{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:49:03Z","timestamp":1753890543260,"version":"3.41.2"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Process # 306036\/2019-3, Process # 311726\/2021-6"],"award-info":[{"award-number":["Process # 306036\/2019-3, Process # 311726\/2021-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, <jats:italic>Plasmodium<\/jats:italic> has acquired multidrug resistance, including the emergence of <jats:italic>P. falciparum<\/jats:italic> strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of <jats:italic>Plasmodium<\/jats:italic>. The tested compound in the <jats:italic>in vitro<\/jats:italic> assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity <jats:italic>in vitro<\/jats:italic> against chloroquine-resistant <jats:italic>P. falciparum<\/jats:italic> W2 strain. The mice model of <jats:italic>P. berghei<\/jats:italic> ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of <jats:italic>Anopheles aquasalis<\/jats:italic> with <jats:italic>P. vivax<\/jats:italic> infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia <jats:italic>in vitro<\/jats:italic>, being considered a molecule with high antiplasmodial activity and low toxicity. The <jats:italic>in vivo<\/jats:italic> analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of <jats:italic>P. berghei<\/jats:italic> ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of <jats:italic>P. vivax<\/jats:italic> in <jats:italic>A. aquasalis<\/jats:italic>, leading to a decrease in the number of oocysts recovered from the mosquitoes\u2019 midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of <jats:italic>P. vivax<\/jats:italic> infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and\/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite.<\/jats:p>","DOI":"10.3389\/fcimb.2022.1047269","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:39:15Z","timestamp":1669869555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex"],"prefix":"10.3389","volume":"12","author":[{"given":"Camila Martins Gomes","family":"Morais","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramayana Morais de Medeiros","family":"Brito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Weselucha-Birczy\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeska Santana de Sena","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordam William","family":"Pereira-Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Menezes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe Arley Costa","family":"Pessoa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martyna","family":"Kucharska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malwina","family":"Birczy\u0144ska-Zych","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia Mar\u00eda","family":"R\u00edos-Vel\u00e1squez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valter Ferreira de","family":"Andrade-Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"B1","unstructured":"Andrade-NetoV. F.\n          Belo Horizonte (MGFederal University of Minas GeraisAtividade antimal\u00e1rica de extratos brutos, fra\u00e7\u00f5es semi-purificadas e de compostos quimicamente definidos isolados de plantas utilizadas Na medicina popular2000"},{"key":"B2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/s0378-8741(03)00141-7","article-title":"Antimalarial activity of Cinchona-like plants udes to treat fever and mal\u00e1ria in Brazil","volume":"87","author":"Andradre-Neto","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.ijpara.2012.02.004","article-title":"Malaria parasite colonisation of the mosquito midgut \u2013 placing the Plasmodium ookinete centre stage","volume":"42","author":"Angrisano","year":"2012","journal-title":"Int. J. Parasitol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.2174\/1568026616999160215151704","article-title":"Copper homeostasis for the developmental progression of intraerythrocytic malarial parasite","volume":"16","author":"Asahi","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N Engl. J. Med."},{"key":"B6","unstructured":"Mal\u00e1ria \u2013 BrasilMinist\u00e9rio da Sa\u00fade2022"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009795","article-title":"Anopheles aquasalis infected by Plasmodium vivax displays unique gene expression profiles when compared to other malaria vectors and plasmodia","volume":"5","author":"Bahia","year":"2010","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","first-page":"6857","DOI":"10.1016\/j.bmc.2010.07.039","article-title":"Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities","volume":"18","author":"Bahl","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1056\/NEJMra043207","article-title":"Effectiveness of antimalarials drugs","volume":"352","author":"Baird","year":"2005","journal-title":"N Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.pt.2005.09.012","article-title":"Spreading the seeds of million-murdering death: metamorphoses of malaria in the mosquito","volume":"21","author":"Baton","year":"2005","journal-title":"Trends Parasitol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3875","DOI":"10.2147\/DDDT.S265602","article-title":"Recent progress in the development of new antimalarial drugs with novel targets","volume":"14","author":"Belete","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.pt.2022.01.011","article-title":"Transmission-blocking drugs for malaria elimination","volume":"38","author":"Birkholtz","year":"2022","journal-title":"Trends Parasitol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1038","DOI":"10.1016\/S2214-109X(17)30333-9","article-title":"Outbreak of human malaria caused by Plasmodium simium in the Atlantic forest in Rio de Janeiro: a molecular epidemiological investigation","volume":"5","author":"Brasil","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1125\/AAC.01472-05","article-title":"Transmission-blocking activities of quinine, primaquine, and artesunate","volume":"50","author":"Chotivanich","year":"2006","journal-title":"Antimacrob. Agents Chemother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.ijpara.2012.08.007","article-title":"On the pathogenesis of Plasmodium vivax malaria: perspectives from the Brazilian field","volume":"42","author":"Costa","year":"2012","journal-title":"Int. J. Parasitol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"12181","DOI":"10.1021\/ic402341n","article-title":"Preface for the f\u00f3rum on metals on medicine and health: New opportunities and approaches to improving health","volume":"52","author":"Crans","year":"2013","journal-title":"Inorg. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1586\/eri.09.68","article-title":"Discovery, mechanisms of action and combination therapy of artemisinin","volume":"7","author":"Cui","year":"2009","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.1016\/j.bmc.2012.03.04","article-title":"Investigating the activity of quinine analogues versus chloroquine resistant Plasmodium falciparum","volume":"20","author":"Dinio","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"455e467","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin resistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N Engl. J. Med."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760200513","article-title":"Transmission-blocking compound against Plasmodium vivax using P. berghei as an initial screening","volume":"116","author":"Fabbri","year":"2021","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"B21","first-page":"48","article-title":"Dual attribute continuous monitoring of cell proliferation\/cytotoxicity","volume":"11","author":"Fields","year":"1993","journal-title":"Am. Biotechnol. Lab."},{"key":"B22","doi-asserted-by":"publisher","first-page":"270","DOI":"10.2174\/138161213804070357","article-title":"Antimalarial drug resistance and early drug discovery","volume":"19","author":"Garcia-Bustos","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1586\/eri.09.93","article-title":"Plasmodium falciparum: new molecular targets with potential for antimalarial drug development","volume":"7","author":"Gardiner","year":"2009","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0020-1693-(03)00047-1","article-title":"Synthesis and characterization of copper(II) complexes of pyridine-2-carboxamidrazones as potent antimalarial agents","volume":"349","author":"Gokhale","year":"2003","journal-title":"Inorg. Chim. Acta"},{"key":"B25","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1015\/j.bmcl.2005.09.061","article-title":"Metalloantimalarials: Synthesis, X-ray crystal structureof potent antimalarial copper (II) complex of arylazo-4-hydroxy-1,2-naphthoquinone","volume":"16","author":"Gokhale","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-3-642-69254-3_2","article-title":"Quinine and quinine analogues","volume-title":"Antimalarial drugs II. handbook of experimental pharmacology","author":"Hofheinz","year":"1984"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1016\/s0140-6736(81)92239-x","article-title":"Resistance of Plasmodium falciparum malaria to sulfadoxine-pyrimethamine (\u2018Fansidar\u2019) in a refugee camp in Thailand","volume":"317","author":"Hurwitz","year":"1981","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1590\/S0074-02762001000800002","article-title":"The search for new antimalarial drugs from plants used to treat fever and malaria or plants randomly selected: a review","volume":"96","author":"Krettli","year":"2001","journal-title":"Mem. Ins. Oswaldo Cruz"},{"key":"B29","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/0035-9203(87)90003-4","article-title":"The antimalarial action on plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress","volume":"5","author":"Krungkrai","year":"1987","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-12","article-title":"Understanding the clinical spectrum of complicated Plasmodium vivax malaria: a systematic review on the contributions of the Brazilian literature","volume":"11","author":"Lacerda","year":"2012","journal-title":"Malar. J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"418","DOI":"10.2307\/3280287","article-title":"Synchronization of Plasmodium falciparum erythrocytic stages in culture","volume":"65","author":"Lambros","year":"1979","journal-title":"J. Parasitol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1056\/NEJMc1612765","article-title":"Emergence of indigenous artemisininresistant Plasmodium falciparum in Africa","volume":"376","author":"Lu","year":"2017","journal-title":"N Engl. J. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.ccr.2014.08.002","article-title":"Noble metals in medicine: latest advances","volume":"284","author":"Medici","year":"2015","journal-title":"Coord. Chem. Rev."},{"key":"B34","first-page":"577","article-title":"Antimalarial ethnopharmacology in the Brazilian Amazon","volume":"35","author":"Meneguetti","year":"2014","journal-title":"Rev. Ci\u00eanc Farm Basica Apl."},{"key":"B35","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s00775-009-0610-9","article-title":"Antimalarial evaluation of copper(II) nanohybrid solids: inhibition of plasmepsin II, a hemoglobin-degrading malarial aspartic protease from Plasmodium falciparum","volume":"15","author":"Mohapatra","year":"2010","journal-title":"J. Biol. Inorg. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"5","DOI":"10.4269\/ajtmh.1961.10.5","article-title":"Observations on two Plasmodium falciparum infections with an abnormal response to chloroquine","volume":"10","author":"Moore","year":"1961","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B37","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.actatropica.2011.03.005","article-title":"Anti-malarial drug formulations and novel delivery systems: A review","volume":"118","author":"Murambiwaa","year":"2011","journal-title":"Acta Trop."},{"key":"B38","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1586\/ecp.13.17","article-title":"Emerging artemisinin resistance in the border areas of Thailand","volume":"6","author":"Na-Bangchang","year":"2013","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.drudis.2010.10.005","article-title":"Metal-based drugs for malaria, trypanosomiasis and leishmaniasis: recent achievements and perspectives","volume":"15","author":"Navarro","year":"2010","journal-title":"Drug Discovery Today"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1056\/NEJMc0805011","article-title":"Evidence of artemisinin-resistant malaria in western Cambodia","volume":"359","author":"Noedl","year":"2008","journal-title":"N Engl. J. Med."},{"key":"B41","first-page":"43","article-title":"In vivo antimalarial activity and toxicological studies of some quinoline methanol metal complexes","volume":"3","author":"Obaleye","year":"2009","journal-title":"Adv. Nat. Appl. Sci."},{"volume-title":"Test no. 425: Acute oral toxicity \u2013 up-and-down procedure, OECD guidelines for the testing of chemicals, section 4","year":"2022","key":"B42"},{"key":"B43","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/s0163-7258(00)00115-7","article-title":"Mode of action and mechanisms of resistance for antimalarial drugs","volume":"89","author":"Olliaro","year":"2001","journal-title":"Pharmacol. Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1021\/cr980419w","article-title":"Medicinal inorganic chemistry:\u2009 introduction","volume":"99","author":"Orvig","year":"1999","journal-title":"Chem. Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/0169-4758(87)90147-5","article-title":"Spread of chloroquine resistance in Plasmodium falciparum","volume":"3","author":"Payne","year":"1987","journal-title":"Parasitol. Today"},{"key":"B46","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1590\/0037-868212382013","article-title":"Plasmodium vivax malaria: related factors to severity in the state of maranh\u00e3o","volume":"46","author":"Raposo","year":"2013","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-460","article-title":"Experimental Plasmodium vivax infection of key Anopheles species from the Brazilian Amazon","volume":"12","author":"Rios-Vel\u00e1squez","year":"2013","journal-title":"Malar. J."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3450","DOI":"10.1021\/cr3001252","article-title":"Metalloantimalarials","volume":"113","author":"Salas","year":"2013","journal-title":"Chem. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"23","DOI":"10.2174\/1389557043487493","article-title":"Metal complexes as chemotherapeutic agents against tropical diseases: trypanosomiasis, malaria and leishmaniasis","volume":"4","author":"Sanchez-Delgado","year":"2004","journal-title":"Mini Rev. Med. Chem."},{"key":"B50","first-page":"52","article-title":"Transition metal-based antimalarial","volume":"3","author":"Sekhon","year":"2012","journal-title":"Am. J. Pharm. Educ. Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"124","DOI":"10.15835\/nbha3926847","article-title":"Antibacterial activity of copper and cobalt amino acids complexes","volume":"39","author":"Stanila","year":"2011","journal-title":"Not. Bot. Horti. Agrobot. Cluj-Na."},{"key":"B52","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1021\/ja00235a007","article-title":"Orientation and mobility of a copper-planar complex in a lipid bilayer","volume":"109","author":"Subczynski","year":"1987","journal-title":"J. Am. Chem. Soc"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jinorgbio.2016.10.004","article-title":"Novel metalloantimalarials: Transmission blocking effects of water soluble Cu(I), Ag(I) and Au(I) phosphane complexes on the murine malaria parasite Plasmodium berghei","volume":"166","author":"Tapanelli","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"B54","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1125\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011880","article-title":"An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia","volume":"5","author":"Valecha","year":"2010","journal-title":"PloS One"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1038\/s41564-0147-0007-4","article-title":"Hexahydroquinolines are antimalarial candidates with potent blood stage and transmission-blocking","volume":"2","author":"Vanaerschot","year":"2017","journal-title":"Nat. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.4155\/fmc-2019-0225","article-title":"Recent advances in transmission-blocking drugs for malaria elimination","volume":"11","author":"Wadi","year":"2019","journal-title":"Future Med. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1016\/s0140-6736(81)91364-7","article-title":"Cinchona alkaloids and malaria","volume":"12","author":"Warhurst","year":"1981","journal-title":"Lancet"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1007\/s00775-015-1307-x","article-title":"SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex","volume":"20","author":"Weintraub","year":"2015","journal-title":"J. Inorg. Chem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.vibspec.2004.01.011","article-title":"Aggregation phenomena of cinchonine in aqueous solutions observed and analysed by 2D FT-raman spectroscopy","volume":"35","author":"Weselucha-Birczynska","year":"2004","journal-title":"Vib. Spectrosc."},{"key":"B61","doi-asserted-by":"publisher","first-page":"4526","DOI":"10.1021\/ic001402a","article-title":"Flexibility of CuCl4-tetrahedra in bis[cinchoninium tetrachlorocuprate(II)] trihydrate single crystals. X-ray diffraction and EPR studies","volume":"40","author":"Weselucha-Birczynska","year":"2001","journal-title":"Inorg. Chem."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/1475-11-418","article-title":"Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common","volume":"11","author":"White","year":"2012","journal-title":"Malar. J."},{"key":"B63","unstructured":"Policy brief on single-dose primaquine as a gametocytocide in plasmodium falciparum malaria2018"},{"volume-title":"World malaria report","year":"2021","key":"B64"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/S0140-6736(09)61856-0","article-title":"Artemisinin resistance on the Thai-Cambodian border","volume":"374","author":"Yeung","year":"2009","journal-title":"Lancet"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.1047269\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:39:23Z","timestamp":1669869563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.1047269\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,1]]},"references-count":65,"alternative-id":["10.3389\/fcimb.2022.1047269"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.1047269","relation":{},"ISSN":["2235-2988"],"issn-type":[{"type":"electronic","value":"2235-2988"}],"subject":[],"published":{"date-parts":[[2022,12,1]]},"article-number":"1047269"}}