{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:00:40Z","timestamp":1763665240129,"version":"build-2065373602"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI140751","U19 AI089688"],"award-info":[{"award-number":["R01 AI140751","U19 AI089688"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["5K08DK123386"],"award-info":[{"award-number":["5K08DK123386"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sickle cell disease (SCD) remains prevalent because heterozygous carriers (HbAS) are partially resistant to <jats:italic>Plasmodium falciparum<\/jats:italic> malaria. Sickle hemoglobin (HbS) polymerization in low and intermediate oxygen (O<jats:sub>2<\/jats:sub>) conditions is the main driver of HbAS\u2010driven resistance to <jats:italic>P. falciparum<\/jats:italic> malaria. However, epidemiological studies have reported mixed malaria morbidity and mortality outcomes in individuals with sickle cell disease (SCD). While maximum\u2010tolerated dose hydroxyurea has been shown to lower malaria incidence, fetal hemoglobin (HbF), an inhibitor of HbS polymerization that is variably packaged in F\u2010erythrocytes, might provide hemoglobin that is accessible to the parasite for feeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To explore that risk, we examined the effect of variable mean corpuscular fetal hemoglobin (MCHF) on <jats:italic>P. falciparum<\/jats:italic> proliferation, invasion, and development in HbSS RBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that greater MCHF in HbSS red blood cells (RBCs) is associated with increased <jats:italic>P. falciparum<\/jats:italic> proliferation in O<jats:sub>2<\/jats:sub> environments comparable with the microcirculation. Moreover, both parasite invasion and intracellular growth, the major components of proliferation, occur predominantly in F\u2010erythrocytes and are augmented with increasing MCHF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HbF modifies <jats:italic>P. falciparum<\/jats:italic> infection in HbSS RBCs, further highlighting the complexity of the molecular interactions between these two diseases. Other inhibitors of HbS polymerization that do not increase HbF or F\u2010erythrocytes should be independently assessed for their effects on <jats:italic>P. falciparum<\/jats:italic> malaria proliferation in HbSS RBCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.27042","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T05:45:29Z","timestamp":1692423929000},"page":"1598-1605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["F\u2010erythrocytes promote <i>Plasmodium falciparum<\/i> proliferation in sickle cell disease"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-5872","authenticated-orcid":false,"given":"Natasha M.","family":"Archer","sequence":"first","affiliation":[{"name":"Pediatric Hematology\/Oncology Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9n\u00e9dicte","family":"Gnangnon","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Center for Communicable Diseases Dynamics, Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Mikdar","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases Harvard T.H. 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