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On 24-25 Jan 2019, investigators met in Bangkok to launch the Developing Triple Artemisinin-based Combination Therapies (DeTACT) Project. Led by MORU and funded by UKaid and the UK Department for International Development (DfID), DeTACT is a large, 14 site trial in 8 African and 5 Asian countries that will study the efficacy, safety and tolerability of two Triple Artemisinin Combination Therapy (TACT) combinations, using combinations of existing antimalarial drugs.

DeTACT will also project the impact of TACTs on controlling the spread or emergence of multi-drug-resistant P. falciparum malaria leading to its elimination, and examine the ethical and commercial considerations of using TACTs across the malaria endemic world.

DeTACT is particularly urgent: strains of P. falciparum malaria parasite highly resistant to artemisinins, our most effective antimalarial drugs, have rapidly spread out of Cambodia and across SE Asia. These malaria ‘superbugs’ have caused a large increase in treatment failures in malaria patients across the Greater Mekong Subregion, and if they emerge in Africa, put millions, especially children under 5, at risk.

“DeTACT is a very important study: Increasing drug resistance in Southeast Asia jeopardizes the treatment of P. falciparum malaria, a potential fatal disease, and malaria elimination is only possible if we have effective drugs to treat the disease,” said Oxford Prof. Arjen Dondorp, Head of Malaria at MORU and principal investigator for DeTACT. “These TACTs can provide an effective and safe malaria treatment, using a combination of already available antimalarial drugs.”

The DeTACT trials will compare two widely used drug combinations (artemether-lumefantrine and arterolane-piperaquine) against two TACTs constituted of one additional drug added to each of these combinations (amodiaquine and mefloquine, respectively).

Based on preliminary results from the recently completed TRACII trials which recruited over 1,000 subjects with uncomplicated falciparum malaria, TACTs already appear to be safe and highly efficacious even against multi-drug resistant falciparum malaria currently prevalent in parts of SE Asia. Before such combinations can be recommended for more widespread use, especially in highly endemic regions of Africa where children are most affected by malaria, their safety and tolerability must be verified.

Stringent assessments to identify cardiac, hepatic, renal or bone marrow toxicity or other study drugs-related dysfunctions will be complemented by predictive mathematical modelling to analyse TACTs’ costs and expected benefits and assess their potential to delay the emergence or spread of drug-resistant P. falciparum malaria.

At the meetings, investigators from the Africa and Asia study sites and researchers leading the complementary work packages and sub-studies presented plans to implement their studies and analyses.

The bioethics component of DeTACT will document patient, practitioner and policy maker views and attitudes on deploying TACTs. It will use focus groups and interviews to identify potential barriers to TACT acceptability and deployment and address ethical issues arising from introducing TACTs to treat African children where current ACT therapy is still efficacious. This work will be supplemented by assessments of the market positioning within and outside donor funded malaria services, and potential market uptake in different malaria epidemiological settings.

Dr Chanaki Amaratunga will jointly coordinate DeTACT with Dr Mehul Dhorda. Chanaki will coordinate the project and focus on the Asia trials and the complementary work packages, while Mehul will coordinate the Africa trials and related activities. DeTACT’s 14 sites include 8 in Africa – the Gambia, Nigeria, Tanzania, Guinea, Niger, Malawi, Burkina Faso and DR Congo – and 6 in Asia – India (2), Cambodia, Bangladesh, Indonesia and Myanmar.

Dr Melanie Renshaw of the African Leaders Malaria Alliance will chair a project steering committee of representatives from the Asia-Pacific Leaders Malaria Alliance, WHO, malaria civil society organisations and academia that will advise the DeTACT management team as it implements activities to make TACTs available to malaria control and elimination campaigns worldwide.

DeTACT is the third of three DfID supported multi-country, multi-site trials (TRAC and TRACII) that have characterised artemisinin resistance and tested multi-drug resistant malaria treatments in SE Asia.

- Thank you, Chanaki Amaratunga and Mehul Dhorda for text and Supa-at (Ice) Asarath for photo