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Background <p>From August to October 2022, a therapeutic efficacy study of Niger’s first-line antimalarial, artemether-lumefantrine (AL), was conducted in four sites (Aderbissinat, Boboye, Aguié, and Baban Tabki) to evaluate its therapeutic efficacy and investigate for molecular markers of antimalarial drug resistance.</p> Methods <p>Children aged 5 to 15&#xa0;years old with uncomplicated malaria were assessed in a 28&#xa0;day in vivo efficacy study. Genotyping using three markers (<i>msp1, msp2</i> and the PolyA microsatellite) and match counting using the WHO three-out-of-three algorithm, were used to distinguish recrudescences from new infections. A two-out-of-three algorithm was also utilized as a sensitivity analysis.</p> Results <p>PCR uncorrected and corrected efficacy results at day 28 were calculated. Resistance markers were analysed by next-generation sequencing. Uncorrected treatment efficacies were 62.0% (95% CI 54–74) in Aderbissinat, 95.4% (95% CI 91–100) in Aguié, 98.7% (95% CI 96–100) in Boboye, and 50.6% (95% CI 42–62) in Baban Tabki. After PCR correction, AL efficacy was 100%, 97.5%, 100%, and 93.5%, respectively. Marker analysis revealed a high prevalence <i>of S108N, C59R,</i> and <i>N51I</i> mutations in the <i>pfdhfr</i> gene, and <i>S436A</i> and <i>A437G</i> mutations in the <i>pfdhps</i> gene. No validated or candidate <i>pfkelch13</i> mutations were observed.</p> Conclusion <p>In all four sites evaluated, AL retains therapeutic efficacies above the 90% WHO-recommended threshold using the primary three-out-of-three match criteria. In Aguié and Baban Tabki, efficacy remained above the threshold with certain match criteria and statistical approaches but fell below the cutoff using two-out-of-three matching and per-protocol methods, suggesting emerging efficacy concerns in southern parts of the country.</p>

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Therapeutic efficacy of artemether-lumefantrine and molecular markers of antimalarial resistance in Niger, 2022

  • 期刊论文

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  • 发表日期：

    2025年12月29日

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  • Ibrahim Maman Laminou,
  • Sanoussi Maman Kabirou,
  • Ibrahima Issa Arzika,
  • Abdou Yahaya,
  • Jehan Ahmed,
  • Awa Bineta Deme,
  • Mamadou Alpha Diallo,
  • Bassirou Ngom,
  • Amy Gaye,
  • Aïta Sene,
  • Djiby Sow,
  • Eric Coulibaly,
  • Zilahatou Bahari-Tohon,
  • Elisha Sanoussi,
  • Daniel Koko,
  • Irene Cavros

摘要

Background

From August to October 2022, a therapeutic efficacy study of Niger’s first-line antimalarial, artemether-lumefantrine (AL), was conducted in four sites (Aderbissinat, Boboye, Aguié, and Baban Tabki) to evaluate its therapeutic efficacy and investigate for molecular markers of antimalarial drug resistance.

Methods

Children aged 5 to 15 years old with uncomplicated malaria were assessed in a 28 day in vivo efficacy study. Genotyping using three markers (msp1, msp2 and the PolyA microsatellite) and match counting using the WHO three-out-of-three algorithm, were used to distinguish recrudescences from new infections. A two-out-of-three algorithm was also utilized as a sensitivity analysis.

Results

PCR uncorrected and corrected efficacy results at day 28 were calculated. Resistance markers were analysed by next-generation sequencing. Uncorrected treatment efficacies were 62.0% (95% CI 54–74) in Aderbissinat, 95.4% (95% CI 91–100) in Aguié, 98.7% (95% CI 96–100) in Boboye, and 50.6% (95% CI 42–62) in Baban Tabki. After PCR correction, AL efficacy was 100%, 97.5%, 100%, and 93.5%, respectively. Marker analysis revealed a high prevalence of S108N, C59R, and N51I mutations in the pfdhfr gene, and S436A and A437G mutations in the pfdhps gene. No validated or candidate pfkelch13 mutations were observed.

Conclusion

In all four sites evaluated, AL retains therapeutic efficacies above the 90% WHO-recommended threshold using the primary three-out-of-three match criteria. In Aguié and Baban Tabki, efficacy remained above the threshold with certain match criteria and statistical approaches but fell below the cutoff using two-out-of-three matching and per-protocol methods, suggesting emerging efficacy concerns in southern parts of the country.