{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:58:45Z","timestamp":1790488725061,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","funder":[{"name":"Military Infectious Diseases Research Program","award":["Q0433_15WR_CS"],"award-info":[{"award-number":["Q0433_15WR_CS"]}]},{"name":"Defense Health Program","award":["P8"],"award-info":[{"award-number":["P8"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1186\/s12936-016-1632-8","type":"journal-article","created":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T03:16:05Z","timestamp":1481080565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cytochrome P450 2D-mediated metabolism is not necessary for tafenoquine and primaquine to eradicate the erythrocytic stages of Plasmodium berghei"],"prefix":"10.1186","volume":"15","author":[{"given":"Erin E.","family":"Milner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Caridha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel P.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Marcsisin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa T.","family":"Read","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Roncal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Vesely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa H.","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qigui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,7]]},"reference":[{"key":"1632_CR1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.4269\/ajtmh.2006.75.402","volume":"75","author":"DR Hill","year":"2006","unstructured":"Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg. 2006;75:402\u201315.","journal-title":"Am J Trop Med Hyg"},{"key":"1632_CR2","unstructured":"FDA. Primaquine Phosphate Label. 2015. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/008316s021lbl.pdf . Accessed 23 Dec 2015."},{"issue":"15","key":"1632_CR3","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1056\/NEJMra043207","volume":"352","author":"JK Baird","year":"2005","unstructured":"Baird JK. Drug therapy: effectiveness of antimalarial drugs. N Engl J Med. 2005;352(15):1565\u201377.","journal-title":"N Engl J Med"},{"key":"1632_CR4","unstructured":"WHO. Updated WHO policy recommendation: single dose primaquine as a gametocytocide in Plasmodium falciparum malaria. Geneva, World Health Organization, 2012. http:\/\/www.who.int\/malaria\/publications\/atoz\/who_pq_policy_recommendation\/en\/ . Accessed 30 Dec 2015."},{"key":"1632_CR5","first-page":"10458","volume":"4","author":"S Rajapakse","year":"2015","unstructured":"Rajapakse S, Rodrigo C, Fernando SD. Tafenoquine for preventing relapse in people with Plasmodium vivax malaria. Cochrane Database Syst Rev. 2015;4:10458.","journal-title":"Cochrane Database Syst Rev"},{"key":"1632_CR6","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1517\/13543784.16.5.705","volume":"16","author":"M Crockett","year":"2007","unstructured":"Crockett M, Kain KC. Tafenoquine: a promising new antimalarial agent. Expert Opin Investig Drugs. 2007;16:705\u201315.","journal-title":"Expert Opin Investig Drugs"},{"key":"1632_CR7","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1186\/1475-2875-11-418","volume":"11","author":"NJ White","year":"2012","unstructured":"White NJ, Qiao LG, Qi G, Luzzatto L. Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common. Malar J. 2012;11:418.","journal-title":"Malar J."},{"key":"1632_CR8","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.ijpara.2012.06.006","volume":"42","author":"JK Baird","year":"2012","unstructured":"Baird JK. Primaquine toxicity forestalls effective therapeutic management of the endemic malarias. Int J Parasitol. 2012;42:1049\u201354.","journal-title":"Int J Parasitol"},{"key":"1632_CR9","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.ejmech.2008.08.011","volume":"44","author":"N Vale","year":"2009","unstructured":"Vale N, Moreira R, Gomes P. Primaquine revisited six decades after its discovery. Eur J Med Chem. 2009;44:937\u201353.","journal-title":"Eur J Med Chem"},{"key":"1632_CR10","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1056\/NEJMc1301936","volume":"369","author":"JW Bennett","year":"2013","unstructured":"Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, et al. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med. 2013;369:1381\u20132.","journal-title":"N Engl J Med"},{"key":"1632_CR11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/1475-2875-12-212","volume":"12","author":"BS Pybus","year":"2013","unstructured":"Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, et al. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J. 2013;12:212.","journal-title":"Malar J."},{"key":"1632_CR12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2016.03.011","volume":"161","author":"SR Marcsisin","year":"2016","unstructured":"Marcsisin SR, Reichard G, Pybus BS. Primaquine pharmacology in the context of CYP 2D6 pharmacogenomics: current state of the art. Pharmacol Ther. 2016;161:1\u201310.","journal-title":"Pharmacol Ther"},{"key":"1632_CR13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1475-2875-13-2","volume":"13","author":"SR Marcsisin","year":"2014","unstructured":"Marcsisin SR, Sousa JC, Reichard GA, Caridha D, Zeng Q, Roncal N, et al. Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds. Malar J. 2014;13:2.","journal-title":"Malar J."},{"key":"1632_CR14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/jtm.12080","volume":"21","author":"GA Deye","year":"2014","unstructured":"Deye GA, Magill AJ. Primaquine for prophylaxis of malaria: has the CYP sailed? J Travel Med. 2014;21:67\u20139.","journal-title":"J Travel Med."},{"key":"1632_CR15","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1517\/14622416.3.2.229","volume":"3","author":"LD Bradford","year":"2002","unstructured":"Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3:229\u201343.","journal-title":"Pharmacogenomics"},{"key":"1632_CR16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s13318-012-0080-2","volume":"37","author":"E Milner","year":"2012","unstructured":"Milner E, Sousa J, Pybus B, Auschwitz J, Caridha D, Gardner S, et al. Ketotifen is an antimalarial prodrug of norketotifen with blood schizonticidal and liver-stage efficacy. Eur J Drug Metabol Pharmacokinet. 2012;37:17\u201322.","journal-title":"Eur J Drug Metabol Pharmacokinet."},{"key":"1632_CR17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1475-2875-13-141","volume":"13","author":"QG Li","year":"2014","unstructured":"Li QG, O\u2019Neil M, Xie L, Caridha D, Zeng Q, Zhang J, et al. Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections. Malar J. 2014;13:141.","journal-title":"Malar J."},{"key":"1632_CR18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1124\/mol.111.075192","volume":"81","author":"N Scheer","year":"2012","unstructured":"Scheer N, Kapelyukh Y, McEwan J, Beuger V, Stanley LA, Rode A, et al. Modeling human cytochrome P450 2D6 metabolism and drug-drug interaction by a novel panel of knockout and humanized mouse lines. Mol Pharmacol. 2012;81:63\u201372.","journal-title":"Mol Pharmacol"},{"key":"1632_CR19","first-page":"23","volume":"21","author":"STM Allard","year":"2008","unstructured":"Allard STM, Kopish K. Luciferase reporter assays: powerful, adaptable tools for cell biology research. Cell Notes. 2008;21:23\u20136.","journal-title":"Cell Notes."},{"key":"1632_CR20","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2307\/3281779","volume":"70","author":"LS Ozaki","year":"1984","unstructured":"Ozaki LS, Gwadz RW, Godson GN. Simple centrifugation method for rapid separation of sporozoites from mosquitoes. J Parasitol. 1984;70:831\u20133.","journal-title":"J Parasitol"},{"key":"1632_CR21","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1017\/S0031182007002661","volume":"134","author":"L Xie","year":"2007","unstructured":"Xie L, Li Q, Johnson J, Zhang J, Milhous W, Kyle D. Development and validation of flow cytometric measurement for parasitaemia using autofluorescence and YOYO-1 in rodent malaria. Parasitology. 2007;134:1151\u201362.","journal-title":"Parasitology"},{"key":"1632_CR22","first-page":"297","volume":"71","author":"QG Li","year":"2007","unstructured":"Li QG, Gerena L, Xie L, Zhang J, Kyle D, Milhous W. Development and validation of flow cytometric measurement for parasitemia in cultures of P. falciparum vitally stained with YOYO-1. Cytometry A. 2007;71:297\u2013307.","journal-title":"Cytometry A."},{"key":"1632_CR23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0035-9203(53)90013-3","volume":"47","author":"JP Thurston","year":"1953","unstructured":"Thurston JP. The morphology of Plasmodium berghei before and after treatment with drugs. Trans R Soc Trop Med Hyg. 1953;47:248\u201356.","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"1632_CR24","first-page":"245","volume":"23","author":"JP Kreier","year":"1972","unstructured":"Kreier JP, Mohan R, Seed T, Pfister RM. Studies of morphology and survival characteristics of erythrocytes from mice and rats with Plasmodium berghei infection. Z Tropenmed Parasitol. 1972;23:245\u201355.","journal-title":"Z Tropenmed Parasitol."},{"key":"1632_CR25","unstructured":"Centrum LUM. 2015. https:\/\/www.lumc.nl\/org\/parasitologie\/research\/malaria\/berghei-model\/Morphology-berghei-LM\/Morphology-berghei-LM-images\/ . Accessed 18 Dec 2015."},{"key":"1632_CR26","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1128\/AAC.00015-15","volume":"59","author":"BM Potter","year":"2015","unstructured":"Potter BM, Xie LH, Vuong C, Zhang J, Zhang P, Duan D, et al. Differential CYP 2D6 metabolism alters primaquine pharmacokinetics. Antimicrob Agents Chemother. 2015;59:2380\u20137.","journal-title":"Antimicrob Agents Chemother"},{"key":"1632_CR27","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/AAC.00343-15","volume":"59","author":"C Vuong","year":"2015","unstructured":"Vuong C, Xie LH, Potter BM, Zhang J, Zhang P, Duan D, et al. Differential cytochrome P450 2D metabolism alters tafenoquine pharmacokinetics. Antimicrob Agents Chemother. 2015;59:3864\u20139.","journal-title":"Antimicrob Agents Chemother"},{"key":"1632_CR28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12936-016-1145-5","volume":"15","author":"PL St Jean","year":"2016","unstructured":"St Jean PL, Xue Z, Carter N, Koh GC, Duparc S, Taylor M, et al. Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial. Malar J. 2016;15:97.","journal-title":"Malar J."},{"key":"1632_CR29","first-page":"429","volume":"44","author":"J Arnold","year":"1954","unstructured":"Arnold J, Alving AS, Hockwald RS, Clayman CB, Dern RJ, Beutler E, et al. The effect of continuous and intermittent primaquine therapy on the relapse rate of Chesson strain vivax malaria. J Lab Clin Med. 1954;44:429\u201338.","journal-title":"J Lab Clin Med"},{"key":"1632_CR30","doi-asserted-by":"crossref","first-page":"659","DOI":"10.4269\/ajtmh.2002.66.659","volume":"66","author":"JK Baird","year":"2002","unstructured":"Baird JK, Wiady I, Sutanihardja A, Suradi Purnomo, Basri H, et al. Therapeutic efficacy of chloroquine combined with primaquine against Plasmodium falciparum in northeastern Papua Indonesia. Am J Trop Med Hyg. 2002;66:659\u201360.","journal-title":"Am J Trop Med Hyg"},{"key":"1632_CR31","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1093\/infdis\/169.4.932","volume":"169","author":"S Pukrittayakamee","year":"1994","unstructured":"Pukrittayakamee S, Vanijanonta S, Chantra A, Clemens R, White NJ. Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria. J Infect Dis. 1994;169:932\u20135.","journal-title":"J Infect Dis"},{"key":"1632_CR32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1475-2875-13-49","volume":"13","author":"GS Dow","year":"2014","unstructured":"Dow GS, McCarthy WF, Reid M, Smith B, Tang D, Shanks GD. A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti-malarials in non-immune individuals during deployment to a malaria-endemic area. Malar J. 2014;13:49.","journal-title":"Malar J."},{"key":"1632_CR33","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1186\/s12936-015-0991-x","volume":"14","author":"GS Dow","year":"2015","unstructured":"Dow GS, Liu J, Lin G, Hetzell B, Thieling S, McCarthy WF, et al. Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries. Malar J. 2015;14:473.","journal-title":"Malar J."},{"key":"1632_CR34","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/AAC.43.3.598","volume":"43","author":"JL Vennerstrom","year":"1999","unstructured":"Vennerstrom JL, Nuzum EO, Miller RE, Dorn A, Gerena L, Dande PA, et al. 8-aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization. Antimicrob Agents Chemother. 1999;43:598\u2013602.","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-016-1632-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T08:45:27Z","timestamp":1568623527000},"score":1,"resource":{"primary":{"URL":"http:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-016-1632-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["1632"],"URL":"https:\/\/doi.org\/10.1186\/s12936-016-1632-8","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]},"article-number":"588"}}