{
  "abstract": "Artemisinin-based combination therapies are the frontline treatment for Plasmodium falciparum malaria, but their efficacy is threatened by Artemisinin partial resistance (ART R ). ART R in Plasmodium falciparum is mediated by Pfkelch13 ( k13 ) mutations but remains rare in West Africa. A critical question is whether short-term drug survival intrinsically predicts long-term evolutionary persistence. Here, using CRISPR-Cas9 editing, and nanopore-assisted allele tracking in a contemporary Senegalese isolate, we evaluated ART R receptivity using the ring-stage survival assay (RSA), a proxy for clinical resistance. We demonstrate that ART R survival and drug-free persistence are biologically separable traits. While the WHO-validated Asian I543T mutation conferred the RSA phenotype, it was rapidly counter-selected during drug-free growth. In contrast, emerging African alleles (R561H, M579I) and a regional novel variant (C473S) establish stable resistance without a competitive penalty. These findings reveal that a parasite’s genetic background acts as a strict evolutionary filter, uncoupling short-term tolerance from long-term persistence and establishing that genomic context determines allele-specific resistance trajectories.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Imran Ullah"
    },
    {
      "name": "Morgan C. Martin"
    },
    {
      "name": "Daouda Ndiaye"
    },
    {
      "name": "Sarah K. Volkman"
    },
    {
      "name": "Dyann F. Wirth"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2mmzcscxz6mqz.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-11221098/v1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734243/",
  "id": "2mmzcscxz6mqz",
  "issns": [
    "2693-5015"
  ],
  "landing_url": "https://doi.org/10.21203/rs.3.rs-11221098/v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
  ],
  "openalex": "W7211965372",
  "pdf_url": "https://www.researchsquare.com/article/rs-11221098/latest.pdf",
  "pmcid": "PMC13734243",
  "pmid": "42990760",
  "published": "2026-10-27",
  "publisher": "American Journal Experts",
  "ris": "https://research.draconitic.com/paper/2mmzcscxz6mqz.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:52Z",
      "native_id": "PMC13734243",
      "source": "pmc",
      "url": "https://doi.org/10.21203/rs.3.rs-11221098/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Malaria Research and Control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Genetic background determines allele-specific Pfkelch13- mediated artemisinin tolerance and persistence in Plasmodium falciparum",
  "title_text": "Genetic background determines allele-specific Pfkelch13- mediated artemisinin tolerance and persistence in Plasmodium falciparum",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:52Z",
  "url": "https://research.draconitic.com/paper/2mmzcscxz6mqz",
  "venue": "Research Square",
  "versions": []
}