{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:33:13Z","timestamp":1792657993316,"version":"4.5.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T00:00:00Z","timestamp":1450656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T00:00:00Z","timestamp":1450656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Current first-line treatments for uncomplicated <jats:italic>falciparum<\/jats:italic> malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic <jats:italic>Plasmodium falciparum<\/jats:italic> reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening. Analyses of sixty-five compounds from the Medicines for Malaria Venture validation and malaria boxes identified 37 compounds with high levels of TRA (&gt;80%); different assay modes allowed discrimination between gametocytocidal and downstream modes of action. Comparison of SMFA data to published assay formats for predicting parasite infectivity indicated that individual <jats:italic>in vitro<\/jats:italic> screens show substantial numbers of false negatives. These results highlight the importance of the SMFA in the screening pipeline for transmission reducing compounds and present a rapid and objective method. In addition we present sixteen diverse chemical scaffolds from the malaria box that may serve as a starting point for further discovery and development of malaria transmission blocking drugs.<\/jats:p>","DOI":"10.1038\/srep18704","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T11:42:40Z","timestamp":1450698160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes"],"prefix":"10.1038","volume":"5","author":[{"given":"Martijn W.","family":"Vos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will J. R.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin M.","family":"Koolen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert-Jan","family":"van Gemert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"van Schaijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Leroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Sauerwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun","family":"Bousema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen J.","family":"Dechering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,21]]},"reference":[{"key":"BFsrep18704_CR1","unstructured":"World Health Organization. World Malaria Report 2013. (World Health Organization, 2013)."},{"key":"BFsrep18704_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/1475-2875-6-151","volume":"6","author":"E Okiro","year":"2007","unstructured":"Okiro, E. et al. The decline in paediatric malaria admissions on the coast of Kenya. Malar J. 6, 151 (2007).","journal-title":"Malar J."},{"key":"BFsrep18704_CR3","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1086\/644645","volume":"200","author":"CL Peatey","year":"2009","unstructured":"Peatey, C. L. et al. Effect of Antimalarial Drugs on Plasmodium falciparum Gametocytes. J. Infect. Dis. 200, 1518\u20131521 (2009).","journal-title":"J. Infect. Dis."},{"key":"BFsrep18704_CR4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0140-6736(03)15162-8","volume":"363","author":"IAS Group","year":"2004","unstructured":"Group, I. A. S. Artesunate combinations for treatment of malaria: meta-analysis. The Lancet 363, 9\u201317 (2004).","journal-title":"The Lancet"},{"key":"BFsrep18704_CR5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1475-2875-7-125","volume":"7","author":"L Okell","year":"2008","unstructured":"Okell, L., Drakeley, C., Ghani, A., Bousema, T. & Sutherland, C. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malar J. 7, 125 (2008).","journal-title":"Malar J."},{"key":"BFsrep18704_CR6","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/1475-2875-9-136","volume":"9","author":"T Bousema","year":"2010","unstructured":"Bousema, T. et al. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar J. 9, 136 (2010).","journal-title":"Malar J."},{"key":"BFsrep18704_CR7","doi-asserted-by":"publisher","first-page":"3535","DOI":"10.1007\/s00436-014-4091-6","volume":"113","author":"R Abdul-Ghani","year":"2014","unstructured":"Abdul-Ghani, R. & Beier, J. Strategic use of antimalarial drugs that block falciparum malaria parasite transmission to mosquitoes to achieve local malaria elimination. Parasitol. Res. 113, 3535\u20133546 (2014).","journal-title":"Parasitol. Res."},{"key":"BFsrep18704_CR8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S1473-3099(12)70198-6","volume":"13","author":"NJ White","year":"2013","unstructured":"White, N. J. Primaquine to prevent transmission of falciparum malaria. Lancet Infect Dis 13, 175\u2013181 (2013).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep18704_CR9","first-page":"CD008152","volume":"6","author":"PM Graves","year":"2014","unstructured":"Graves, P. M., Gelband, H. & Garner, P. Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission. Cochrane Database Syst Rev 6, CD008152 (2014).","journal-title":"Cochrane Database Syst Rev"},{"key":"BFsrep18704_CR10","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1186\/1475-2875-11-360","volume":"11","author":"AC Eziefula","year":"2012","unstructured":"Eziefula, A. C. et al. Rationale for short course primaquine in Africa to interrupt malaria transmission. Malar J. 11, 360 (2012).","journal-title":"Malar J."},{"key":"BFsrep18704_CR11","doi-asserted-by":"publisher","first-page":"3268","DOI":"10.1128\/AAC.00325-13","volume":"57","author":"MJ Delves","year":"2013","unstructured":"Delves, M. J. et al. Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs. Antimicrob Agents. Chemother. 57, 3268\u20133274 (2013).","journal-title":"Antimicrob Agents. Chemother."},{"key":"BFsrep18704_CR12","doi-asserted-by":"publisher","first-page":"7292","DOI":"10.1128\/AAC.03666-14","volume":"58","author":"A Ruecker","year":"2014","unstructured":"Ruecker, A. et al. A Male and Female Gametocyte Functional Viability Assay To Identify Biologically Relevant Malaria Transmission-Blocking Drugs. Antimicrob Agents. Chemother. 58, 7292\u20137302 (2014).","journal-title":"Antimicrob Agents. Chemother."},{"key":"BFsrep18704_CR13","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1093\/jac\/dkv003","volume":"70","author":"JM Bolscher","year":"2015","unstructured":"Bolscher, J. M. et al. A combination of new screening assays for prioritization of transmission-blocking antimalarials reveals distinct dynamics of marketed and experimental drugs. J. Antimicrob. Chemother. 70, 1357\u20131366 (2015).","journal-title":"J. Antimicrob. Chemother."},{"key":"BFsrep18704_CR14","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1093\/infdis\/jit284","volume":"208","author":"J Wang","year":"2013","unstructured":"Wang, J. et al. Anopheles gambiae Circumsporozoite Protein\u2013Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands. J. Infect. Dis. 208, 1161\u20131169 (2013).","journal-title":"J. Infect. Dis."},{"key":"BFsrep18704_CR15","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1093\/infdis\/jiu271","volume":"210","author":"WJ Stone","year":"2014","unstructured":"Stone, W. J. et al. A scalable assessment of Plasmodium falciparum transmission in the standard membrane-feeding assay, using transgenic parasites expressing green fluorescent protein-luciferase. J Infect Dis 210, 1456\u20131463 (2014).","journal-title":"J Infect Dis"},{"key":"BFsrep18704_CR16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.molbiopara.2012.10.004","volume":"186","author":"AM Vaughan","year":"2012","unstructured":"Vaughan, A. M. et al. A transgenic Plasmodium falciparum NF54 strain that expresses GFP\u2013luciferase throughout the parasite life cycle. Mol. Biochem. Parasitol. 186, 143\u2013147 (2012).","journal-title":"Mol. Biochem. Parasitol."},{"key":"BFsrep18704_CR17","doi-asserted-by":"publisher","first-page":"e30949","DOI":"10.1371\/journal.pone.0030949","volume":"7","author":"LM Sanz","year":"2012","unstructured":"Sanz, L. M. et al. P. falciparum in vitro killing rates allow to discriminate between different antimalarial mode-of-action. PloS one 7, e30949 (2012).","journal-title":"PloS one"},{"key":"BFsrep18704_CR18","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1093\/nar\/gkj517","volume":"34","author":"M Llin\u00e1s","year":"2006","unstructured":"Llin\u00e1s, M., Bozdech, Z., Wong, E. D., Adai, A. T. & DeRisi, J. L. Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains. Nucleic Acids Res. 34, 1166\u20131173 (2006).","journal-title":"Nucleic Acids Res."},{"key":"BFsrep18704_CR19","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1093\/jac\/dkt165","volume":"68","author":"S D\u2019Alessandro","year":"2013","unstructured":"D\u2019Alessandro, S. et al. A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection. J. Antimicrob. Chemother. 68, 2048\u20132058 (2013).","journal-title":"J. Antimicrob. Chemother."},{"key":"BFsrep18704_CR20","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.molbiopara.2011.02.005","volume":"177","author":"TQ Tanaka","year":"2011","unstructured":"Tanaka, T. Q. & Williamson, K. C. A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue. Mol. Biochem. Parasitol. 177, 160\u2013163 (2011).","journal-title":"Mol. Biochem. Parasitol."},{"key":"BFsrep18704_CR21","doi-asserted-by":"publisher","first-page":"e35019","DOI":"10.1371\/journal.pone.0035019","volume":"7","author":"J Leli\u00e8vre","year":"2012","unstructured":"Leli\u00e8vre, J. et al. Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence \u201ctransmission blocking\u201d assay. PloS one 7, e35019 (2012).","journal-title":"PloS one"},{"key":"BFsrep18704_CR22","doi-asserted-by":"publisher","first-page":"6050","DOI":"10.1128\/AAC.00870-13","volume":"57","author":"L Lucantoni","year":"2013","unstructured":"Lucantoni, L., Duffy, S., Adjalley, S. H., Fidock, D. A. & Avery, V. M. Identification of MMV Malaria Box Inhibitors of Plasmodium falciparum Early-Stage Gametocytes Using a Luciferase-Based High-Throughput Assay. Antimicrob Agents. Chemother. 57, 6050\u20136062 (2013).","journal-title":"Antimicrob Agents. Chemother."},{"key":"BFsrep18704_CR23","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.ijpara.2012.08.009","volume":"42","author":"MJ Delves","year":"2012","unstructured":"Delves, M. J. et al. A high-throughput assay for the identification of malarial transmission-blocking drugs and vaccines. Int. J. Parasitol. 42, 999\u20131006 (2012).","journal-title":"Int. J. Parasitol."},{"key":"BFsrep18704_CR24","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1128\/AAC.01500-13","volume":"58","author":"JD Bowman","year":"2014","unstructured":"Bowman, J. D. et al. Antiapicoplast and gametocytocidal screening to identify the mechanisms of action of compounds within the malaria box. Antimicrob Agents. Chemother. 58, 811\u2013819 (2014).","journal-title":"Antimicrob Agents. Chemother."},{"key":"BFsrep18704_CR25","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1186\/1475-2875-12-408","volume":"12","author":"S Duffy","year":"2013","unstructured":"Duffy, S. & Avery, V. M. Identification of inhibitors of Plasmodium falciparum gametocyte development. Malar J. 12, 408 (2013).","journal-title":"Malar J."},{"key":"BFsrep18704_CR26","doi-asserted-by":"publisher","first-page":"e105817","DOI":"10.1371\/journal.pone.0105817","volume":"9","author":"NG Sanders","year":"2014","unstructured":"Sanders, N. G., Sullivan, D. J., Mlambo, G., Dimopoulos, G. & Tripathi, A. K. Gametocytocidal screen identifies novel chemical classes with Plasmodium falciparum transmission blocking activity. PloS one 9, e105817 (2014).","journal-title":"PloS one"},{"key":"BFsrep18704_CR27","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1128\/MCB.19.2.967","volume":"19","author":"KJ Dechering","year":"1999","unstructured":"Dechering, K. J. et al. Isolation and functional characterization of two distinct sexual-stage-specific promoters of the human malaria parasite Plasmodium falciparum. Mol. Cell. Biol. 19, 967\u2013978 (1999).","journal-title":"Mol. Cell. Biol."},{"key":"BFsrep18704_CR28","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1101\/gr.189225.115","volume":"25","author":"F Faucon","year":"2015","unstructured":"Faucon, F. et al. Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing. Genome Res. 25, 1347\u20131359 (2015).","journal-title":"Genome Res."},{"key":"BFsrep18704_CR29","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12936-015-0665-8","volume":"14","author":"T Li","year":"2015","unstructured":"Li, T. et al. Robust, reproducible, industrialized, standard membrane feeding assay for assessing the transmission blocking activity of vaccines and drugs against Plasmodium falciparum. Malar J. 14, 150 (2015).","journal-title":"Malar J."},{"key":"BFsrep18704_CR30","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/1475-2875-5-68","volume":"5","author":"GE Zollner","year":"2006","unstructured":"Zollner, G. E. et al. Population dynamics of sporogony for Plasmodium vivax parasites from western Thailand developing within three species of colonized Anopheles mosquitoes. Malar J. 5, 68 (2006).","journal-title":"Malar J."},{"key":"BFsrep18704_CR31","doi-asserted-by":"crossref","unstructured":"Stone, W. J. R. et al. The relevance and applicability of oocyst prevalence as a read-out for mosquito feeding assays. Sci. Rep. 3, 10.1038\/srep03418 (2013).","DOI":"10.1038\/srep03418"},{"key":"BFsrep18704_CR32","doi-asserted-by":"publisher","first-page":"574","DOI":"10.4269\/ajtmh.1991.45.574","volume":"45","author":"R Rosenberg","year":"1991","unstructured":"Rosenberg, R. & Rungsiwongse, J. The number of sporozoites produced by individual malaria oocysts. Am J Trop Med Hyg 45, 574\u2013577 (1991).","journal-title":"Am J Trop Med Hyg"},{"key":"BFsrep18704_CR33","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1074\/jbc.M110.179440","volume":"286","author":"YJ Yoon","year":"2011","unstructured":"Yoon, Y. J. et al. KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1 function by impairing the recruitment of positive transcription elongation factor b to the hsp70 promoter. J. Biol. Chem 286, 1737\u20131747 (2011).","journal-title":"J. Biol. Chem"},{"key":"BFsrep18704_CR34","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.jphotobiol.2011.11.008","volume":"107","author":"R Bedford","year":"2012","unstructured":"Bedford, R. et al. Luciferase inhibition by a novel naphthoquinone. J. Photochem. Photobiol. B: Biol. 107, 55\u201364 (2012).","journal-title":"J. Photochem. Photobiol. B: Biol."},{"key":"BFsrep18704_CR35","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/j.ijpara.2012.09.002","volume":"42","author":"TS Churcher","year":"2012","unstructured":"Churcher, T. S. et al. Measuring the blockade of malaria transmission\u2014An analysis of the Standard Membrane Feeding Assay. Int. J. Parasitol. 42, 1037\u20131044 (2012).","journal-title":"Int. J. Parasitol."},{"key":"BFsrep18704_CR36","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.pt.2008.07.009","volume":"24","author":"R Rosenberg","year":"2008","unstructured":"Rosenberg, R. Malaria: some considerations regarding parasite productivity. Trends Parasitol. 24, 487\u2013491 (2008).","journal-title":"Trends Parasitol."},{"key":"BFsrep18704_CR37","doi-asserted-by":"publisher","first-page":"e8410","DOI":"10.1371\/journal.pone.0008410","volume":"4","author":"AL Ou\u00e9draogo","year":"2009","unstructured":"Ou\u00e9draogo, A. L. et al. Substantial contribution of submicroscopical Plasmodium falciparum gametocyte carriage to the infectious reservoir in an area of seasonal transmission. PLoS ONE 4, e8410 (2009).","journal-title":"PLoS ONE"},{"key":"BFsrep18704_CR38","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1128\/CMR.00051-10","volume":"24","author":"T Bousema","year":"2011","unstructured":"Bousema, T. & Drakeley, C. Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination. Clin. Microbiol. Rev. 24, 377\u2013410 (2011).","journal-title":"Clin. Microbiol. Rev."},{"key":"BFsrep18704_CR39","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1186\/1475-2875-7-S1-S8","volume":"7","author":"N White","year":"2008","unstructured":"White, N. The role of anti-malarial drugs in eliminating malaria. Malar J. 7, S8 (2008).","journal-title":"Malar J."},{"key":"BFsrep18704_CR40","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12936-015-0718-z","volume":"14","author":"J Reader","year":"2015","unstructured":"Reader, J. et al. Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination. Malar J. 14, 213 (2015).","journal-title":"Malar J."},{"key":"BFsrep18704_CR41","doi-asserted-by":"publisher","first-page":"e1001169","DOI":"10.1371\/journal.pmed.1001169","volume":"9","author":"M Delves","year":"2012","unstructured":"Delves, M. et al. The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites. PLoS Med 9, e1001169 (2012).","journal-title":"PLoS Med"},{"key":"BFsrep18704_CR42","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/S0020-7519(97)00079-9","volume":"27","author":"GA Butcher","year":"1997","unstructured":"Butcher, G. A. Antimalarial drugs and the mosquito transmission of Plasmodium. Int. J. Parasitol. 27, 975\u2013987 (1997).","journal-title":"Int. J. Parasitol."},{"key":"BFsrep18704_CR43","doi-asserted-by":"publisher","first-page":"111","DOI":"10.4269\/ajtmh.2003.68.111","volume":"68","author":"GA Butcher","year":"2003","unstructured":"Butcher, G. A. & Sinden, R. E. Persistence of atovaquone in human sera following treatment: inhibition of P. falciparum development in vivo and in vitro. Am J Trop Med Hyg 68, 111\u2013114 (2003).","journal-title":"Am J Trop Med Hyg"},{"key":"BFsrep18704_CR44","doi-asserted-by":"publisher","first-page":"3018","DOI":"10.1073\/pnas.87.8.3018","volume":"87","author":"DS Peterson","year":"1990","unstructured":"Peterson, D. S., Milhous, W. K. & Wellems, T. E. Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proc. Natl. Acad. Sci. USA 87, 3018\u20133022 (1990).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep18704_CR45","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1128\/AAC.03942-14","volume":"59","author":"LM Upton","year":"2015","unstructured":"Upton, L. M. et al. Lead clinical and preclinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations. Antimicrob Agents. Chemother. 59, 490\u2013497 (2015).","journal-title":"Antimicrob Agents. Chemother."},{"key":"BFsrep18704_CR46","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","volume":"46","author":"CA Lipinski","year":"2001","unstructured":"Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev. 46, 3\u201326 (2001).","journal-title":"Adv. Drug Del. Rev."},{"key":"BFsrep18704_CR47","doi-asserted-by":"publisher","first-page":"e62906","DOI":"10.1371\/journal.pone.0062906","volume":"8","author":"T Spangenberg","year":"2013","unstructured":"Spangenberg, T. et al. The open access malaria box: a drug discovery catalyst for neglected diseases. PloS one 8, e62906 (2013).","journal-title":"PloS one"},{"key":"BFsrep18704_CR48","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nature12782","volume":"504","author":"CW McNamara","year":"2013","unstructured":"McNamara, C. W. et al. Targeting Plasmodium PI(4)K to eliminate malaria. Nature 504, 248\u2013253 (2013).","journal-title":"Nature"},{"key":"BFsrep18704_CR49","doi-asserted-by":"publisher","first-page":"296ra111","DOI":"10.1126\/scitranslmed.aaa6645","volume":"7","author":"MA Phillips","year":"2015","unstructured":"Phillips, M. A. et al. A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci. Transl. Med. 7, 296ra111 (2015).","journal-title":"Sci. Transl. Med."},{"key":"BFsrep18704_CR50","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nature14451","volume":"522","author":"B Baragana","year":"2015","unstructured":"Baragana, B. et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature 522, 315\u2013320 (2015).","journal-title":"Nature"},{"key":"BFsrep18704_CR51","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/nrd4573","volume":"14","author":"TNC Wells","year":"2015","unstructured":"Wells, T. N. C., Van Huijsduijnen, R. H. & Van Voorhis, W. C. Malaria medicines: a glass half full? Nat. Rev. Drug Discov. 14, 424\u2013442 (2015).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFsrep18704_CR52","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1111\/j.1365-2125.2012.04368.x","volume":"75","author":"JJ Moehrle","year":"2013","unstructured":"Moehrle, J. J. et al. First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials. Br. J. Clin. Pharmacol. 75, 524\u2013537 (2013).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"BFsrep18704_CR53","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/1475-2875-12-187","volume":"12","author":"JN Burrows","year":"2013","unstructured":"Burrows, J. N., Van Huijsduijnen, R. H., M\u00f6hrle, J. J., Oeuvray, C. & Wells, T. N. C. Designing the next generation of medicines for malaria control and eradication. Malar J. 12, 187 (2013).","journal-title":"Malar J."},{"key":"BFsrep18704_CR54","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/294364a0","volume":"294","author":"T Ifediba","year":"1981","unstructured":"Ifediba, T. & Vanderberg, J. P. Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature 294, 364\u2013366 (1981).","journal-title":"Nature"},{"key":"BFsrep18704_CR55","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1017\/S0031182000062065","volume":"98","author":"T Ponnudurai","year":"1989","unstructured":"Ponnudurai, T. et al. Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes. Parasitology 98 Pt 2, 165\u2013173 (1989).","journal-title":"Parasitology"},{"key":"BFsrep18704_CR56","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/0035-9203(82)90116-X","volume":"76","author":"T Ponnudurai","year":"1982","unstructured":"Ponnudurai, T., Lensen, A. H. W., Leeuwenberg, A. D. E. M. & Meuwissen, J. H. E. T. Cultivation of fertile Plasmodium falciparum gametocytes in semi-automated systems. 1. Static cultures. Trans R Soc Trop Med Hyg 76, 812\u2013818 (1982).","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"BFsrep18704_CR57","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.molbiopara.2006.06.014","volume":"150","author":"AG Maier","year":"2006","unstructured":"Maier, A. G., Braks, J. A. M., Waters, A. P. & Cowman, A. F. Negative selection using yeast cytosine deaminase\/uracil phosphoribosyl transferase in Plasmodium falciparum for targeted gene deletion by double crossover recombination. Mol. Biochem. Parasitol. 150, 118\u2013121 (2006).","journal-title":"Mol. Biochem. Parasitol."},{"key":"BFsrep18704_CR58","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0020-7519(01)00345-9","volume":"32","author":"MT Duraisingh","year":"2002","unstructured":"Duraisingh, M. T., Triglia, T. & Cowman, A. F. Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination. Int. J. Parasitol. 32, 81\u201389 (2002).","journal-title":"Int. J. Parasitol."},{"key":"BFsrep18704_CR59","doi-asserted-by":"publisher","first-page":"10931","DOI":"10.1073\/pnas.94.20.10931","volume":"94","author":"DA Fidock","year":"1997","unstructured":"Fidock, D. A. & Wellems, T. E. Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of\u2009proguanil. Proc. Natl. Acad. Sci. USA 94, 10931\u201310936 (1997).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep18704_CR60","doi-asserted-by":"publisher","first-page":"e15121","DOI":"10.1371\/journal.pone.0015121","volume":"5","author":"BCL van Schaijk","year":"2010","unstructured":"van Schaijk, B. C. L., Vos, M. W., Janse, C. J., Sauerwein, R. W. & Khan, S. M. Removal of Heterologous Sequences from Plasmodium falciparum Mutants Using FLPe-Recombinase. PLoS ONE 5, e15121 (2010).","journal-title":"PLoS ONE"},{"key":"BFsrep18704_CR61","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.molbiopara.2005.09.007","volume":"145","author":"CJ Janse","year":"2006","unstructured":"Janse, C. J. et al. High efficiency transfection of Plasmodium berghei facilitates novel selection procedures. Mol. Biochem. Parasitol. 145, 60\u201370 (2006).","journal-title":"Mol. Biochem. Parasitol."},{"key":"BFsrep18704_CR62","unstructured":"Thaithong, S. In Application of genetic engineering to research on tropical disease pathogens with special reference to Plasmodia (ed S. Panjim, Wilairat, P., Yuthavong, Y. ) 379\u2013387 (1985)."},{"key":"BFsrep18704_CR63","doi-asserted-by":"publisher","first-page":"8716","DOI":"10.1073\/pnas.96.15.8716","volume":"96","author":"CB Mamoun","year":"1999","unstructured":"Mamoun, C. B., Gluzman, I. Y., Goyard, S., Beverley, S. M. & Goldberg, D. E. A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 96, 8716\u20138720 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep18704_CR64","unstructured":"Ponnudurai, T. In Parasitology (ed A. E. R. Taylor, Baker, J. R. ) 153\u2013179 (London and New York, Academic Press, 1987)."},{"key":"BFsrep18704_CR65","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1017\/S0031182000062065","volume":"98","author":"T Ponnudurai","year":"1989","unstructured":"Ponnudurai, T. et al. Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes. Parasitology 98, 165\u2013173 (1989).","journal-title":"Parasitology"},{"key":"BFsrep18704_CR66","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.tree.2008.10.008","volume":"24","author":"BM Bolker","year":"2009","unstructured":"Bolker, B. M. et al. Generalized linear mixed models: a practical guide for ecology and evolution. Trends. Ecol. Evol. (Personal edition) 24, 127\u2013135 (2009).","journal-title":"Trends. Ecol. Evol. (Personal edition)"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep18704","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep18704.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep18704.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:56:02Z","timestamp":1672966562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep18704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,21]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,11,22]]}},"alternative-id":["BFsrep18704"],"URL":"https:\/\/doi.org\/10.1038\/srep18704","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,21]]},"assertion":[{"value":"21 September 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"KJD and RWS own stock in TropIQ Health Sciences. All other authors have no competing financial interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18704"}}