{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:23:21Z","timestamp":1781853801389,"version":"3.54.5"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IRTG2290"],"award-info":[{"award-number":["IRTG2290"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000995","name":"Australian National University","doi-asserted-by":"publisher","award":["IRTG2290"],"award-info":[{"award-number":["IRTG2290"]}],"id":[{"id":"10.13039\/501100000995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:p>\n                    Studies from the 1980s and 1990s conducted in Italy, where malaria was once endemic, hypothesized that individuals with erythrocytes deficient in flavin mononucleotide and flavin adenine dinucleotide (FAD)\u2014collectively known as flavins\u2014are partially protected against malaria. The condition was reported to be familial, consistent with a genetic element. This hypothesis, however, has never been tested. Using an erythrocyte FAD-dependent glutathione reductase activity assay, we identified individuals with flavin-deficient erythrocytes (FDE) in Ferrara, Italy (23% of 150 individuals screened), and in Huye, Rwanda (13% of 169 individuals). None of the individuals with FDE had a dietary riboflavin deficiency. Importantly, FDE from individuals in Ferrara, as well as erythrocytes depleted of flavins in vitro by riboflavin starvation, inhibited the intraerythrocytic proliferation of\n                    <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                    . We provide evidence that these erythrocytes are susceptible to oxidative stress, potentially explaining their inhibitory effect on parasite proliferation. Genetic analysis identified mutations in the FAD synthase gene of three individuals with FDE from Huye, consistent with a potential genetic basis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2504687122","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T19:06:57Z","timestamp":1756148817000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Flavin-deficient erythrocytes offer protection against malaria parasites"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2881-747X","authenticated-orcid":false,"given":"Ayman","family":"Hemasa","sequence":"first","affiliation":[{"name":"Research School of Biology, The Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Welmoed","family":"van Loon","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center for Global Health, Institute of International Health, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Fu","sequence":"additional","affiliation":[{"name":"Research School of Biology, The Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-7070","authenticated-orcid":false,"given":"Christina","family":"Spry","sequence":"additional","affiliation":[{"name":"Research School of Biology, The Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center for Global Health, Institute of International Health, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donelly A.","family":"van Schalkwyk","sequence":"additional","affiliation":[{"name":"Research School of Biology, The Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-1337","authenticated-orcid":false,"given":"Roberto","family":"Reverberi","sequence":"additional","affiliation":[{"name":"Blood Transfusion Service, Azienda Ospedaliera Universitaria","place":["Ferrara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1705-2099","authenticated-orcid":false,"given":"Jules","family":"Ndoli","sequence":"additional","affiliation":[{"name":"Clinical Education and Research Division, University Teaching Hospital of Butare","place":["Butare, Rwanda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank P.","family":"Mockenhaupt","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center for Global Health, Institute of International Health, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-6470","authenticated-orcid":false,"given":"Carlo","family":"Contini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Infectious Diseases and Dermatology, University of Ferrara","place":["Ferrara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-8440","authenticated-orcid":false,"given":"Kevin J.","family":"Saliba","sequence":"additional","affiliation":[{"name":"Research School of Biology, The Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"World malaria report 2024: addressing inequity in the global malaria response (World Health Organization 2024)."},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","unstructured":"J. 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