Susceptibility of Colombian Plasmodium falciparum isolates to 4-aminoquinolines and the definition of amodiaquine resistance in vitro

Echeverry, Diego F.; Murillo, Claribel; Piedad, Restrepo P; Osório, Lyda

doi:10.1590/s0074-02762006000300022

Cited by 3 publications

(3 citation statements)

References 26 publications

(37 reference statements)

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“…Resistance to AQ and its metabolite DEAQ has been linked to mutations in Pfmdr1 [11], [12]. Whereas resistance to AQ has been extensively reported in South America [13], [14], this drug has remained relatively effective in Africa, especially as a viable partner drug for ART [15]. The selection by the AL combination for Pfmdr1 alleles has recently been observed [16].…”

Section: Introductionmentioning

confidence: 99%

The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008–2011

et al. 2013

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Single Nucleotide Polymorphisms (SNPs) in the Pfmdr1, and Pfcrt, genes of Plasmodium falciparum may confer resistance to a number of anti-malaria drugs. Pfmdr1 86Y and haplotypes at Pfcrt 72-76 have been linked to chloroquine (CQ) as well as amodiaquine (AQ) resistance. mefloquine (MQ) and lumefantrine (LU) sensitivities are linked to Pfmdr1 86Y. Additionally, Pfcrt K76 allele carrying parasites have shown tolerance to LU. We investigated the association between Pfmdr1 86/Pfcrt 72-76 and P. falciparum resistance to CQ, AQ, MQ and LU using field samples collected during 2008–2011 from malaria endemic sites in western Kenya. Genomic DNA from these samples was genotyped to examine SNPs and haplotypes in Pfmdr1 and Pfcrt respectively. Additionally, immediate ex vivo and in vitro drug sensitivity profiles were assessed using the malaria SYBR Green I fluorescence-based assay. We observed a rapid but steady percent increase in wild-type parasites with regard to both Pfmdr1 and Pfcrt between 2008 and 2011 (p<0.0001). Equally, a significant reciprocate decrease in AQ and CQ median IC50 values occurred (p<0.0001) during the same period. Thus, the data in this study point to a significantly rapid change in parasite response to AQ and CQ in the study period. This may be due to releasing of drug pressure on the parasite from reduced use of AQ in the face of increased Artemisinin (ART) Combination Therapy (ACT) administration following the intervention of the Global Fund in 2008. LU has been shown to select for 76K genotypes, thus the observed increase in 76K genotypes coupled with significant cross resistance between LU and MQ, may herald emergence of tolerance against both drugs in future.

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Section: Introductionmentioning

confidence: 99%

The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008–2011

et al. 2013

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“…Studies have indicated consensus on the thresholds to define resistance to N- 18 . The same study maintains that understanding the mechanism of resistance to amodiaquine is useful in the design of new drugs, particularly 4-aminoquinoline derivatives.…”

Section: Discussionmentioning

confidence: 99%

3-HMG-Coa Reductase Inhibitor Modulates Parasitological Response in Malaria Patients Treated with Amodiaquine

Nwobodo¹,

Okonkwo²

2014

Biomed. Pharmacol. J.

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The occurrence of parasitological resistance to amodiaquine has been reported globally. The 3-HMG CoA reductase inhibitors, otherwise known as statins have been shown to inhibit the growth of malaria parasite.This study was aimed at evaluating the effects of simvastatin in modulating parasitological response to amodiaquine in the chemotherapy of malaria. Subjects with frank malaria (n=60) diagnosed by thick blood film and and confirmed using immunological tests were nominated for the study. Informed written content was obtained and subjects randomized into amodiaquine plus simvastatin (test) and amodiaquine alone (control) groups. The ethical clearance certificate was obtained from the University of Nigeria Teaching Hospital Research Ethics Committee (NHREC/05/01/2008B). The assessment of parasitological response was done in line with WHO criteria and patients followed up on days D0, D3, D7, D14 and D28 posttreatment. The GraphPad Prism 4.0 was employed in the analysis of data which was presented as tables and graphs. Revealed a statistically significant difference in parasitological response (p<0.05) between test and control groups. The mean value of low level resistance, RI was given as 1.3±0.14%, mid-level resistance, RII as 2.7±0.15%, high level parasitological resistance, RIII as 2.4±0.17% and the late parasitological failure, LPF as 3.3±0.26% in the test group. This contrasts with the value of RI given as 8.7±0.42%, RII as 12.8±0.49%, RIII as 4.6±0.17% and the LPF given as 6.7±0.21% in the control group. The outcome of this study suggests that the 3-HMG-CoA reductase inhibitor, simvastatin, is implicated in modulating parasitological response to amodiaquine in the chemotherapy of malaria.

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“…AQ is a more active antimalarial then DEAQ, with half-maximal inhibitory concentration (IC 50 ) values 2-8-fold lower [27,42,43]. The little information available shows that the C max of AQ is relatively low -approximately 30 nM (600 mg dose) - [44], falling anyway inside the in vitro IC 50 values of a significant fraction of field analyzed AQ sensitive parasites [41,[45][46][47][48][49].…”

Section: Can Cyp2c8 Polymorphisms Influence Amodiaquine Regimens Effimentioning

confidence: 99%

CYP2C8 and Antimalaria Drug Efficacy

Gil

Berglund

2007

Pharmacogenomics

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Malaria is a major infectious disease. In the last 10 years it has killed more than 20 million people, mainly small children in Africa. The highly efficacious artemisinine combination therapy is being launched globally, constituting the main hope for fighting the disease. Amodiaquine is a main partner in these combinations. Amodiaquine is almost entirely metabolized by the polymorphic cytochrome P450 (CYP) isoform 2C8 to the pharmacologically active desethylamodiaquine. The question remains whether the efficacy of amodiaquine is affected by the gene polymorphism. Genotype-inferred low metabolizers are found in 1-4% of African populations, which corresponds to millions of expected exposures to the drug. In vivo pharmacokinetic data on amodiaquine is limited. By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. Chloroquine and dapsone, both substrates of CYP2C8, are also discussed in the same context.

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Susceptibility of Colombian Plasmodium falciparum isolates to 4-aminoquinolines and the definition of amodiaquine resistance in vitro

Cited by 3 publications

References 26 publications

The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008–2011

The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008–2011

3-HMG-Coa Reductase Inhibitor Modulates Parasitological Response in Malaria Patients Treated with Amodiaquine

CYP2C8 and Antimalaria Drug Efficacy

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