2006 |
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Halidou Tinto, Claude Rwagacondo, Corinne Karema, Denise Mupfasoni, Waltruda Vandoren, Emmanuel Rusanganwa, Annette Erhart, Chantal Van Overmeir, Eric Van Marck, Umberto D'Alessandro In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda Journal Article In: Trans. R. Soc. Trop. Med. Hyg., vol. 100, no. 6, pp. 509–514, 2006. @article{Tinto2006-iz, Plasmodium falciparum in-vitro susceptibility to chloroquine (CQ), monodesethylamodiaquine, quinine and dihydroartemisinin was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested. Resistance to chloroquine was 45% (33/74) and that to monodesethylamodiaquine 7% (5/74). All the tested isolates were susceptible to quinine. The mean IC(50) of monodesethylamodiaquine, quinine and dihydroartemisinin was significantly higher for chloroquine-resistant than for chloroquine-sensitive strains (P<0.05). The IC(50) of each drug was significantly and positively correlated to that of the other three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance is linked to that of the other drugs tested. Most worrying is the positive correlation between the IC(50) of dihydroartemisinin and the other drugs, more particularly with CQ, suggesting an increased tolerance of the parasites to all drugs. | |||
2005 |
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Journal Articles |
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Halidou Tinto, Boroma Sanou, Jean-Claude Dujardin, Jean Bosco Ouédraogo, Chantal VAN Overmeir, Annette Erhart, Eric VAN Marck, Tinga Robert Guiguemdé, Umberto D'Alessandro Usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso Journal Article In: Am. J. Trop. Med. Hyg., vol. 73, no. 1, pp. 171–173, 2005. @article{Tinto2005-vz, The prevalence of chloroquine (CQ) treatment failure and the genotype failure index was determined in four sentinel sites in Burkina Faso. In three sites, the genotype failure index varied between 1.7 and 3, a result confirming the relationship between the Plasmodium falciparum CQ resistance transporter (Pfcrt) T76 mutation and CQ resistance. In the remaining site, the genotype failure index was unusually low, 1.1, which was significantly different than that in the other sites (P < 0.00001). These findings are discussed. Often but not always, the prevalence of CQ resistance can be correctly estimated by the Pfcrt T76 genotype failure index. | |||
2004 |
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Journal Articles |
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Halidou Tinto, Jean Bosco Ouédraogo, Maminata Traoré, Tinga Robert Guiguemdé Parasitological resistance of Plasmodium falciparum to antimalarial drugs: what physicians should keep in mind Journal Article In: Sante, vol. 14, no. 2, pp. 69–73, 2004. @article{Tinto2004-sw, Plasmodium falciparum drug resistance has considerably modified the attitude of physicians in terms of malaria case management. However, a bad understanding of the resistance phenomenon can lead to non-appropriate therapeutic and/or public health practices. The objective of this paper was to contribute to clarify the concept of parasitological resistance by analysing the different types of resistance observed in vivo. We showed through some examples that the precision of in vivo parasitological results depends on the type of microscopical technique used. We also showed that the classification system into resistance levels RI, RII, and RIII does not correspond to an increase in the resistance of the parasite itself but rather to an increase in the proportion of the resistant strains compared to the sensitive ones circulating in a given population. Mutant strains are circulating in low proportions as long as there is no selective drug pressure. They can be first detected in vitro and, later on, when their proportion increase, they are detected in vivo, first in non-immune subjects and later in semi-immune subjects. Therefore, the role of the host immunity is important in malaria drug resistance. To conclude, increasing use of antimalarial drugs (especially in monotherapy) cannot thwart the resistance, but rather leads to the selection of mutants strains. As the proportion of the mutant strains increases compared to the sensitive (wild) ones, it will reach the microscopic detection level and then, the clinical level. It is important that physicians involved in malaria case management understand these notions in order to avoid non-appropriate therapeutic decisions. | |||
2003 |
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Journal Articles |
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Halidou Tinto, Jean Bosco Ouédraogo, Annette Erhart, Chantal Van Overmeir, Jean-Claude Dujardin, Eric Van Marck, Tinga Robert Guiguemdé, Umberto D'Alessandro Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 mutations in Plasmodium falciparum and in vitro/in vivo chloroquine resistance in Burkina Faso, West Africa Journal Article In: Infect. Genet. Evol., vol. 3, no. 4, pp. 287–292, 2003. @article{Tinto2003-pn, The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in Plasmodium falciparum was explored in samples from patients with uncomplicated malaria and tested in vitro and in vivo with chloroquine (CQ) in Burkina Faso. The two mutations were strongly related. The Pfcrt T76 mutation was found in 82% of the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half (16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1 Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the presence of the Pfcrt T76 mutation. This suggests that the occurrence of the Pfmdr-1 Y86 mutation is dependent on that of Pfcrt T76 mutation and could explain previous reports linking the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild (WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50 geometric mean (GMIC50) values, while those carrying both Pfcrt T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single mutant Pfcrt T76 (MW) had the highest. Among pre-treatment samples there was a strong linkage disequilibrium with an excess of MM and WW and a deficit of single mutants (MW and WM), suggesting that parasite fitness is higher for the former and lower for the latter. | |||
2002 |
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Nicolai Zederkopff Ballin, Maminata Traore, Halidou Tinto, Archibald Sittie, Per Mølgaard, Carl Erik Olsen, Arsalan Kharazmi, Søren Brøgger Christensen Antiplasmodial compounds from Cochlospermum tinctorium Journal Article In: J. Nat. Prod., vol. 65, no. 9, pp. 1325–1327, 2002. @article{Ballin2002-cl, Fractionation of an ethanol extract of roots of Cochlospermum tinctorium afforded five compounds: 3-O-E-p-coumaroylalphitolic acid (1), cochloxanthin (2), dihydrocochloxanthin (3), alphitolic acid (4), and 1-hydroxytetradecan-3-one (5). This is the first example of a 1-hydroxyalkan-3-one obtained from plant material after gentle workup. The antiplasmodial activities of the compounds were determined, and the IC(50) value of 3-O-E-p-coumaroylalphitolic acid was 2.3 microM. |
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