Intrahost Selection of Plasmodium falciparum pfmdr1 Alleles after Antimalarial Treatment on the Northwestern Border of Thailand

Uhlemann, Anne-Catrin; McGready, Rose; Ashley, Elizabeth A.; Brockman, Alan; Singhasivanon, Pratap; Krishna, Sanjeev; White, Nicholas J.; Nosten, François; Price, Ric N.
January 2007
Journal of Infectious Diseases;1/1/2007, Vol. 195 Issue 1, p134
Academic Journal
Background. Increased pfmdr1 copy number is associated with reduced susceptibility to structurally unrelated antimalarial drugs. We assessed how administration of different antimalarial drugs altered pfmdr1 polymorphism in parasites from patients who experienced treatment failure. Methods. In studies conducted on the northwestern border of Thailand, amplifications and single-nucleotide polymorphisms in pfmdr1 were compared before and after antimalarial drug treatment. Results. Intrahost changes in pfmdr1 copy number were observed in 20% (26/132) of patients with recurrent infections. Among infections that recrudesced after mefloquine-containing regimens, increases in pfmdr1 copy number occurred in 68% (95% confidence interval [CI], 46%-85%), and decreases occurred in 2% (95% CI, 0.4%-11%) of isolates; corresponding proportions after artemether-lumefantrine were 25% (2/8) and 11% (2/19); after quinine, 50% (1/2) and 40% (4/10); and after artemisinins alone, 0% (0/10) and 19% (3/16) of isolates (overall P < .001). Conclusions. Intrahost selection based on pfmdr1 copy number occurs frequently in parasite populations within individual patients. Amplification confers multidrug resistance but probably imposes a significant fitness cost to the parasites.


Related Articles

  • In Vitro–Reduced Susceptibility to Artemether in P. falciparum and Its Association With Polymorphisms on Transporter Genes. Bustamante, Carolina; Folarin, Onikepe A.; Gbotosho, Grace O.; Batista, Camila N.; Mesquita, Elieth A.; Brindeiro, Rodrigo M.; Tanuri, Amilcar; Struchiner, Claudio J.; Sowunmi, Akintunde; Oduola, Ayoade; Wirth, Dyann F.; Zalis, Mariano G.; Happi, Christian T. // Journal of Infectious Diseases;Aug2012, Vol. 206 Issue 3, p324 

    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...

  • Analysis of sulphadoxine/pyrimethamine resistance-conferring mutations of Plasmodium falciparum from Mozambique reveals the absence of the dihydrofolate reductase 164L mutant. Fernandes, Natércia; Figueiredo, Paula; Do Rosário, Virgilio E.; Cravo, Pedro // Malaria Journal;2007, Vol. 6, p1 

    Background: Plasmodium falciparum is the predominant human malaria species in Mozambique and a lead cause of mortality among children and pregnant women nationwide. Sulphadoxine/pyrimethamine (S/P) is used as first line antimalarial treatment as a partner drug in combination with artesunate....

  • Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro.  // Malaria Journal;2011, Vol. 10 Issue 1, p187 

    The article reports on a study whose objective was to determine polymorphisms in the putative pfATPase6 and pftctp, pfmdr1, pfcrt genes in Ghanaian Plasmodium falciparum (P. falciparum) isolates. It reports on the evaluation of sensitivity of parasite isolates to anti-malaria drugs becuase of a...

  • In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon. Zatra, Rafika; Lekana-douki, Jean Bernard; Lekoulou, Faustin; Bisvigou, Ulrick; Ngoungou, Edgard Brice; Toure Ndouo, Fousseyni S. // BMC Infectious Diseases;2012, Vol. 12 Issue 1, p307 

    Background: Malaria remains a major public health problem, due largely to emergence and widespread P. falciparum drug resistance. WHO recommends artemisinine combination based therapy (ACT) to overcome P. falciparum drug resistance, but reports of declining ACT efficacy have been published. A...

  • A Genome Wide Association Study of Plasmodium falciparum Susceptibility to 22 Antimalarial Drugs in Kenya. Wendler, Jason P.; Okombo, John; Amato, Roberto; Miotto, Olivo; Kiara, Steven M.; Mwai, Leah; Pole, Lewa; O'Brien, John; Manske, Magnus; Alcock, Dan; Drury, Eleanor; Sanders, Mandy; Oyola, Samuel O.; Malangone, Cinzia; Jyothi, Dushyanth; Miles, Alistair; Rockett, Kirk A.; MacInnis, Bronwyn L.; Marsh, Kevin; Bejon, Philip // PLoS ONE;May2014, Vol. 9 Issue 5, p1 

    Background: Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial...

  • Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate. Natalang, Onguma; Bischoff, Emmanuel; Deplaine, Guillaume; Proux, Caroline; Dillies, Marie-Agnès; Sismeiro, Odile; Guigon, Ghislaine; Bonnefoy, Serge; Patarapotikul, Jintana; Mercereau-Puijalon, Odile; Coppée, Jean-Yves; David, Peter H. // BMC Genomics;2008, Vol. 9, Special section p1 

    Background: Translation of the genome sequence of Plasmodium sp. into biologically relevant information relies on high through-put genomics technology which includes transcriptome analysis. However, few studies to date have used this powerful approach to explore transcriptome alterations of P....

  • Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy. Gama, Bianca E.; Oliveira, Natália K. Almeida de; de Souza, José M.; Santos, Fátima; de Carvalho, Leonardo J. M.; Melo, Yonne F.C.; Rosenthal, Philip J.; Daniel-Ribeiro, Cláudio T.; Ferreira-da-Cruz, Maria de Fátima // Malaria Journal;2010, Vol. 9, p355 

    Background: This study was performed to better understand the genetic diversity of known polymorphisms in pfatpase6 and pfmdr1 genes before the introduction of ACT in Brazil, in order to get a genotypic snapshot of Plasmodium falciparum parasites that may be used as baseline reference for future...

  • In-Vitro Susceptibility of Plasmodium falciparum to Antimalarial Drugs in Abuja, Nigeria. Peletiri, I. C.; Matur, B.M.; Ibecheozor, N.K.O.; Ihongbe, J. C.; Wakama, T. T. // Internet Journal of Parasitic Diseases;2012, Vol. 5 Issue 1, p3 

    The susceptibility of Plasmodium falciparum to Chloroquine, Quinine, Dihydroartemisinin and Monodesethylamodiaquine was investigated in the Federal Capital Territory (FCT), Abuja. The standard WHO in vitro micro test methodology was used in the study. Of 18 isolates evaluated for susceptibility...

  • Metabolic Dysregulation Induced in Plasmodium falciparum by Dihydroartemisinin and Other Front-Line Antimalarial Drugs. Cobbold, Simon A.; Chua, Hwa H.; Nijagal, Brunda; Creek, Darren J.; Ralph, Stuart A.; McConville, Malcolm J. // Journal of Infectious Diseases;1/15/2016, Vol. 213 Issue 2, p276 

    Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics