Scientists have uncovered mutations of a gene that make the most dangerous malarial parasite resistant to front line drug therapy.
More than half a million children die each year from malaria caused by Plasmodium falciparum. Drugs with artemisinin have led the fight against this single-celled parasite's depredations and contributed to a decline in the world's burden of malaria.
However, strains of P. falciparum that are resistant to artemisinin have been detected in Cambodia, Thailand, Myanmar and Vietnam, raising fears that these drug-resistant forms could spread to other parts of the world and put at risk the advances that have been made in combating malaria.
An international team of scientists have identified a parasite gene whose mutations are associated with artemisinin resistance. Such mutations could be “a useful molecular marker for tracking the emergence and spread” of resistance, noted Frédéric Ariey of the Institut Pasteur in France and his colleagues in a paper published last week in Nature.
These scientists “seem to have won the race to identify if not the gene, at the very least a key gene, responsible for artemisinin resistance,” remarked Christopher V. Plowe of the Howard Hughes Medical Institute in the U.S. in a commentary published in the same issue of the journal.
The team took a drug-sensitive P. falciparum parasite isolated from a malaria-sufferer in Tanzania and then cultured in it in the laboratory, subjecting it to 125 cycles of escalating doses of artemisinin over five years. Genome sequences of the resistant forms that emerged were compared to that of a sensitive strain cultured in parallel without being exposed to the drug. The analysis revealed that the resistant parasites had eight mutations in seven genes that the sensitive ones lacked.
With this information in hand, the scientists examined the genomes of 49 P. falciparum isolates from Cambodia with varying levels of artemisinin resistance. Mutations in a gene producing a protein called K13 stood out.
Dr. Ariey and his colleagues then analysed the K13 gene sequence from over 900 parasites isolated from patients in various Cambodian provinces. The K13 mutations were widespread in provinces where artemisinin resistance had been reported and hardly found elsewhere. They also showed that these mutations were a good molecular marker to identify patients with drug-resistant parasites.