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

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posted on 2023-06-09, 17:05 authored by Hsiao-Han Chang, Elamaran Meibalan, Justin Zelin, Rachel Daniels, Chi EziefulaChi Eziefula, Evan C Meyer, Fitsum Tadesse, Lynn Grignard, Regina C Joice, Chris Drakeley, Dyann F Wirth, Sarah K Volkman, Caroline Buckee, Teun Bousema, Matthias Marti
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Scientific Reports

ISSN

2045-2322

Publisher

Nature Research

Issue

26330

Volume

6

Page range

1-8

Department affiliated with

  • Global Health and Infection Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-02-28

First Open Access (FOA) Date

2019-02-28

First Compliant Deposit (FCD) Date

2019-02-28

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