In Vitro Activities of Piperaquine, Lumefantrine, and Dihydroartemisinin in Kenyan Plasmodium falciparum Isolates and Polymorphisms in pfcrt and pfmdr1▿
AUTOR(ES)
Mwai, Leah
FONTE
American Society for Microbiology (ASM)
RESUMO
We have analyzed the in vitro chemosensitivity profiles of 115 Kenyan isolates for chloroquine (CQ), piperaquine, lumefantrine (LM), and dihydroartemisinin in association with polymorphisms in pfcrt at codon 76 and pfmdr1 at codon 86, as well as with variations of the copy number of pfmdr1. The median drug concentrations that inhibit 50% of parasite growth (IC50s) were 41 nM (interquartile range [IQR], 18 to 73 nM), 50 nM (IQR, 29 to 96 nM), 32 nM (IQR, 17 to 46 nM), and 2 nM (IQR, 1 to 3 nM) for CQ, LM, piperaquine, and dihydroartemisinin, respectively. The activity of CQ correlated inversely with that of LM (r2 = −0.26; P = 0.02). Interestingly, parasites for which LM IC50s were higher were wild type for pfcrt-76 and pfmdr1-86. All isolates had one pfmdr1 copy. Thus, the decrease in LM activity is associated with the selection of wild-type pfcrt-76 and pfmdr1-86 parasites, a feature that accounts for the inverse relationship between CQ and LM. Therefore, the use of LM-artemether is likely to lead to the selection of more CQ-susceptible parasites.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2786317Documentos Relacionados
- Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes in Plasmodium falciparum isolates from Odisha, India
- In Vitro Activities of Piperaquine and Other 4-Aminoquinolines against Clinical Isolates of Plasmodium falciparum in Cameroon
- Pfcrt and pfmdr1 alleles associated with chloroquine resistance in Plasmodium falciparum from Guyana, South America
- In Vitro Activity of Lumefantrine (Benflumetol) against Clinical Isolates of Plasmodium falciparum in Yaoundé, Cameroon
- Plasmodium falciparum Drug Resistance in Madagascar: Facing the Spread of Unusual pfdhfr and pfmdr-1 Haplotypes and the Decrease of Dihydroartemisinin Susceptibility▿