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Bill & Melinda Gates Foundation award grant for genomic analysis in large-scale study of artemisinin resistance in P. falciparum

28 June 2012

The emergence of artemisinin resistance (ART-R) in Plasmodium falciparum malaria parasites, recently reported in Cambodia and Thailand, has become one of the most pressing global health emergencies. If ART-R is not effectively contained, its spread from South-East Asia could undermine antimalarial treatment globally, jeopardizing eradication efforts and causing a massive death toll. At present, the highest priorities are to define the geographical extent of artemisinin resistance, and to identify molecular markers, critical for monitoring efficiently the spread of ART-R, and studying its causes.

These needs have led to the formation of the Tracking Resistance to Artemisinins Collaboration (TRAC), a multi-site project funded the UK Department for International development (DFID) and co-ordinated by the Mahidol-Oxford Research Unit (MORU) in Bangkok, Thailand. Encompassing 13 sites distributed around South-East Asia and two in Africa, the project initially aims to study 1,500 patients in a single malaria season, mapping levels of ART-R across the region. With the resulting clinical data, the project will be able to define the current geographical extent of ART-R.

To address the pressing question of identifying molecular markers, TRAC has partnered with the MRC Centre for Genomics and Global Health to conduct large-scale genomic analyses to identify mutations associated with ART-R. The MRC Centre will work with the Malaria Programme at the Wellcome Trust Sanger Institute in Hinxton, UK, which will sequence the DNA of all parasites samples collected by TRAC, supported by Wellcome Trust funding. The resulting dataset of approximately 1,500 parasite genomes will be the most extensive ever assembled by a single project; in combination with the clinical data generated by TRAC, it is slated to provide the best available resource for shortlisting high-quality candidate markers. Sharing this vision, the Bill and Melinda Gates Foundation (BMGF) has awarded a grant of USD 900,000 to fund this large-scale analysis. The genomic analysis project will be led by Olivo Miotto, a Senior Informatics Fellow funded by the MRC Centre and based at MORU, in Bangkok. According to him, working closely with TRAC investigators in South-East Asia will be essential for the success of this project: “TRAC is a complex collaboration between many institutions and sites, so it is crucial to harmonize data, but also to foster trust and respect for everyone’s contribution. Working with MORU, the MRC Centre has an open dialogue with investigators in the field, ensuring that the genomic analysis makes sense to everyone, and is integral to the investigation, on par with clinical work.”

The quest for molecular markers presents itself as a complex task, as Olivo explains: “There is evidence that artemisinin resistance has emerged on the Thai-Burmese border, as well as in western Cambodia; however, it is not clear whether these changes have a common origin. Our initial analyses show that there may be important epidemiological differences between the two regions, particularly because of marked population structure in western Cambodia. Most likely, the analysis of the large quantities of high-quality data generated by TRAC will depend upon a detailed and accurate understanding of the epidemiology of P. falciparum in Cambodia and its neighbouring countries. The BMGF award is a clear statement that our funders understand this complexity, and have a high level of confidence in the capabilities afforded by genomic technologies.