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Malaria is an evolutionary arms race between the human host, the Plasmodium parasite and the Anopheles mosquito that transmits the parasite from one person to another. New genome technologies allow scientists to develop a deeper understanding of this process, which is essential for the development of an effective vaccine and for combating drug resistance in the parasite and insecticide resistance in the mosquito.

Q: How can genomics help us fight infections?

DK: Most infectious diseases are a sort of evolutionary arms race between the microbe - the pathogen - and the human. Microbes are continually evolving to try to beat the human immune system and try to beat the drugs that humans use to treat the infection. And equally humans are trying to adapt to defend themselves against the microbes. All of that is Darwinian evolution in action. Bugs are constantly evolving and actually our genomes have evolved over the years; understanding those evolutionary processes can be a huge help in trying to understand where we go next in terms of fighting infections.

Q: Why do you mainly focus on malaria?

DK: I'm a pediatrician and I went to work in the Gambia in West Africa in the mid 1980s. As a pediatrician working there you could see that the major reason why children came into hospital and the main cause of death was malaria. It just is a very common disease and it inflicts huge mortality and morbidity on the population, so it's a really important disease. It's also a really interesting disease and a disease where I think we could make a big difference if we can get the right technologies in place.

Q: Is your research truly global?

DK: Actually 100 years ago malaria was existent in almost every country in the world apart from the very far North and the very deep South. It was certainly for example in many parts of Europe and North America where we don't see it anymore. It is still in about 100 countries around the world. We don't work in 100 countries but we do have partners in 30 countries around the world to try and tackle the problem.

Q: What do you consider to be the most important research opportunities at present?

DK: There are lots of them and in the short term the real struggle we are having is to make sure that the existing drugs that are being used to treat malaria, and the insecticides that are being used to treat the mosquitoes that transmit malaria, remain effective. Because what happened in the past as global health campaigns have been mounted and more of the anti malarial drugs are used, the parasites have become resistant to the drugs. And actually now we have new drugs but there is evidence that parasites are starting to become resistant. And in just the same way we now have effective ways of tackling the mosquitoes that transmit malaria using bed nets treated with insecticide for example, but again there is evidence that the mosquitoes are becoming resistant. I think it is very important to bring out all the tools we can to work out what is going on, how the parasite and mosquito populations are changing, and to provide new tools to track the spread of drug resistance and to stop it. I think we are starting to see ways we can do that, bringing together some of the new technologies.

And at the same time looking forward, we know that if we could develop a cheap, safe, effective malaria vaccine that would be the most marvelous thing. It is very difficult to develop a malaria vaccine because the bug is so clever at fighting the immune system and for multiple other reasons. Here genomics both of the parasite and of the human immune system, understanding those things may help a lot in developing an effective vaccine, so that is more blue skies research. Both of those are very exciting opportunities, one very practical and near term and the other being longer term.

Q: How does your research fit into Translational Medicine within the department?

DK: Let me give you a very specific example. We are working with partners in 20 countries to sequence the genome of malaria parasites. This is one of the projects and we are also working on humans and mosquitoes. But in that project what we are doing is bringing together parasite sequencing data from thousands of samples around the world. We have already sequenced over a thousand samples, which is a lot, but we are scaling up to try to do at least ten thousand samples over the next few years. And what we are starting to see using that sequencing data is how the parasite population is changing and has changed over the last few years. With that we can start to pick out the regions of the genome which may be responsible for drug resistance. We can certainly provide information how any particular intervention strategy may be changing the parasite population. And actually just very recently, hot off the press and unpublished, we are seeing some extremely strange things going on in the parasite population in Cambodia. Cambodia is a place where drug resistance has often originated and we never knew why, but we actually think we might have part of the explanation.

Although all of the information will go into scientific journals, we are trying to push more and more of that firstly out onto the web, open access so anyone can use it, but more importantly trying to push it in the direction of policy makers. We are trying to form the information in such a way that it is not just of interest to expert scientists, but in a way that it could actually help to inform policy. A remarkable thing that is happening right now is that as we do more genome sequencing data, in some ways the results get simpler. This is because there are more headline results that would affect simple things like where should you be deploying drugs, what drugs should you be deploying, what should you think about doing next year. So very much as a translational agenda, and our mission over the next five years is to change the profile of our work from being just scientists to being much more involved with delivery and public health.

Dominic Kwiatkowski

Genetics

Prof. Dominic Kwiatkowski leads a global network of researchers and clinicians working to develop new tools to control malaria. A central theme of his work is to translate advances in genomics, statistics and computer science into practical applications for epidemiological surveillance and public health.

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