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Role of Known Molecular Markers of Resistance in the Antimalarial Potency of Piperaquine and Dihydroartemisinin In Vitro

Muangnoicharoen, Sant, Johnson, David, Looareesuwan, S., Krudsood, S. and Ward, Steve (2009) 'Role of Known Molecular Markers of Resistance in the Antimalarial Potency of Piperaquine and Dihydroartemisinin In Vitro'. Antimicrobial Agents and Chemotherapy, Vol 53, Issue 4, pp. 1362-1366.

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Abstract

Using a range of laboratory-adapted and genetically modified Plasmodium falciparum parasite isolates, we investigated the interaction between dihydroartemisinin and piperaquine (PIP), the individual components of an artemisinin combination therapy currently under development, in addition to the role of known drug resistance genes in parasite susceptibility in vitro. All but one parasite line investigated displayed an interaction of dihydroartemisinin and PIP that was antagonistic, although the degree of antagonism was isolate dependent. In terms of resistance markers, the pfcrt haplotypes CVIET and SVMNT were positively associated with reduced sensitivity to PIP, with parasites carrying the South American CQR (SVMNT) allele being generally less sensitive than CVIET parasites. Parasites carrying the CQS (CVMNK) allele displayed a further increase in PIP sensitivity compared with CVIET and SVMNT parasites. Our data indicate that PIP sensitivity was not affected by pfmdr1 sequence status, despite positive correlations between the structurally related compound amodiaquine and pfmdr1 mutations in other studies. In contrast, neither the pfcrt nor pfmdr1 sequence status had any significant impact on susceptibility to dihydroartemisinin.

Item Type: Article
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
QW Microbiology and Immunology > Immunity by Type > QW 551 Acquired immunity. Artificial immunity
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QV Pharmacology > QV 38 Drug action.
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WA Public Health > WA 100 General works
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole.
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1128/AAC.01656-08
Depositing User: Mary Creegan
Date Deposited: 02 Jun 2010 17:38
Last Modified: 06 Feb 2018 12:59
URI: http://archive.lstmed.ac.uk/id/eprint/338

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