Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda

Artemisinin resistance is rapidly spreading in Southeast Asia. The efficacy of artemisinin-combination therapy (ACT) continues to be excellent across Africa. We performed parasite transcriptional profiling and genotyping on samples from an antimalarial treatment trial in Uganda. We used qRT-PCR and...

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Main Authors:	Chang, Hsiao-Han, Meibalan, Elamaran, Zelin, Justin, Daniels, Rachel, Eziefula, Alice C., Meyer, Evan C., Tadesse, Fitsum, Grignard, Lynn, Joice, Regina C., Drakeley, Chris, Wirth, Dyann F., Volkman, Sarah K., Buckee, Caroline, Bousema, Teun, Marti, Matthias
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873826/

id	pubmed-4873826
recordtype	oai_dc
spelling	pubmed-48738262016-06-02 Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda Chang, Hsiao-Han Meibalan, Elamaran Zelin, Justin Daniels, Rachel Eziefula, Alice C. Meyer, Evan C. Tadesse, Fitsum Grignard, Lynn Joice, Regina C. Drakeley, Chris Wirth, Dyann F. Volkman, Sarah K. Buckee, Caroline Bousema, Teun Marti, Matthias Article Artemisinin resistance is rapidly spreading in Southeast Asia. The efficacy of artemisinin-combination therapy (ACT) continues to be excellent across Africa. We performed parasite transcriptional profiling and genotyping on samples from an antimalarial treatment trial in Uganda. We used qRT-PCR and genotyping to characterize residual circulating parasite populations after treatment with either ACT or ACT-primaquine. Transcripts suggestive of circulating ring stage parasites were present after treatment at a prevalence of >25% until at least 14 days post initiation of treatment. Greater than 98% of all ring stage parasites were cleared within the first 3 days, but subsequently persisted at low concentrations until day 14 after treatment. Genotyping demonstrated a significant decrease in multiplicity of infection within the first 2 days in both ACT and ACT-primaquine arms. However, multiple clone infections persisted until day 14 post treatment. Our data suggest the presence of genetically diverse persisting parasite populations after ACT treatment. Although we did not demonstrate clinical treatment failures after ACT and the viability and transmissibility of persisting ring stage parasites remain to be shown, these findings are of relevance for the interpretation of parasite clearance transmission dynamics and for monitoring drug effects in Plasmodium falciparum parasites. Nature Publishing Group 2016-05-20 /pmc/articles/PMC4873826/ /pubmed/27197604 http://dx.doi.org/10.1038/srep26330 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chang, Hsiao-Han Meibalan, Elamaran Zelin, Justin Daniels, Rachel Eziefula, Alice C. Meyer, Evan C. Tadesse, Fitsum Grignard, Lynn Joice, Regina C. Drakeley, Chris Wirth, Dyann F. Volkman, Sarah K. Buckee, Caroline Bousema, Teun Marti, Matthias
spellingShingle	Chang, Hsiao-Han Meibalan, Elamaran Zelin, Justin Daniels, Rachel Eziefula, Alice C. Meyer, Evan C. Tadesse, Fitsum Grignard, Lynn Joice, Regina C. Drakeley, Chris Wirth, Dyann F. Volkman, Sarah K. Buckee, Caroline Bousema, Teun Marti, Matthias Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
author_facet	Chang, Hsiao-Han Meibalan, Elamaran Zelin, Justin Daniels, Rachel Eziefula, Alice C. Meyer, Evan C. Tadesse, Fitsum Grignard, Lynn Joice, Regina C. Drakeley, Chris Wirth, Dyann F. Volkman, Sarah K. Buckee, Caroline Bousema, Teun Marti, Matthias
author_sort	Chang, Hsiao-Han
title	Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
title_short	Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
title_full	Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
title_fullStr	Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
title_full_unstemmed	Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
title_sort	persistence of plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in uganda
description	Artemisinin resistance is rapidly spreading in Southeast Asia. The efficacy of artemisinin-combination therapy (ACT) continues to be excellent across Africa. We performed parasite transcriptional profiling and genotyping on samples from an antimalarial treatment trial in Uganda. We used qRT-PCR and genotyping to characterize residual circulating parasite populations after treatment with either ACT or ACT-primaquine. Transcripts suggestive of circulating ring stage parasites were present after treatment at a prevalence of >25% until at least 14 days post initiation of treatment. Greater than 98% of all ring stage parasites were cleared within the first 3 days, but subsequently persisted at low concentrations until day 14 after treatment. Genotyping demonstrated a significant decrease in multiplicity of infection within the first 2 days in both ACT and ACT-primaquine arms. However, multiple clone infections persisted until day 14 post treatment. Our data suggest the presence of genetically diverse persisting parasite populations after ACT treatment. Although we did not demonstrate clinical treatment failures after ACT and the viability and transmissibility of persisting ring stage parasites remain to be shown, these findings are of relevance for the interpretation of parasite clearance transmission dynamics and for monitoring drug effects in Plasmodium falciparum parasites.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873826/
_version_	1613581928893513728

Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda

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