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

Victor Asua¹  Arthur Mpimbaza¹  James Kapisi¹  Samuel Gonahasa¹  Jane Frances Namuganga¹  Chris Ebong¹  Asadu Sserwanga¹  Sam L. Nsobya²  Moses R. Kamya²  Adoke Yeka²  Eric S. Halsey³  Naomi W. Lucchi³  Samaly S. Svigel Souza³  Leah F. Moriarty³  Daniel Kyabayinze⁴  Denis Rubahika⁴  Agaba Bosco⁴  Damian Rutazana⁴  Jimmy Opigo⁴  Kassahun Belay⁵  Gloria Sebikaari⁵  Mame Niang⁵  Ruth Kigozi⁶  Sam Gudoi⁶  James Tibenderana⁶  John Bosco Bwanika⁶ 

[1] Infectious Diseases Research Collaboration, Kampala, Uganda;Infectious Diseases Research Collaboration, Kampala, Uganda;Makerere University College of Health Sciences, Kampala, Uganda;Malaria Branch, Centers for Disease Control and Prevention & President’s Malaria Initiative, Atlanta, GA, USA;National Malaria Control Division, Ministry of Health Uganda, Kampala, Uganda;U.S. President’s Malaria Initiative, Kampala, Uganda;USAID’s Malaria Action Program for Districts, Kampala, Uganda;

关键词: Efficacy;    Artemether-lumefantrine;    Dihydroartemisinin-piperaquine;    Malaria;    Uganda;   

DOI  :  10.1186/s12936-021-04021-5

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsThis 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.ResultsThere 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.ConclusionsDP 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 trail was also registered with the ISRCTN registry with study Trial No. PACTR201811640750761

【 授权许可】

CC BY