title: Recent clinical and molecular insights into emerging artemisinin resistance in Plasmodium falciparum.
abstract: OBJECTIVE
  Artemisinin-based combination therapies (ACTs) have been deployed globally with remarkable success for more than 10 years without having lost their malaria treatment efficacy. However, recent reports from the Thai-Cambodian border reveal evidence of emerging resistance to artemisinins. The latest published clinical and molecular findings are summarized herein.
  
  
  RESULTS
  Clinical studies have identified delayed parasite clearance time as the most robust marker of artemisinin resistance. Resistance has only been documented from South-east Asia and has been observed in isolates that show no significant decrease in drug susceptibility in vitro. Genetic investigations have yet to uncover robust molecular markers. In-vitro studies have identified parasite quiescence or dormancy mechanisms that protect early 'ring-stage' intra-erythrocytic parasites against short-term artemisinin exposure. This might be achieved by reducing the rate of hemoglobin degradation, important for artemisinin bioactivation.
  
  
  CONCLUSIONS
  Should ACTs fail, no suitable alternatives exist as first-line treatments of P. falciparum malaria. Intensified efforts are essential to monitor the spread of resistance, define therapeutic and operational strategies to counter its impact, and understand its molecular basis. Success in these areas is critical to ensuring that recent gains in reducing the burden of malaria are not lost.
authors: Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors: Connor
authors: C
authors: O'Brien
authors: Philipp P
authors: PP
authors: Henrich
authors: Neha
authors: N
authors: Passi
authors: David A
authors: DA
authors: Fidock
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001210:Asia, Southeastern; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin