Tracking Resistance to Artemisinin Collaboration (TRAC I and TRAC II)
Monitoring the spread and novel emergence of artemisinin-resistant malaria is crucial to guide malaria containment and elimination interventions. In the past both chloroquine and pyrimethamine resistance started on Thailand’s borders with Cambodia and Myanmar before spreading westward to India and then to Africa where they were responsible for millions of malaria deaths.
Coordinated by MORU and led by Dr Elizabeth Ashley, the original Tracking Resistance to Artemisinin Collaboration (TRAC) documented in a July 2014 NEJM article the alarming extensive spread of artemisinin resistance in falciparum malaria over Cambodia, southern Vietnam, eastern Myanmar, Thailand and southern Laos. Involving 15 study sites in 10 countries across Asia and Africa, TRAC also characterized further the resistance phenotype and confirmed the molecular marker in a parasite gene on chromosome 13 coding for the propeller region of a Kelch protein (Kelch 13), which has been a game-changer in the surveillance for artemisinin resistance. In collaboration with the Sanger Institute the study further elucidated the underlying molecular determinants of artemisinin resistance.
This work made it clear that the main battleground to prevent the spread of artemisinin-resistant malaria to Africa is currently in Myanmar and along its borders with India and Bangladesh.
Coordinated by MORU’s Dr Rob van der Pluijm, the TRAC II study recruited its first patient in August 2015. As of 1 May 2017, 700 patients have been recruited in 16 sites in 8 countries – Bangladesh, Cambodia, Democratic Republic of Congo (DRC), India, Lao PDR, Myanmar, Thailand and Viet Nam.
TRAC II aims to map resistance to antimalarials and assess the tolerability, safety and efficacy of two new triple artemisinin combination treatments (TACTs): Dihydroartemisinin-Piperaquine combined with Mefloquine and Artemether-Lumefantrine combined with Amodiaquine. The triple combinations will hopefully restore efficacy in areas where ACTs are currently starting to fail dramatically, whereas TACTs also aim to prolong the longevity of the artemisinins and partner drugs in areas where ACTs still work.
In addition, from July 2017 TRAC II will assess the safety tolerability and safety of another Triple ACT (arterolane-piperaquine combined with mefloquine in collaboration with the Kenya Medical Research Institute (KEMRI). A team from the London School of Hygiene and Tropical Medicine (LSHTM) is currently assessing the feasibility and efficacy of community led malaria elimination efforts. Finally, the entomological (i.e. mosquito) factors in the spread of artemisinin resistance will be studied.
The UK’s Department For International Development (DFID) is the funder of the TRAC II trial.