Decreasing pfmdr1 Copy Number Suggests that Plasmodium falciparum in Western Cambodia Is Regaining In Vitro Susceptibility

Dihydroartemisinin-piperaquine is the current frontline artemisinin combination therapy (ACT) for Plasmodium falciparum malaria in Cambodia but is now failing in several western provinces. To investigate artesunate plus mefloquine (ASMQ) as a replacement ACT, wemeasured the prevalence of multiple pfmdr1 copies—amolecular marker for MQ resistance—in 844 P. falciparum clinical isolates collected in 2008 to 2013. The pfmdr1 copy number is decreasing inWestern Cambodia, suggesting that P. falciparum is regaining in vitro susceptibility to MQ. Artemisinin-based combination therapy (ACT) is used world-wide to treat uncomplicated Plasmodium falciparummalaria. Artesunate plus mefloquine (ASMQ) was adopted as Cambo-dia’s first-line treatment in 2000. ASMQ treatment failures were first observed in 10 to 20 % of patients in Pailin and Battambang Provinces, Western Cambodia, in 2003 to 2004 (1, 2). The pres-ence of multiple (i.e., 2) pfmdr1 copies—a genetic marker of MQ resistance—was associated with ASMQ failures and re-duced parasite in vitro susceptibility to MQ not only in Pailin and Battambang but in neighboring Pursat and Kampot Provinces as well (3–5). This development, along with emerging evidence o