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Clinical symptoms of severe malaria are similar to those of other diseases like pneumonia and meningitis. In tropical countries, poor diagnosis often results in sub-optimal treatments. Integrating proteomic, genomic and clinical data will help us explain differences in clinical outcome in severe malaria.

Q: What is severe malaria and how is it diagnosed in tropical countries where hospitals often lack access to high tech analytical labs?

CC-P: I think I should start by explaining what malaria is. Malaria is an infectious disease. It is caused by a parasite. The name of the parasite is Plasmodium; there are a few species but one of them is more important than the others- that's Plasmodium falciparum. We get it from infected mosquitoes that bite us and then when this mosquito bites you this parasite goes to your liver then it stays there for a week or two and then it goes into the bloodstream. Once it is in the bloodstream it invades new red blood cells and that's when all the symptoms begin to occur. So the problem is that the symptomatology, the signs that we see in those patients, are not very different from a patient with flu and sometimes it's very complicated to know how severe it is. So what is severe malaria? In some cases these patients develop severe symptoms: some of them go into a coma, some become breathless, some become very anemic because the parasites are in the red cells so they destroy them. Sometimes it blocks the bone marrow; you produce no more red blood cells. So the problem with that is the mortality increases to the extent that when some of these malaria symptoms overlap we get mortalities of up to 35%, which is pretty serious for an infectious disease. So answering your second question, it is funny because the reality is that to diagnose malaria you don't need a lot. You just need someone who can read a malaria slide and a microscope. In places where malaria takes place you need a microscope in place but the problem is you don't have an uninterrupted power supply. You don't have very good technicians. So the reality is although in the UK it would be very easy to make this diagnosis, in Africa it's far more complicated. So the reality is we need to create alternative tools for that.

Q: What could we do to manage malaria diagnosis and clinical management?

CC-P: We can do many things because there is a real need for improvement. I think the best way to convey this is to give a scenario, so let's imagine we are in Gambia in a rural area and we are at the peripheral health post. Then a mum comes with a little baby, a 2 year old, sick with fever, and this is the complaint 'my baby is sick with high fever and he's prostrated' -which just means he cannot sit down, he cannot feed and sometimes he's breathless. So the person who is seeing this child has a challenge because there will be 100 more kids in the line and they will have to make a decision- Is this malaria? Is this pneumonia? What treatment should I give? During the malaria season people tend to over diagnose malaria, give them anti-malarias and send them home. The problem is that if you get it wrong this kid may die when he gets home because sometimes you need to play it safe and sometimes if it is a bacterial infection or it is malaria you don't know. You need to give anti-malarias, you need to give antibiotics. This is suboptimal. So the thing is there's an information gap. We're trying to develop tools to bridge this gap to some extent so yes there's a lot of room for improvement.

Q: What are the most important lines of research that have been developed in the last 5-10 years in this area?

CC-P: Well in relation to this, perhaps its better if I explain what I have been doing that led me to do this. I think that when I first started working on malaria I was addressing some very specific questions so the first interest I had was trying to understand what happens to children with severe malaria and severe anemia and just trying to work out what were the mechanisms. That always leads you to one or two molecules and with these molecules you try to explain a lot of things. The reality is that the more I've been doing this the more I realize that I don't see the bigger picture. So what I'm trying to do now with my research is actually rather than zooming in and focusing on a single molecule just to zoom out and look for patterns and hoping that within these patterns I will understand the disease better, how it develops and also identify markers that could be useful clinically.

Q: Could your research produce a simple kit that could be used anywhere in the world?

CC-P: You want to develop something like a pregnancy test where you get a drop of blood, you put it in the kit and you get a positive cross then it says to this person that works in that environment: this boy or girl who is sick will have to go to hospital, this can receive treatment and go home. So this is the long-term vision. My research now would be more actually looking for this molecule so if we come up with good candidates, good molecules, that makes sense. The next step is to do what we call prospective clinical validation. The reality means you just need to design a specific piece of research to see how the marker that you identified actually perform in real life, it's nothing more than that. And once you get there the important thing is to develop partnership with the industry, and with them actually develop the simple kit that will be used in practical terms.

Q: Why do you feel your research is important? Why should we put money into your research?

CC-P: It's very relevant. It is an important health problem. I'll give you some relevant figures for malaria. We see nearly 250 million cases of malaria per year and nearly a million deaths. Most of these deaths occur in children in sub-Saharan Africa under the age of 5, it's a massive public health problem. Another question is what does the health economics say? In this cycle of poverty and disease it's also important to see the impact is of malaria, and some people have modeled that, if you could eliminate malaria from a specific country you would increase the GDP by 30% so the impact seems to be pretty striking. Another question is why should the UK or an organization here be bothered about this? I think this doesn't need an answer. For lots of the research councils in the UK, it's part of their strategy to invest in poverty in developing countries and health inequalities, so it is already in the agenda.

Q: And finally, how do you feel your research fits into translational medicine within this department?

CC-P: I think it fits very nicely. There are a lot of very good scientists working in global health and for me it's a fantastic opportunity to collaborate with some of them so we know the NDM cares about this. From a translational point of view, I think you cannot get more translational than that, we are looking for tools that improve health, we are looking for markers that can help in the decision making process to actually improve the management of these patients so from my point of view that's very translational, I would say.

Climent Casals-Pascual

Malaria and Global Health

Dr Climent Casals-Pascual is interested in severe malaria, particularly its diagnosis and clinical management. Severe malaria is an important cause of global mortality and loss of productivity. The development of new tools to diagnose and manage malaria more effectively will allow us to decrease the mortality of this condition.

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