{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:37:38Z","timestamp":1773794258374,"version":"3.50.1"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":314,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    There is compelling evidence that complement plays a major role in the elimination of nonparasitized erythrocytes (np\u2010Es) in the anemia of malaria. In fact, for every erythrocyte destroyed after infection by\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (Pf) or\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    , at least 10 np\u2010Es are cleared, most likely due to C3b opsonization. In malaria, complement is activated by three breakdown products released from lysed parasitized erythrocytes (p\u2010Es): hemin\/hematin, the digestive vacuole (DV), and hemozoin. Both childhood anemia in malaria and post\u2010artesunate delayed\u2010hemolysis in individuals with malaria treated with artesunate can be ascribed to complement activation. These findings are important with respect to development of potential therapies for malarial anemia because there are now available FDA\u2010approved drugs that completely inhibit complement at the C3 activation step for several days at a time. We review key clinical findings and basic science investigations that implicate complement and in particular C3b opsonization as a significant factor in malarial anemia. Extension of these basic science studies to examine FDA\u2010approved drugs that block complement at the C3b opsonization step are needed to justify their potential utilization in treatment of malarial anemia. In particular, in vitro studies in blood cultures of Pf\/\n                    <jats:italic>vivax<\/jats:italic>\n                    should determine whether deposition of C3 activation products on np\u2010Es can be completely prevented in the presence of complement inhibitors. If these experiments validate proof of concept, then extension of this paradigm to a clinical trial based on combined treatment with artesunate plus an FDA\u2010approved complement inhibitor would be indicated.\n                  <\/jats:p>","DOI":"10.1155\/jimr\/3534692","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:04:04Z","timestamp":1762859044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Complement Will Substantially Reduce the Anemia of Malaria"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1578-8382","authenticated-orcid":false,"given":"Ronald P.","family":"Taylor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4203-405X","authenticated-orcid":false,"given":"Margaret A.","family":"Lindorfer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021015055"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2509-9"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003327"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/10.1.9"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(00)90080-4"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-021-02033-1"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61924-1"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3041"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0948-0"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0269391"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14030504"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2022.08.017"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-77258-5_2"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1999.60.733"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1179\/102453312X13221316477336"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200303000-00002"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(01)90095-1"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182099004564"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2001.65.614"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01524-6"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00926-1"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2003.68.410"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.10.3863"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3460"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.2307\/3279074"},{"key":"e_1_2_14_26_2","first-page":"119","article-title":"Direct Coombs Antiglobulin Reactions in Gambian Children With Plasmodium Falciparum Malaria. 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