{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:44:12Z","timestamp":1792597452887,"version":"4.5.0"},"reference-count":44,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Effective treatments for genetic disorders that coevolved with pathogens require simultaneous betterment of both conditions. Hydroxyurea (HU) offers safe and efficacious treatment for sickle cell anemia (SCA) by reducing clinical complications, transfusions, and death rates. Despite concerns that the HU treatment for SCA would increase infection risk by the human malaria Plasmodium falciparum, (the genetic driver of the sickle mutation), HU instead reduced clinical malaria. We used physiologically relevant drug exposures that mimic in\u00a0vivo pharmacokinetics in humans. Under these conditions, we showed that HU and other ribonucleotide reductase (RNR) inhibitors have significant, intrinsic killing activity in\u00a0vitro against schizont stages of P falciparum in both normal and sickle red blood cells. Long-term in\u00a0vitro selection with HU increased the expression of Pfrnr genes but showed a low risk of eliciting stably resistant parasites or compromising the potency of current antimalarial drugs. Additive activity devoid of antagonism by HU was observed with a wide spectrum of commonly used antimalarial treatments. These data endorse broad, safe, and long-term use of HU for SCA in malaria-endemic countries and provide a novel biological model for the treatment of a genetic disorder with simultaneous, adjunct therapy of a life-threatening infection needed in a global health setting.<\/jats:p>","DOI":"10.1182\/bloodadvances.2022009124","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T15:59:12Z","timestamp":1682351952000},"page":"5970-5981","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["Simultaneous adjunctive treatment of malaria and its coevolved genetic disorder sickle cell anemia"],"prefix":"10.1182","volume":"7","author":[{"given":"Innocent","family":"Safeukui","sequence":"first","affiliation":[{"name":"1Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Eck Institute of Global Health, University of Notre Dame, Notre Dame, 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