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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
In vitro-reduced susceptibility to artemether in p. falciparum and its association with polymorphisms on transporter genes
Journal of Infectious Diseases, Volume 206, No. 3, Year 2012
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Description
Plasmodium falciparum with reduced sensitivity to artemisinin derivatives has been observed in endemic areas, but the molecular mechanisms for this reduced sensitivity remain unclear. We evaluated the association between in vitro susceptibility of P. falciparum isolates obtained from southwest Nigeria and polymorphisms in selected putative transporter genes (PFE0775C, PF13-0271, pfmrp1, pfcrt, and pfmdr1). Modified schizont inhibition assay was used to determine the in vitro parasite susceptibility to artemether (ATH). Polymorphisms in selected genes were detected by polymerase chain reaction followed by direct DNA sequencing. The half-maximal inhibitory concentration (IC50) geometric mean (GM) for all P. falciparum isolates was 1.78 nM (range, 0.03-10.43 nM). Polymorphisms at codons 241, 86, and 76 of PFE0775C, pfmdr1, and pfcrt genes, respectively, were associated with reduced susceptibility to ATH. A new S263P single-nucleotide polymorphism on the PFE0775C gene was also detected in 27 of the isolates. Patient isolates harboring V241L or S263P polymorphisms on the PFE0775C gene showed increased IC50 (GM: 3.08 nM and 1.79 nM, respectively). Plasmodium falciparum isolates harboring mutant Y86 pfmdr1 and P263 PFE0775C alleles showed a 2.5-5.5-fold increase in ATH IC50. This study shows that polymorphisms on the PFE0775C and pfmdr1 genes are associated with reduced sensitivity to ATH in fresh isolates of P. falciparum from Nigeria. © 2012 The Author.
Authors & Co-Authors
Bustamante, Carolina
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Nigeria, Ibadan
University of Ibadan
Folarin, Onikepe Abiola
Nigeria, Ibadan
University of Ibadan
Nigeria, Ede
Redeemer‘s University
Gbotosho, Grace Olusola
Nigeria, Ibadan
University of Ibadan
Batista, Camila N.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Mesquita, Elieth A.
Portugal
Centro de Pesquisas em Medicina Tropical de Rondônia
Brindeiro, Rodrigo De Moraes
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Tanuri, Amílcar
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Struchiner, Cláudio José
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Sowunmi, Akintunde
Nigeria, Ibadan
University of Ibadan
Oduola, Ayoade M.J.
Switzerland, Geneva
Organisation Mondiale de la Santé
Wirth, Dyann F.
United States, Boston
Harvard T.h. Chan School of Public Health
Zalis, Mariano G.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Happi, Christian Tientcha
Nigeria, Ibadan
University of Ibadan
Nigeria, Ede
Redeemer‘s University
United States, Boston
Harvard T.h. Chan School of Public Health
Statistics
Citations: 29
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1093/infdis/jis359
ISSN:
00221899
Research Areas
Genetics And Genomics
Health System And Policy
Study Locations
Nigeria