{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:07:44Z","timestamp":1790554064066,"version":"4.1.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19 AI089672"],"award-info":[{"award-number":["U19 AI089672"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43 TW006571"],"award-info":[{"award-number":["D43 TW006571"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The malaria elimination plan of the Greater Mekong Subregion (GMS) is jeopardized by the increasing number of <jats:italic>Plasmodium vivax<\/jats:italic> infections and emergence of parasite strains with reduced susceptibility to the frontline drug treatment chloroquine\/primaquine. This study aimed to determine the evolution of the <jats:italic>P. vivax multidrug resistance 1<\/jats:italic> (<jats:italic>Pvmdr1<\/jats:italic>) gene in <jats:italic>P. vivax<\/jats:italic> parasites isolated from the China\u2013Myanmar border area during the major phase of elimination.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Clinical isolates were collected from 275 <jats:italic>P. vivax<\/jats:italic> patients in 2008, 2012\u20132013 and 2015 in the China\u2013Myanmar border area and from 55 patients in central China. Comparison was made with parasites from three border regions of Thailand.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, genetic diversity of the <jats:italic>Pvmdr1<\/jats:italic> was relatively high in all border regions, and over the seven years in the China\u2013Myanmar border, though slight temporal fluctuation was observed. Single nucleotide polymorphisms previously implicated in reduced chloroquine sensitivity were detected. In particular, M908L approached fixation in the China\u2013Myanmar border area. The Y976F mutation sharply decreased from 18.5% in 2008 to 1.5% in 2012\u20132013 and disappeared in 2015, whereas F1076L steadily increased from 33.3% in 2008 to 77.8% in 2015. While neutrality tests suggested the action of purifying selection on the <jats:italic>pvmdr1<\/jats:italic> gene, several likelihood-based algorithms detected positive as well as purifying selections operating on specific amino acids including M908L, T958M and F1076L. Fixation and selection of the nonsynonymous mutations are differently distributed across the three border regions and central China. Comparison with the global <jats:italic>P. vivax<\/jats:italic> populations clearly indicated clustering of haplotypes according to geographic locations. It is noteworthy that the temperate-zone parasites from central China were completely separated from the parasites from other parts of the GMS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study showed that <jats:italic>P. vivax<\/jats:italic> populations in the China\u2013Myanmar border has experienced major changes in the Pvmdr1 residues proposed to be associated with chloroquine resistance, suggesting that drug selection may play an important role in the evolution of this gene in the parasite populations.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13071-020-3934-5","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T18:03:08Z","timestamp":1581530588000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination"],"prefix":"10.1186","volume":"13","author":[{"given":"Huguette Gaelle","family":"Ngassa Mbenda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza Amber","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerayuth","family":"Kittichai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jetsumon","family":"Sattabongkot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaming","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-1974","authenticated-orcid":false,"given":"Liwang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"3934_CR1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.ijpara.2016.06.006","volume":"47","author":"JK Baird","year":"2017","unstructured":"Baird JK. Asia-Pacific malaria is singular, pervasive, diverse and invisible. Int J Parasitol. 2017;47:371\u20137.","journal-title":"Int J Parasitol."},{"key":"3934_CR2","doi-asserted-by":"publisher","first-page":"e2882","DOI":"10.1371\/journal.pntd.0002882","volume":"8","author":"AT Bright","year":"2014","unstructured":"Bright AT, Manary MJ, Tewhey R, Arango EM, Wang T, Schork NJ, et al. A high resolution case study of a patient with recurrent Plasmodium vivax infections shows that relapses were caused by meiotic siblings. PLoS Negl Trop Dis. 2014;8:e2882.","journal-title":"PLoS Negl Trop Dis."},{"key":"3934_CR3","unstructured":"WHO. World malaria report 2018. Geneva: World Health Organisation; 2018. https:\/\/www.who.int\/malaria\/publications\/world-malaria-report-2018\/en\/. Accessed 29 Jan 2020."},{"key":"3934_CR4","doi-asserted-by":"publisher","first-page":"4","DOI":"10.4269\/ajtmh.16-0160","volume":"95","author":"PL Olliaro","year":"2016","unstructured":"Olliaro PL, Barnwell JW, Barry A, Mendis K, Mueller I, Reeder JC, et al. Implications of Plasmodium vivax biology for control, elimination, and research. Am J Trop Med Hyg. 2016;95:4\u201314.","journal-title":"Am J Trop Med Hyg."},{"key":"3934_CR5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.actatropica.2011.02.016","volume":"121","author":"L Cui","year":"2012","unstructured":"Cui L, Yan G, Sattabongkot J, Cao Y, Chen B, Chen X, et al. Malaria in the Greater Mekong Subregion: heterogeneity and complexity. Acta Trop. 2012;121:227\u201339.","journal-title":"Acta Trop."},{"key":"3934_CR6","first-page":"674","volume":"40","author":"C Delacollette","year":"2009","unstructured":"Delacollette C, D\u2019Souza C, Christophel E, Thimasarn K, Abdur R, Bell D, et al. Malaria trends and challenges in the Greater Mekong Subregion. Southeast Asian J Trop Med Public Health. 2009;40:674\u201391.","journal-title":"Southeast Asian J Trop Med Public Health."},{"key":"3934_CR7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1475-2875-11-14","volume":"11","author":"A Arnott","year":"2012","unstructured":"Arnott A, Barry AE, Reeder JC. Understanding the population genetics of Plasmodium vivax is essential for malaria control and elimination. Malar J. 2012;11:14.","journal-title":"Malar J."},{"key":"3934_CR8","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1128\/CMR.00008-09","volume":"22","author":"JK Baird","year":"2009","unstructured":"Baird JK. Resistance to therapies for infection by Plasmodium vivax. Clin Microbiol Rev. 2009;22:508\u201334.","journal-title":"Clin Microbiol Rev."},{"key":"3934_CR9","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/S1473-3099(14)70855-2","volume":"14","author":"RN Price","year":"2014","unstructured":"Price RN, von Seidlein L, Valecha N, Nosten F, Baird JK, White NJ. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14:982\u201391.","journal-title":"Lancet Infect Dis."},{"key":"3934_CR10","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1093\/cid\/ciy319","volume":"67","author":"CS Chu","year":"2018","unstructured":"Chu CS, Phyo AP, Lwin KM, Win HH, San T, Aung AA, et al. Comparison of the cumulative efficacy and safety of chloroquine, artesunate, and chloroquine-primaquine in Plasmodium vivax malaria. Clin Infect Dis. 2018;67:1543\u20139.","journal-title":"Clin Infect Dis."},{"key":"3934_CR11","doi-asserted-by":"publisher","first-page":"e0157666","DOI":"10.1371\/journal.pone.0157666","volume":"11","author":"K Saravu","year":"2016","unstructured":"Saravu K, Kumar R, Ashok H, Kundapura P, Kamath V, Kamath A, et al. Therapeutic assessment of chloroquine-primaquine combined regimen in adult cohort of Plasmodium vivax malaria from primary care centres in southwestern India. PLoS ONE. 2016;11:e0157666.","journal-title":"PLoS ONE."},{"key":"3934_CR12","doi-asserted-by":"publisher","first-page":"789","DOI":"10.2307\/3283259","volume":"80","author":"RD Cooper","year":"1994","unstructured":"Cooper RD. Studies of a chloroquine-resistant strain of Plasmodium vivax from Papua New Guinea in Aotus and Anopheles farauti s.l. J Parasitol. 1994;80:789\u201395.","journal-title":"J Parasitol."},{"key":"3934_CR13","doi-asserted-by":"publisher","first-page":"4075","DOI":"10.1128\/AAC.48.11.4075-4083.2004","volume":"48","author":"JK Baird","year":"2004","unstructured":"Baird JK. Chloroquine resistance in Plasmodium vivax. Antimicrob Agents Chemother. 2004;48:4075\u201383.","journal-title":"Antimicrob Agents Chemother."},{"key":"3934_CR14","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.3201\/eid1307.061386","volume":"13","author":"FS de Santana Filho","year":"2007","unstructured":"de Santana Filho FS, Arcanjo AR, Chehuan YM, Costa MR, Martinez-Espinosa FE, Vieira JL, et al. Chloroquine-resistant Plasmodium vivax, Brazilian Amazon. Emerg Infect Dis. 2007;13:1125\u20136.","journal-title":"Emerg Infect Dis."},{"key":"3934_CR15","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/j.1365-3156.2007.01978.x","volume":"13","author":"JP Guthmann","year":"2008","unstructured":"Guthmann JP, Pittet A, Lesage A, Imwong M, Lindegardh N, Min Lwin M, et al. Plasmodium vivax resistance to chloroquine in Dawei, southern Myanmar. Trop Med Int Health. 2008;13:91\u20138.","journal-title":"Trop Med Int Health."},{"key":"3934_CR16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1756-3305-4-46","volume":"4","author":"T Ketema","year":"2011","unstructured":"Ketema T, Getahun K, Bacha K. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia. Parasit Vectors. 2011;4:46.","journal-title":"Parasit Vectors."},{"key":"3934_CR17","doi-asserted-by":"publisher","first-page":"600","DOI":"10.4269\/ajtmh.2009.09-0102","volume":"81","author":"SW Lee","year":"2009","unstructured":"Lee SW, Lee M, Lee DD, Kim C, Kim YJ, Kim JY, et al. Biological resistance of hydroxychloroquine for Plasmodium vivax malaria in the Republic of Korea. Am J Trop Med Hyg. 2009;81:600\u20134.","journal-title":"Am J Trop Med Hyg."},{"key":"3934_CR18","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.trstmh.2006.06.008","volume":"101","author":"A Ratcliff","year":"2007","unstructured":"Ratcliff A, Siswantoro H, Kenangalem E, Wuwung M, Brockman A, Edstein MD, et al. Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia. Trans R Soc Trop Med Hyg. 2007;101:351\u20139.","journal-title":"Trans R Soc Trop Med Hyg."},{"key":"3934_CR19","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S0035-9203(00)90344-4","volume":"94","author":"RK Singh","year":"2000","unstructured":"Singh RK. Emergence of chloroquine-resistant vivax malaria in south Bihar (India). Trans R Soc Trop Med Hyg. 2000;94:327.","journal-title":"Trans R Soc Trop Med Hyg."},{"key":"3934_CR20","doi-asserted-by":"publisher","first-page":"7411","DOI":"10.1128\/AAC.00791-15","volume":"59","author":"PV Thanh","year":"2015","unstructured":"Thanh PV, Hong NV, Van NV, Louisa M, Baird K, Xa NX, et al. Confirmed Plasmodium vivax resistance to chloroquine in Central Vietnam. Antimicrob Agents Chemother. 2015;59:7411\u20139.","journal-title":"Antimicrob Agents Chemother."},{"key":"3934_CR21","doi-asserted-by":"publisher","first-page":"e128","DOI":"10.1371\/journal.pmed.0050128","volume":"5","author":"E Tjitra","year":"2008","unstructured":"Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, et al. Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med. 2008;5:e128.","journal-title":"PLoS Med."},{"key":"3934_CR22","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1186\/s12936-015-0845-6","volume":"14","author":"DI Chung","year":"2015","unstructured":"Chung DI, Jeong S, Dinzouna-Boutamba SD, Yang HW, Yeo SG, Hong Y, et al. Evaluation of single nucleotide polymorphisms of pvmdr1 and microsatellite genotype in Plasmodium vivax isolates from Republic of Korea military personnel. Malar J. 2015;14:336.","journal-title":"Malar J."},{"key":"3934_CR23","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1186\/1475-2875-13-346","volume":"13","author":"B Huang","year":"2014","unstructured":"Huang B, Huang S, Su XZ, Tong X, Yan J, Li H, et al. Molecular surveillance of pvdhfr, pvdhps, and pvmdr-1 mutations in Plasmodium vivax isolates from Yunnan and Anhui provinces of China. Malar J. 2014;13:346.","journal-title":"Malar J."},{"key":"3934_CR24","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1086\/592451","volume":"198","author":"R Suwanarusk","year":"2008","unstructured":"Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, et al. Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. J Infect Dis. 2008;198:1558\u201364.","journal-title":"J Infect Dis."},{"key":"3934_CR25","doi-asserted-by":"publisher","first-page":"e1089","DOI":"10.1371\/journal.pone.0001089","volume":"2","author":"R Suwanarusk","year":"2007","unstructured":"Suwanarusk R, Russell B, Chavchich M, Chalfein F, Kenangalem E, Kosaisavee V, et al. Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms. PLoS ONE. 2007;2:e1089.","journal-title":"PLoS ONE."},{"key":"3934_CR26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/1475-2875-8-55","volume":"8","author":"C Fernandez-Becerra","year":"2009","unstructured":"Fernandez-Becerra C, Pinazo MJ, Gonzalez A, Alonso PL, del Portillo HA, Gascon J. Increased expression levels of the pvcrt-o and pvmdr1 genes in a patient with severe Plasmodium vivax malaria. Malar J. 2009;8:55.","journal-title":"Malar J."},{"key":"3934_CR27","doi-asserted-by":"publisher","first-page":"e105922","DOI":"10.1371\/journal.pone.0105922","volume":"9","author":"GC Melo","year":"2014","unstructured":"Melo GC, Monteiro WM, Siqueira AM, Silva SR, Magalhaes BM, Alencar AC, et al. Expression levels of pvcrt-o and pvmdr-1 are associated with chloroquine resistance and severe Plasmodium vivax malaria in patients of the Brazilian Amazon. PLoS ONE. 2014;9:e105922.","journal-title":"PLoS ONE."},{"key":"3934_CR28","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/1475-2875-12-226","volume":"12","author":"YF Chehuan","year":"2013","unstructured":"Chehuan YF, Costa MR, Costa JS, Alecrim MG, Nogueira F, Silveira H, et al. In vitro chloroquine resistance for Plasmodium vivax isolates from the western Brazilian Amazon. Malar J. 2013;12:226.","journal-title":"Malar J."},{"key":"3934_CR29","doi-asserted-by":"publisher","first-page":"e0166124","DOI":"10.1371\/journal.pone.0166124","volume":"11","author":"Y Hamedi","year":"2016","unstructured":"Hamedi Y, Sharifi-Sarasiabi K, Dehghan F, Safari R, To S, Handayuni I, et al. Molecular epidemiology of P. vivax in Iran: high diversity and complex sub-structure using neutral markers, but no evidence of Y976F mutation at pvmdr1. PLoS ONE. 2016;11:e0166124.","journal-title":"PLoS ONE."},{"key":"3934_CR30","doi-asserted-by":"publisher","first-page":"e0004196","DOI":"10.1371\/journal.pntd.0004196","volume":"9","author":"ML Schousboe","year":"2015","unstructured":"Schousboe ML, Ranjitkar S, Rajakaruna RS, Amerasinghe PH, Morales F, Pearce R, et al. Multiple origins of mutations in the mdr1 gene\u2014a putative marker of chloroquine resistance in P vivax. PLoS Negl Trop Dis. 2015;9:e0004196.","journal-title":"PLoS Negl Trop Dis."},{"key":"3934_CR31","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/ng.3588","volume":"48","author":"DN Hupalo","year":"2016","unstructured":"Hupalo DN, Luo Z, Melnikov A, Sutton PL, Rogov P, Escalante A, et al. Population genomics studies identify signatures of global dispersal and drug resistance in Plasmodium vivax. Nat Genet. 2016;48:953\u20138.","journal-title":"Nat Genet."},{"key":"3934_CR32","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1038\/ng.2373","volume":"44","author":"DE Neafsey","year":"2012","unstructured":"Neafsey DE, Galinsky K, Jiang RH, Young L, Sykes SM, Saif S, et al. The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum. Nat Genet. 2012;44:1046\u201350.","journal-title":"Nat Genet."},{"key":"3934_CR33","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.meegid.2018.06.027","volume":"64","author":"V Kittichai","year":"2018","unstructured":"Kittichai V, Nguitragool W, Ngassa Mbenda HG, Sattabongkot J, Cui L. Genetic diversity of the Plasmodium vivax multidrug resistance 1 gene in Thai parasite populations. Infect Genet Evol. 2018;64:168\u201377.","journal-title":"Infect Genet Evol."},{"key":"3934_CR34","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.meegid.2018.02.018","volume":"61","author":"HG Ngassa Mbenda","year":"2018","unstructured":"Ngassa Mbenda HG, Zeng W, Bai Y, Siddiqui FA, Yang Z, Cui L. Genetic diversity of the Plasmodium vivax phosphatidylinositol 3-kinase gene in two regions of the China\u2013Myanmar border. Infect Genet Evol. 2018;61:45\u201352.","journal-title":"Infect Genet Evol."},{"key":"3934_CR35","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1128\/AAC.04270-14","volume":"59","author":"L Yuan","year":"2015","unstructured":"Yuan L, Wang Y, Parker DM, Gupta B, Yang Z, Liu H, et al. Therapeutic responses of Plasmodium vivax malaria to chloroquine and primaquine treatment in northeastern Myanmar. Antimicrob Agents Chemother. 2015;59:1230\u20135.","journal-title":"Antimicrob Agents Chemother."},{"key":"3934_CR36","doi-asserted-by":"publisher","first-page":"518","DOI":"10.4269\/ajtmh.1999.61.518","volume":"61","author":"MC Bruce","year":"1999","unstructured":"Bruce MC, Galinski MR, Barnwell JW, Snounou G, Day KP. Polymorphism at the merozoite surface protein-3\u03b1 locus of Plasmodium vivax: global and local diversity. Am J Trop Med Hyg. 1999;61:518\u201325.","journal-title":"Am J Trop Med Hyg."},{"key":"3934_CR37","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.actatropica.2006.10.011","volume":"100","author":"Z Yang","year":"2006","unstructured":"Yang Z, Miao J, Huang Y, Li X, Putaporntip C, Jongwutiwes S, et al. Genetic structures of geographically distinct Plasmodium vivax populations assessed by PCR\/RFLP analysis of the merozoite surface protein 3\u03b2 gene. Acta Trop. 2006;100:205\u201312.","journal-title":"Acta Trop."},{"key":"3934_CR38","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/1471-2105-5-113","volume":"5","author":"RC Edgar","year":"2004","unstructured":"Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics. 2004;5:113.","journal-title":"BMC Bioinformatics."},{"key":"3934_CR39","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1093\/molbev\/msw054","volume":"33","author":"S Kumar","year":"2016","unstructured":"Kumar S, Stecher G, Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33:1870\u20134.","journal-title":"Mol Biol Evol."},{"key":"3934_CR40","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1093\/bioinformatics\/btp187","volume":"25","author":"P Librado","year":"2009","unstructured":"Librado P, Rozas J. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009;25:1451\u20132.","journal-title":"Bioinformatics."},{"key":"3934_CR41","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/genetics\/105.2.437","volume":"105","author":"F Tajima","year":"1983","unstructured":"Tajima F. Evolutionary relationship of DNA sequences in finite populations. Genetics. 1983;105:437\u201360.","journal-title":"Genetics."},{"key":"3934_CR42","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/genetics\/123.3.585","volume":"123","author":"F Tajima","year":"1989","unstructured":"Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989;123:585\u201395.","journal-title":"Genetics."},{"key":"3934_CR43","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/genetics\/133.3.693","volume":"133","author":"YX Fu","year":"1993","unstructured":"Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics. 1993;133:693\u2013709.","journal-title":"Genetics."},{"key":"3934_CR44","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1093\/molbev\/msl204","volume":"24","author":"LB Zhang","year":"2007","unstructured":"Zhang LB, Ge S. Multilocus analysis of nucleotide variation and speciation in Oryza officinalis and its close relatives. Mol Biol Evol. 2007;24:769\u201383.","journal-title":"Mol Biol Evol."},{"key":"3934_CR45","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/351652a0","volume":"351","author":"JH McDonald","year":"1991","unstructured":"McDonald JH, Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991;351:652\u20134.","journal-title":"Nature."},{"key":"3934_CR46","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S0169-5347(00)01994-7","volume":"15","author":"Z Yang","year":"2000","unstructured":"Yang Z, Bielawski JP. Statistical methods for detecting molecular adaptation. Trends Ecol Evol. 2000;15:496\u2013503.","journal-title":"Trends Ecol Evol."},{"key":"3934_CR47","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/978-1-59745-251-9_8","volume":"537","author":"AF Poon","year":"2009","unstructured":"Poon AF, Frost SD, Pond SL. Detecting signatures of selection from DNA sequences using Datamonkey. Methods Mol Biol. 2009;537:163\u201383.","journal-title":"Methods Mol Biol."},{"key":"3934_CR48","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1093\/oxfordjournals.molbev.a004148","volume":"19","author":"Z Yang","year":"2002","unstructured":"Yang Z, Nielsen R. Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol. 2002;19:908\u201317.","journal-title":"Mol Biol Evol."},{"key":"3934_CR49","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1371\/journal.pcbi.0020062","volume":"2","author":"SL Pond","year":"2006","unstructured":"Pond SL, Frost SD, Grossman Z, Gravenor MB, Richman DD, Brown AJ. Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol. 2006;2:e62.","journal-title":"PLoS Comput Biol."},{"key":"3934_CR50","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nmeth.3213","volume":"12","author":"J Yang","year":"2015","unstructured":"Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER suite: protein structure and function prediction. Nat Methods. 2015;12:7\u20138.","journal-title":"Nat Methods."},{"key":"3934_CR51","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1093\/infdis\/jiy188","volume":"218","author":"FA Siddiqui","year":"2018","unstructured":"Siddiqui FA, Cabrera M, Wang M, Brashear A, Kemirembe K, Wang Z, et al. Plasmodium falciparum falcipain-2a polymorphisms in southeast Asia and their association with artemisinin resistance. J Infect Dis. 2018;218:434\u201342.","journal-title":"J Infect Dis."},{"key":"3934_CR52","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.actatropica.2010.08.011","volume":"117","author":"F Lu","year":"2011","unstructured":"Lu F, Lim CS, Nam DH, Kim K, Lin K, Kim TS, et al. Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries. Acta Trop. 2011;117:69\u201375.","journal-title":"Acta Trop."},{"key":"3934_CR53","doi-asserted-by":"publisher","first-page":"e23875","DOI":"10.1371\/journal.pone.0023875","volume":"6","author":"PE Ferreira","year":"2011","unstructured":"Ferreira PE, Holmgren G, Veiga MI, Uhlen P, Kaneko A, Gil JP. PfMDR1: mechanisms of transport modulation by functional polymorphisms. PLoS ONE. 2011;6:e23875.","journal-title":"PLoS ONE."},{"key":"3934_CR54","doi-asserted-by":"crossref","first-page":"437168","DOI":"10.1155\/2013\/437168","volume":"2013","author":"SK Patel","year":"2013","unstructured":"Patel SK, George LB, Prasanth Kumar S, Highland HN, Jasrai YT, Pandya HA, et al. A computational approach towards the understanding of Plasmodium falciparum multidrug resistance protein 1. ISRN Bioinform. 2013;2013:437168.","journal-title":"ISRN Bioinform."},{"key":"3934_CR55","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1093\/molbev\/msi105","volume":"22","author":"SLK Pond","year":"2005","unstructured":"Pond SLK, Frost SD. Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol. 2005;22:1208\u201322.","journal-title":"Mol Biol Evol."},{"key":"3934_CR56","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1093\/molbev\/mst030","volume":"30","author":"B Murrell","year":"2013","unstructured":"Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL, et al. FUBAR: a fast, unconstrained Bayesian approximation for inferring selection. Mol Biol Evol. 2013;30:1196\u2013205.","journal-title":"Mol Biol Evol."},{"key":"3934_CR57","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1093\/bioinformatics\/btq429","volume":"26","author":"W Delport","year":"2010","unstructured":"Delport W, Poon AF, Frost SD, Kosakovsky Pond SL. Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics. 2010;26:2455\u20137.","journal-title":"Bioinformatics."},{"issue":"Suppl. 1","key":"3934_CR58","first-page":"46","volume":"44","author":"S Hewitt","year":"2013","unstructured":"Hewitt S, Delacollette C, Chavez I. Malaria situation in the Greater Mekong Subregion. Southeast Asian J Trop Med Public Health. 2013;44(Suppl. 1):46\u201372 (discussion 306\u20137).","journal-title":"Southeast Asian J Trop Med Public Health."},{"key":"3934_CR59","first-page":"179","volume-title":"Towards malaria elimination: a leap forward","author":"L Cui","year":"2018","unstructured":"Cui L, Cao Y, Kaewkungwal J, Khamsiriwatchara A, Lawpoolsri S, Soe TN, et al. Malaria elimination in the Greater Mekong Subregion: challenges and prospects. In: Manguin S, Dev V, editors. Towards malaria elimination: a leap forward. London: IntechOpen; 2018. p. 179\u2013200."},{"key":"3934_CR60","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1186\/s12936-019-2924-6","volume":"18","author":"J Geng","year":"2019","unstructured":"Geng J, Malla P, Zhang J, Xu S, Li C, Zhao Y, et al. Increasing trends of malaria in a border area of the Greater Mekong Subregion. Malar J. 2019;18:309.","journal-title":"Malar J."},{"key":"3934_CR61","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1093\/infdis\/jix106","volume":"216","author":"E Lo","year":"2017","unstructured":"Lo E, Lam N, Hemming-Schroeder E, Nguyen J, Zhou G, Lee MC, et al. Frequent spread of Plasmodium vivax malaria maintains high genetic diversity at the Myanmar-China border, without distance and landscape barriers. J Infect Dis. 2017;216:1254\u201363.","journal-title":"J Infect Dis."},{"key":"3934_CR62","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ijpddr.2018.04.003","volume":"8","author":"K Tantiamornkul","year":"2018","unstructured":"Tantiamornkul K, Pumpaibool T, Piriyapongsa J, Culleton R, Lek-Uthai U. The prevalence of molecular markers of drug resistance in Plasmodium vivax from the border regions of Thailand in 2008 and 2014. Int J Parasitol Drugs Drug Resist. 2018;8:229\u201337.","journal-title":"Int J Parasitol Drugs Drug Resist."},{"key":"3934_CR63","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1534\/genetics.104.031567","volume":"168","author":"A Das","year":"2004","unstructured":"Das A, Mohanty S, Stephan W. Inferring the population structure and demography of Drosophila ananassae from multilocus data. Genetics. 2004;168:1975\u201385.","journal-title":"Genetics."},{"key":"3934_CR64","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1093\/genetics\/147.2.915","volume":"147","author":"YX Fu","year":"1997","unstructured":"Fu YX. Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics. 1997;147:915\u201325.","journal-title":"Genetics."},{"key":"3934_CR65","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1534\/genetics.107.074732","volume":"176","author":"A Wagner","year":"2007","unstructured":"Wagner A. Rapid detection of positive selection in genes and genomes through variation clusters. Genetics. 2007;176:2451\u201363.","journal-title":"Genetics."},{"key":"3934_CR66","doi-asserted-by":"publisher","first-page":"e0177134","DOI":"10.1371\/journal.pone.0177134","volume":"12","author":"DE Benavente","year":"2017","unstructured":"Benavente DE, Ward Z, Chan W, Mohareb FR, Sutherland CJ, Roper C, et al. Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure. PLoS ONE. 2017;12:e0177134.","journal-title":"PLoS ONE."},{"key":"3934_CR67","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1186\/s13071-016-1899-1","volume":"9","author":"X Zhu","year":"2016","unstructured":"Zhu X, Zhao P, Wang S, Liu F, Liu J, Wang J, et al. Analysis of Pvama1 genes from China\u2013Myanmar border reveals little regional genetic differentiation of Plasmodium vivax populations. Parasit Vectors. 2016;9:614.","journal-title":"Parasit Vectors."},{"key":"3934_CR68","doi-asserted-by":"crossref","first-page":"e01689","DOI":"10.1128\/AAC.01689-16","volume":"61","author":"W Zeng","year":"2017","unstructured":"Zeng W, Bai Y, Wang M, Wang Z, Deng S, Ruan Y, et al. Significant divergence in sensitivity to antimalarial drugs between neighboring Plasmodium falciparum populations along the eastern border of Myanmar. Antimicrob Agents Chemother. 2017;61:e01689\u2013716.","journal-title":"Antimicrob Agents Chemother."},{"key":"3934_CR69","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/S0166-6851(01)00278-X","volume":"115","author":"DJ Conway","year":"2001","unstructured":"Conway DJ, Machado RL, Singh B, Dessert P, Mikes ZS, Povoa MM, et al. Extreme geographical fixation of variation in the Plasmodium falciparum gamete surface protein gene Pfs48\/45 compared with microsatellite loci. Mol Biochem Parasitol. 2001;115:145\u201356.","journal-title":"Mol Biochem Parasitol."},{"key":"3934_CR70","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1186\/s13071-015-1232-4","volume":"8","author":"H Feng","year":"2015","unstructured":"Feng H, Gupta B, Wang M, Zheng W, Zheng L, Zhu X, et al. Genetic diversity of transmission-blocking vaccine candidate Pvs48\/45 in Plasmodium vivax populations in China. Parasit Vectors. 2015;8:615.","journal-title":"Parasit Vectors."},{"key":"3934_CR71","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1534\/genetics.114.166454","volume":"197","author":"AR Rogers","year":"2014","unstructured":"Rogers AR. How population growth affects linkage disequilibrium. Genetics. 2014;197:1329\u201341.","journal-title":"Genetics."},{"key":"3934_CR72","doi-asserted-by":"publisher","first-page":"e1424","DOI":"10.1371\/journal.pntd.0001424","volume":"5","author":"C Koepfli","year":"2011","unstructured":"Koepfli C, Ross A, Kiniboro B, Smith TA, Zimmerman PA, Siba P, et al. Multiplicity and diversity of Plasmodium vivax infections in a highly endemic region in Papua New Guinea. PLoS Negl Trop Dis. 2011;5:e1424.","journal-title":"PLoS Negl Trop Dis."}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-020-3934-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13071-020-3934-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-020-3934-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T10:04:25Z","timestamp":1613037865000},"score":1,"resource":{"primary":{"URL":"https:\/\/parasitesandvectors.biomedcentral.com\/articles\/10.1186\/s13071-020-3934-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,12]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3934"],"URL":"https:\/\/doi.org\/10.1186\/s13071-020-3934-5","relation":{},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,12]]},"assertion":[{"value":"28 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approvals were obtained from the institutional review boards of China Medical University, Kunming Medical University, Mahidol University and Pennsylvania State University. Written consent was obtained from all donors of the blood samples or their guardians.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"67"}}