It was first reported that artemisinin was becoming less effective in Cambodia in 20085. Soon, artemisinin was seen to lose potency in other countries in the region too. The situation had worsened by 2013, as resistance to combination therapies was also reported.
In 2016, researchers based at the Sanger Institute who were also part of the MalariaGEN network, published research into piperaquine resistance in South East Asia. Piperaquine (related to chloroquine) was used in combination with artemisinin as a first-line treatment in several southeast Asian countries at the time. The combination of the two drugs was initially successful, but in 2013, research showed that malaria parasites in Cambodia had become resistant to both. A rise in the number of treatment failures in the country was recorded in 2016.
The researchers wanted to uncover the molecular markers of resistance in the parasites’ DNA. These could then be used to identify and track resistance across the region. The markers could also be used to understand the mechanisms of resistance – how was the parasite evading the drug. Underlying both those aims was a desire to support national malaria control programmes and provide information that could help public health officials decide if and when to switch treatments.
They carried out a genome-wide association study, looking at thousands of variations in the DNA of the parasites from Cambodia, comparing these across samples with different levels of resistance to piperaquine. This was followed up with laboratory studies. The team found two genetic markers linked with piperaquine resistance.
Now that specific markers in the genome had been identified, which could be looked for across the region, it would be possible to map how far the resistance had spread.
The MalariaGEN network, including organisations in malaria endemic countries and scientists across Africa and South East Asia, aimed to make the data available and useful for national malaria control programmes. This data sharing was vital so that they could rapidly deploy alternative therapies where possible and where needed, enhancing treatment for patients
Speaking at the time, Professor Dominic Kwiatkowski, who led the research, said:
“Our study shows that modern genomic surveillance can detect patterns of resistance much sooner than was possible in the past, providing vital information and allowing public health officials to respond as soon as possible. There is now an urgent need to provide national malaria control programmes with the tools for active genomic surveillance that will help to detect new emergences of resistance as soon as they arise and thereby reduce the risk of a major global outbreak.”