A team of researchers has sequenced the genome of Plasmodium falciparum and found that 33 regions on the genome appear to be under strong selection for artemisinin resistance. On further scrutiny, the team was able to narrow down to seven specific genes on chromosome 13.
This particular section of the chromosome can account for 35 per cent reduction in the time taken to clear parasites from the blood (parasite clearance rates) after treatment, in both western Cambodia and western Thailand.
Artemisinin resistance results in reduced parasite clearance rate after treatment. The results were published today (April 6) in Science.
Artemisinin-based combination therapies have been recommended by the World Health Organisation as the first-line treatment for uncomplicated falciparum malaria.
The genomes were sequenced from 91 P. falciparum parasites taken from three countries — Cambodia, Thailand and Laos. Unlike Cambodia and Thailand, resistance to artemisinin has not been reported from Laos.
Resistance to artemisinin has been confirmed in western Cambodia, and has recently emerged in western Thailand. The actual mechanism by which the genes confer resistance to the drug is, however, not known. “The spread of artemisinin-resistant parasites would be catastrophic for malaria control,” the authors write.
In a related study published in The Lancet today (April 6), the authors “provide the first unequivocal proof that resistance has emerged [in western Thailand].”
To test for drug resistance in western Thailand, the authors studied the time taken to clear the parasites from the blood of 3,202 patients treated with drugs over a 10-year period (2001 to 2010). Most of the patients were younger than 15 years.
They found that the time taken for reducing the number of parasites in the blood by half (parasite clearance half-life) using artemisinin-containing medications increased from an average of 2.6 hours in 2001 to a mean of 3.7 hours in 2010.
The corresponding figure in the case of 116 patients from western Cambodia was an average of 5.5 hours. The patients from western Cambodia were studied between 2007 and 2010.
Most importantly, the proportion of western Thailand patients with slow-clearing infections (where clearance half-life is more than 6.2 hours) increased from 0.6 per cent in 2001 to 20 per cent in 2010. In the case of western Cambodia, the percentage of people who had slow-clearing infections in 2010 was 42 per cent.
The Lancet study provides clear evidence of reducing effectiveness of artemisinin drug in western Thailand.
“One way of reducing the incidence of malaria is by increasing the availability of artemisinin resistance-containment strategies. But such strategies would “provide a selection pressure driving artemisinin resistance,” it warns.