Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia

• DOI: 10.1186/s12936-017-1845-5
• Publication Date: 2017-05-12T02:25:49Z
• Authors: Angana Mukherjee; Selina Bopp; Pamela Magistrado; Wesley Wong; Rachel Daniels; Allison Demas; Stephen Schaffner; Chanaki Amaratunga; Pharath Lim; Mehul Dhorda; Olivo Miotto; Charles Woodrow; Elizabeth A. Ashley; Arjen M. Dondorp; Nicholas J. White; Dyann Wirth; Rick Fairhurst; Sarah K. Volkman
• Keywords: Piperaquine; Dihydroartemisinin; Parasitology

Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates ring-stage survival under dihydroartemisinin vitro. Both phenotypes are mutations the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin emerging piperaquine Southeast Asia show that combination therapy, such as dihydroartemisinin–piperaquine, losing clinical effectiveness, prompting investigation drug mechanisms development strategies to surmount anti-malarial resistance. Sixty-eight parasites isolates data were obtained from two Tracking Resistance Collaboration study sites Cambodia, culture-adapted, genotyped for other including pfmdr1 copy number; RSA0–3h rates response antimalarial drugs vitro measured 36 these isolates. Among one isolate demonstrated increased a PfKelch13 mutation (D584V, = 8%), previously slow but not yet tested Several exhibited survival, lack mutations, showed evidence This 68 culture-adapted Plasmodium falciparum Cambodia known values, D584V identified exhibit survival. These suggest than those found may be involved conferring P. falciparum. Piperaquine was also detected among same Cambodian samples, consistent reports field. permit further both prevent or overcome