Back to Search
Start Over
Measuring windows of selection for anti-malarial drug treatments.
- Source :
-
Malaria journal [Malar J] 2015 Jul 31; Vol. 14, pp. 292. Date of Electronic Publication: 2015 Jul 31. - Publication Year :
- 2015
-
Abstract
- Background: The long half-lives of malaria 'partner' drugs are a potent force selecting for drug resistance. Clinical trials can quantify this effect by estimating a window of selection (WoS), defined as the amount of time post-treatment when drug levels are sufficiently high that resistant parasites can re-establish an infection while preventing drug-sensitive parasites from establishing viable infections.<br />Methods: The ability of clinical data to accurately estimate the true WoS was investigated using standard pharmacokinetic-pharmacodynamic models for three widely used malaria drugs: artemether-lumefantrine (AR-LF), artesunate-mefloquine (AS-MQ) and dihydroartemisinin-piperaquine (DHA-PPQ). Estimates of the clinical WoS either (1) ignored all new infections occurring after the 63-day follow-up period, as is currently done in clinical trials, or, (2) recognized that all individuals would eventually be re-infected and arbitrarily assigned them a new infection day.<br />Results: The results suggest current methods of estimating the clinical WoS underestimate the true WoS by as much as 9 days for AR-LF, 33 days for AS-MQ and 7 days for DHA-PPQ. The new method of estimating clinical WoS (i.e., retaining all individuals in the analysis) was significantly better at estimating the true WoS for AR-LF and AS-MQ.<br />Conclusions: Previous studies, based on clinically observed WoS, have probably underestimated the 'true' WoS and hence the role of drugs with long half-lives in driving resistance. This has important policy implications: high levels of drug use are inevitable in mass drug administration programmes and intermittent preventative treatment programmes and the analysis herein suggests these policies will be far more potent drivers of resistance than previously thought.
- Subjects :
- Artemether, Lumefantrine Drug Combination
Artemisinins administration & dosage
Artemisinins pharmacokinetics
Artemisinins pharmacology
Artemisinins therapeutic use
Drug Combinations
Ethanolamines administration & dosage
Ethanolamines pharmacokinetics
Ethanolamines pharmacology
Ethanolamines therapeutic use
Fluorenes administration & dosage
Fluorenes pharmacokinetics
Fluorenes pharmacology
Fluorenes therapeutic use
Humans
Models, Biological
Quinolines administration & dosage
Quinolines pharmacokinetics
Quinolines pharmacology
Quinolines therapeutic use
Antimalarials administration & dosage
Antimalarials pharmacokinetics
Antimalarials pharmacology
Antimalarials therapeutic use
Malaria, Falciparum drug therapy
Malaria, Falciparum parasitology
Plasmodium falciparum drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2875
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Malaria journal
- Publication Type :
- Academic Journal
- Accession number :
- 26228915
- Full Text :
- https://doi.org/10.1186/s12936-015-0810-4