The spread of drug-resistant parasites in Southeast Asia could undermine artemisinin-based antimalarial therapies and imperil global malaria control.
[Photo: Mosquito, by Mr. Andy Langager/creative commons]
Artemisinin is isolated from the sweet wormwood plant, an herb used in Chinese traditional medicine. It also can be produced using genetically engineered yeast. Because the drug is such an effective antimalarial, the World Health Organization recommended that it be combined with other drugs to treat malaria so artemisinin resistance would not develop.
A consortium of investigators from nine endemic countries led by Dr. Jonathan Juliano, assistant professor of medicine at the UNC School of Medicine and adjunct professor of epidemiology at the UNC Gillings School of Global Public Health, and Dr. Steve M. Taylor, assistant professor of medicine in the Duke University School of Medicine and adjunct assistant professor in Gillings School’s epidemiology department, conducted a survey that screened for genetic mutations associated with resistance in the parasite populations of sub-Saharan Africa.
Their report, “Absence of putative Plasmodium falciparum artemisinin resistance in sub-Saharan Africa: A molecular epidemiologic study”, was published online September 9 in the Journal of Infectious Diseases. The work was highlighted recently by the Worldwide Antimalarial Resistance Network.
Dr. Juliano and his colleagues, who included Mr. Christian Parobek, an MD/PhD candidate in the UNC Curriculum in Genetics and Molecular Biology in the UNC School of Medicine, and Dr. Steven Meshnick, professor of epidemiology at the Gillings School, conducted what is believed to be the first large-scale survey of artemisinin-resistance polymorphisms in African parasites. These polymorphisms — genetic variations within a population — may extend an organism’s ability to survive when treated with an artemisinin antimalarial.
In the current survey, Dr. Juliano and his team found no previously identified artemisinin-resistance mutations that have been confirmed to confer resistance in Southeast Asia. However, they identified a large number of novel polymorphisms in the gene associated with resistance. A better understanding of the biological and clinical impact of these genotypes will require coordinated clinical and molecular genetic investigations.
The report acknowledges that the antimalarial efficacy of artemisinin combination therapies remains high in Africa. However, resistance mutations that have cropped up in Southeast Asia may soon appear in Africa, and molecular surveillance can provide a framework to monitor for the emergence or importation of resistant mutations.
The research included a novel pooled second-generation sequencing approach that is sensitive, inexpensive and scalable. Only two months following the publication of a study identifying the gene associated with resistance, Dr. Juliano and colleagues were able to design the protocol, pilot it using laboratory parasites, and apply it to more than 1,100 field parasites. The polymorphisms associated with an artemisinin-resistant phenotype are numerous and unlinked and occur on a diverse background, making their novel sequencing approach an attractive new method for molecular surveillance. Ongoing surveillance will be needed to detect the appearance of new mutations, shifts in frequencies of existing African variants, and the importation of known Asian resistance mutations.
The researchers believe that complementing these studies with ongoing, large-scale molecular epidemiologic surveillance will add to the ability to monitor artemisinin resistance. Together, these integrated efforts may help forestall the spread of resistance and enhance the global durability of artemisinin therapies.