Significant achievements in Malaria 2009-2014
Arjen Dondorp (top, 4th from left) and members of the MORU Malaria Department
- First detailed description of the emergence of artemisinin resistant falciparum malaria in western Cambodia. The Tracking Resistance to Artemisinin (TRAC) study, involving 15 sites in 10 countries, defined the extent of resistance in Cambodia, the Thai-Myanmar border, the Greater Mekong Subregion, and beyond and validated the Kelch-13 molecular marker (Figure 2). This was the first comprehensive phenotypic and genotypic characterisation of artemisinin resistance in falciparum malaria.
- Identified reduced ring stage sensitivity as the cause of artemisinin resistance through modelling, modified in-vitro sensitivity tests and transcriptomic studies.
- Developed a new method of dose-optimisation during the development of antimalarial drugs based on pharmacokinetic-pharmacodynamic characterization which has been adopted by Novartis and the Medicines for Malaria Venture.
- Major contributions in the development and testing of new antimalarial drugs including KAE609 (spiroindolone) and OZ439 (ozonide).
- Development of an ultrasensitive qPCR method to detect Plasmodium parasitaemia in asymptomatic carriers which has led to a revised understanding of malaria epidemiology in the region. Establishment of a regional network for testing targeted malaria elimination in areas identified by this technique as transmission reservoirs as a prelude for regional falciparum malaria elimination.
- Completion and publication of AQUAMAT, the largest RCT in severe malaria to date, in 11 sites in 9 African countries demonstrating the life-saving benefit of parenteral artesunate over quinine for the treatment of severe falciparum malaria in African children. This has led to a change in the WHO treatment guidelines.
- Development and evaluation of plasma PfHRP2, a measure of total parasite burden, as a diagnostic and prognostic tool in adult and paediatric severe falciparum malaria.
- Confirmation of the pivotal role of microcirculatory compromise in severe malaria pathophysiology, by direct visualization and quantitation using orthogonal polarizing spectrometry and retinoscopy. Refuting the role of cerebral oedema as the cause of coma in adult cerebral malaria through imaging and pathology studies, and a clinical trial on mannitol in cerebral malaria presenting with cerebral swelling.
- Development and validation of a new theory of hypnozoite activation in vivax malaria, which explains the very high rates of vivax malaria which follow falciparum malaria (ten times more than P. falciparum recrudescences) and P. vivax persistence, and rediscovery of the importance of long latency P. vivax.
- Increased advisory and management roles supporting translation of evidence into policy and practice on the topics of malaria treatment and antimalarial drug resistance through WHO advisory committees (MPAC and TEGs) and the regional steering committee of the Global Fund RAI initiative.