Recent clinical and molecular insights into emerging artemisinin resistance in Plasmodium falciparum
Open Access
- 1 December 2011
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Infectious Diseases
- Vol. 24 (6), 570-577
- https://doi.org/10.1097/qco.0b013e32834cd3ed
Abstract
Purpose of review 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. Recent findings 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. Summary 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.Keywords
This publication has 70 references indexed in Scilit:
- Artemisinin activity againstPlasmodium falciparumrequires hemoglobin uptake and digestionProceedings of the National Academy of Sciences of the United States of America, 2011
- Intrahost modeling of artemisinin resistance in Plasmodium falciparumProceedings of the National Academy of Sciences of the United States of America, 2010
- Artemisinin‐Induced Dormancy inPlasmodium falciparum: Duration, Recovery Rates, and Implications in Treatment FailureThe Journal of Infectious Diseases, 2010
- Drug-Resistant Malaria: The Era of ACTCurrent Infectious Disease Reports, 2010
- Artemisinin-based combination therapies: a vital tool in efforts to eliminate malariaNature Reviews Microbiology, 2009
- Artemisinin Resistance inPlasmodium falciparumMalariaThe New England Journal of Medicine, 2009
- Disruption of a Plasmodium falciparum Multidrug Resistance-associated Protein (PfMRP) Alters Its Fitness and Transport of Antimalarial Drugs and GlutathioneJournal of Biological Chemistry, 2009
- Accumulation of artemisinin trioxane derivatives within neutral lipids of Plasmodium falciparum malaria parasites is endoperoxide-dependentBiochemical Pharmacology, 2009
- Evidence of Artemisinin-Resistant Malaria in Western CambodiaThe New England Journal of Medicine, 2008
- Transporters involved in resistance to antimalarial drugsTrends in Pharmacological Sciences, 2006