This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Humphreys, G. S.
Right arrow Articles by Hallett, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Humphreys, G. S.
Right arrow Articles by Hallett, R. L.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2007, p. 991-997, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00875-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Amodiaquine and Artemether-Lumefantrine Select Distinct Alleles of the Plasmodium falciparum mdr1 Gene in Tanzanian Children Treated for Uncomplicated Malaria{triangledown}

G. S. Humphreys,1 I. Merinopoulos,1 J. Ahmed,1 C. J. M. Whitty,1 T. K. Mutabingwa,1,2 C. J. Sutherland,1 and R. L. Hallett1*

London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom,1 National Institute for Medical Research, Dar-es-Salaam, Tanzania2

Received 15 July 2006/ Returned for modification 11 September 2006/ Accepted 13 December 2006

The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum.

* Corresponding author. Mailing address: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: 44 20 7927 2338. Fax: 44 20 7636 8739. E-mail: Rachel.Hallett{at}lshtm.ac.uk.

{triangledown} Published ahead of print on 28 December 2006.

Antimicrobial Agents and Chemotherapy, March 2007, p. 991-997, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00875-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Asih, P. B. S., Dewi, R. M., Tuti, S., Sadikin, M., Sumarto, W., Sinaga, B., van der Ven, A. J. A. M., Sauerwein, R. W., Syafruddin, D. (2009). Efficacy of Artemisinin-Based Combination Therapy for Treatment of Persons with Uncomplicated Plasmodium falciparum Malaria in West Sumba District, East Nusa Tenggara Province, Indonesia, and Genotypic Profiles of the Parasite. Am J Trop Med Hyg 80: 914-918 [Abstract] [Full Text]  
  • Muangnoicharoen, S., Johnson, D. J., Looareesuwan, S., Krudsood, S., Ward, S. A. (2009). Role of Known Molecular Markers of Resistance in the Antimalarial Potency of Piperaquine and Dihydroartemisinin In Vitro. Antimicrob. Agents Chemother. 53: 1362-1366 [Abstract] [Full Text]  
  • Happi, C. T., Gbotosho, G. O., Folarin, O. A., Sowunmi, A., Hudson, T., O'Neil, M., Milhous, W., Wirth, D. F., Oduola, A. M. J. (2009). Selection of Plasmodium falciparum Multidrug Resistance Gene 1 Alleles in Asexual Stages and Gametocytes by Artemether-Lumefantrine in Nigerian Children with Uncomplicated Falciparum Malaria. Antimicrob. Agents Chemother. 53: 888-895 [Abstract] [Full Text]  
  • Mehlotra, R. K., Mattera, G., Bockarie, M. J., Maguire, J. D., Baird, J. K., Sharma, Y. D., Alifrangis, M., Dorsey, G., Rosenthal, P. J., Fryauff, D. J., Kazura, J. W., Stoneking, M., Zimmerman, P. A. (2008). Discordant Patterns of Genetic Variation at Two Chloroquine Resistance Loci in Worldwide Populations of the Malaria Parasite Plasmodium falciparum. Antimicrob. Agents Chemother. 52: 2212-2222 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»