Important resistance surveillance project begins its second phase

20 October 2015

A new collaborative study is investigating the safety, tolerability and efficacy of two Triple Artemisinin-based Combination Therapies (TACTs) to help prolong the lifespan of the important ACTs in the face of increasing artemisinin and partner drug resistance.

In July 2014, the Tracking Artemisinin Resistance Collaboration (TRAC), a three year project to monitor the spread and emergence of artemisinin drug resistance in Southeast Asia and Africa, published their findings in the New England Journal of Medicine.

The study confirmed that malaria parasites resistant to artemisinins were widespread in many parts of Southeast Asia, with signs of emergence appearing in other parts of the region. Reassuringly, the project found no evidence for the presence of artemisinin resistance in Africa.

Following the important findings from the TRAC project, the team are now implementing a second phase, known as TRAC II. TRAC II is monitoring for the extension and emergence of artemisinin and partner drug resistance across Asia and Africa. In addition it will trial the efficacy, safety and tolerability of Triple Artemisinin-based Combination Therapies (TACTs) at 17 sites in 8 different countries in Asia and Africa. These TACTs combine the standard Artemisinin-based Combination Therapies (ACTs) with a third partner drug with likely opposing resistance mechanisms. The combinations include dihydroartemisinin-piperaquine with mefloquine and artemether-lumefantrine with amodiaquine.

In addition to the clinical trials, TRAC II is studying clinical, molecular, pharmacokinetic and socio-economic aspects of artemisinin resistance.

“We are facing a real threat that falciparum malaria is becoming increasingly multidrug resistant and impossible to cure. New antimalarial compounds are years away, so we have to be innovative with the existing arsenal. The triple combinations studied in TRAC II will hopefully provide not only effective treatment, but also delay the further extension and emergence of artemisinin and partner drug resistance. The latter will have to be carefully monitored as well, which is another aim of TRAC II,” says Prof Arjen Dondorp, Head of TRAC II, and Deputy Director of the Mahidol Oxford Tropical Medicine Research Unit (MORU).

‘’This study will assess whether TACTs could be a viable alternative to ACT treatment in areas affected by drug resistance. Potentially TACTs could also be deployed in areas with neither artemisinin nor partner drug resistance in order to prevent the emergence or spread of artemisinin and partner drug resistance. The study also aims to track genetic markers associated with artemisinin and partner drug resistance. A TRAC II substudy will assess whether artemisinin resistance affects the effectivity of parenteral artesunate in severe and complicated malaria. The entomological studies will assess the infectivity of resistant parasites for various Anopheles vectors. Finally demand factors associated with antimalarial resistance will be studied.” says Dr Rob van der Pluijm, TRAC II Project Manager.

As a key partner, the WWARN Asia Regional Centre is working closely with MORU on the collaboration to manage the Specimen Management Centre, provide quality assurance and training in laboratory and clinical procedures, develop procedures for collecting and preserving samples for molecular analysis and training in their use, and provide study site assessments.

“To tackle the problem of antimalarial resistance, we need to ensure that the data collected are of the highest quality,” says Dr Mehul Dhorda, Head of the WWARN Asia Regional Centre and key TRAC II collaborator. “For this reason, we are offering researchers and collaborators the tools and resources they need to assure the overall quality of the research data captured.”

Partners from National Institutes for Health and the Mahidol-Oxford Tropical Medicine Research Unit will present initial findings from the project at the American Society of Tropical Medicine and Hygiene 64th Annual Meeting. If you are attending the Meeting and would like to find out more about the TRAC II project, why not join the symposium?

Location: Marriott - Grand Ballroom Salon F

Related publications:

  • Ashley EA, et al. ‘Spread of Artemisinin Resistance in Plasmodium falciparum Malaria’ New England Journal of Medicine (2014). DOI: 10.1056/NEJMoa1314981