Researchers from Mahidol University in Bangkok have
observed an increase in the rate of artemisinin-resistant Plasmodium
falciparum malaria along the ThailandMyanmar 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
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 ThailandMyanmar 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.
- Phyo AP. Lancet. 2012;doi:10.1016/S0140-6736(12)60484-X.
- Uhlemann AC. Lancet. 2012;doi:10.1016/S0140-6736(12)60488-7.
- The researchers and Drs. Uhlemann and Fidock report no relevant