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Primaquine is a drug used to eliminate vivax malaria from the liver and prevent relapses. However, it causes anaemia in patients with G6PD deficiency. A new, slightly longer regimen with increasing doses of primaquine could allow to safely treat all patients with vivax malaria.

I’m James Watson I’m working here as a post doc with Nick White in the clinical therapeutics unit, working on malaria mostly and drug pharmacokinetics. There are two types of malaria, falciparum and vivax. Falciparum is the better known one and it’s spread across Africa; there isn’t much vivax in Africa and it’s predominantly in Asia where it’s more than half the malaria, and it counts for maybe 15 million cases per year.

Malaria gives you a fever and the primary fever you treat exactly the same way for falciparum and vivax. However vivax has a characteristic of relapsing: you have these hidden parasites in your liver that come out and give you a new illness every three or four weeks. There’s only one drug that cleans your liver and stops this relapse which is primaquine. The problem with primaquine is that it causes anaemia in people with a genetic deficiency called G6PD deficiency. This is the most common deficiency in the world, so you can’t give primaquine to lots of people.

Primaquine destroys the older rather than the young red blood cells. We believe that it’s possible, by giving primaquine over a slightly longer duration - three weeks instead of two weeks - and starting with low doses and slowly escalating the dose over time, it’s possible to do something similar to control burning, where you start off and you burn a little bit. That stops dangerous anaemia in a patient and it gives the bone marrow time to respond and make new, younger red blood cells that are resistant to this toxic effect of primaquine.

The most important new research is a drug called tafenoquine developed by GSK. This is exactly the same as primaquine and it has the same toxic side effects, except that you can give it as one single dose. This is an important progress because you have to take primaquine over two weeks and lots of people don’t finished their treatment and therefore don’t cure themselves of these relapsing infections.

This research started off as a project trying to understand the dynamics of red blood cells and how this drug primaquine destroys red blood cells, and then we’ve transformed that into a new regimen that we could possibly give to G6PD deficient patients. In Asia, we think that there are millions of people who are G6PD deficient and who can’t take primaquine, so these people would directly benefit from a new regimen that would be safe. We have ethical approval to try this new regimen of primaquine in healthy volunteers. We’re starting this in the next few months, and this should hopefully enrol about 20 patients, and will be a proof of concept whether this idea works or not.

James Watson

James Watson analysis genetic and epidemiological data to characterize relapses in vivax malaria. He also develops statistical models to better understand the pharmacology of antimalarial drugs. James has a particular interest in G6PD deficiency in the context of radical curative drugs for vivax malaria, and works on developing a new primaquine regimen which would be safe in G6PD deficiency.

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