Publication: Plasmodium vivax trophozoites insensitive to chloroquine
Submitted Date
2008-05-27
Accepted Date
2008-05-27
Issued Date
2008-05-27
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eng
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application/pdf
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1.31 mb
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Mahidol University
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BioMed Central
Bibliographic Citation
Malaria Journal. Vol.7, No.1 (2008), 1-7
Suggested Citation
Sharrock, Wesley W, Rossarin Suwanarusk, Usa Lek-Uthai, Edstein, Michael D, Varakorn Kosaisavee, Travers, Thomas, Anchalee Jaidee, Kanlaya Sriprawat, Price, Ric N, Nosten, François, Russell, Bruce, อุษา เล็กอุทัย, วรากร โกศัยเสวี Plasmodium vivax trophozoites insensitive to chloroquine. Malaria Journal. Vol.7, No.1 (2008), 1-7. doi:10.1186/1475-2875-7-94 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/2182
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Title
Plasmodium vivax trophozoites insensitive to chloroquine
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Abstract
Plasmodium vivax is a major cause of malaria and is still primarily treated with chloroquine.
Chloroquine inhibits the polymerization of haem to inert haemozoin. Free haem monomers are thought
to catalyze oxidative damage to the Plasmodium spp. trophozoite, the stage when haemoglobin catabolism
is maximal. However preliminary in vitro observations on P. vivax clinical isolates suggest that only ring
stages (early trophozoites) are sensitive to chloroquine. In this study, the stage specific action of
chloroquine was investigated in synchronous cryopreserved isolates of P. vivax.
Methods: The in vitro chloroquine sensitivity of paired ring and trophozoite stages from 11 cryopreserved
P. vivax clinical isolates from Thailand and two Plasmodium falciparum clones (chloroquine resistant K1 and
chloroquine sensitive FC27) was measured using a modified WHO microtest method and fluorometric
SYBR Green I Assay. The time each stage was exposed to chloroquine treatment was controlled by
washing the chloroquine off at 20 hours after the beginning of treatment.
Results: Plasmodium vivax isolates added to the assay at ring stage had significantly lower median IC50s to
chloroquine than the same isolates added at trophozoite stage (median IC50 12 nM vs 415 nM p < 0.01).
Although only 36% (4/11) of the SYBR Green I assays for P. vivax were successful, both microscopy and
SYBR Green I assays indicated that only P. vivax trophozoites were able to develop to schizonts at
chloroquine concentrations above 100 nM.
Conclusion: Data from this study confirms the diminished sensitivity of P. vivax trophozoites to
chloroquine, the stage thought to be the target of this drug. These results raise important questions about
the pharmacodynamic action of chloroquine, and highlight a fundamental difference in the activity of chloroquine between P. vivax and P. falciparum.
Sponsorship
This study was funded by the Faculty of Public Health,
Mahidol University (UL), Charles Darwin University and MSHR, Honours
student grant (WWS). RS and RNP were funded by a Wellcome Trust
Career Development Award, affiliated to the Wellcome Trust – Mahidol
University – Oxford Tropical Medicine Research Programme (074637).
HPLC analysis was funded by the Australian Defence Organisation (ADO).