Plasmodium vivax trophozoites insensitive to chloroquine
Abstract Background 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 haemogl...
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ftdoajarticles:oai:doaj.org/article:4fbb91094def4b2e97043946b79c7f75 2023-05-15T15:11:56+02:00 Plasmodium vivax trophozoites insensitive to chloroquine Jaidee Anchalee Travers Thomas Kosaisavee Varakorn Edstein Michael D Lek-Uthai Usa Suwanarusk Rossarin Sharrock Wesley W Sriprawat Kanlaya Price Ric N Nosten François Russell Bruce 2008-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-7-94 https://doaj.org/article/4fbb91094def4b2e97043946b79c7f75 EN eng BMC http://www.malariajournal.com/content/7/1/94 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-7-94 1475-2875 https://doaj.org/article/4fbb91094def4b2e97043946b79c7f75 Malaria Journal, Vol 7, Iss 1, p 94 (2008) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2008 ftdoajarticles https://doi.org/10.1186/1475-2875-7-94 2022-12-31T00:40:36Z Abstract Background 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 IC 50s to chloroquine than the same isolates added at trophozoite stage (median IC 50 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 . Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 7 1 94 |
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ftdoajarticles |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Jaidee Anchalee Travers Thomas Kosaisavee Varakorn Edstein Michael D Lek-Uthai Usa Suwanarusk Rossarin Sharrock Wesley W Sriprawat Kanlaya Price Ric N Nosten François Russell Bruce Plasmodium vivax trophozoites insensitive to chloroquine |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background 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 IC 50s to chloroquine than the same isolates added at trophozoite stage (median IC 50 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 . |
format |
Article in Journal/Newspaper |
author |
Jaidee Anchalee Travers Thomas Kosaisavee Varakorn Edstein Michael D Lek-Uthai Usa Suwanarusk Rossarin Sharrock Wesley W Sriprawat Kanlaya Price Ric N Nosten François Russell Bruce |
author_facet |
Jaidee Anchalee Travers Thomas Kosaisavee Varakorn Edstein Michael D Lek-Uthai Usa Suwanarusk Rossarin Sharrock Wesley W Sriprawat Kanlaya Price Ric N Nosten François Russell Bruce |
author_sort |
Jaidee Anchalee |
title |
Plasmodium vivax trophozoites insensitive to chloroquine |
title_short |
Plasmodium vivax trophozoites insensitive to chloroquine |
title_full |
Plasmodium vivax trophozoites insensitive to chloroquine |
title_fullStr |
Plasmodium vivax trophozoites insensitive to chloroquine |
title_full_unstemmed |
Plasmodium vivax trophozoites insensitive to chloroquine |
title_sort |
plasmodium vivax trophozoites insensitive to chloroquine |
publisher |
BMC |
publishDate |
2008 |
url |
https://doi.org/10.1186/1475-2875-7-94 https://doaj.org/article/4fbb91094def4b2e97043946b79c7f75 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 7, Iss 1, p 94 (2008) |
op_relation |
http://www.malariajournal.com/content/7/1/94 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-7-94 1475-2875 https://doaj.org/article/4fbb91094def4b2e97043946b79c7f75 |
op_doi |
https://doi.org/10.1186/1475-2875-7-94 |
container_title |
Malaria Journal |
container_volume |
7 |
container_issue |
1 |
container_start_page |
94 |
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1766342703794094080 |