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Reference: White, NJ, Pongtavornpinyo, W, Maude, RJ et al., (2009). Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance. Malaria Journal, 8 (1), Article: 253.Citable link to this page:

 

Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance.

Abstract: BACKGROUND: Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce satisfactory results. METHODS: The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. RESULTS: Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. CONCLUSION: Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the greatest risk of selecting de-novo resistant parasites. This emphasizes the importance of ensuring that only quality-assured anti-malarial combinations are used, that treatment doses are optimized on the basis of pharmacodynamic and pharmacokinetic assessments in the target populations, and that patients with heavy parasite burdens are identified and receive sufficient treatment to prevent recrudescence.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Wellcome Trust   Notes:© 2009 White et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Bibliographic Details

Publisher: BioMed Central Ltd.

Publisher Website: http://www.biomedcentral.com/

Journal: Malaria Journalsee more from them

Publication Website: http://www.malariajournal.com/

Issue Date: 2009

pages:Article: 253Identifiers

Urn: uuid:2268eb69-3590-42ec-a302-60a8a4c87e61

Source identifier: 8669

Eissn: 1475-2875

Doi: https://doi.org/10.1186/1475-2875-8-253

Issn: 1475-2875 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Humans Plasmodium Parasitemia Malaria Recurrence Dose-Response Relationship, Drug Artemisinins Antimalarials Drug Resistance Tiny URL: pubs:8669

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Author: White, NJ - institutionUniversity of Oxford Oxford, MSD, Clinical Medicine, Thailand-Laos MOP - - - Pongtavornpinyo, W - - - Maud

Source: https://ora.ox.ac.uk/objects/uuid:2268eb69-3590-42ec-a302-60a8a4c87e61



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