Joel Tarning: Getting the dose right
Too high a dose can result in toxicity and side-effects, too low a dose can cause the illness to come back and at worse develop resistance. In the case of malaria, it is particularly important to get the dosage right for more vulnerable patients such as children and pregnant women. Professor Joel Tarning's findings have now been adopted by the World Health Organisation.
This is a podcast from the Nuffield Department of Medicine. Today we are asking Professor Joel Tarning about his research in malaria treatment.
Q. Why is it important to get the dosage of anti-malarial drugs right?
Joel Tarning: Malaria is one of the most important parasitic diseases in the world, and we need to treat patients with anti-malarial drugs in order to kill all of the parasites in the body. If the patients receive a dose that is too high, they can suffer adverse reactions and toxicity, which might harm them. If they instead get a dose that is too low, not all of the parasites in the body will be killed. These remaining parasites can grow back and cause new infections, which will result in unnecessary suffering, and in the worst-case scenario, death.
If a parasite survives the treatment, it has also had a chance to ‘sample’ the drug. It could then develop drug resistance. It is therefore absolutely crucial that we give all patients the correct drug dosage in order to cure the disease by killing all the parasites in the body. This also minimizes the risk of the development of resistance.
Q. How do you get the dosage of the anti-malarial drug right?
JT: To determine the correct dosage, we need to conduct clinical studies in sick patients: we enrol patients with malaria and treat them with anti-malarial drugs. We then take blood samples from these patients over the course of the treatment, and we measure the amount of the drug in these samples.
We do this in order to understand how these drugs behave in the body. For example, I might wan to know how fast a drug is absorbed into the bloodstream, or how a drug is distributed in the body, or how fast it is eliminated. Some of these processes can differ between young children and adults. It is only by understanding how these processes work and the differences between patients that we can understand how to treat these patients correctly. This helps us give all patients an equal chance of being cured.
Q. How has this line of research changed malaria treatment?
JT: My work has shown that young children need a higher dosage of two commonly used anti-malarial drugs. This finding was recently picked up by the World Health Organisation: recently published anti-malarial treatment guidelines now recommend a higher dosage of these two drugs. I have also shown that there are similar trends in young children and pregnant women for other drugs, but we need more studies in order to determine the correct dosage for these other drugs and these specific groups of patients.
We have also studied how to treat drug-resistant malaria: these infections are very difficult to treat, and one option is to use several anti-malarial drugs in order to treat resistant infections.
Q. What are the most important lines of research that have emerged in the last 5-10 years?
JT: I believe that the identification and characterization of artemisinin-resistant malaria is the most important recent development.
Artemisinin is the first-line therapy that we use for malaria today: world-wide resistance to this drug would be catastrophic, as we have no alternative drugs to treat this disease. We recently mapped the development artemisinin resistance: resistance is now appearing in Myanmar, and moving towards India. If this movement continues to Africa, where 85% of all malaria infections occur, the situation is potentially very serious. I think that this is the single greatest threat we face today for treating and controlling malaria.
Q. Why is your work important? Why should this line of research be funded?
JT: Half of the world’s population is at risk of contracting malaria. There were about 200 million cases of malaria worldwide last year: that is a larger number than the entire population of the UK contracting malaria three times during a year! I therefore think it is absolutely crucial that we determine the correct dosage for anti-malarial drugs.
Malaria also kills about 2,000 people every day, most of them young children under the age of five. So it is very crucial that we treat all patients correctly, especially children, who bear the highest burden of death due to malaria. My research aims to determine the correct drug dosage for vulnerable populations such as children and pregnant women.
Q. How does your research fit in to translational medicine within the Department?
JT: I work closely with other scientists both within and outside the department to collect blood samples from clinical studies. My lab then measures the drug amount in these samples to identify how much of the drug gets into the patients systems. Combined with mathematical and statistical modelling techniques, I then use this information to help us understand how these drugs behave in the body and in different patients. For example, we might use this information to understand how age or pregnancy might affect drug distribution or treatment responses.
I think this is a true translational approach, because we combine data from many different disciplines in order to maximize the information that we can get from clinical studies. In short, my research translates drug measurements into new dosage regimens: I hope that this will create better treatments for patients with malaria.
This interview was recorded in May 2015