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<p>The emergence of antimalarial drug resistance threatens malaria control and elimination efforts in Africa. Ethiopia, once a success story in case reduction, is now experiencing a resurgence. Here we examine key drug resistance genes (<i>Pfmdr1</i>, <i>Pfcrt</i>, <i>Pfk13</i>, <i>Pfdhfr</i> and <i>Pfdhps</i>) and mitochondrial genomes from 605 <i>Plasmodium falciparum</i> isolates collected across 15 districts in Ethiopia with varying transmission intensity and <i>Plasmodium vivax</i> co-endemicity. Although chloroquine was withdrawn for <i>P. falciparum</i> long ago, it remains the first-line treatment for <i>P. vivax</i>; this overlapping use may shape selection pressure in co-endemic settings that influences resistance markers to artemether–lumefantrine, the current first-line therapy for <i>P. falciparum</i>. A dominant <i>Pf</i>MDR1 NFSND haplotype, associated with reduced lumefantrine susceptibility, was identified alongside near fixation of the chloroquine-resistant <i>Pf</i>CRT CVIET haplotype in specific areas. Concerningly, <i>Pf</i>K13 variants associated with partial artemisinin resistance, R622I (10%), A675V (1.7%) and P441L (1.1%), were expanding. Multilevel models demonstrated robust, independent associations of R622I with <i>Pf</i>CRT CVIET and <i>Pf</i>DHFR AICNI, while ecological predictors were weaker and less consistent. These findings highlight genetic co-occurrence of <i>Pfcrt</i> and <i>Pfk13</i> mutations in <i>P. vivax</i>–<i>P. falciparum</i> co-endemic settings and can inform antimalarial policy in Ethiopia.</p>

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Genomic surveillance reveals co-occurrence of Plasmodium falciparum drug resistance variants across diverse transmission settings in Ethiopia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Alemayehu Letebo,
  • Leen N. Vanheer,
  • Mengst Engdaw,
  • Legesse Alamerie Ejigu,
  • Dawit Hailu Alemayehu,
  • Jimma Dinsa Deressa,
  • Bethlehem Adnew,
  • Abaysew Ayele,
  • Migbaru Keffale Bezabih,
  • Mulugeta Demisse,
  • Tamrayehu Seyoum,
  • Meklit Shiferaw,
  • Heven Sime,
  • Atsbeha Gebreegziabxier Weldemariam,
  • Amanuel Shimelash,
  • Elias B. Tafa,
  • Wakweya Chali,
  • Lina Alemayehu,
  • Fikregabrail Aberra Kassa,
  • Ayalew Jejaw Zeleke,
  • Tajudin Abdurhaman Hamza,
  • Abel Beliyu Tamirat,
  • Tadesse Misganaw,
  • Alayu Bogale,
  • Zufan Yiheyis Abriham,
  • Yasin Nasir,
  • Gutema Jebessa,
  • Metmiku Yohannes,
  • Betelhem Akililu Kebede,
  • Matiwos Kidane Ayele,
  • Melat Abdo,
  • Getinet Habtamu,
  • Addisu Gizat,
  • Jody Phelan,
  • Bryce Matlock,
  • David A. Fidock,
  • Susana Campino,
  • Ashenafi Assefa,
  • Cristian Koepfli,
  • Fekadu Massebo,
  • Fitsum G. Tadesse

摘要

The emergence of antimalarial drug resistance threatens malaria control and elimination efforts in Africa. Ethiopia, once a success story in case reduction, is now experiencing a resurgence. Here we examine key drug resistance genes (Pfmdr1, Pfcrt, Pfk13, Pfdhfr and Pfdhps) and mitochondrial genomes from 605 Plasmodium falciparum isolates collected across 15 districts in Ethiopia with varying transmission intensity and Plasmodium vivax co-endemicity. Although chloroquine was withdrawn for P. falciparum long ago, it remains the first-line treatment for P. vivax; this overlapping use may shape selection pressure in co-endemic settings that influences resistance markers to artemether–lumefantrine, the current first-line therapy for P. falciparum. A dominant PfMDR1 NFSND haplotype, associated with reduced lumefantrine susceptibility, was identified alongside near fixation of the chloroquine-resistant PfCRT CVIET haplotype in specific areas. Concerningly, PfK13 variants associated with partial artemisinin resistance, R622I (10%), A675V (1.7%) and P441L (1.1%), were expanding. Multilevel models demonstrated robust, independent associations of R622I with PfCRT CVIET and PfDHFR AICNI, while ecological predictors were weaker and less consistent. These findings highlight genetic co-occurrence of Pfcrt and Pfk13 mutations in P. vivax–P. falciparum co-endemic settings and can inform antimalarial policy in Ethiopia.