{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:57:18Z","timestamp":1793365038059,"version":"4.5.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","award":["02202"],"award-info":[{"award-number":["02202"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In 2021 and 2023, the World Health Organization approved RTS,S\/AS01 and R21\/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of <jats:italic>Plasmodium falciparum<\/jats:italic> circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the <jats:italic>Pfcsp<\/jats:italic> genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright\u2019s inbreeding coefficient (F<jats:sub>ws<\/jats:sub>), Wright\u2019s fixation index (F<jats:sub>ST<\/jats:sub>), principal component analysis, nucleotide diversity, and Tajima\u2019s D were used to assess within-host parasite diversity, population structure and natural selection.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Based on F<jats:sub>ws<\/jats:sub> (&lt;\u20090.95), there was high polyclonality (ranging from 69.23% in Nachingwea to 56.9% in Muheza). No population structure was detected in the <jats:italic>Pfcsp<\/jats:italic> gene in the five regions (mean F<jats:sub>ST<\/jats:sub>\u2009=\u20090.0068). The average nucleotide diversity (<jats:bold>\u03c0<\/jats:bold>), nucleotide differentiation (K) and haplotype diversity (Hd) in the five regions were 4.19, 0.973 and 0.0035, respectively. The C-terminal region of <jats:italic>Pfcsp<\/jats:italic> showed high nucleotide diversity at Th2R and Th3R regions. Positive values for the Tajima\u2019s D were observed in the Th2R and Th3R regions consistent with balancing selection. The <jats:italic>Pfcsp<\/jats:italic> C-terminal sequences revealed 50 different haplotypes (H_1 to H_50), with only 2% of sequences matching the 3D7 strain haplotype (H_50). Conversely, with the NF54 strain, the <jats:italic>Pfcsp<\/jats:italic> C-terminal sequences revealed 49 different haplotypes (H_1 to H_49), with only 0.4% of the sequences matching the NF54 strain (Hap_49).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The findings demonstrate high diversity of the <jats:italic>Pfcsp<\/jats:italic> gene with limited population differentiation. The <jats:italic>Pfcsp<\/jats:italic> gene showed positive Tajima\u2019s D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-024-04974-3","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T15:01:52Z","timestamp":1715180512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genetic polymorphism and evidence of signatures of selection in the Plasmodium falciparum circumsporozoite protein gene in Tanzanian regions with different malaria endemicity"],"prefix":"10.1186","volume":"23","author":[{"given":"Beatus M.","family":"Lyimo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Bakari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary R.","family":"Popkin-Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Giesbrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misago D.","family":"Seth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dativa","family":"Pereus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulfa I.","family":"Shabani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramadhan","family":"Moshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Boniface","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine I.","family":"Mandara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Madebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deus S.","family":"Ishengoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"4974_CR1","volume-title":"World malaria report 2021","author":"WHO","year":"2021","unstructured":"WHO. World malaria report 2021. Geneva: World Health Organization; 2021."},{"key":"4974_CR2","unstructured":"WHO. World Malaria Report 2022. Geneva: World Health Organization; 2022. https:\/\/apps.who.int\/iris\/rest\/bitstreams\/1484818\/retrieve. Accessed 10 Dec 2022."},{"key":"4974_CR3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12936-022-04107-8","volume":"21","author":"CL Mitchell","year":"2022","unstructured":"Mitchell CL, Ngasala B, Janko MM, Chacky F, Edwards JK, Pence BW, et al. Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children. Malar J. 2022;21:80.","journal-title":"Malar J"},{"key":"4974_CR4","volume-title":"Global technical strategy for malaria","author":"WHO","year":"2021","unstructured":"WHO. Global technical strategy for malaria. Geneva: World Health Organization; 2021."},{"key":"4974_CR5","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/S0140-6736(19)31139-0","volume":"394","author":"RGA Feachem","year":"2019","unstructured":"Feachem RGA, Chen I, Akbari O, Bertozzi-Villa A, Bhatt S, Binka F, et al. Malaria eradication within a generation: ambitious, achievable, and necessary. Lancet. 2019;394:1056\u2013112.","journal-title":"Lancet"},{"key":"4974_CR6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40249-019-0524-x","volume":"8","author":"S Dhiman","year":"2019","unstructured":"Dhiman S. Are malaria elimination efforts on right track? An analysis of gains achieved and challenges ahead. Infect Dis Poverty. 2019;8:14.","journal-title":"Infect Dis Poverty"},{"key":"4974_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12936-015-0802-4","volume":"14","author":"P Guyant","year":"2015","unstructured":"Guyant P, Corbel V, Gu\u00e9rin PJ, Lautissier A, Nosten F, Boyer S, et al. Past and new challenges for malaria control and elimination: the role of operational research for innovation in designing interventions. Malar J. 2015;14:279.","journal-title":"Malar J"},{"key":"4974_CR8","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12936-020-03315-4","volume":"19","author":"H-Y Huang","year":"2020","unstructured":"Huang H-Y, Liang X-Y, Lin L-Y, Chen J-T, Ehapo CS, Eyi UM, et al. Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis. Malar J. 2020;19:245.","journal-title":"Malar J"},{"key":"4974_CR9","doi-asserted-by":"publisher","first-page":"4880","DOI":"10.1016\/j.vaccine.2010.05.033","volume":"28","author":"S Casares","year":"2010","unstructured":"Casares S, Brumeanu T-D, Richie TL. The RTS, S malaria vaccine. Vaccine. 2010;28:4880\u201394.","journal-title":"Vaccine"},{"key":"4974_CR10","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/ni.2871","volume":"15","author":"WC Koff","year":"2014","unstructured":"Koff WC, Gust ID, Plotkin SA. Toward a human vaccines project. Nat Immunol. 2014;15:589\u201392.","journal-title":"Nat Immunol"},{"key":"4974_CR11","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3390\/vaccines10050713","volume":"10","author":"AY Nadeem","year":"2022","unstructured":"Nadeem AY, Shehzad A, Islam SU, Al-Suhaimi EA, Lee YS. Mosquirix\u2122 RTS, S\/AS01 vaccine development, immunogenicity, and efficacy. Vaccines (Basel). 2022;10:713.","journal-title":"Vaccines (Basel)"},{"key":"4974_CR12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41541-020-0196-3","volume":"5","author":"PE Duffy","year":"2020","unstructured":"Duffy PE, Patrick GJ. Malaria vaccines since 2000: progress, priorities, products. NPJ Vaccines. 2020;5:48.","journal-title":"NPJ Vaccines"},{"key":"4974_CR13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.1365-3024.2011.01340.x","volume":"34","author":"KG Le Roch","year":"2012","unstructured":"Le Roch KG, Chung DWD, Ponts N. Genomics and integrated systems biology in Plasmodium falciparum: a path to malaria control and eradication. Parasite Immunol. 2012;34:50\u201360.","journal-title":"Parasite Immunol"},{"key":"4974_CR14","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1186\/s12936-021-03971-0","volume":"20","author":"NS Mohamed","year":"2021","unstructured":"Mohamed NS, AbdElbagi H, Elsadig AR, Ahmed AE, Mohammed YO, Elssir LT, et al. Assessment of genetic diversity of Plasmodium falciparum circumsporozoite protein in Sudan: the RTS, S leading malaria vaccine candidate. Malar J. 2021;20:436.","journal-title":"Malar J"},{"key":"4974_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.775659","volume":"12","author":"L Kurtovic","year":"2021","unstructured":"Kurtovic L, Drew DR, Dent AE, Kazura JW, Beeson JG. Antibody targets and properties for complement-fixation against the circumsporozoite protein in malaria immunity. Front Immunol. 2021;12: 775659.","journal-title":"Front Immunol"},{"key":"4974_CR16","volume-title":"Guidelines for malaria","author":"WHO","year":"2022","unstructured":"WHO. Guidelines for malaria. Geneva: World Health Organization; 2022."},{"key":"4974_CR17","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1056\/NEJM199701093360202","volume":"336","author":"JA Stoute","year":"1997","unstructured":"Stoute JA, Slaoui M, Heppner DG, Momin P, Kester KE, Desmons P, et al. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria RTS, S. Malaria Vaccine Evaluation Group. N Engl J Med. 1997;336:86\u201391.","journal-title":"N Engl J Med"},{"key":"4974_CR18","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1586\/erv.11.57","volume":"10","author":"JA Regules","year":"2011","unstructured":"Regules JA, Cummings JF, Ockenhouse CF. The RTS, S vaccine candidate for malaria. Expert Rev Vaccines. 2011;10:589\u201399.","journal-title":"Expert Rev Vaccines"},{"key":"4974_CR19","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S1473-3099(11)70100-1","volume":"11","author":"KP Asante","year":"2011","unstructured":"Asante KP, Abdulla S, Agnandji S, Lyimo J, Vekemans J, Soulanoudjingar S, et al. Safety and efficacy of the RTS, S\/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 2011;11:741\u20139.","journal-title":"Lancet Infect Dis"},{"key":"4974_CR20","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1016\/S0140-6736(01)06957-4","volume":"358","author":"KA Bojang","year":"2001","unstructured":"Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, et al. Efficacy of RTS, S\/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet. 2001;358:1927\u201334.","journal-title":"Lancet"},{"key":"4974_CR21","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/S0140-6736(07)61542-6","volume":"370","author":"JJ Aponte","year":"2007","unstructured":"Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, et al. Safety of the RTS, S\/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I\/IIb trial. Lancet. 2007;370:1543\u201351.","journal-title":"Lancet"},{"key":"4974_CR22","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","volume":"386","author":"RTS,S Clinical Trials Partnership","year":"2015","unstructured":"RTS,S Clinical Trials Partnership. Efficacy and safety of RTS, S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015;386:31\u201345.","journal-title":"Lancet"},{"key":"4974_CR23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2147\/VDT.S53028","volume":"6","author":"KP Asante","year":"2016","unstructured":"Asante KP, Adjei G, Enuameh Y, Owusu-Agyei S. RTS, S malaria vaccine development: progress and considerations for postapproval introduction. Vaccine Dev Ther. 2016;6:25\u201352.","journal-title":"Vaccine Dev Ther"},{"key":"4974_CR24","doi-asserted-by":"publisher","first-page":"46621","DOI":"10.1038\/srep46621","volume":"7","author":"KA Collins","year":"2017","unstructured":"Collins KA, Snaith R, Cottingham MG, Gilbert SC, Hill AVS. Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine. Sci Rep. 2017;7:46621.","journal-title":"Sci Rep"},{"key":"4974_CR25","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1126\/science.2988126","volume":"228","author":"WR Ballou","year":"1985","unstructured":"Ballou WR, Rothbard J, Wirtz RA, Gordon DM, Williams JS, Gore RW, et al. Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum. Science. 1985;228:996\u20139.","journal-title":"Science"},{"key":"4974_CR26","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1016\/S0140-6736(21)00943-0","volume":"397","author":"MS Datoo","year":"2021","unstructured":"Datoo MS, Natama MH, Som\u00e9 A, Traor\u00e9 O, Rouamba T, Bellamy D, et al. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021;397:1809\u201318.","journal-title":"Lancet"},{"key":"4974_CR27","unstructured":"Datoo MS, Dicko A, Tinto H, Ou\u00e9draogo JB, Hamaluba M, Olotu A, Beaumont E, Ramos-Lopez F,\nMagloire Natama H, Weston S, et al. A Phase III Randomised Controlled Trial Evaluating the Malaria Vaccine\nCandidate R21\/Matrix-M\u2122 in African Children. https:\/\/papers.ssrn.com\/sol3\/papers.cfm?abstract_id=4584076."},{"issue":"21","key":"4974_CR28","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1056\/NEJMoa1505819","volume":"373","author":"DE Neafsey","year":"2015","unstructured":"Neafsey DE, Juraska M, Bedford T, Benkeser D, Valim C, Griggs A, et al. Genetic diversity and protective efficacy of the RTS, S\/AS01 malaria vaccine. N Engl J Med. 2015;373(21):2025\u201337.","journal-title":"N Engl J Med"},{"key":"4974_CR29","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.vaccine.2020.12.055","volume":"39","author":"S Chaudhury","year":"2021","unstructured":"Chaudhury S, MacGill RS, Early AM, Bolton JS, King CR, Locke E, et al. Breadth of humoral immune responses to the C-terminus of the circumsporozoite protein is associated with protective efficacy induced by the RTS,S malaria vaccine. Vaccine. 2021;39:968\u201375.","journal-title":"Vaccine"},{"key":"4974_CR30","doi-asserted-by":"publisher","first-page":"26784","DOI":"10.1074\/jbc.M104038200","volume":"276","author":"C Pinzon-Ortiz","year":"2001","unstructured":"Pinzon-Ortiz C, Friedman J, Esko J, Sinnis P. The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for plasmodium sporozoite attachment to target cells. J Biol Chem. 2001;276:26784\u201391.","journal-title":"J Biol Chem"},{"key":"4974_CR31","doi-asserted-by":"publisher","first-page":"7092","DOI":"10.1074\/jbc.M106862200","volume":"277","author":"D Rathore","year":"2002","unstructured":"Rathore D, Sacci JB, de la Vega P, McCutchan TF. Binding and invasion of liver cells by Plasmodium falciparum sporozoites. Essential involvement of the amino terminus of circumsporozoite protein. J Biol Chem. 2002;277:7092\u20138.","journal-title":"J Biol Chem"},{"key":"4974_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101783","volume":"9","author":"K Gandhi","year":"2014","unstructured":"Gandhi K, Thera MA, Coulibaly D, Traor\u00e9 K, Guindo AB, Ouattara A, et al. Variation in the circumsporozoite protein of Plasmodium falciparum: vaccine development implications. PLoS ONE. 2014;9: e101783.","journal-title":"PLoS ONE"},{"key":"4974_CR33","doi-asserted-by":"publisher","first-page":"775","DOI":"10.4269\/ajtmh.2012.11-0478","volume":"86","author":"K Gandhi","year":"2012","unstructured":"Gandhi K, Thera MA, Coulibaly D, Traor\u00e9 K, Guindo AB, Doumbo OK, et al. Next generation sequencing to detect variation in the Plasmodium falciparum circumsporozoite protein. Am J Trop Med Hyg. 2012;86:775\u201381.","journal-title":"Am J Trop Med Hyg"},{"key":"4974_CR34","doi-asserted-by":"publisher","first-page":"166","DOI":"10.4269\/ajtmh.1993.49.166","volume":"49","author":"JE Egan","year":"1993","unstructured":"Egan JE, Hoffman SL, Haynes JD, Sadoff JC, Schneider I, et al. Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 1993;49:166\u201373.","journal-title":"Am J Trop Med Hyg"},{"key":"4974_CR35","doi-asserted-by":"publisher","first-page":"26951","DOI":"10.1074\/jbc.M109.013706","volume":"284","author":"ML Plassmeyer","year":"2009","unstructured":"Plassmeyer ML, Reiter K, Shimp RL, Kotova S, Smith PD, Hurt DE, et al. Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate. J Biol Chem. 2009;284:26951\u201363.","journal-title":"J Biol Chem"},{"key":"4974_CR36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008497","volume":"4","author":"AE Barry","year":"2009","unstructured":"Barry AE, Schultz L, Buckee CO, Reeder JC. Contrasting population structures of the genes encoding ten leading vaccine-candidate antigens of the human malaria parasite Plasmodium falciparum. PLoS ONE. 2009;4: e8497.","journal-title":"PLoS ONE"},{"key":"4974_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043430","volume":"7","author":"M Zeeshan","year":"2012","unstructured":"Zeeshan M, Alam MT, Vinayak S, Bora H, Tyagi RK, Alam MS, et al. Genetic variation in the Plasmodium falciparum circumsporozoite protein in India and its relevance to RTS,S malaria vaccine. PLoS ONE. 2012;7: e43430.","journal-title":"PLoS ONE"},{"key":"4974_CR38","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1186\/s12936-018-2513-0","volume":"17","author":"HG L\u00ea","year":"2018","unstructured":"L\u00ea HG, Kang J-M, Moe M, Jun H, Th\u00e1i TL, Lee J, et al. Genetic polymorphism and natural selection of circumsporozoite surface protein in Plasmodium falciparum field isolates from Myanmar. Malar J. 2018;17:361.","journal-title":"Malar J"},{"key":"4974_CR39","first-page":"2","volume":"3","author":"D Ishengoma","year":"2016","unstructured":"Ishengoma D, Shayo A, Mandara C, Baraka V, Madebe R, Ngatunga, et al. The role of malaria rapid diagnostic tests in screening of patients to be enrolled in clinical trials in low malaria transmission settings. Health Syst Policy Res. 2016;3:2.","journal-title":"Health Syst Policy Res"},{"key":"4974_CR40","doi-asserted-by":"publisher","first-page":"42","DOI":"10.12688\/wellcomeopenres.16168.1","volume":"6","author":"A Ahouidi","year":"2021","unstructured":"Ahouidi A, Ali M, Almagro-garcia J, Amambua-ngwa A, Amaratunga C, MalariaGEN, et al. An open dataset of Plasmodium falciparum genome variation in 7000 worldwide samples. Wellcome Open Res. 2021;6:42.","journal-title":"Wellcome Open Res"},{"key":"4974_CR41","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1126\/science.1259423","volume":"345","author":"A Ghansah","year":"2014","unstructured":"Ghansah A, Amenga-Etego L, Amambua-Ngwa A, Andagalu B, Apinjoh T, Bouyou-Akotet M, et al. Monitoring parasite diversity for malaria elimination in sub-Saharan Africa. Science. 2014;345:1297\u20138.","journal-title":"Science"},{"key":"4974_CR42","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1186\/1475-2875-13-376","volume":"13","author":"A Shayo","year":"2014","unstructured":"Shayo A, Mandara CI, Shahada F, Buza J, Lemnge MM, Ishengoma DS. Therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in North-Eastern Tanzania. Malar J. 2014;13:376.","journal-title":"Malar J"},{"key":"4974_CR43","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s12936-018-2409-z","volume":"17","author":"CI Mandara","year":"2018","unstructured":"Mandara CI, Kavishe RA, Gesase S, Mghamba J, Ngadaya E, Mmbuji P, et al. High efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania. Malar J. 2018;17:261.","journal-title":"Malar J"},{"key":"4974_CR44","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1475-2875-11-41","volume":"11","author":"M Venkatesan","year":"2012","unstructured":"Venkatesan M, Amaratunga C, Campino S, Auburn S, Koch O, Lim P, et al. Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples. Malar J. 2012;11:41.","journal-title":"Malar J"},{"key":"4974_CR45","doi-asserted-by":"publisher","first-page":"22","DOI":"10.12688\/wellcomeopenres.18681.1","volume":"8","author":"MalariaGEN","year":"2023","unstructured":"MalariaGEN. Pf7: an open dataset of Plasmodium falciparum genome. Wellcome Open Res. 2023;8:22.","journal-title":"Wellcome Open Res"},{"key":"4974_CR46","doi-asserted-by":"crossref","unstructured":"Jung Y, Han D. BWA-MEME: BWA-MEM emulated with a machine learning approach. BioRxiv. 2021.","DOI":"10.1101\/2021.09.01.457579"},{"key":"4974_CR47","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559\u201375.","journal-title":"Am J Hum Genet"},{"key":"4974_CR48","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297\u2013303.","journal-title":"Genome Res"},{"key":"4974_CR49","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nature11174","volume":"487","author":"M Manske","year":"2012","unstructured":"Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J, Maslen G, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012;487:375\u20139.","journal-title":"Nature"},{"key":"4974_CR50","first-page":"1043","volume":"4","author":"S Lee","year":"2015","unstructured":"Lee S, Harrison A, Tessier N, Tavul L, Miotto O. Assessing clonality in malaria parasites from massively parallel sequencing data. F1000Research. 2015;4:1043.","journal-title":"F1000Research"},{"key":"4974_CR51","first-page":"203","volume-title":"Handbook of statistics","author":"R Chakraborty","year":"1991","unstructured":"Chakraborty R, Danker-Hopfe H. Analysis of population structure: a comparative study of different estimators of wright\u2019s fixation indices. In: Rao CR, Chakraborty R, editors. Handbook of statistics, vol. 8. Elsevier; 1991. p. 203\u201354."},{"key":"4974_CR52","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1093\/molbev\/msx248","volume":"34","author":"J Rozas","year":"2017","unstructured":"Rozas J, Ferrer-Mata A, S\u00e1nchez-DelBarrio JC, Guirao-Rico S, Librado P, Ramos-Onsins SE, et al. Dnasp 6: DNA sequence polymorphism analysis of large data sets. Mol Biol Evol. 2017;34:3299\u2013302.","journal-title":"Mol Biol Evol"},{"key":"4974_CR53","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/oxfordjournals.molbev.a026036","volume":"16","author":"HJ Bandelt","year":"1999","unstructured":"Bandelt HJ, Forster P, R\u00f6hl A. Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol. 1999;16:37\u201348.","journal-title":"Mol Biol Evol"},{"key":"4974_CR54","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","volume":"27","author":"P Danecek","year":"2011","unstructured":"Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011;27:2156\u20138.","journal-title":"Bioinformatics"},{"key":"4974_CR55","doi-asserted-by":"publisher","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":"4974_CR56","doi-asserted-by":"publisher","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":"4974_CR57","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1093\/molbev\/msab120","volume":"38","author":"K Tamura","year":"2021","unstructured":"Tamura K, Stecher G, Kumar S. MEGA11: molecular evolutionary genetics analysis version 11. Mol Biol Evol. 2021;38:3022\u20137.","journal-title":"Mol Biol Evol"},{"key":"4974_CR58","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s12936-020-03250-4","volume":"19","author":"SG Thawer","year":"2020","unstructured":"Thawer SG, Chacky F, Runge M, Reaves E, Mandike R, Lazaro S, et al. Sub-national stratification of malaria risk in mainland Tanzania: a simplified assembly of survey and routine data. Malar J. 2020;19:177.","journal-title":"Malar J"},{"key":"4974_CR59","unstructured":"Ministry of Health, Community Development, Gender, Elderly and Children. National Malaria Strategic Plan 2021\u20132025, Transitioning to malaria elimination in phases. National Malaria Control Programme, Tanzania, 2021."},{"key":"4974_CR60","volume-title":"WHO recommends R21\/Matrix-M vaccine for malaria prevention in updated advice on immunization","author":"World Health Organization","year":"2023","unstructured":"World Health Organization. WHO recommends R21\/Matrix-M vaccine for malaria prevention in updated advice on immunization. Geneva: World Health Organization; 2023."},{"key":"4974_CR61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062427","volume":"8","author":"NR Aragam","year":"2013","unstructured":"Aragam NR, Thayer KM, Nge N, Hoffman I, Martinson F, Kamwendo D, et al. Diversity of T cell epitopes in Plasmodium falciparum circumsporozoite protein likely due to protein-protein interactions. PLoS ONE. 2013;8: e62427.","journal-title":"PLoS ONE"},{"key":"4974_CR62","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/s12936-019-3023-4","volume":"18","author":"JC Pringle","year":"2019","unstructured":"Pringle JC, Wesolowski A, Berube S, Kobayashi T, Gebhardt ME, Mulenga M, et al. High Plasmodium falciparum genetic diversity and temporal stability despite control efforts in high transmission settings along the international border between Zambia and the Democratic Republic of the Congo. Malar J. 2019;18:400.","journal-title":"Malar J"},{"key":"4974_CR63","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1186\/s12936-020-03510-3","volume":"19","author":"EA Amegashie","year":"2020","unstructured":"Amegashie EA, Amenga-Etego L, Adobor C, Ogoti P, Mbogo K, Amambua-Ngwa A, et al. Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana. Malar J. 2020;19:437.","journal-title":"Malar J"},{"key":"4974_CR64","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1186\/s12936-022-04275-7","volume":"21","author":"Z-Q He","year":"2022","unstructured":"He Z-Q, Zhang Q-Q, Wang D, Hu Y-B, Zhou R-M, Qian D, et al. Genetic polymorphism of circumsporozoite protein of Plasmodium falciparum among Chinese migrant workers returning from Africa to Henan Province. Malar J. 2022;21:248.","journal-title":"Malar J"},{"key":"4974_CR65","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1111\/mec.14066","volume":"26","author":"CW Duffy","year":"2017","unstructured":"Duffy CW, Ba H, Assefa S, Ahouidi AD, Deh YB, Tandia A, et al. Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution. Mol Ecol. 2017;26:2880\u201394.","journal-title":"Mol Ecol"},{"key":"4974_CR66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002992","volume":"8","author":"A Amambua-Ngwa","year":"2012","unstructured":"Amambua-Ngwa A, Tetteh KKA, Manske M, Gomez-Escobar N, Stewart LB, Deerhake ME, et al. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites. PLoS Genet. 2012;8: e1002992.","journal-title":"PLoS Genet"},{"key":"4974_CR67","doi-asserted-by":"publisher","first-page":"6622","DOI":"10.1038\/s41598-018-24585-8","volume":"8","author":"JC Pringle","year":"2018","unstructured":"Pringle JC, Carpi G, Almagro-Garcia J, Zhu SJ, Kobayashi T, Mulenga M, et al. RTS, S\/AS01 malaria vaccine mismatch observed among Plasmodium falciparum isolates from southern and central Africa and globally. Sci Rep. 2018;8:6622.","journal-title":"Sci Rep"},{"key":"4974_CR68","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/infdis\/jis329","volume":"206","author":"JA Bailey","year":"2012","unstructured":"Bailey JA, Mvalo T, Aragam N, Weiser M, Congdon S, Kamwendo D, et al. Use of massively parallel pyrosequencing to evaluate the diversity of and selection on Plasmodium falciparum csp T-cell epitopes in Lilongwe. Malawi J Infect Dis. 2012;206:580\u20137.","journal-title":"Malawi J Infect Dis"},{"key":"4974_CR69","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1093\/genetics\/158.4.1505","volume":"158","author":"SD Polley","year":"2001","unstructured":"Polley SD, Conway DJ. Strong diversifying selection on domains of the Plasmodium falciparum apical membrane antigen 1 gene. Genetics. 2001;158:1505\u201312.","journal-title":"Genetics"},{"key":"4974_CR70","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12936-022-04081-1","volume":"21","author":"T Nirmolia","year":"2022","unstructured":"Nirmolia T, Ahmed MA, Sathishkumar V, Sarma NP, Bhattacharyya DR, Mohapatra PK, et al. Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development. Malar J. 2022;21:62.","journal-title":"Malar J"},{"key":"4974_CR71","doi-asserted-by":"publisher","first-page":"16215","DOI":"10.1038\/s41598-021-95442-4","volume":"11","author":"O Ajibola","year":"2021","unstructured":"Ajibola O, Diop MF, Ghansah A, Amenga-Etego L, Golassa L, Apinjoh T, et al. In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations. Sci Rep. 2021;11:16215.","journal-title":"Sci Rep"},{"key":"4974_CR72","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1475-2875-7-93","volume":"7","author":"SM Chenet","year":"2008","unstructured":"Chenet SM, Branch OH, Escalante AA, Lucas CM, Bacon DJ. Genetic diversity of vaccine candidate antigens in Plasmodium falciparum isolates from the Amazon basin of Peru. Malar J. 2008;7:93.","journal-title":"Malar J"},{"key":"4974_CR73","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/1475-2875-10-126","volume":"10","author":"JC Reeder","year":"2011","unstructured":"Reeder JC, Wapling J, Mueller I, Siba PM, Barry AE. Population genetic analysis of the Plasmodium falciparum 6-cys protein Pf38 in Papua New Guinea reveals domain-specific balancing selection. Malar J. 2011;10:126.","journal-title":"Malar J"},{"key":"4974_CR74","unstructured":"DHS. Malaria Indicator Survey 2017; 2018. https:\/\/dhsprogram.com\/pubs\/pdf\/MIS31\/MIS31.pdf. Accessed 15 Jan 2024."}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-024-04974-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-024-04974-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-024-04974-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T15:05:59Z","timestamp":1715180759000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-024-04974-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4974"],"URL":"https:\/\/doi.org\/10.1186\/s12936-024-04974-3","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]},"assertion":[{"value":"31 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study utilized sequence data downloaded from the open-source, MalariaGEN (). The study protocols for the projects that collected the samples were reviewed and approved by the Tanzanian Medical Research Coordinating Committee (MRCC) of the National Institute for Medical Research (NIMR). Permission to conduct the study in Morogoro, Muheza\u2014Tanga, Muleba\u2014Kagera, Nachingwea\u2014Lindi and Ujiji\u2014Kigoma was sought in writing and obtained from the district and regional medical officers. Written informed consent was obtained from patients or parents\/guardians in the case of children. Appropriate information (about the study and the protocol\/methods) in a language that was understood by the parents\/guardians of the study patients (in Kiswahili) was compiled and provided before consent was obtained. Permission to publish was sought and obtained from the Director General of NIMR.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"139"}}