An interview with Arjen Dondorp
Prof Arjen Dondorp is the Deputy Director and Head of Malaria Research at the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand. His main research interests include the pathophysiology and treatment of severe malaria, antimalarial drug resistance and the improvement of intensive care practice in developing countries. Arjen chairs the World Health Organization Technical Expert Group (TEG) on Antimalarial Drug Resistance and Containment. Philippe Guérin, WWARN Executive Director, is a TEG observer.
Prof Arjen Dondorp
How did you become involved in malaria research?
As a medical student I became involved in rheology, studies on blood flow properties. During my internal medicine residency I studied rheological changes in Dutch travellers returning with falciparum malaria and found that red cell deformability is remarkably reduced in these patients. This led to a PhD thesis on the pathophysiology of severe falciparum malaria, for which I did clinical studies in Thailand and Kenya under the guidance of Piet Kager, Nick White and Kevin Marsh.
Can you recall how the first signs of resistance to artemisinin-combination therapy (ACT) were identified?
It started with worrying observations in the early 2000s from surveillance studies suggesting declining efficacy of artemether-lumefantrine and artesunate-mefloquine in the Cambodian-Thailand border region. Initially most people thought that reduced efficacy of the partner drug was to blame for this. WHO and the National Malaria Control Programmes of Cambodia and Thailand then established a multipartite task force to study this in more depth. Evaluation of the initial parasite clearance characteristics were included as an important endpoint for assessing efficacy of the artemisinin component of ACTs. It then became evident that parasite clearance was severely delayed in this region.
Southeast Asia has incubated treatment-resistant malaria in the past: what are the factors which make this region susceptible to resistance?
Firstly, there has been massive drug pressure on the parasite population in western Cambodia, where artemisinins were used as monotherapies since the late 1970s. Secondly, the low malaria transmission in the area has probably contributed to allow resistant parasite populations to establish themselves. Finally it is also possible that certain genetic parasite factors facilitate development of antimalarial drug resistance.
What recent progress are you seeing in the fight in antimalarial resistance?
I’m extremely encouraged by the huge amount of collaborative research currently taking place to address the problem of artemisinin resistance. The hunt for a molecular marker is making fast progress. Better in vitro tests to identify the artemisinin resistant phenotype are being developed and we have a better understanding of the mechanisms of artemisinin resistance. A large-scale containment programme along the Cambodia-Thailand border region succeeded in reducing falciparum malaria in these areas. However, these gains are fragile, as evidenced by the recent emergence of artemisinin resistance on the Thailand-Burma border.
What role is the World Health Organization Technical Expert Group on Antimalarial Drug Resistance and Containment tasked with?
This Technical Expert Group has an advisory role for the WHO on a variety of issues regarding antimalarial drug resistance. The initial focus will be on aspects of the containment programme for artemisinin resistance, including specifics on the design and execution of the programme, as well as identification of important knowledge gaps.
What do you hope to achieve in your role as chair?
The composition of the TEG is very broad, with representation from a large variety of backgrounds and expertises. In my role as chair, I hope to contribute to the success of the meetings by maximizing the use of all this expertise, so that relevant and useful recommendations can be made.