Ric Price: Curing Plasmodium vivax malaria
Vivax malaria used to be considered benign but is now recognised as an important cause of morbidity and mortality. Resistance to chloroquine (given to treat the parasite blood stage) is growing and ACT (artemisinin-based combination therapy) is becoming common treatment for vivax malaria. New drugs and better public health strategies can help elimination targets, anticipated for 2030.
My name is Ric Price, I’m a Professor of Tropical Medicine at the Nuffield Department of Medicine in Oxford.
There are 5 species of malaria that cause disease in humans, and Plasmodium vivax is probably the second most important after falciparum. P. vivax can cause an appreciable morbidity and mortality; it was once known as a benign malaria, but it’s certainly not benign. It can reoccur weeks to months after the initial infection and that causes anaemia and recurrent diseases, and young children and pregnant women are particularly vulnerable to the disease.
You have to treat both the blood stage of the parasite, that’s the one that causes the illness and the fever, and you also have to treat the stages that go to sleep in the liver, they’re called the dormant hypnozoites. We have to give a combination of two drugs; most of the world uses chloroquine and you add to that primaquine for the liver stages. But the tricky thing is that the parasite is now becoming resistant to chloroquine, and primaquine you have to treat for 14 days, and if they don’t take a complete treatment course then the parasite will come back and will reoccur or relapse. There’re new drugs coming: there’s an exciting drug called tafenoquine which can be given as a single dose instead of a 14 day regimen. But now we have to identify new diagnostics so that people can safely be given this drug, even in areas where there’s G6PD deficiency.
Drug resistant vivax was first reported in about 1991 in the island of Irian Jaya, and now it’s at very high levels: maybe 50-60% of people fail their treatment with chloroquine. On a recent review we found evidence of low grade resistance throughout most of the vivax endemic world, so chloroquine resistance is here and it’s probably getting worse and we need to do something about it. ACT (artemisinin-based combination therapy) is used for falciparum malaria and it’s also highly effective for vivax malaria. So several countries now are abandoning chloroquine and are using ACT for both falciparum and vivax malaria.
I think that the biggest progress we’ve made in the last 10 years is to appreciate that vivax is important. It was neglected and people didn’t think that it would cause disease. We now have clear evidence that the repeated infections are associated with significant morbidity and mortality. As the policy makers and the funders appreciate the burden, they’re paying more attention, so this disease was once neglected is now becoming increasingly important in the elimination agenda. The burden of vivax is difficult to gauge, but it’s probably in the order of 20-30 million cases a year, and we estimate that that costs health care communities and patients and their families about half a billion dollars a year.
Our research is specifically focused on changing policy and impacting on health. If we don’t achieve that with P. vivax, we’ll never achieve the elimination targets, which in Southeast Asia is anticipated to be in 2030, that’s only 12 years away. There’s no opportunity for complacency and if we want to achieve that, we have to eliminate the parasite. My translational research agenda aims to tackle the primary obstacles for vivax elimination, and we divide that into three themes: surveillance – which populations are at risk of the disease? Diagnostics – so new diagnostics of how can we diagnose vivax and also people with G6PD deficiency? And thirdly – how can we give better treatments which are more effective and impact upon the disease? All of those activities are focused around the management of the patient and the public health strategies to reduce the parasite, so that’s very translational.