Reduced Susceptibility of Plasmodium falciparum to Artesunate in Southern Myanmar

Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reporte...

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Veröffentlicht in:PloS one Jg. 8; H. 3; S. e57689
Hauptverfasser: Kyaw, Myat P., Nyunt, Myat H., Chit, Khin, Aye, Moe M., Aye, Kyin H., Lindegardh, Niklas, Tarning, Joel, Imwong, Mallika, Jacob, Christopher G., Rasmussen, Charlotte, Perin, Jamie, Ringwald, Pascal, Nyunt, Myaing M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 08.03.2013
Public Library of Science (PLoS)
Schlagworte:
Adult
Adults
Antimalarials - administration & dosage
Antimalarials - pharmacokinetics
Artemisinin
Artemisinins - administration & dosage
Artemisinins - pharmacokinetics
Artesunate
Bioavailability
Biology
Cambodia - epidemiology
Clearing
Clinical medicine
Clinical trials
Containment
Drug Resistance
Erythrocytes
Female
Genomes
Half-life
Humans
Infections
Malaria
Malaria, Falciparum - drug therapy
Malaria, Falciparum - epidemiology
Malaria, Falciparum - transmission
Male
Medical research
Medicine
Myanmar - epidemiology
Parasitemia
Parasites
Pharmacokinetics
Pharmacology
Plasmodium falciparum
Plasmodium falciparum - pathogenicity
Plasmodium vivax
Public health
Smear
Vector-borne diseases
Cambodia
Myanmar
Myanmar (Burma)
United States > US
Thailand
Maryland
Baltimore Maryland
Bangkok Thailand
ISSN:1932-6203, 1932-6203
Online-Zugang:Volltext
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Zusammenfassung:Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries. A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days) was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia), parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope), and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels. The median (range) parasite clearance half-life and time were 4.8 (2.1-9.7) and 60 (24-96) hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours) in approximately 1/3 of infections. Fourteen of 52 participants (26.9%) had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics. A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this location from its site of origin in western Cambodia. Resistance containment efforts are underway in Myanmar. Australian New Zealand Clinical Trials Registry ACTRN12610000896077.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: MPK MHN NL JT JP PR MMN. Performed the experiments: MPK MHN KC MMA KHA MMA MI JT CR CGJ PR MMN. Analyzed the data: MPK MHN JT PR JP CGJ MMN. Contributed reagents/materials/analysis tools: NL JT CR PR JP CGJ MMN. Wrote the paper: MPK MHN KC MMA KHA MMA MI JT CR CGJ PR MMN.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0057689