Artemisinin-resistant malaria rate increased along Thailand border

Researchers from Mahidol University in Bangkok have observed an increase in the rate of artemisinin-resistant Plasmodium falciparum malaria along the Thailand–Myanmar border within the past 8 years, and they suggest these rates could potentially reach the rates reported in Cambodia within 2 to 6 years.

“Artemisinin combination treatments are the recommended first-line therapy for falciparum malaria,” the researchers wrote. “Plasmodium falciparum parasites with reduced in vivo susceptibility to artemisinin derivatives have emerged in western Cambodia. This finding threatens worldwide initiatives to control and eliminate malaria.”

The study included 3,202 patients from malaria clinics along the northwestern border of Thailand between 2001 and 2010. They measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria who had been treated with artemisinin regimens. They estimated the parasite clearance half-lives and genotyped the parasites. Slow parasite clearance is an indicator of artemisinin resistance.

In 2001, the parasite clearance half-lives had a geometric mean of 2.6 hours vs. 3.7 hours in 2010. In Cambodia, the average geometric mean was 5.5 hours between 2007 and 2010. The proportion of slow-clearing infections along the Thailand–Myanmar border was 0.6% in 2001 when compared with 20% in 2010. In Cambodia, the proportion of slow-clearing infections was 42% between 2007 and 2010.

Among the 1,583 infections that were genotyped, the researchers identified 148 multilocus parasite genotypes, each of which affected two to 13 patients. Between 2001 and 2004, parasite genotype had a significant effect on parasite clearance half-life, but the effect was much stronger between 2007 and 2010.

“Identification of a molecular marker will be crucial to monitor the distribution and spread of resistance and to understand the evolution of this treatment and the mechanism of action of artemisinin,” the researchers wrote.

In an accompanying editorial, Anne-Catrin Uhlemann, MD, PhD, and David A. Fidock, PhD, both of Columbia University in New York, said artemisinin combination treatments have led to significant reductions in malaria mortality and morbidity, and as a result of this study, containment efforts for artemisinin-resistant malaria should no longer be restricted to Cambodia.

“Whether initial signs of decreased parasite responsiveness will result in high-grade resistance and a loss of clinical effectiveness [of artemisinin] cannot yet be judged,” they wrote.

References:

  • Phyo AP. Lancet. 2012;doi:10.1016/S0140-6736(12)60484-X.
  • Uhlemann AC. Lancet. 2012;doi:10.1016/S0140-6736(12)60488-7.

Disclosures:

  • The researchers and Drs. Uhlemann and Fidock report no relevant financial disclosures.

Researchers from Mahidol University in Bangkok have observed an increase in the rate of artemisinin-resistant Plasmodium falciparum malaria along the Thailand–Myanmar border within the past 8 years, and they suggest these rates could potentially reach the rates reported in Cambodia within 2 to 6 years.

“Artemisinin combination treatments are the recommended first-line therapy for falciparum malaria,” the researchers wrote. “Plasmodium falciparum parasites with reduced in vivo susceptibility to artemisinin derivatives have emerged in western Cambodia. This finding threatens worldwide initiatives to control and eliminate malaria.”

The study included 3,202 patients from malaria clinics along the northwestern border of Thailand between 2001 and 2010. They measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria who had been treated with artemisinin regimens. They estimated the parasite clearance half-lives and genotyped the parasites. Slow parasite clearance is an indicator of artemisinin resistance.

In 2001, the parasite clearance half-lives had a geometric mean of 2.6 hours vs. 3.7 hours in 2010. In Cambodia, the average geometric mean was 5.5 hours between 2007 and 2010. The proportion of slow-clearing infections along the Thailand–Myanmar border was 0.6% in 2001 when compared with 20% in 2010. In Cambodia, the proportion of slow-clearing infections was 42% between 2007 and 2010.

Among the 1,583 infections that were genotyped, the researchers identified 148 multilocus parasite genotypes, each of which affected two to 13 patients. Between 2001 and 2004, parasite genotype had a significant effect on parasite clearance half-life, but the effect was much stronger between 2007 and 2010.

“Identification of a molecular marker will be crucial to monitor the distribution and spread of resistance and to understand the evolution of this treatment and the mechanism of action of artemisinin,” the researchers wrote.

In an accompanying editorial, Anne-Catrin Uhlemann, MD, PhD, and David A. Fidock, PhD, both of Columbia University in New York, said artemisinin combination treatments have led to significant reductions in malaria mortality and morbidity, and as a result of this study, containment efforts for artemisinin-resistant malaria should no longer be restricted to Cambodia.

“Whether initial signs of decreased parasite responsiveness will result in high-grade resistance and a loss of clinical effectiveness [of artemisinin] cannot yet be judged,” they wrote.

References:

  • Phyo AP. Lancet. 2012;doi:10.1016/S0140-6736(12)60484-X.
  • Uhlemann AC. Lancet. 2012;doi:10.1016/S0140-6736(12)60488-7.

Disclosures:

  • The researchers and Drs. Uhlemann and Fidock report no relevant financial disclosures.