Browsing by Author "Wiklund, Lisa"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted parasitological cure rates in an antimalarial-drug trial conducted in TanzaniaPublication . Martensson, Andreas; Ngasala, Billy; Ursing, Johan; Veiga, M. Isabel; Wiklund, Lisa; Membi, Christopher; Montgomery, Scott M.; Premji, Zul; Farnert, Anna; Bjorkman, AndersWe assessed the influence that consecutive-day blood sampling, compared with single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted parasitological cure after stepwise genotyping of merozoite surface proteins 2 (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum malaria treated with either sulfadoxine-pyrimethamine or artemether-lumefantrine; 78 of these children developed recurrent parasitemia during the 42-day follow-up period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of single-and consecutive-day sampling, respectively; in subsequent msp1 genotyping, 17 and 21 of these episodes, respectively, were still classified as recrudescences; these results indicate a similar sensitivity of the standard single-day PCR protocol-that is, 82% (27/33) and 81% (17/21), in both genotyping steps. Interpretation of PCR-adjusted results will significantly depend on methodology.
- Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in AfricaPublication . Dahlstrom, Sabina; Ferreira, Pedro; Veiga, Maria Isabel; Sedighi, Nazli; Wiklund, Lisa; Martensson, Andreas; Farnert, Anna; Sisowath, Christin; Osorio, Lyda; Darban, Hamid; Andersson, Bjoern; Kaneko, Akira; Conseil, Gwanaelle; Bjorkman, Anders; Gil, José PedroPlasmodium falciparum response mechanisms to the major artemisinin-based combination therapies (ACTs) are largely unknown. Multidrug-resistance protein (MRP)-like adenosine triphosphate (ATP)-binding cassette transporters are known to be related to multidrug resistance in many organisms. Therefore, we hypothesized that sequence variation in pfmrp1 can contribute to decreased parasite sensitivity to ACT. Through sequencing of the pfmrp1 open reading frame for 103 geographically diverse P. falciparum infections, we identified 27 single-nucleotide polymorphisms (SNPs), of which 21 were nonsynonymous and 6 synonymous. Analyses of clinical efficacy trials with artesunate-amodiaquine and artemether-lumefantrine detected a specific selection of the globally prevalent I876V SNP in recurrent infections after artemether-lumefantrine treatment. Additional in silico studies suggested an influence of variation in amino acid 876 on the ATP hydrolysis cycle of pfMRP1 with potential impact on protein functionality. Our data suggest for the first time, to our knowledge, the involvement of pfMRP1 in P. falciparum in vivo response to ACT.