Mehul Dhorda: Finding the best malaria treatments
For malaria, parasite resistance and treatment efficacy is dynamic. Resistance to artemisinin, sometimes induced by poor quality medicines, causes artemisinin-based combination therapies (ACTs) to start failing. A robust system for surveillance of resistance can help ensure people get the right treatment at the right time.
Mehul Dhorda: WWARN stands for the Worldwide Anti-malarial Resistance Network. It was set up 6 or 7 years ago with the aim of generating intelligence and high-quality evidence to inform policy on malaria treatments around the world. To do that, we collect information from researchers around the world who are working on testing anti-malarial medicines in the field, to try and generate evidence that at this time, for this particular location, it is the best treatment. Then we keep doing that over time because for malaria, the situation in terms of resistance and efficacy is dynamic, you have to keep monitoring it. We collate all that information.
Historically resistance has always somehow come out of South East Asia (SEA)– there have been other foci where resistance has developed in South America. But typically resistance will develop in SEA, it will be exported across India and into East Africa and then the rest of Africa. And that’s precisely where the problem is: if the resistance that is developing here (in SEA) right now does get exported to Africa the impact in morbidly and mortality is much higher. The problem is getting worse because we’re now starting to see ACTs (Artemisinin-based Combination Therapies) to some extent failing. This is related to the fact that the parasites in the region have become tolerant to artemisinins. This means that the partner drugs are more exposed to the parasites. That has led to partner drug resistance evolving, changing over time. We need to track that. That’s what we’re doing through the TRACI and TRACII (Tracking Resistance to Artemisinin Collaboration) studies.
Q: Why does this line of work matter, and why should we fund it?
MD: It matters because malaria is a disease that can have devastating consequences on the lives of people. It’s difficult to prove a causal relationship, but wherever there’s malaria, there’s poverty. Whether one causes the other, it’s difficult to tell. We want to make sure that people are not suffering from a curable disease all the time, disease that affects their performance at school or at work, their economic viability and that of the country.
It is important to make sure that people who are living in malaria endemic regions are getting the best possible treatment. One way of doing that is to have a well developed, robust system for surveillance of resistance which will help make sure that people get the right treatment at the right time. Poor quality medicines also play into resistance. You do get cases where medicines do not contain enough of the active ingredient. If you are given a sub-optimal dose, that does promote the development of resistance.
So there is the drug quality, there is also the pharmaco-kinetics and pharmaco-metrics, there is the in vitro module, the molecular module, the clinical module. All of these people try to collect different pieces of evidence from all over the world, wherever these studies are done, to come up with recommendations on treatment and dosing.
Q: What important lines of research have emerged in the past few years in your field?
MD: What has become increasingly important is to have as broad a network for surveillance of resistance as possible. There was a study led by Dr Kyaw Myo Tun who is also working in our unit: they collected samples from all over Myanmar, and could map the extent of the spread – or independent emergence – of artemisinin resistance.
Q: How does your work fit into translational medicine within the Department?
MD: The mapping of resistance is a good example. The samples that we collected through the TRAC study actually helped with the clinical validation of the K13 marker, which is a genetic marker of resistance to artemisinins. Now, we're trying to roll it out and get as broad a coverage as possible in terms of the prevalence of the resistance marker. We’re translating genomics into something that is a relatively easily implementable surveillance tool. I’d say that’s a good example of translational medicine.
Q: What do you enjoy about your work?
MD: What I enjoy is knowing that I’m working doing something that is useful. It’s as simple as that. I have some background working in a biotech company before and it was just not satisfying. Working here at MORU (Mahidol Oxford Tropical Medicine Research Unit), and before that with MSF (Médecins sans Frontières) in Africa, the feeling that I knew that I was doing something useful was deeply satisfying. And I think that’s one of the best things ever.