Efficacy and safety of artemether‑lumefantrine and dihydroartemisinin‑piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Malaria Journal
Abstract
In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP)
second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL
and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers
of resistance in three sentinel sites in Uganda from 2018 to 2019.
Methods: This was a randomized, open-label, phase IV clinical trial. Children aged 6 months to 10 years with uncomplicated
falciparum malaria were randomly assigned to treatment with AL or DP and followed for 28 and 42 days,
respectively. Genotyping was used to distinguish recrudescence from new infection, and a Bayesian algorithm was
used to assign each treatment failure a posterior probability of recrudescence. For monitoring resistance, Pfk13 and
Pfmdr1 genes were Sanger sequenced and plasmepsin-2 copy number was assessed by qPCR.
Results: There were no early treatment failures. The uncorrected 28-day cumulative efficacy of AL ranged from 41.2
to 71.2% and the PCR-corrected cumulative 28-day efficacy of AL ranged from 87.2 to 94.4%. The uncorrected 28-day
cumulative efficacy of DP ranged from 95.8 to 97.9% and the PCR-corrected cumulative 28-day efficacy of DP ranged
from 98.9 to 100%. The uncorrected 42-day efficacy of DP ranged from 73.5 to 87.4% and the PCR-corrected 42-day
efficacy of DP ranged from 92.1 to 97.5%. There were no reported serious adverse events associated with any of the
regimens. No resistance-associated mutations in the Pfk13 gene were found in the successfully sequenced samples.
In the AL arm, the NFD haplotype (N86Y, Y184F, D1246Y) was the predominant Pfmdr1 haplotype, present in 78 of 127 (61%) and 76 of 110 (69%) of the day 0 and day of failure samples, respectively. All the day 0 samples in the DP arm
had one copy of the plasmepsin-2 gene.
Conclusions: DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda. Recurrent
infections with AL were common. In Busia and Arua, the 95% confidence interval for PCR-corrected AL efficacy fell
below 90%. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended.
Trial registration The trial was also registered with the Pan African Clinical Trial Registry (https:// pactr. samrc. ac. za/) with
study Trial No. PACTR201811640750761.
Description
Keywords
Efficacy, Artemether-lumefantrine, Dihydroartemisinin-piperaquine, Malaria, Uganda
Citation
Ebong, C., Sserwanga, A., Namuganga, J. F., Kapisi, J., Mpimbaza, A., Gonahasa, S., ... & Yeka, A. (2022). Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda. Malaria Journal, 21(1), 1-2. https://doi.org/10.1186/s12936-021-04021-5