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 Happi, C. T.
Right arrow Articles by Oduola, A. M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Happi, C. T.
Right arrow Articles by Oduola, A. M. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2009, p. 888-895, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00968-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Selection of Plasmodium falciparum Multidrug Resistance Gene 1 Alleles in Asexual Stages and Gametocytes by Artemether-Lumefantrine in Nigerian Children with Uncomplicated Falciparum Malaria {triangledown}

C. T. Happi,1,2* G. O. Gbotosho,1 O. A. Folarin,1 A. Sowunmi,1 T. Hudson,3 M. O'Neil,3 W. Milhous,3,{dagger} D. F. Wirth,2 and A. M. J. Oduola4

Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria,1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,2 Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland,3 Special Programme for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland4

Received 21 July 2008/ Returned for modification 15 August 2008/ Accepted 18 November 2008

We assessed Plasmodium falciparum mdr1 (Pfmdr1) gene polymorphisms and copy numbers as well as P. falciparum Ca2+ ATPase (PfATPase6) gene polymorphisms in 90 Nigerian children presenting with uncomplicated falciparum malaria and enrolled in a study of the efficacy of artemether-lumefantrine (AL). The nested PCR-restriction fragment length polymorphism and the quantitative real-time PCR methodologies were used to determine the alleles of the Pfmdr1 and PfATPase6 genes and the Pfmdr1 copy number variation, respectively, in patients samples collected prior to treatment and at the reoccurrence of parasites during a 42-day follow-up. The Pfmdr1 haplotype 86N-184F-1246D was significantly associated (P < 0.00001) with treatment failures and was selected for among posttreatment samples obtained from patients with newly acquired or recrudescing infections (P < 0.00001; {chi}2 = 36.5) and in gametocytes (log rank statistic = 5; P = 0.0253) after treatment with AL. All pre- and posttreatment samples as well as gametocytes harbored a single copy of the Pfmdr1 gene and the wild-type allele (L89) at codon 89 of the PfATPase6 gene. These findings suggest that polymorphisms in the Pfmdr1 gene are under AL selection pressure. Pfmdr1 polymorphisms may result in reduction in the therapeutic efficacy of this newly adopted combination treatment for uncomplicated falciparum malaria in Saharan countries of Africa.

* Corresponding author. Mailing address: Malaria Research Laboratories, IMRAT, College of Medicine, University of Ibadan, Ibadan, Nigeria. Phone: 234-802-338-3684. Fax: 234-2-241-1768. E-mail: chappi{at}hsph.harvard.edu

{triangledown} Published ahead of print on 15 December 2008.

{dagger} Present address: Department of Public Health, Faculty of Global Health, University of South Florida, Tampa.

Antimicrobial Agents and Chemotherapy, March 2009, p. 888-895, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00968-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mwai, L., Kiara, S. M., Abdirahman, A., Pole, L., Rippert, A., Diriye, A., Bull, P., Marsh, K., Borrmann, S., Nzila, A. (2009). In Vitro Activities of Piperaquine, Lumefantrine, and Dihydroartemisinin in Kenyan Plasmodium falciparum Isolates and Polymorphisms in pfcrt and pfmdr1. Antimicrob. Agents Chemother. 53: 5069-5073 [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»