Resistance to the frontline malaria drug artemisinin can be identified by surveying the genomes of malaria parasite populations, a worldwide research collaboration has shown.
The effectiveness of artemisinin – this key drug against malaria – is weakening, threatening hundreds of thousands of lives. It is a major objective of the World Health Organization to stop the spread of malaria parasites that are resistant to drugs.
The team, led by researchers at the University of Oxford and the Wellcome Trust Sanger Institute, discovered multiple strains of the malaria-causing parasite Plasmodium falciparum that appear to be rapidly expanding throughout the local parasite population in Western Cambodia, a known hotspot for drug resistance. These strains have emerged recently and are all artemisinin-resistant.
The scientists were able to characterise distinct genetic patterns or 'fingerprints' for each of the strains, showing the approach offers a rapid and novel way to detect and track the global emergence of drug resistance. Their findings provide deep insights into how resistance emerges and is maintained by certain parasite populations.
The international group used new genome sequencing technologies to investigate how genetic monitoring of malaria on a large scale could be used to track drug resistance. They sequenced the entire DNA of malaria parasites in over 800 samples from Africa and from South East Asia.
'Our survey of genetic variation showed that Western Cambodian malaria parasites had a population structure that was strikingly different to those of the other countries we analysed,' says Professor Dominic Kwiatkowski, senior author of the paper from the University of Oxford and the Wellcome Trust Sanger Institute near Cambridge. 'Different not just from countries in Africa, but also different from malaria parasite populations in neighbouring Thailand, Vietnam, and even Eastern Cambodia.
'Initially, we thought our findings might be just an anomaly. But when we investigated further we found three distinct sub-populations of drug-resistant parasites that differ not only from the susceptible parasites, but also from one another. It is as if there are different ethnic groups of artemisinin-resistant parasites inhabiting the same region.'
One important benefit of this genetic approach is that, even without knowing the precise genetic causes of drug resistance, researchers are able to quickly identify resistant strains – an important step towards effective worldwide surveillance.
'Public health authorities need rapid and efficient ways to genetically detect drug-resistant parasites in order to track their emergence and spread,' says Dr Olivo Miotto, first author of the paper from Oxford University, Mahidol University in Thailand, and the MRC Centre for Genomics and Global Health. 'Our approach allows us to identify emerging populations of artemisinin-resistant parasites, and monitor their spread and evolution in real time. This knowledge will play a key role in informing strategic health planning and malaria elimination efforts.'
Western Cambodia appears to be a hotspot for the emergence of drug resistance, but it is not fully known why. Resistance to other malaria drugs, namely chloroquine and sulfadoxine/pyrimethamine, first developed in Southeast Asia before spreading to Africa. This study offers new leads that the consortium will be pursuing as to why drug resistance arises more readily in some locations when compared with others.
'Whilst we have not yet identified the precise mechanism of action or resistance to artemisinin, this research represents substantial progress in that direction,' says Professor Nicholas White of Oxford University and Mahidol University. 'It also provides an important insight into why antimalarial drug resistance (previously to chloroquine and antifols, and now to artemisinin) arises in Western Cambodia.'
He adds: 'Artemisinin resistance is an emergency which could derail all the good work of global malaria control in recent years. We desperately need methods to track it in order to contain it, and molecular fingerprinting provides this.'