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The clinical impactof artemisininresistance inSoutheast Asia andthe potential forfuture spread Charles J. WoodrowNicholas J. White2016 год

The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread
review

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Аннотация: Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately, Plasmodium falciparum infections with mutations in the 'K13' gene, with reduced ring-stage susceptibility to artemisinins, and slow parasite clearance in patients treated with ACTs, are now widespread in Southeast Asia. We review clinical efficacy data from the region (2000-2015) that provides strong evidence that the loss of first-line ACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance and ACT failure are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multidrug-resistant parasite genotypes are taking over and threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency.
Год издания: 2016
Авторы: Charles J. Woodrow, Nicholas J. White
Издательство: Oxford University Press
Источник: FEMS Microbiology Reviews
Ключевые слова: Malaria Research and Control, Computational Drug Discovery Methods, Drug-Induced Hepatotoxicity and Protection
Другие ссылки: FEMS Microbiology Reviews (PDF)
FEMS Microbiology Reviews (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
Oxford University Research Archive (ORA) (University of Oxford) (PDF)
Oxford University Research Archive (ORA) (University of Oxford) (HTML)
PubMed Central (HTML)
PubMed (HTML)