Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum

Gatton, M. L., Martin, L. B. and Cheng, Q. (2004) Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrobial Agents and Chemotherapy, 48 6: 2116-2123. doi:10.1128/AAC.48.6.2116-2123.2004

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Author Gatton, M. L.
Martin, L. B.
Cheng, Q.
Title Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
Publication date 2004
Sub-type Article (original research)
DOI 10.1128/AAC.48.6.2116-2123.2004
Open Access Status File (Publisher version)
Volume 48
Issue 6
Start page 2116
End page 2123
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2004
Language eng
Subject C1
321299 Public Health and Health Services not elsewhere classified
730212 Disease distribution and transmission
Abstract The development of resistance to sulfadoxine-pyrimethamine by Plasmodium parasites is a major problem for the effective treatment of malaria, especially P. falciparum malaria. Although the molecular basis for parasite resistance is known, the factors promoting the development and transmission of these resistant parasites are less clear. This paper reports the results of a quantitative comparison of factors previously hypothesized as important for the development of drug resistance, drug dosage, time of treatment, and drug elimination half-life, with an in-host dynamics model of P. falciparum malaria in a malaria-naive host. The results indicate that the development of drug resistance can be categorized into three stages. The first is the selection of existing parasites with genetic mutations in the dihydrofolate reductase or dihydropteroate synthetase gene. This selection is driven by the long half-life of the sulfadoxine-pyrimethamine combination. The second stage involves the selection of parasites with allelic types of higher resistance within the host during an infection. The timing of treatment relative to initiation of a specific anti-P. falciparum EMP1 immune response is an important factor during this stage, as is the treatment dosage. During the third stage, clinical treatment failure becomes prevalent as the parasites develop sufficient resistance mutations to survive therapeutic doses of the drug combination. Therefore, the model output reaffirms the importance of correct treatment of confirmed malaria cases in slowing the development of parasite resistance to sulfadoxine-pyrimethamine.
Keyword Microbiology
Pharmacology & Pharmacy
Thymidylate Synthase Gene
In-vivo Resistance
Dihydrofolate-reductase
Dihydropteroate Synthetase
Malaria Parasites
Drug-resistance
Sequence Variations
Molecular-basis
Dhps Genes
Vitro
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2005 Higher Education Research Data Collection
School of Information Technology and Electrical Engineering Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 29 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 05:19:57 EST