing tools that have given us the success so far are starting to face risks that we need to mitigate.

Rob Wiblin: What are those?

James Tibenderana: Insecticide resistance. Indoor residual spraying and insecticide-treated nets contributed something like 70% in the decline over the last two decades. But insecticide resistance is starting to have a potential impact. Those tools are still effective, but there are situations where there is data that says that a particular insecticide may not be working in a particular location, or a particular net may not be as optimal in that setting as it could be if insecticide resistance was absent. And making those choices not only requires the data, but also requires the new tools - so new insecticide, new nets that one can deploy to those locations - and coincidentally, those new tools are more expensive than what we currently have.

Rob Wiblin: I see. Which is why you weren't already using them.

James Tibenderana: Exactly. One, we weren't using them because they weren't developed. But they've taken a huge effort in research and development to develop them. So there's a tradeoff: as the tools get more expensive for a constrained budget, there's a loss in coverage. With indoor residual spraying, the number of households that can be sprayed with the new insecticides reduces. So over the years, you've actually seen the coverage of indoor residual spraying in some countries start to decline.

Rob Wiblin: Because the budget's the same, but the cost per house is higher.

James Tibenderana: Exactly. And same thing with nets. Nets are highly effective, but there is data that in some locations there could be pyrethroid resistance. Pyrethroid is the insecticide that is present on the net. There is a new synergist that's now put on some nets with pyrethroid called PBO, piperonyl butoxide, that really enhances the effect of the pyrethroid so that the mosquito that may not be killed by pyrethroid alone will be killed by this combination.

James Tibenderana: So in those locations where there is evidence of pyrethroid resistance, one would like to deploy these PBO nets. Currently I would say the price of both the pyrethroid and the PBO nets are probably quite similar. But for the next generation of insecticides that may be even more potent against some of these mosquitoes, there will be an increase in cost, an incremental cost that's going to have a potential tradeoff in coverage. And so, whereas we're experiencing a funding gap, I think that funding gap is likely to increase.

James Tibenderana: Then you have drug resistance that is also starting to really establish itself. Artemisinins have been our mainstay in terms of artemisinin-based combinations, and for different combinations, the different antimalarials that are combined. In Southeast Asia we've seen artemisinin resistance really have an impact on the choice of antimalarials that can be used. Presently we don't have loss of therapeutic efficacy - and what I mean by that is that if an individual takes artemisinin-based combination therapy in most parts of Africa, it will work - but we're starting to see molecular markers for artemisinin resistance starting to appear.

James Tibenderana: They are not contributing to the loss of effectiveness, but they need to be monitored because that could be the beginning of a potential situation where artemisinins themselves could be compromised in terms of their effectiveness. But it's still a long way off, so I don't want to create a situation where people think the ACTs aren't working. The ACTs are working. But I think as a risk, one has got to be attentive to the fact that in some years' time, we may need to be using either triple combination therapy - where instead of two antimalarials, one is using three - or other antimalarials that we know manufacturers are working on in the pipeline, that could potentially be as effective as artemisinin or even more effective.

Rob Wiblin: So I guess the good news is that we have backup treatments and backup insecticides and so on that we can escalate to if it becomes necessary. The downside is that they cost more, so the budget gap is going to grow larger unless there's a lot more funding provided.

Rob Wiblin: I guess the question I asked there about why is there still any malaria has this kind of negative edge to it, but we should emphasize that between, I guess, 2000 and 2017, the number of deaths from malaria roughly halved or so. So massive progress is made using these techniques. So the question is, "Why haven't we gotten rid of all of it?" rather than "Why haven't we gotten rid of it at all?"

James Tibenderana: Because the next part of the journey is more complex.

Rob Wiblin: So it sounds like, on the current margin, with extra funding, we can just reach more people with these existing treatments. So there's people who are easy enough to reach if there's money for it. But I imagine at some point, the problem would not become funding only, but also just that the places are very hard to get to. It seems like there's very high rates of malaria, for example, in some really rural parts of the DRC, which I imagine is not a trivial location in which to operate, just logistically. And I suppose if that's the margin, then it becomes maybe also an issue of skill in delivering and figuring out how to operate in such locations.

James Tibenderana: Yes. Rob, I would say that we can achieve more. Certainly, with more funding we can achieve more, because we still have a coverage gap that is huge for many of these interventions. So even with our existing interventions, we can do more. Seasonal malaria chemoprevention, for example: we have got to 31 million kids out of the 40 million eligible kids. We should be at 40 million. And soon we will have a situation where seasonal malaria chemoprevention could be introduced into new geographies, which will then expand the eligible population even further, which is a gap that needs closing. With nets, in some locations we're still at about 60% coverage, so there's still a 40% gap that needs to be filled. So I think even with current tools, with additional funding -

Rob Wiblin: The scaling is straightforward.

James Tibenderana: - the scaling is straightforward, and we can make progress. And even with insecticide resistance, as I've tried to elaborate, there are mechanisms to rotate insecticides, to make choices about which insecticides to introduce. There are four classes of insecticides, so you can rotate or you can introduce a mosaic type of distribution.

James Tibenderana: So I think even with our current tools, there's more that we can achieve if we are able to address the funding gap. And if we are able, as I have stressed, to really bring in these enablers in quite an aggressive manner - the social behavior change, the surveillance and response - as well as the capacity building: making sure that the ministries of health, making sure that the partners really have the technical know-how as well as the management skills to be able to deploy these interventions to high coverage.

James Tibenderana: Then there's the delivery to hard-to-reach environments, or the delivery that has to happen when you have conflict or displacements, because those disrupt the malaria ecosystem and create vulnerabilities. So in conflict regions, people get displaced and they don't take their nets, and they may move from areas with low transmission into areas of high transmission.

Rob Wiblin: Healthcare services aren't available.

James Tibenderana: And healthcare services aren't available. And as I've mentioned, there are parts of the world where reaching communities can be very difficult. Even just getting nets during the rainy season can be a challenge. You've probably seen photos of cars getting stuck, lorries and things like that getting stuck. So there are logistic challenges, but they are surmountable if we are able to cover that funding gap.

What James is responsible for as technical director [01:30:52]

Rob Wiblin: Over the last five years or so, what has been your bread and butter as Global Technical Director at Malaria Consortium? What are you responsible for primarily?

James Tibenderana: I'm responsible for quite a bit. First of all, I work with a team of experts and colleagues who really are dedicated and committed to the mission that we have as an organization. In the UK we have a team of experts, but also in our country offices, we have nationals who are really engaged and really heavily involved in activities in those countries. So, working with the team, mentoring some of our experts, but also listening to them in how they're designing new interventions or designing programs that can deliver some of our new interventions. It's also critical that we quality-assure our work. When we're deploying tools, it's important for me, at my level, to really think through what some of the risks are and ensure that we've mitigated those risks.

James Tibenderana: I'm also a member of our global management team that oversees the strategy, the financing, and the decisions that are made to ensure that as an organization, we continue to add value to the ecosystem. We've just recently launched our new strategy, so I've spent quite a bit of time with my colleagues in designing that strategy, and I think we're looking forward to implementing that strategy over the next five years.

James Tibenderana: I spend a lot of time giving technical assistance to governments. Governments have requirements, we have needs, and really supporting governments in how they develop their strategies, what their policies are - and ensuring that those policies are either aligned with WHO guidance or aligned with the evidence that we and others generate, and demonstrate best practice. Then, I would say I do quite a bit of looking ahead to some of the new tools that we need to be paying attention to, to potential disruptions that could unsettle some of the work that we do, and really looking out for that, as well as the potential mitigations.

Rob Wiblin: One thing I didn't appreciate when we booked this interview is just how many academic papers your name is on, and also just how many publications Malaria Consortium is involved with. It seems like this is a big part of your work: doing research into what's the cutting edge? What's the very best way of delivering these treatments? Which treatments work the best? How effective are they? Do you want to talk about that for a second?

James Tibenderana: Yes, Rob. I would say writing and collaborating is a huge part of my role. Actually, one of the things I probably could have done even better is to have written more. Because getting that information from the field, and being able to document it and share it, for me, is an important part of being technically excellent in one's role - in that if you're not able to document and share, then the experiences that you have don't get disseminated to others, but also don't get peer reviewed. I think a big element of publications is having yourself potentially acknowledged or criticized by other experts in the field. I think putting work out there for peer review is an important quality-assurance measure, for me as an expert, but also the organization as a whole.

James Tibenderana: For example, last year, Malaria Consortium published I think 39 papers, which is one of the highest numbers we've achieved since our inception in 2003. And that took a huge amount of effort from teams, from even management, making sure that we can provide the funding for open access and also making sure that our experts and teams in-country have the opportunity to spend time, read, write, really challenge themselves. So writing is an integral part, and I do feel very strongly that as an organization and as technicians in the field, being able to document and share is critical.

James Tibenderana: Malaria Consortium is an evidence-based organization, and we do the research within where we work to ensure that we are able to generate that evidence and share it. We find that being evidence-driven creates a certain level of trust with our partners and with our governments. When we speak about some of the things that need to be changed, or some of the tools that may not be working effectively, governments have learned that we do that from an evidence base, as opposed to, "It's James's opinion or someone else's opinion." That's a critical part of what we do as an organization.

Rob Wiblin: Just quickly, what are the countries that you operate in? And I guess malaria is the key focus, but Malaria Consortium also works on a few other diseases and programs as well.

James Tibenderana: Yes. Malaria is I think our major focus, but we do work on other diseases, and I'll explain a bit about that. We're currently based in 11 offices in Africa and Asia. I can mention them: Nigeria, Togo, Chad, Burkina Faso, Eastern and Southern Africa, Uganda, South Sudan, Ethiopia, Mozambique. And then we have offices in Thailand, Cambodia, and Myanmar. Our headquarters is based in the UK in London, and then we have an office in the US.

Rob Wiblin: Malaria is, I think, where the majority of the money goes, but it seems like maybe you've built this infrastructure to treat malaria, and then are you layering other disease treatments on top of that? Or is it more integrated than that?

James Tibenderana: It's a logical progression. Malaria was, I would say, our entry point into the variety of things that we do. I think by starting with malaria, we appreciated that a child who comes in with a fever will potentially have malaria, but could have other diseases as well. For example, pneumonia. It made sense that in targeting malaria, we are also able to provide the diagnostics, as well as the treatments, for some of the other diseases that that child was facing, so that we are treating the child as a whole.

James Tibenderana: In addition, we have infrastructure for delivery, infrastructure for our research, and our technical assistance that allows us to tag on other technical assistance on other communicable diseases. As you rightly said, we do have a huge infrastructure - for example, for the delivery of seasonal malaria chemoprevention - that we can use to tag on some of the other cost-effective or impactful interventions that could benefit from that platform.

Rob Wiblin: I think vitamin A supplementation is an example of that?

James Tibenderana: Yes. For example, vitamin A supplementation because of the need, the fact that in locations where we are deploying seasonal malaria chemoprevention, the impact of vitamin A supplementation would contribute to improving the health of children in that age group. So, by looking at the needs of the context in which we're working, we are able to identify what to layer on and what delivery strategies to use.

Rob Wiblin: I did an interview with Karen Levy. She mentioned that people very often want to group together diseases, or get an organization working on a bunch of different things, without actually understanding what other synergies are available. She was saying that people want to say, "We'll make an organization that works on neglected tropical diseases" - but that is not natural in any way, because they tend to be in different locations and spread by different mechanisms. So there's not actually any synergies treating those kinds of things.

Rob Wiblin: She was suggesting exactly what you guys have done, which is build this infrastructure and then say, "Given that we are delivering tablets at this particular age, what else can we deliver at that point that makes a ton of sense?" And I guess this allows you to be more cost effective, because you have twice as much impact without having to do that much extra work.

James Tibenderana: Yes. We are very particular in terms of how we extend ourselves, so that we are really maximizing value that can be achieved. And we are conscious that the health system itself also has a certain capacity, and as we roll out malaria interventions, we are constantly looking out for opportunities where we can strengthen the health system so that the health system can cope with some of the other interventions that we can lay on.

James Tibenderana: We've really been big in deploying community-based health services. Seasonal malaria chemoprevention is one, but integrated community case management of malaria, diarrhea, and pneumonia is another - where we've worked very closely with community health workers in different locations to really understand what they are able to do, and the effective use of that platform to reach a large number of children and really reduce some of the inequities that we currently find in health systems.

Malaria Consortium's current strategy [01:39:59]

Rob Wiblin: Let's talk about Malaria Consortium's current strategy, why you do things the way you do, and how you make those decisions. How do you split your funding between the various different options? It seems like the chemoprevention is the biggest category, and then there's nets, and then I guess other things, is that right?

James Tibenderana: Seasonal malaria chemoprevention, at least in 2021, really is a huge component of our delivery. I think it's probably close to more than 50% or about 50% of our total income per annum. Now the way Malaria Consortium works, we're very integrated into the health system. So the choices that we make tend to be embedded within the malaria strategies at the country level, aligned with the global technical strategy that WHO has provided as normative guidance. So we work very closely with governments in Africa and Asia, to help them make those choices based on the evidence - that either they generate, others generate, or we generate - such that their strategies are evidence based. And within those strategies, we then make choices in terms of, one, Malaria Consortium as an organization, our strategy, but also looking at the combination of interventions that are likely to achieve the maximum impact. So we work very closely.

James Tibenderana: Another thing to understand in terms of our business model is that we have to generate new business by bidding for programs that donors put out there. So if the US government, or the UK government, or The Global Fund put out a call and say, "We need a program that delivers nets in a particular country, or a program that delivers SMC in a particular country," then we would be competing with other partners to try and get the most value for money - the most technically sound proposal that then gets approved by the particular donor. So a large part of what we do is based on what donors themselves will prioritize, or what requirements they have for their funding in countries that have strategies that are evidence based.

James Tibenderana: It's only recently, I think probably in the last five years, where we are having access to more unrestricted funding that allows Malaria Consortium itself to start to make some choices. Otherwise, a large proportion of our income is restricted, either because of a donor priority or a country priority, or - if it's philanthropic funding - restricted to a particular program, and we then deliver that program cost efficiently, trying to achieve the highest value for money.

James Tibenderana: But over the last few years, we are now starting to have unrestricted funding, which is really fortunate. That allows us to make some of those choices in the programs that we support governments with, but also in some of the research that we're able to do that can complement what other programs are doing, what other donor priorities there are, and to some extent, addressing the needs that countries have.

Rob Wiblin: Is that unrestricted funding coming from Good Ventures and effective altruist-flavored sources? Or is it coming from elsewhere?

James Tibenderana: It's a combination, but I think it's largely coming from philanthropic sources, just giving on our website. We've got Malaria Consortium US, who are heavily involved in generating funding as well. So it's a variety of sources that I would say is uniquely giving us that chance to make choices. An example is a piece of work we did on the interaction between COVID and malaria. So when the COVID pandemic started, we had seen the modeling and the figures that showed that the interaction between malaria and COVID was going to be disastrous.

Rob Wiblin: In what way?

James Tibenderana: Because of the health systems being weak, and the fact that you have these comorbidities, where you won't have access to treatment and diagnostics because of disruptions. And then you have a pandemic coming in, and that mix would really lead to high mortality rates, high morbidity rates.

James Tibenderana: And we launched a study in April to look at that interaction from a clinical perspective, but also from a molecular perspective in terms of laboratory indices. We were very fortunate to be able to react that rapidly, because we had unrestricted funding. At that time there weren't calls that we could compete for, right? And we very rapidly set up a study in Uganda that could look at SARS‑CoV‑2 and malaria plasmodium falciparum, the interactions. That's a study that was published last year and has really got quite a bit of media attention, and also our target agencies have been interested. So that's an example of what we can do when we are able to make our own choices with unrestricted funding.

James Tibenderana: Then we have a couple of other programs where we are making those choices by identifying what the need is, but then identifying what the potential for impact is now and looking two or three years into the horizon to what some of the questions could be - such that we're able to start either the research or the programming early to be able to have those answers by the time those questions come to play. And then some of the results measurement around some of our programs, that either we've not been able to get funding from the donor or we would prefer to do more elaborate measurements. So we can use some of that funding for that purpose.

Rob Wiblin: So until recently, most of your programs were running on a kind of contractual basis, where an aid agency or potentially a local government would say, "We want to deliver nets to tons of people, or we want to deliver these drugs to lots of people. We need to find a partner to actually do the logistics and the delivery." And you would say, "We could do that," and you take an amount of money and do it. And I guess that's still part of what you do, but now you've got more funding that goes to you specifically, and you can decide what's the best way to delegate this funding.

James Tibenderana: Yes.

Rob Wiblin: Interesting. So as I understand it, Malaria Consortium has been one of GiveWell's top-recommended charities for four years or so - I think since 2016-17 - and it's had higher or lower prominence. I think at the moment it's very prominent; I think it might be the first thing on that page. I think I'm right that they largely want to fund the seasonal malaria chemoprevention. So maybe that funding is coming in as kind of restricted?

James Tibenderana: Yes.

Rob Wiblin: It is. I think GiveWell has thought a bunch about this issue of restricted versus unrestricted funding. And as you're pointing out, there's big benefits to having unrestricted funding available, because it means that you can react as opportunities become available. You can respond more quickly. Why do you think it is that GiveWell wants to maybe tie your hands to some extent, funding the chemoprevention, rather than say it's up to you what country you want to operate in and what you want to deliver?

James Tibenderana: That's a good question, Rob.

Rob Wiblin: I think actually someone from GiveWell might have asked this.

James Tibenderana: Obviously, as you know, GiveWell has sort of different funding mechanisms, and I think as a top charity, our seasonal malaria chemoprevention is the program that has been ascribed that status.

Rob Wiblin: That status, I see. Right, that's the thing that they can say, "We are confident it's evidence based."

James Tibenderana: You've got the evidence, the capacity, the organization efficiency, effectiveness, our reach - that's the program that is being highlighted within that status. And I think rightfully so; it is a strategy that is highly efficacious, is effective, and needs to achieve coverage where there are eligible children. There's no point having a strategy and 40 million kids, of whom some of them are not getting access to a highly cost-effective tool that can be deployed, right? The deployment is not rocket science; it's actually just logistics and good planning and making sure you have the financing that allows you to do that. Because with SMC, our planning cycle is always one year ahead, so we're constantly one year ahead of where we are at. And so you really have to be ahead of the game, working very closely with governments.

James Tibenderana: So I think there is certainly value. As I said, as a top charity, it's been the seasonal malaria chemoprevention that we've really scaled up, and we've also worked very closely with other partners to ensure that the funding we have can also catalyze. So for example, in Nigeria, it's not just philanthropic funding - you have The Global Fund, you have a variety of donors who are involved in seasonal malaria chemoprevention. So we not only deliver, but we're also working very closely to see how to catalyze, and to make sure that the coordination and the partnership that is required for maximum impact and scaleup is taking place at the national level and the subnational level. So we've been really fortunate in that regard.

James Tibenderana: I think GiveWell is open to looking at other programs. And what I think is key is that the amount of evidence - the information that GiveWell requires for it to make those decisions - is something that has to be made available.

Rob Wiblin: Yeah, I see. So I guess to some extent, they're restricted by what their promise is to their supporters and people who are reading them, which is, "We'll find evidence-based, cost-effective interventions." And they feel more comfortable saying that about the seasonal malaria chemoprevention than just giving to Malaria Consortium to do whatever they feel like, because then you could spend it on something that they don't have particular confidence in. It could be better, it could be worse.

James Tibenderana: Yeah. So I think it's the evidence, making the choices that really are adding value into the system. But I will say that as an organization, we have seen the value of unrestricted funding, whoever it is from. We are technically based, we are transparent, we're accountable, and we would increasingly like to see situations where we are able to make choices about some of the things we do in terms of the short term, but also some of the things that we can research or prepare for in the medium term.

James Tibenderana: We haven't been able to do that in the past, and I would say that it's something as an organization, if we are able to have more capacity to do that, it would certainly benefit us, as well as benefit the governments that we provide technical assistance to. For example, integrated community case management of malaria, or surveillance and response. If you try to do a cost effectiveness for surveillance and response in sub-Saharan Africa, it's difficult to get that number. You can get some numbers in terms of reactive case detection, these elimination strategies that have a surveillance component where malaria transmission is low. But if you look at that in a context of malaria in Uganda, in Nigeria, or DRC, you can't get a number.

James Tibenderana: But surveillance and response, from our perspective, is a critical intervention that needs to go alongside the other tools. Because increasingly, we are seeing it: you've got to be able to prioritize and make choices and react. You can't wait to have an epidemic, you can't wait to have a resurgence, then think about your solution. Or you can't not have the right data at the right time. And putting in that effort, and working with governments to make the data available, and share that data, and use that data for decision making at a subnational level and at a national level is very difficult to put a cost-effectiveness number or a cost to.

Rob Wiblin: Yeah. I think I might have had this misconception that in parts of Africa the climate causes malaria to be very common, but it's kind of at the same level basically every year - that it's always there at roughly a similar prevalence. It's a contagious disease, of course, and so it's probably going to have the same kind of spikes - like you suddenly get a local epidemic where tons of people get malaria all at once, and then maybe it fades away. And other areas, maybe it doesn't take off nearly so much, like we see with COVID, and like we see with the flu.

Rob Wiblin: I suppose something I had never thought about is that maybe you want to know where is malaria taking off this year? Then you can throw extra resources at getting the drugs to those places, and the nets in those locations, to stop a pandemic before it reaches extremely high levels of prevalence. Is that right?

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.

Rob Wiblin: It seems like the decisions would be things like, "Malaria is more prevalent here or malaria is increasing in prevalence here, so we need to invest more money in that particular location." Do we need something as sophisticated as machine learning to make these decisions? Is that going to add a lot of value beyond what a human decision-maker can do?

James Tibenderana: It will add value, especially as the data elements increase. Because as I've stressed, you have the parasite, the vector, and human behavior. So looking at the mosquito data: the breeding sites, the breeding habits, the human-biting elements. There are situations where the malaria mosquito is changing its habits, so rather than biting at night, some mosquitoes are starting to bite earlier in the evening, or later in the morning. Bringing that data together. The parasite data: what's happening in terms of some of the genomics, some of the changes that are taking place.

James Tibenderana: And then really the trend data: bringing those data elements together more comprehensively, to allow us not only to anticipate what's happening now, but also to anticipate what's coming forward. Climate change, climate variability is going to affect malaria. And the variability is going to increase and become more complex. For seasonal malaria chemoprevention, for example, we are constantly monitoring the start of the rainy season, the duration of the rainy season. In some of our locations, we've had to change from four treatments one month apart to five treatments, because the season of malaria transmission with rain is getting a bit longer. And there will be some locations where it is shorter, because of climate variability. And so you're bringing in climate data as well.

James Tibenderana: So these data elements I think will give us the opportunity to be a bit more precise in some of the choices that we make, but also some of the transitions. Now malaria goes down, you scale up. What happens if, as a result of success, a donor says, "We no longer need to support indoor residual spraying. We no longer need to support seasonal malaria chemoprevention. We no longer need to support nets." Right?

Rob Wiblin: Right. Yeah.

James Tibenderana: The transmission potential will exist. But then could you switch from one thing to another? Can you switch from indoor residual spraying to nets? Can you switch from seasonal malaria chemoprevention to integrated community case management? What are the switches that we need to be making as it's coming down? So we continue to maintain a cost-effective approach, and we continue to sustain the downward trend of malaria until we have those game changers - whether it's gene drive, whether it's the transmission-blocking vaccine - in which case, the decision making will probably be simplified.

Rob Wiblin: Yeah, that makes a ton of sense.

Elimination vs. control [02:01:49]

Rob Wiblin: A listener wrote in with a question. If you look at some countries in Africa like Uganda, Congo, Nigeria, you see rates of malaria that are 10 to 100 times what you typically see in Asia or in South America. The prevalence and the number of deaths is just dramatically higher, which is why about 90% of malaria deaths are in sub-Saharan Africa. They're saying, despite that, globally, quite a lot of money is spent on malaria control and even attempts of local elimination in South America and Southeast Asia, where malaria is already not very prevalent.

Rob Wiblin: The listener was kind of asking, should we reorient spending away from those places where malaria is already largely removed, and put more effort into places like Nigeria, where the prevalence is phenomenally higher and the death rate is very high? I'm sure you'll be loath to ever say that we should spend less on malaria control in Bolivia or in Thailand. But would we potentially save more lives if we did that, or would then malaria take off in these other places where it's been 90% reduced?

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.

Rob Wiblin: In the absence of gene drives, how practical is it to eliminate malaria, given that that would require you to have very good malaria control everywhere? It seems like you could almost always end up with some location that has the worst possible weather for malaria spread. And maybe has a civil war going on or something else that's preventing delivery of treatment and nets and so on. Then of course it could always spread from there potentially. It could always go back and potentially resettle other locations. We've managed to get rid of smallpox - it's the only human disease that we've managed to completely eradicate - and we're very close with polio, but I wonder with a disease as contagious as malaria, is it realistic to think that we can get rid of it completely?

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.

Rob Wiblin: You mentioned Nigeria. As I understand it, Nigeria just has a phenomenal fraction of all of the malaria deaths in the world. I think I've got 32% of all deaths globally in my notes here. Nigeria is a very big country, but still it's very disproportionate. Is there anything worth saying about how we can best go about malaria control in Nigeria specifically?

James Tibenderana: One is the resource gap, whether it's domestic financing or development assistance. There's more resources required because the coverage gaps are still huge.

Rob Wiblin: So that's the basic reason, is people don't have nets, people don't have -

James Tibenderana: Yes. I think that would be one major one. I think the other would be the private sector. And I'm not looking at the private sector as a challenge; I'm looking at the private sector as an opportunity. One has got to find ways to engage the private sector, because roughly 60% of Nigerians seek care in the private sector. So you can't just deploy interventions that are targeting the public sector - diagnostics, treatment should be accessible in both the public and the private sector.

James Tibenderana: And Nigeria is increasingly trying to see how to work collaboratively across the private sector, but it's certainly a challenge that needs to be addressed. Fortunately, things like seasonal malaria chemoprevention are equitable - because you're reaching whole communities, you're reaching children who may be in hard-to-reach environments - so that is agnostic of that fracture between the public and the private sector. But things like diagnostics, the right treatments, and quality-assured treatments require you to be able to collaborate across the public and the private sector.

Rob Wiblin: You're saying that most Nigerians, when they fall ill, they go to private healthcare providers, and they pay for that out of pocket, I guess. Is that a reflection of the low quality or low availability of government-provided healthcare in those locations?

James Tibenderana: It's a mix. It's geographical access, perceptions of quality, also time spent. You get your drug shop next to you or your patent medicine vendors, because they are providers that are mobile or very close to the home who you can very rapidly get to and get treatment without having to go and wait in a long line in the public sector.

Rob Wiblin: Honestly, it's exactly the same in the UK. If you really want to get treated and you don't have time, then it's faster to pay for a private provider.

James Tibenderana: And then the private sector is also dynamic. If it identifies an access gap, they will go.

Rob Wiblin: And move in first.

James Tibenderana: They'll move in. So they're quite dynamic and are responsive. They also have a variety of commodities. If you have a fever, they can give you a variety of things - sometimes not following national guidelines, oftentimes not following national guidelines - whereas if you go to the public sector, if you have a fever -

Rob Wiblin: They'll do exactly what it says.

James Tibenderana: Yeah, you do exactly what it says. You may not be able to give an antimalarial because that person is negative, but the person says, "Oh, by the way, I have a fever. So I need something." And the nurse says, "No, you are negative. We can't give it to you." So there's a variety of variables.

Rob Wiblin: Patients don't like that. Even if, I mean, it might be the right call, but patients don't like it.

James Tibenderana: Yeah. But I think it's a combination. Including access.

Rob Wiblin: Yeah. And you're saying if we're going to aim to control malaria in a country where 60% of doctor visits are with the private sector, then one thing you've got to do is improve treatment of malaria in those private hospitals or GP clinics. In what ways could they be better? And is that something that Malaria Consortium actively works on? Talking to healthcare companies in Nigeria to get them to do a better job?

James Tibenderana: Yes. In many of our locations, we are at a coordination level, where we work within the coordination platforms to really encourage a public-private-philanthropic mix - whereby governments are not just thinking about what is happening in the public sector, but are also able to engage the private sector. And in some countries like in Nigeria, the philanthropic sector as well, because some of the private sector is actually philanthropic funded.

James Tibenderana: So for example, in Nigeria, we've been instrumental in helping the government put those platforms in place, and really convincing some of the major players in the private sector that it is in their best interest to be working with the public sector. Because sometimes the two sectors don't talk to each other, but they also don't see the mutual benefit. And they will either be competing with each other, or just not understanding each other because the private sector mentality can be very different from the public sector mentality. And yet what goes on in the public sector can adversely affect the private sector.

James Tibenderana: For example, when you distribute nets or when you distribute free tests and drugs through the public sector, sometimes they can leak into the community and then affect sales or reach of the private sector. And then you have situations where the private sector's not following guidelines - not using quality-assured medicines, or not using the right tests. That obviously has an adverse impact on what the public sector's trying to achieve. So it's really getting them to understand that there's a win-win, but how do they work together?

James Tibenderana: I think there are a couple of examples out there of how to create the landscape that allows both to coexist. So can you get the private sector to benefit from the training of health workers? Instead of them relying on information they've gotten because they sometimes work both in the public sector and private sector, but to extend public sector trainings to the private sector. The monitoring systems that are in the public sector, some of the supervision - how do you get that to be extended? Or some of the private sector players, what approaches do they need to have in place that can allow them to continue to mentor and to supervise their users?

James Tibenderana: And then at the community level, working with patent medicine vendors in Nigeria, or drug shops in some other places, where they see that it is in their interest to use national guidelines because the quality of care that they deliver is higher. They may not necessarily get the same profit because they're not giving as many drugs as they could, but they're able to then have better outcomes from the treatments that they're providing. Also they can create repeat clients that are coming back because of the quality of services that they're provided. And then the fact that there's a public good that is there to be had if we are able to provide the right treatments to the right people at the right time, as opposed to the profit incentive that may sometimes dominate.

Delivery and practicalities [02:16:23]

Rob Wiblin: Yeah. So Malaria Consortium and other organizations in this space are trying to provide drugs or nets or other services to millions and ultimately tens of millions of people every year. It's an enormous operational project by any standard. What are some of the biggest challenges you face delivering chemoprevention to millions or tens of millions of people every year? And in trying to expand that number year on year?

James Tibenderana: Within our seasonal malaria chemoprevention, we've seen, roughly every year, a 60% or a 50% increase in the number of children that we can reach or that we have reached. I think what we have experienced more recently are the challenges with security, and the fact that some of our locations where we have been working are insecure. We need more measures in place to provide duty of care to our staff, but also the government workers who are participating and hosting the work that we are doing. So I think there's an issue of security that has started to create some challenges, which we are mitigating by best practices.

Rob Wiblin: So you operate in Ethiopia, which is in the middle of a civil war at the moment. That's one of the cases of this, I imagine.

James Tibenderana: Yes. But also Nigeria and places like Borno State, where we've distributed. Borno State, Boko Haram, where we've been able to distribute SMC as well. So there's locations where we are having to be really more security aware and put in place protocols to ensure we can provide duty of care, but also working closely with governments on the right planning. That's one. COVID obviously has created another.

Rob Wiblin: A lot of headaches. Yeah.

James Tibenderana: Disruptions. You really have got to get your planning right well in advance, otherwise there are delays and disruptions - and with seasonal malaria chemoprevention, you can't afford to be late. You've got to kick it off at the right time.

Rob Wiblin: Yeah. And I guess arrive every month, right? So if you arrive late, then people are unprotected for some time.

James Tibenderana: Yes. That contributes to transmission, and also when people don't see the benefits of our program, then they start to have doubts as to why they should continue to be part of that program. So security, COVID, and then I think with all things, there's the planning - the microplanning that has to take place to really ensure you have efficiencies and effectiveness. And that planning involves not just governments, but also partners who are either distributing commodities in another location. Or like we've seen in some programs - not our SMC program, but in some other programs - where we are doing one component and another partner with another funding stream is doing another component. So being able to make sure that we can synchronize and plan and bring things in at the right time.

James Tibenderana: But with seasonal malaria chemoprevention, I think it's security and it's COVID that have really created some challenges that we are mitigating and we've continued to mitigate. With COVID, we've had to adapt our approach. We've had to put in infection prevention protocols. So we've been able to adapt, but I think we are fortunate that we've been able to do that.

James Tibenderana: I think that's one of the virtues of philanthropic funding, in that you can do your planning a couple of years in advance in such a way that you've got a bit more say in what you can do and when you can do it. You're not very constrained by budget lines where suddenly we need infection prevention and control (IPC) material. We don't have many months for a decision - you've got to react quite quickly because otherwise your SMC won't be delivered. So I would say budgeting, the logistics that we have in hand, and really working within a coordinated platform with other players who are on board. Those would be some of the potential key challenges that we are currently facing.

Rob Wiblin: Going to deliver chemoprevention to a million kids, I imagine this requires hiring between 1,000 and maybe 10,000 people to do the delivery over that four- or five-month period, and they're going to need support staff as well. Does Malaria Consortium directly employ thousands of staff basically to go and stick tablets in mouths and tell the parents to do it again the next few days, or is it operated through other bodies somehow?

James Tibenderana: It's a combination. Our programs are embedded in the health system. So we work very closely with health workers, community health workers - even the planning structure is within the health system.

Rob Wiblin: I see. So you're paying to provide the drugs and I guess providing instruction, but most of the staff are part of the public healthcare system in the country.

James Tibenderana: Yes. So it's a combination. You have the public health system, which has got to function, and then you have the complementary staff on board that can either support things like the supervision, support things like the recordkeeping. It's a combination. You have staff within the government or the health system. And then you have staff who Malaria Consortium does hire or, in some situations, there are allowances that have to be paid to ensure that the government officials are able to deliver. And those are statutory allowances; they're not allowances that are additional incentives. Those are standard incentives that are there for the health workers to be able to participate and deliver.

James Tibenderana: But then you have some of the logistics, like the transports. There are things that would not be available either with the intensity or the geographical reach that we need. So it's a combination. Sometimes we have staff in some countries that we need to put on board, but those complement what exists in the health system.

Rob Wiblin: Yeah. That makes sense. So Ethiopia is in the middle of a civil war and you're trying to deliver malaria treatment. I imagine the security environment is quite poor in some places? What can actually be done there, other than just withdrawing?

James Tibenderana: In our Ethiopia program, we are very embedded within the system. In all our locations we have staff who are nationals. We have staff who really understand the context and work closely with governments, but also work within partnerships with other non-governmental organizations, donors, and subnational entities. So I think we are fortunate in that regard, that many of our teams are already able to make use of context-specific information, and understand some of the risks as well as some of the triggers for those risks.

James Tibenderana: In one of our programs in Ethiopia, we're working very closely with communities and the subnational structures to deliver indoor residual spraying in a manner that sustains itself. So rather than it being a project, it's, how does the community actually engage within indoor residual spraying and ensure that it's something that can continuously happen?

James Tibenderana: So it's really about having security protocols in place, being able to connect with information and use that information. Because what we've seen is that you've got to have access to the security system in your location that allows you to make the right choices, but also utilizes the communities as well as the structures at that level. Because they themselves will know what's happening, will know what risks are involved, and will give you advice in terms of what locations not to go to and where you need to put enhanced security measures in place. So I think having nationals in those roles means that they're plugged in to what is going on. They are trusted by the communities.

James Tibenderana: And as an organization, we emphasize being technically sound and being evidence based. We avoid situations where we are using our opinions, or we are getting involved in politics at a subnational level. We really are an organization just like many organizations, that are neutral, that are looking out for social impact, for social good, and making the best use of the assets that we have to achieve that. And communities see that. Communities engage with that because they have needs. And those needs continue to be important.

James Tibenderana: Now, when we obviously have a conflict situation, because we're not a humanitarian organization, we will back off or restrict our movements. We have an office in Myanmar. We have two programs, of which we are closing one because we just can't run it. We've waited. We've done as much as we can. The situation isn't changing. And so we've pulled one of our programs. The donor gave us a decision point, and we decided with our collaborators that that program was not viable.

Rob Wiblin: Yeah.

James Tibenderana: We have another program which is delivering telemedicine remotely and therefore does not put our staff at risk. And that's something where there's a huge need and we'll continue to do that. But we just can't operate in Myanmar, and we've made the choice to really limit our activities. We are not a humanitarian organization. There are other players who are better at that. So when we find ourselves in those situations, we will sort of hold back. And when the situation changes, we will reconsider.

James Tibenderana: And then we've done delivering SMC in Borno, where we do see the value add of our capabilities, and the fact that we can maintain duty of care of our staff, but also provide the right security measures for our government partners. Then we will be able to operate.

Relationships with governments [02:26:38]

Rob Wiblin: Turning back now to countries that don't have these particular security challenges. Somebody in the audience was very keen to hear about how Malaria Consortium approaches building and maintaining relationships with government partners, both at the technical and political levels. Do you have any thoughts on that, or any lessons to share?

James Tibenderana: Yes. We do have lessons to share in terms of partnerships and working closely with governments. Most of our country teams are nationals and that's something we feel strongly about, where we can. Because nationals will understand some of the context-specific issues, or non-nationals who have been in that context for quite a while. Over time, they will have relationships that really strengthen the trust between the organization, as well as between some of the government entities. But also the fact that you need some repute and you need some integrity.

Rob Wiblin: Trust.

James Tibenderana: Yeah. You need some integrity that allows you to influence and to position. An important element of our work is evidence based. You will find that our teams will strive to identify the evidence or the data, and use that to justify some of the recommendations or some of the opinions that we have. That allows us to maintain that neutrality. Where even when we need to say things that governments may not necessarily agree with, we're saying it from the point of the data or the evidence that we have, or the information or the experiences that either we've generated or others have generated.

James Tibenderana: And we've been able to package that evidence and put it on the table so that we are having informed conversations and supporting decision making from a point of being neutral. We will also say what needs to be said - we don't have to always throw a diplomatic line. We will say what needs to be said. And I think our partners have learned that when Malaria Consortium does say that something isn't going right, it's not because we have a bad intention. But as a technical agency, we should be able to say what we feel is going well and what we feel isn't going well.

Rob Wiblin: Yeah.

James Tibenderana: So from a government-to-organization level, I think there's an element of trust. There's understanding the context. The fact that in many of our locations, we've actually been there for quite a while, so we are committed to being there and providing that support to governments. There's an element of, we have a vested interest in being there and we will continue to provide that support.

James Tibenderana: Then when it comes to partnerships, we do make the effort to work collaboratively. There are coordination platforms at the country level - like technical working groups or specific initiatives - where our teams participate and facilitate. During the COVID pandemic, in some countries, we had to transition some of those platforms from a face-to-face meeting to a virtual meeting. And we used our Zoom capability or our Teams capability to provide that service to some governments - for example, in Uganda, with the National Malaria Control Division - for that coordination to continue.

James Tibenderana: So we really look at the coordination platforms and try to work collaboratively and emphasize the value that we have. We don't try to do everything. We really look at the context and what's the value add, and then we play to our strengths. We won't be trying to compete to do everything, or blowing the trumpet that we are the best at things that we may not necessarily be good at. We're technical. We provide technical guidance. We really emphasize integrity as one of our values. We are accountable, and we share our data.

Rob Wiblin: Yeah. For those who are interested to learn more, the Malaria Consortium website is just packed with papers and publications and lessons learned. And you have reports on everything that you're doing. It's very beautifully designed as well. Whoever is responsible for your website deserves a lot of credit. I was very impressed when I was doing some background research for this.

Funding gap [02:31:03]

Rob Wiblin: What were you saying was the global funding gap for providing these basic antimalarial treatments? Talking like $5 billion or $10 billion?

James Tibenderana: So WHO estimates to achieve its annual targets within the global technical strategy for malaria, it's about $6.8 billion per annum.

Rob Wiblin: OK. Yeah.

James Tibenderana: And in 2020 or 2019, we were at $3 billion per annum.

Rob Wiblin: Left to go?

James Tibenderana: Yeah.

Rob Wiblin: OK. So that's quite a bit of money. But in the scheme of government budgets, philanthropic budgets globally, it's not that huge. We wouldn't be so shocked if we found that actually, that was being filled by foreign aid or by philanthropists one way or another. Is there any explanation other than just competing priorities for why that gap isn't fully filled though? Why there isn't enough funding to provide all of these treatments?

James Tibenderana: I think it's a good question, Rob. And it's good to have that in mind, because when we think in terms of $6 billion, $7 billion - why it's an interesting question is, if that could be filled, there's huge benefits that can be had. Why isn't it? I guess it's how to position that need. How to position that need in a manner that makes it financeable.

Rob Wiblin: Yeah. Can you explain that?

James Tibenderana: One of the things I'm learning is that using mortality and morbidity as an argument to raise funding is probably not effective.

Rob Wiblin: Because it's not enough?

James Tibenderana: It's not enough.

Rob Wiblin: It's effective with some people, I guess?

James Tibenderana: It's effective with some people, but it's not enough. There's more to raising this funding of that size than just articulating that X number of children are dying, or X number of pregnant women don't have access.

Rob Wiblin: Yeah.

James Tibenderana: I wonder sometimes whether it's that funders don't want to get into things where they don't see an attributable benefit - that you can actually say, this amount of money has gone in, and this is what one is getting out of it. They worry about things like accountability, and how that money is used in an accountable and transparent manner. That you don't have fraud, you don't have corruption taking place. Some people then have the argument that national governments should be raising the majority of that funding, when we know that they're struggling to meet all their needs. And yet we do need them to continue to support education, health systems, and roads.

James Tibenderana: So I think it's how to position that need in a manner that makes it acceptable for new funding streams, because what we need is new funding streams. And funding streams that are also reliable, because it would be more ideal if it's consistent. So if you can get that gap filled, can we have that gap filled for the next three, four, five years - so that the impact that we can achieve can be sustained? And then that transmission potential I was talking about, you are able to really drive it down so that we don't have these ups and downs.

Rob Wiblin: Yeah.

James Tibenderana: So it needs to be consistent and reliable. But I just think we've got to find the right arguments. If it's a cost-effectiveness argument, what is it? We know that there are many interventions that we don't have that data on cost effectiveness. How do we package that? And then what is the long-term goal? I think a combination of near-term objectives and long-term objectives where malaria elimination is valued, and there's a cost put to malaria elimination. You know that sub-Saharan Africa loses $12 or $15 billion per annum in lost productivity because of malaria.

Rob Wiblin: Yeah. That is something that's odd about the situation, is that it's profitable. I mean, we have to be a bit clear about exactly what we mean in the sense that it pays for itself. I suppose it's that, if you spent the money to provide all these treatments, then you would end up with more GDP in those countries than what you spent. So it's returning. Now, it can't quite pay for itself, because you can't recapture that easily and use it to fund the program.

James Tibenderana: Yes.

Rob Wiblin: If you could, then it would be just a win, because in a sense it would cost nothing. And then you would have all this leftover benefit of the lives that you saved.

James Tibenderana: Yeah.

Rob Wiblin: But it is funny when you see programs that the GDP that they produce is less than what they cost, and yet they're not being funded. It's perverse.

James Tibenderana: Yeah. So I think it's the argument. And that's something we are trying to get more astute at in Malaria Consortium, in terms of how we build those justifications or the business case for additional funding. Because, at least from a personal perspective, I've observed that it just can't be a mortality/morbidity question. There's got to be the economic justification.

James Tibenderana: And then really this whole value to malaria elimination, and what will be the long-term benefits for a malaria-free world to us sooner rather than later? What happens when climate change kicks in and we have more areas that potentially could be at risk of malaria? So achieving that objective sooner, what's the cost to that? And what's the cost to then investing in these new novel innovations? Interventions like gene drive that could potentially help us get there faster.

Rob Wiblin: Yeah. If we're talking about spending $3 billion more per year in order to generate an extra $10 or $15 billion a year, then it is possible that - even if the government then is only recapturing 20% of that extra GDP in terms of taxation - it can plausibly pay for itself fiscally in the long term, for the government itself.

James Tibenderana: Yes.

Rob Wiblin: I guess it's not quite as simple as that, because they don't have perfect access to credit markets in order to pay for it back. And there's also risk. They're uncertain, potentially, about how large the rewards are. But it should be persuasive to departments of finance, and the treasury, and so on that these things are significantly self-sustaining for the country itself and for the government.

Rob Wiblin: I suppose the argument back might just be, "We have other projects as well that are also fantastically profitable in this sense" - improving education or solving other diseases as well also have these huge rates of return or internal rates of return. That's just kind of the nature of a country that has lots of preventable diseases or preventable problems that can be fixed at acceptable cost.

James Tibenderana: Yeah. But as I have mentioned, in our landscape, in terms of these partnerships, when I talk about public-private partnerships, we are increasingly emphasizing philanthropy as an important stakeholder within these partnerships. So in Nigeria, in one of our programs we've really been emphasizing public-private-philanthropic partnerships. Just the amazing work that we've been able to do in Nigeria with seasonal malaria chemoprevention - and then you have local philanthropists in Nigeria who are also funding service delivery, but sometimes are not at the table when decisions are being made, or when budgeting and financing is being discussed.

James Tibenderana: So I think there is more scope to really bring those elements together. Not only in the delivery, but also in the innovative financing mechanisms that need some attention. Because we do need new financing, and some of it will be domestic as countries increasingly improve their taxation. But we know what COVID has done to global economies. What are the innovative financing mechanisms that could look at this near-term, long-term benefit and really turn it into financial numbers that some of these governments may actually decide to buy in?

Rob Wiblin: Right. Yeah.

Access and use gap [02:39:10]

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? How do you measure whether things are actually being used, and to what degree they are being used?

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.

Rob Wiblin: I suppose a natural response would be, "Well, let's give them a bed net and a fishing net."

James Tibenderana: Yes, for example, right?

Rob Wiblin: But oddly enough, that's not the policy proposal that jumps to people's minds. It's, "Let's not give them the bed net."

James Tibenderana: Yeah, exactly. "Let's not give them the bed net." And then potentially they may not benefit. I think it distracts from the good that is to be had by having nets. And when you look at the access-use gap, it's somewhere between 5% and 10% on average. With any intervention, whether it's nets or whether it's -

Rob Wiblin: You always get some leakage.

James Tibenderana: They will always be leakage. But when I say 10%, I'm not referring to the nets part, all right? I'm referring to the fact that sometimes there are mothers who get nets and keep them at home.

Rob Wiblin: And don't hang them up?

James Tibenderana: Yeah, because they're waiting for the child to be born.

Rob Wiblin: Oh, I see. Right. So that would be a mismeasurement then if you said that.

James Tibenderana: Yeah, they want to keep the net for the child to be born and then use the net with the child. So there's sometimes reasons why households will not use that net. There are times when a household gets a net and there's another relative who doesn't have a net. They have been given two nets or three nets for that household, and then another household didn't get a net where they have a relative, and they give that one net to that household. So there's an element that those sort of stories can distract from the good that is to be had by increasing access, because access is a determinant of use.

James Tibenderana: Earlier I mentioned social behavior change, and all that needs to go into engaging communities and making them engage and own and buy in, and that's one of the mitigating measures for that. Then the monitoring systems that have been put in place and have continued to increase - for example, some of the studies to identify who's using the net, but also to identify what the barriers are for use so that you can address some of those barriers. Then if you find that your specifications for the net don't resonate with the expectations of the users, then you have to tailor a response - either for that location to have slightly different nets, or engage one of their respected leaders to really put the message out.

Rob Wiblin: Explain the value.

James Tibenderana: Explain the value. And even social accountability. If they are identifying people who are misusing the nets, then they should be able to discuss with those people and emphasize the value of the nets and why those nets need to be used. So there are mitigations. And the answer to that isn't, "Let's not give a net." For me, it's highlighting the pivotal role that lack of livelihoods and poverty is playing within malaria transmission.

Rob Wiblin: Yeah, we're slightly verging on me just ranting at this point. But there is this general phenomenon that people who are trying to do good and charities are held to bizarrely high standards of performance, where almost any weakness can be criticized and is viewed as a decisive problem. So look, if 90% of nets were not being hung up and they were being used for something else or just thrown out, then that would be a very serious problem. But given that 90%-plus are probably being used as far as we can tell, that misuse and non-use problem, it's odd that it gets such a high degree of focus.

Rob Wiblin: People just want to pick on a program, or show how it's not quite as good as people think, and they don't compare it to other things. Companies constantly send me products, or I buy things, and I don't use the products that I buy 90% of the time. There's almost always some wastage. People buy exercise equipment, they don't use it. They buy food, they throw some of that out. That is just kind of a normal part of life: not everything runs at 100% efficiency.

Rob Wiblin: And there's no particular reason why you should expect a nonprofit to be different. In fact, if a nonprofit was somehow getting 100% use, then they're almost certainly spending too much time following up trends that people are using the nets in order to be efficient in that dimension, while wasting money on constant followup visits to persuade people. Some degree of inefficiency is actually efficient, if that makes sense. Do-goodery is one area where people are not inclined to accept those kinds of tradeoffs, I think.

James Tibenderana: Yeah, it is a high standard, certainly, and the bar is very high. We do try to achieve that high bar, and I think often we are achieving that high bar, but there's also the reality. We are operating in a real-world setting and with all tools, the diffusion of innovation graph: there's early adopters, late majority, and then you have always the laggers at the end. Then as you've mentioned, they are measures that can be put in place. But for all interventions, there will be a minority who may misuse or not necessarily use the way it's intended - but that should not distract from the good that is to be had by reaching the majority.

The value of local researchers [02:49:26]

Rob Wiblin: You were involved in spearheading a national research center for malaria in Uganda some time ago. What's the value of having local research centers in areas that are seriously affected by malaria, focused on that specific location rather than just having researchers that are thinking about it purely at the global level?

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.

Rob Wiblin: I see. OK.

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.

Rob Wiblin: Yeah. So I think I've seen three benefits there. One is that a study done in one country may not transfer accurately to another country - because just the mosquitoes are different, the parasite is different, the urban layout is different, and so on - so it pays to have research that's at the specific place that you're actually thinking about rolling out a program.

Rob Wiblin: Then there's the fact that local researchers from a particular country doing the research are going to be more credible potentially to the government. Or they're going to be more able to coordinate with other people in that country, because they're all from the same place, they speak the same language both literally and potentially figuratively.

Rob Wiblin: And then the third thing is having local technical experts who have experience doing this research, meaning that they're available locally to tweak and improve the program once it actually starts getting delivered. They have the technical know-how to make things go really smoothly, rather than just relying on someone in another country who you may not be able to contact.

James Tibenderana: Yeah.

Rob Wiblin: Nice. If you had a large budget for research into new ways to tackle malaria or ways to improve existing interventions, what would your top priorities be?

James Tibenderana: Research to optimize what we currently have. So operational research to really close the access gap, the coverage gap, why some community is not using a particular intervention. Research to optimize what we currently have would be one area.

James Tibenderana: Then I think a second area would be on some of the new novel interventions that are on the horizon: next-generation nets, next-generation insecticides. We've talked about insecticides that are more effective, so the role they're going to play within a comprehensive malaria program, where they should fit, how they will be adopted by local communities, how long they will last. I think obviously RTS,S and a malaria vaccine and its introduction - whether through a seasonal malaria chemoprevention platform or whether through an EPI (expanded program of immunization) platform - really the rollouts of RTS,S and how it fits within the mix that allows you to really maintain the cost effectiveness of the comprehensive program.

James Tibenderana: I would say the surveillance and response and the value that it will have, and the data that's required to make that a valuable tool. So it's not just about cases, but also the mosquito, the biting habits, the breeding sites of the mosquito - and bringing that information in a manner that allows us to make better decisions. Then gene drives, certainly, as the evidence builds. Target Malaria is doing an amazing job; certainly kudos to them. I think there will be a question in terms of when we are at that point: what does an introduction in a field setting look like? It's something we would certainly be keen to participate in some of the research.

James Tibenderana: Then there's the "omics" technologies - proteomics, genomics, all of that - and the fact that with some tools like lab-on-a-chip diagnostics, which is also another area that is improving, and could be a disruption. Imperial College has led on a tool called Lacewing that can have an assay that can detect, for example, on the parasite, you can detect potentially the genomics of the parasite. And as they improve that, you can be able to say that this is plasmodium falciparum, but also that this has a gene for resistance to that antimalarial. So how that technology can be improved, but again can also contribute to decision making. So omics technologies and lab-on-a-chip diagnostics would be important.

James Tibenderana: Anything that can improve our decision-making capacity I think is a research opportunity. And then optimizing our current interventions, and speeding up the deployment in terms of having the results that can then contribute to global guidance and then national policy adoption and then scaleup would be my priority.

Past research findings [02:57:10]

Rob Wiblin: In the past, as I mentioned in your bio, you've been involved in studying parasite-based diagnosis for malaria, and doing that before treatment, rather than treating people without any diagnosis. That resulted in changes to Uganda's standard treatment approaches for people who have malaria symptoms. Are there any interesting stories to share from that? What was the nature of the research, and why did that end up changing the default approach?

James Tibenderana: Well, it was a lot of research work and collaboration, because policy change at the country level involves stakeholders, especially WHO, who provide normative guidance and work very closely with governments on adoption. But I think what was necessary there is the evidence that rapid diagnostic tests could actually be safely used in the hands of community health workers. And we were lucky at that time to have a grant from TDR WHO that was able to study how rapid diagnostic tools could be used by community health workers.

James Tibenderana: We were also fortunate at that time we had some funding from DFID, which is now FCDO, to look at the efficacy of the treatments that Uganda was using and the fact that the combination of chloroquine and sulfadoxine-pyrimethamine was not as effective as it had been. So I think I was in a fortunate situation - again, with Malaria Consortium, but also with the research center - that we were able to do the research that provided the evidence that was able to initiate the policy changes that were required.

Rob Wiblin: What was the safety concern that people had? What were the reasons why people weren't using the diagnostics by default to begin with?

James Tibenderana: First of all, the challenge was could a layperson, who's a community health worker, use a rapid diagnostic test that would involve taking a blood sample by using a lancet to do a finger prick. So the question was, could that be done safely? And if it was done safely, could that community health worker read the test result and then transmit that result accurately up the information chain? So the safety concern was, would they be able to do it safely? Would they create more harm?

Rob Wiblin: A risk of transmission, possibly.

James Tibenderana: Risk of transmission. So we did a study, and really there were some insights there in that community health workers were able to follow instructions to the letter.

Rob Wiblin: More than people expected?

James Tibenderana: More than people thought, and to some extent, even better than people who were more skilled.

Rob Wiblin: Because they don't want to read it, they just do their own thing?

James Tibenderana: Possibly. But I think also the fact that they were not able to question things. For them it was, "This is what it is, and I will do it." They weren't looking for shortcuts, or they weren't saying "No, I don't need to do this this way, I can do it some other way." So literally they were able to follow instructions and perform the tests as described and as they were trained.

James Tibenderana: So we had training in place, we observed how they used the tests. And then a further worry was, would they give the treatment according to the test result or will they just still go ahead and give the treatment? Because potentially there could be fear that communities will apply pressure on the community health worker to continue giving treatments, even when the test result was negative.

James Tibenderana: But one of the things we made sure of is that the community health worker was an integral part of the community - so they were from the community, and they were acknowledged as community health workers, and that that person was doing what they could in the best interests of the community - so if they refused to give an antimalarial because the test is negative, that's accepted. And so we went through all that effort, but the outcome was that community health workers were able to do the test and give antimalarials as outlined in the protocol.

Rob Wiblin: I guess actually a key benefit there is if someone has a fever but they don't have malaria, then you can go on and investigate what they have exactly, what's going on - because previously they were probably walking away with malaria medication and not getting any help.

James Tibenderana: Exactly. So they could, for example, go to the private sector or go to the nearest health facility to then get treated.

Rob Wiblin: Further investigation.

James Tibenderana: Where I do emphasize the issues around evidence is that as a researcher, you've got to be careful about conflicts of interest.

Rob Wiblin: In what way?

James Tibenderana: Commodities. For example, with rapid diagnostic tests at that time, there wasn't a quality assurance system in place. But obviously WHO has, and an organization called FIND Diagnostics, put in some kind of system that they're able to rank the quality of rapid diagnostic tests. There's a quality assurance process for antimalarials already, but when you pick tools to carry your research on, your choices have really got to be very clear and transparent - because why are you choosing one test, not the other?

Rob Wiblin: It could be that there's some commercial interests at play, basically.

James Tibenderana: Exactly. And manufacturers will be watching: you've chosen that commodity to do your research and not the other, and why. So with the choices we made, we went through a process that allowed us to make the right choices based on sensitivity and specificity. Again, you've got to be transparent. I remember when I was presenting some data in one of the meetings, and this person said, "No, James, you're making money out of this commodity," because I was providing results that said this tool is effective. And the question was, "No, no, no, no, the reason you're saying that tool is working is because you have commercial interests."

Rob Wiblin: How do you deal with that?

James Tibenderana: Fortunately, for that meeting I had actually printed the studies that had been done on rapid diagnostic tests prior to that period - sensitivity, specificity, et cetera - so I had the papers. So when I was accused of having commercial interest, I said, "Here are the papers that have either similar evidence to what I'm describing or have evidence to suggest that some of the choices that were made are evidence based. These are the papers. I have no commercial interest and the data I'm presenting is based on a well-designed study that has collaborators."

Rob Wiblin: So they just assumed that you must have a commercial interest, is that right?

James Tibenderana: Yes.

Rob Wiblin: OK, right. Because that's just what you would expect?

James Tibenderana: Yes. That's what you'd expect.

Rob Wiblin: So the levels of trust are just potentially quite low in some contexts, so you have to really be careful about how they will perceive what you're saying.

James Tibenderana: Yes. Especially when it's choices between commodities. Again, you've got to be evidence based. Fortunately, as I said, WHO now has a prequalification process in place, so you already have choices that you can make. But if it's new products and you're carrying out research, you've really got to be attentive to some of the conflicts of interest that can undermine some of the results that you put out, or sometimes perceived conflicts of interest that you have in pushing a particular result towards policy.

James Tibenderana: And I think that's another role that we play as an organization: where in situations where you have really good evidence, we can actually sometimes take that evidence and use that evidence within the policy framework. Similar to what happened with SMC: with SMC as we transitioned into the policy arena, some of the work we did was at the interface with adopting policy. So here's all this evidence, and we are working on this project to demonstrate that this evidence can work in this context, and is in the real-world setting. And then goes into policy change. Which is why national organizations are really, really key, because sometimes they can play that interlocutor role when the evidence exists, and they can't show it works or adapt it for that particular context.

James Tibenderana: So there were many lessons, but I think one lesson was a qualitative study we did. And researchers, we tend to really look at randomized controlled trials, quantitative things. And we looked at this one qualitative element as we rolled out rapid diagnostic tests: we looked at acceptance and use amongst the early adopters, and used that to create a framework that we proposed as a way to optimize acceptance and use. It was an eye opener for me in terms of how useful qualitative research can be when you have quantitative results.

How to help [03:06:30]

Rob Wiblin: I see. Back it up, yeah. OK, so we're almost done. We've been going for many hours and I'm starting to flag, so I suspect you might be as well. But I think there could be quite a lot of people in the audience who are very excited about this conversation and very excited about the opportunities to control malaria and some of the other things that Malaria Consortium works on.

Rob Wiblin: What kinds of roles do you hire for in the countries where most listeners are - which is going to be UK, US, Australia, continental Europe - what kind of careers can people pursue in this area?

James Tibenderana: I think we are constantly hiring, partly because we continue to grow. So we have technical roles, whether in the UK or in our country offices. And then we have roles within management, within our enabling functions like finance and operations, as well as business development. And we have a huge interest in continuing to connect with our audiences by putting out publications, so there's probably opportunities within our external relations team.

James Tibenderana: Obviously as an organization, we prudently create vacancies. One of the areas that we're keen to expand on is our health economics capabilities, so we will be working on that in the next few months. We've just launched our new strategy and so there are aspects within the strategy that require us to hire expertise: as I mentioned, health economics, health systems strengthening. We will be looking at fundraising and how we resource that in the UK and also in some of our country offices.

James Tibenderana: And then really, management. We need good managers who are able to take a strategy and implement it, but also prudently use the unrestricted or restricted funding that we have in a manner that allows us to continue to be a valuable and influential organization for the foreseeable future. And we're constantly looking for new opportunities, so we do react to calls for proposals that donors put out there, and sometimes that requires us to hire new staff - either when we get the contract, or sometimes donors require you to have hired the staff and name them in the contract.

James Tibenderana: So we're constantly looking, and I think we are fortunate that we continue to grow. With our new strategy, we do envisage that we continue to aggressively pursue our mission, but also to look at things like universal health coverage, which are increasingly becoming important; looking at how we can strengthen health systems after the devastation that the pandemic has caused and is still causing. Because I think it's easy to forget that immunization rates in sub-Saharan Africa and some parts of Asia are still quite low.

James Tibenderana: The epidemiology of COVID has not yet been influenced by high immunization rates. So we do envisage that COVID is going to continue being a disruptor in our programs. We will need the staff that can help us to cope with some of these disruptions and to continue raising the funding that we need to continue doing the work that we feel is important.

Rob Wiblin: Nice. For those who don't imagine working at Malaria Consortium, but are interested in having an impact through donations - we have quite a lot of listeners who are earning to give one way or another - do you want to make an appeal for how they can learn more about Malaria Consortium, and what the case is for donating to you specifically?

James Tibenderana: So our website has a lot of information about the work we do, and I think one of our priorities is to make sure we are able to share and connect with our audiences. So we have a lot of information on our website that describes the projects that we run, the work that we do, and the people who are involved in this work. We also have the opportunity now through our link on our website, but also opportunities through Malaria Consortium US, which is an independent entity that we work very closely with. So I think those opportunities exist for your listeners to be able to participate.

James Tibenderana: We also run a scholarship fund for the late Dr. Sylvia Meek, who was one of the founders of Malaria Consortium and was the technical director before I joined. Unfortunately, she died of breast cancer, and we set up a scholarship fund for entomology, because she had always emphasized the importance of entomology, and the fact that there were very few entomologists for the magnitude of malaria in terms of the devastation that it causes, especially in sub-Saharan Africa and in Asia.

Rob Wiblin: Entomologists study insects, right?

James Tibenderana: Yes. Entomologists study insects. So we set up a scholarship fund called the Dr. Sylvia Meek Scholarship Fund for Entomology and we've been fortunate using her legacy to be able to sponsor, so far, I think we've sponsored about seven. There are two more in universities. We have a collaboration with the University of Victoria. We had two students in the University of Nsukka in Nigeria and are working very closely with Mahidol University in Thailand to really train more entomologists. I've been fortunate to interact with some of the scholars who've graduated. Highly motivated, want to do good. And that scholarship fund is also another opportunity to contribute good in terms of creating the next generation of practitioners who will be running some of these gene drive technologies, next-generation nets, and trying to keep ahead of the mosquito.

James Tibenderana: So there are a variety of opportunities, and as I have mentioned, we do get restricted funding and unrestricted funding as an organization. The more unrestricted funding we can have really enables us to make choices and to work with our partners in-country to identify how that funding can really complement what exists, and also do the research that we feel is really important. So I would really emphasize that combination of restricted, which we know is important, and then unrestricted funding as well.

Rob Wiblin: Yeah, of course. Listeners who are interested to learn more about the case for giving to Malaria Consortium can also of course turn to GiveWell, which has a very long report of the various strengths of MC, and I suppose also the reservations that people have or the questions that they've asked, and where they've come down on them - ultimately deciding to fund you to a very high degree. It is useful to keep in mind most of the funding that's coming through GiveWell is the restricted funding for the chemoprevention, so one way that people can potentially get an edge if they've been persuaded by the various other things that you've mentioned here is to just offer unrestricted funding that you can use however you think is best.

How James ended up where he is today [03:13:45]

Rob Wiblin: One final question: you've got a very serious job, and have had for a very long time, and I imagine it's very meaningful. But if you had to completely change careers to just do something where you were totally indifferent to improving the world, and instead just trying to have a good time, what would you think that career might be instead?

James Tibenderana: You would be surprised. I would've been a pilot.

Rob Wiblin: OK, yeah. Why's that?

James Tibenderana: From a very young age, I've always been fascinated about aerodynamics, and just fascinated about the concept that you can have something so heavy that can stay in the air. So I've always wanted to be a pilot, and anytime my parents would take us on planes, I would be looking at these pilots with white shirts and dark glasses -

Rob Wiblin: Yeah. Looking very cool.

James Tibenderana: Yeah, looking very cool. So I really wanted to be a pilot and a couple of times I did get onto sort of single-engine or twin-engine planes and sit in the copilot seat to see what's going on. So I would've been a pilot. One of my childhood superheroes was Batman, and I had this action man you could throw and he would have a parachute. I thought, "Hmm, this is rather interesting." So I remember I took my mom's umbrella and climbed the top of the building, and I jumped off with the umbrella open to sort of -

Rob Wiblin: Oh no. How did that go for you?

James Tibenderana: I was really lucky. I didn't get injured. But the umbrella got really damaged. The concept for me was if this thing could remain, then I could get off and drop slowly. I was very fortunate I didn't break anything. But I've always been fascinated, and even in my work when I travel, I'm really keen to know the plane I'm traveling in. I read about the plane, read about its strengths, the technology behind it. So that's one of my fascinations. I would've been a pilot.

Rob Wiblin: What got you into medicine instead?

James Tibenderana: I'll tell you why. There was a point where I got very ill and I had to go into hospital. Two illnesses in my life that almost killed me. One was malaria and I was very fortunate that my parents reacted quickly enough. But then I was really sick and I was in hospital and a very close friend of my father, Dr. Ghataoura, who's now late, piqued interest and he realized that I was going to struggle being in the hospital. And he was a doctor attached. He was, I think, in his final year or just recently graduated.

James Tibenderana: He asked the hospital if he could admit me in his home just next door, and the hospital agreed. And Dr. Ghataoura took me home with a drip and everything, and looked after me. And from that experience, it struck me that I wanted to be that person that could make me feel secure. I was so worried, my parents were so worried that I was going to die. And it just struck me that I needed to be someone who could do that to others. He's always been a mentor because he was a very close family friend, actually lived in England and died in England, and he was one of the strong influences on my life as I built my career.

James Tibenderana: One of the things he stressed as I got into medicine was that it is a profession for you to do good. It's not a profession that is for you to make money, et cetera. It's that you as a doctor or you as a health professional should be doing good. And that's something I've tried to emphasize in my career as well as in the work that I do.

Rob Wiblin: Yeah. I'm sure he would be very proud of what you ended up doing. I imagine that he probably lived to see a bunch of it.

James Tibenderana: Yes he did.

Rob Wiblin: My guest today has been Dr. James Tibenderana. Thanks so much for coming on The 80,000 Hours Podcast, James.

James Tibenderana: Thank you very much, Rob. It's been my pleasure and I hope your listeners have enjoyed the conversation.

Rob's outro [03:17:53]

Rob Wiblin: If you'd like to work with James, Malaria Consortium is currently hiring for all sorts of roles, which you can find by going to malariaconsortium.org then going to About > Careers.

As of today, they're looking for a Senior Technical Advisor, Fundraising Officer, Senior Research Specialist, Technical Support Officer, and a Monitoring & Evaluation Specialist in London, as well as Procurement Coordinators in a range of different countries.

You can find those roles as well as another 300 related to global health and development on our job board at 80000hours.org/jobs.

There's also of course another 700 jobs, scholarships, and funding opportunities across all the sorts of issues we discuss on this show.

One other role I'll quickly highlight is the position of In-House Legal Counsel at the broader legal entity in which 80,000 Hours is housed, which is called the Centre for Effective Altruism. It has become a real powerhouse, supporting an ever-growing number of valuable projects trying to improve the world in a major way.

They're looking for a lawyer to fill a senior role that will help them innovate quickly and manage risk as they grow, and aren't finding it trivial to find the right person. Applications close at the end of May, and you can learn more about that one at centreforeffectivealtruism.org/careers.

If you know someone who could be a fit for any of those roles, then dropping them a WhatsApp to let them know could be the most good you can possibly do in two minutes.

All right, The 80,000 Hours Podcast is produced and edited by Keiran Harris.

Audio mastering and technical editing for this episode by Ryan Kessler.

Full transcripts and an extensive collection of links to learn more are available on our site and put together by Katy Moore.

Thanks for joining, talk to you again soon.

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James Tibenderana on the state of the art in malaria control and elimination

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Rob Wiblin: Hi listeners, this is The 80,000 Hours Podcast, where we have unusually in-depth conversations about the world's most pressing problems, what you can do to solve them, and whether people are still using bed nets for fishing even when they don't live near a body of water.

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This image really captures the essence of neartermism versus longtermism.

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This image really captures the essence of neartermism versus longtermism.

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Who is choosing now? Who is choosing the future?