{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:27:30Z","timestamp":1786742850283,"version":"build-2736575974"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The first-line treatments for uncomplicated Plasmodium falciparum malaria are artemisinin-based combination therapies (ACTs), consisting of an artemisinin derivative combined with a longer acting partner drug. However, the spread of P. falciparum with decreased susceptibility to artemisinin and partner drugs presents a significant challenge to malaria control efforts. To stem the spread of drug resistant parasites, novel chemotherapeutic strategies are being evaluated, including the implementation of triple artemisinin-based combination therapies (TACTs). Currently, there is limited knowledge on the pharmacodynamic and pharmacogenetic interactions of proposed TACT drug combinations. To evaluate these interactions, we established an in vitro high-throughput process for measuring the drug concentration\u2013response to three distinct antimalarial drugs present in a TACT. Sixteen different TACT combinations were screened against 15 parasite lines from Cambodia, with a focus on parasites with differential susceptibilities to piperaquine and artemisinins. Analysis revealed drug\u2013drug interactions unique to specific genetic backgrounds, including antagonism between piperaquine and pyronaridine associated with gene amplification of plasmepsin II\/III, two aspartic proteases that localize to the parasite digestive vacuole. From this initial study, we identified parasite genotypes with decreased susceptibility to specific TACTs, as well as potential TACTs that display antagonism in a genotype-dependent manner. Our assay and analysis platform can be further leveraged to inform drug implementation decisions and evaluate next-generation TACTs.<\/jats:p>","DOI":"10.1021\/acsptsci.0c00110","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T11:54:18Z","timestamp":1604318058000},"page":"1144-1157","source":"Crossref","is-referenced-by-count":19,"title":["Modulation of Triple Artemisinin-Based Combination\nTherapy Pharmacodynamics by\n                    <i>Plasmodium falciparum<\/i>\n                    Genotype"],"prefix":"10.1021","volume":"3","author":[{"given":"Megan R.","family":"Ansbro","sequence":"first","affiliation":[{"name":"National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]},{"name":"Wellcome Sanger Institute , ,","place":["Hinxton, U.K., CB10 1SA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zina","family":"Itkin","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , 9800 Medical Center Drive , , ,","place":["Rockville, Maryland, United States, 20850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , 9800 Medical Center Drive , , ,","place":["Rockville, Maryland, United States, 20850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergely","family":"Zahoranszky-Kohalmi","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , 9800 Medical Center Drive , , ,","place":["Rockville, Maryland, United States, 20850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanaki","family":"Amaratunga","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivo","family":"Miotto","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , ,","place":["Hinxton, U.K., CB10 1SA"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10400"]},{"name":"University of Oxford , , ,","place":["Oxford, U.K., OX3 7LF"]},{"name":"University of Oxford , , ,","place":["Oxford, U.K., OX3 7BN"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Peryea","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , 9800 Medical Center Drive , , ,","place":["Rockville, Maryland, United States, 20850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte V.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center , , , ,","place":["Jackson, Mississippi, United States, 39216"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seila","family":"Suon","sequence":"additional","affiliation":[{"name":"National Center for Parasitology, Entomology, and Malaria Control , ,","place":["Phnom Penh, Cambodia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana M.","family":"Sa\u0301","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen M.","family":"Dondorp","sequence":"additional","affiliation":[{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10400"]},{"name":"University of Oxford , , ,","place":["Oxford, U.K., OX3 7LF"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob W.","family":"van der Pluijm","sequence":"additional","affiliation":[{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10400"]},{"name":"University of Oxford , , ,","place":["Oxford, U.K., OX3 7LF"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-8454","authenticated-orcid":true,"given":"Thomas E.","family":"Wellems","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Simeonov","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , 9800 Medical Center Drive , , ,","place":["Rockville, Maryland, United States, 20850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3580-380X","authenticated-orcid":true,"given":"Richard T.","family":"Eastman","sequence":"additional","affiliation":[{"name":"National Institutes of Health , , 9800 Medical Center Drive , , ,","place":["Rockville, Maryland, United States, 20850"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"2026081416170745500_cit1","unstructured":"(2018) World\nMalaria Report 2018, World Health Organization."},{"key":"2026081416170745500_cit2","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12876","article-title":"A molecular\nmarker of artemisinin-resistant Plasmodium falciparum malaria","volume":"505","author":"Ariey","year":"2014","journal-title":"Nature"},{"key":"2026081416170745500_cit3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/j.1365-2958.2012.08180.x","article-title":"Mechanisms of in vitro resistance to dihydroartemisinin\nin Plasmodium falciparum","volume":"86","author":"Cui","year":"2012","journal-title":"Mol.\nMicrobiol."},{"key":"2026081416170745500_cit4","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1128\/AAC.01636-09","article-title":"Increased tolerance to artemisinin\nin Plasmodium falciparum is mediated by a quiescence\nmechanism","volume":"54","author":"Witkowski","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081416170745500_cit5","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.1073\/pnas.1217452110","article-title":"Altered temporal\nresponse of malaria parasites determines differential sensitivity\nto artemisinin","volume":"110","author":"Klonis","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S.\nA."},{"key":"2026081416170745500_cit6","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1038\/s41591-020-1005-2","article-title":"Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum\nkelch13 R561H mutant parasites in Rwanda","volume":"26","author":"Uwimana","year":"2020","journal-title":"Nat. Med."},{"key":"2026081416170745500_cit7","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1172\/JCI21682","article-title":"Antimalarial drug resistance","volume":"113","author":"White","year":"2004","journal-title":"J. Clin. Invest."},{"key":"2026081416170745500_cit8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3390\/tropicalmed4010026","article-title":"Resistance\nto Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner\nDrug!","volume":"4","author":"Nsanzabana","year":"2019","journal-title":"Trop Med. Infect Dis."},{"key":"2026081416170745500_cit9","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/S0140-6736(04)16767-6","article-title":"Mefloquine\nresistance in Plasmodium falciparum and increased pfmdr1 gene copy number","volume":"364","author":"Price","year":"2004","journal-title":"Lancet"},{"key":"2026081416170745500_cit10","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1086\/503423","article-title":"Molecular and pharmacological determinants of the therapeutic\nresponse to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria","volume":"42","author":"Price","year":"2006","journal-title":"Clin.\nInfect. Dis."},{"key":"2026081416170745500_cit11","doi-asserted-by":"publisher","first-page":"18883","DOI":"10.1073\/pnas.0911317106","article-title":"Geographic\npatterns of Plasmodium falciparum drug resistance\ndistinguished by differential responses to amodiaquine and chloroquine","volume":"106","author":"Sa","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081416170745500_cit12","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/S1473-3099(16)30409-1","article-title":"Genetic markers associated with dihydroartemisinin-piperaquine\nfailure in Plasmodium falciparum malaria in Cambodia:\na genotype-phenotype association study","volume":"17","author":"Amato","year":"2017","journal-title":"Lancet\nInfect. Dis."},{"key":"2026081416170745500_cit13","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1038\/s41467-018-05652-0","article-title":"Emerging\nSoutheast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine","volume":"9","author":"Ross","year":"2018","journal-title":"Nat. Commun."},{"key":"2026081416170745500_cit14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/S1473-3099(16)30415-7","article-title":"A Surrogate\nMarker of Piperaquine-Resistant Plasmodium Falciparum Malaria: A Phenotype-Genotype\nAssociation Study","volume":"17","author":"Witkowski","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"2026081416170745500_cit15","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nm.4381","article-title":"Antimalarial\ndrug resistance: linking Plasmodium falciparum parasite\nbiology to the clinic","volume":"23","author":"Blasco","year":"2017","journal-title":"Nat. Med."},{"key":"2026081416170745500_cit16","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/S0140-6736(20)30552-3","article-title":"Triple artemisinin-based combination\ntherapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label,\nrandomised clinical trial","volume":"395","author":"van der Pluijm","year":"2020","journal-title":"Lancet"},{"key":"2026081416170745500_cit17","doi-asserted-by":"publisher","first-page":"13891","DOI":"10.1038\/srep13891","article-title":"High-throughput matrix screening identifies synergistic\nand antagonistic antimalarial drug combinations","volume":"5","author":"Mott","year":"2015","journal-title":"Sci. Rep."},{"key":"2026081416170745500_cit18","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/nmeth.2143","article-title":"Site-specific genome editing in Plasmodium\nfalciparum using engineered zinc-finger nucleases","volume":"9","author":"Straimer","year":"2012","journal-title":"Nat. Methods"},{"key":"2026081416170745500_cit19","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S1473-3099(12)70181-0","article-title":"Artemisinin-resistant Plasmodium\nfalciparum in Pursat province, western Cambodia: a parasite\nclearance rate study","volume":"12","author":"Amaratunga","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"2026081416170745500_cit20","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S1473-3099(15)00487-9","article-title":"Dihydroartemisinin-piperaquine resistance\nin Plasmodium falciparum malaria in Cambodia: a multisite\nprospective cohort study","volume":"16","author":"Amaratunga","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"2026081416170745500_cit21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1021\/ci990086j","article-title":"Comparison of 2D\nfingerprint types and hierarchy level selection methods for structural\ngrouping using Ward\u2019s clustering","volume":"40","author":"Wild","year":"2000","journal-title":"J.\nChem. Inf. Comput. Sci."},{"key":"2026081416170745500_cit22","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1748-7188-4-12","article-title":"Breaking the hierarchy--a new cluster\nselection mechanism for hierarchical clustering methods","volume":"4","author":"Zahoranszky","year":"2009","journal-title":"Algorithms Mol. Biol."},{"key":"2026081416170745500_cit23","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13321-016-0127-5","article-title":"Impact of similarity threshold on\nthe topology of molecular similarity networks and clustering outcomes","volume":"8","author":"Zahoranszky-Kohalmi","year":"2016","journal-title":"J. Cheminf."},{"key":"2026081416170745500_cit24","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nrmicro2239","article-title":"Artemisinin-based\ncombination therapies: a vital tool in efforts to eliminate malaria","volume":"7","author":"Eastman","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"2026081416170745500_cit25","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/1475-2875-11-270","article-title":"Review of pyronaridine\nanti-malarial properties and product characteristics","volume":"11","author":"Croft","year":"2012","journal-title":"Malar. J."},{"key":"2026081416170745500_cit26","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1126\/science.7051285","article-title":"Plasmodium falciparum gametocytes from culture in vitro develop to sporozoites\nthat are infectious to primates","volume":"217","author":"Campbell","year":"1982","journal-title":"Science"},{"key":"2026081416170745500_cit27","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1586\/eri.09.68","article-title":"Discovery, mechanisms\nof action and combination therapy of artemisinin","volume":"7","author":"Cui","year":"2009","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"2026081416170745500_cit28","volume-title":"World Health Organization Model List of Essential Medicines\n21st List 2019","year":"2019"},{"key":"2026081416170745500_cit29","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/S1473-3099(19)30392-5","article-title":"Evolution and expansion of multidrug-resistant\nmalaria in southeast Asia: a genomic epidemiology study","volume":"19","author":"Hamilton","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"2026081416170745500_cit30","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/S1473-3099(19)30391-3","article-title":"Determinants of dihydroartemisinin-piperaquine\ntreatment failure in Plasmodium falciparum malaria\nin Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological,\nand genetic study","volume":"19","author":"van der Pluijm","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"2026081416170745500_cit31","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ijpddr.2018.11.004","article-title":"Overexpression\nof plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine","volume":"9","author":"Loesbanluechai","year":"2019","journal-title":"Int. J. Parasitol.: Drugs Drug Resist."},{"key":"2026081416170745500_cit32","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1093\/infdis\/jix334","article-title":"Association of a Novel Mutation in\nthe Plasmodium falciparum Chloroquine Resistance\nTransporter With Decreased Piperaquine Sensitivity","volume":"216","author":"Agrawal","year":"2017","journal-title":"J. Infect. Dis."},{"key":"2026081416170745500_cit33","doi-asserted-by":"publisher","first-page":"e00303-17","DOI":"10.1128\/mBio.00303-17","article-title":"A Variant PfCRT Isoform Can Contribute\nto Plasmodium falciparum Resistance to the First-Line\nPartner Drug Piperaquine","volume":"8","author":"Dhingra","year":"2017","journal-title":"mBio"},{"key":"2026081416170745500_cit34","doi-asserted-by":"publisher","first-page":"3908","DOI":"10.1128\/AAC.01793-10","article-title":"Piperaquine resistance is associated with a copy number\nvariation on chromosome 5 in drug-pressured Plasmodium falciparum parasites","volume":"55","author":"Eastman","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081416170745500_cit35","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/S1473-3099(19)30689-9","article-title":"Multigenic architecture of piperaquine\nresistance trait in Plasmodium falciparum","volume":"20","author":"Silva","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"2026081416170745500_cit36","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/3-540-29088-5_11","article-title":"Hemoglobin degradation","volume":"295","author":"Goldberg","year":"2005","journal-title":"Curr.\nTop Microbiol Immunol."},{"key":"2026081416170745500_cit37","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nrmicro2239","article-title":"Artemisinin-based combination therapies:\na vital tool in efforts to eliminate malaria","volume":"7","author":"Eastman","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"issue":"2","key":"2026081416170745500_cit38","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1128\/AAC.00840-06","article-title":"Synergistic\nInteractions of the Antiretroviral Protease Inhibitors Saquinavir\nand Ritonavir with Chloroquine and Mefloquine against Plasmodium\nfalciparum In Vitro","volume":"51","author":"Skinner-Adams","year":"2007","journal-title":"Antimicrob. Agents\nChemother."},{"issue":"5","key":"2026081416170745500_cit39","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1128\/AAC.00166-12","article-title":"Saquinavir Inhibits the Malaria Parasite\u2019s Chloroquine\nResistance Transporter","volume":"56","author":"Martin","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081416170745500_cit40","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.pt.2019.05.004","article-title":"Next-Generation\nPhenotypic Screening in Early Drug Discovery for Infectious Diseases","volume":"35","author":"Aulner","year":"2019","journal-title":"Trends Parasitol."},{"key":"2026081416170745500_cit41","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/nrd.2017.111","article-title":"Opportunities and challenges in phenotypic drug discovery:\nan industry perspective","volume":"16","author":"Moffat","year":"2017","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026081416170745500_cit42","unstructured":"(2017) The cardiotoxicity of antimalarials, Malaria Policy Advisory Committee Meeting, World Health Organization."},{"key":"2026081416170745500_cit43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002212","article-title":"Population Pharmacokinetic Properties\nof Piperaquine in Falciparum Malaria: An Individual Participant Data\nMeta-Analysis","volume":"14","author":"Hoglund","year":"2017","journal-title":"PLoS Med."},{"key":"2026081416170745500_cit44","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1128\/AAC.03829-14","article-title":"Pharmacokinetic\ninteractions between primaquine and pyronaridine-artesunate in healthy\nadult Thai subjects","volume":"59","author":"Jittamala","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081416170745500_cit45","doi-asserted-by":"publisher","first-page":"205ra135","DOI":"10.1126\/scitranslmed.3006684","article-title":"Model system to define pharmacokinetic\nrequirements for antimalarial drug efficacy","volume":"5","author":"Bakshi","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"2026081416170745500_cit46","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1128\/AAC.49.7.2983-2985.2005","article-title":"Antimalarial\nactivity of human immunodeficiency virus type 1 protease inhibitors","volume":"49","author":"Parikh","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081416170745500_cit47","unstructured":"(2019) UNAIDS Data Report, UNAIDS."},{"key":"2026081416170745500_cit48","unstructured":"(2019) Guidelines for the Use of Antiretroviral Agents\nin Pediatric HIV Infection. AIDSinfo. aids.nlm.nih.gov (accessed\n2020-10-25)."},{"key":"2026081416170745500_cit49","unstructured":"(2019) Update of Recommendations on First and\nSecond-line Antiretroviral Regimens, World\nHealth Organization."},{"key":"2026081416170745500_cit50","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1007\/s40265-018-0911-9","article-title":"Drugs in Development for Malaria","volume":"78","author":"Ashley","year":"2018","journal-title":"Drugs"},{"key":"2026081416170745500_cit51","doi-asserted-by":"publisher","first-page":"17050","DOI":"10.1038\/nrdp.2017.50","article-title":"Malaria","volume":"3","author":"Phillips","year":"2017","journal-title":"Nat.\nRev. Dis Primers."},{"key":"2026081416170745500_cit52","doi-asserted-by":"publisher","first-page":"4533","DOI":"10.1128\/AAC.00519-09","article-title":"Improved murine model of malaria using Plasmodium\nfalciparum competent strains and non-myelodepleted NOD-scid\nIL2Rgamma null mice engrafted with human erythrocytes","volume":"53","author":"Jimenez-Diaz","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081416170745500_cit53","doi-asserted-by":"publisher","first-page":"e00479-17","DOI":"10.1128\/IAI.00479-17","article-title":"Controlled\nHuman Malaria Infection: Applications, Advances, and Challenges","volume":"86","author":"Stanisic","year":"2018","journal-title":"Infect. Immun."},{"key":"2026081416170745500_cit54","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2017-000371","article-title":"Randomised controlled trial of two sequential artemisinin-based\ncombination therapy regimens to treat uncomplicated falciparum malaria\nin African children: a protocol to investigate safety, efficacy and\nadherence","volume":"2","author":"Schallig","year":"2017","journal-title":"BMJ. Glob Health."},{"key":"2026081416170745500_cit55","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/ng.3189","article-title":"Genetic\narchitecture of artemisinin-resistant Plasmodium falciparum","volume":"47","author":"Miotto","year":"2015","journal-title":"Nat. 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