{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:58:55Z","timestamp":1790690335415,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"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":["R21AI137891"],"award-info":[{"award-number":["R21AI137891"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Multiple infections of genetically distinct clones of the same\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    species are common in many malaria endemic settings. Mean multiplicity of infection (MOI) and the proportion of polyclonal infections are often reported as surrogate marker of transmission intensity, yet the relationship with traditional measures such as parasite prevalence is not well understood. We have searched Pubmed for articles on\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    multiplicity, and compared the proportion of polyclonal infections and mean MOI to population prevalence. The impact of the genotyping method, number of genotyping markers, method for diagnosis (microscopy\/RDT vs. PCR), presence of clinical symptoms, age, geographic region, and year of sample collection on multiplicity indices were assessed. For\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    , 153 studies met inclusion criteria, yielding 275 individual data points and 33,526 genotyped individuals. The proportion of polyclonal infections ranged from 0\u201396%, and mean MOI from 1\u20136.1. For\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    , 54 studies met inclusion criteria, yielding 115 data points and 13,325 genotyped individuals. The proportion of polyclonal infections ranged from 0\u2013100%, and mean MOI from 1\u20133.8. For both species, the proportion of polyclonal infections ranged from very low to close to 100% at low prevalence, while at high prevalence it was always high. Each percentage point increase in prevalence resulted in a 0.34% increase in the proportion of polyclonal\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    infections (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001), and a 0.78% increase in the proportion of polyclonal\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    infections (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001). In multivariable analysis, higher prevalence, typing multiple markers, diagnosis of infections by PCR, and sampling in Africa were found to result in a higher proportion of\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    polyclonal infections. For\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    , prevalence, year of study, typing multiple markers, and geographic region were significant predictors. In conclusion, polyclonal infections are frequently present in all settings, but the association between multiplicity and prevalence is weak.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0249382","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T13:23:35Z","timestamp":1623417815000},"page":"e0249382","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Systematic review of Plasmodium falciparum and Plasmodium vivax polyclonal infections: Impact of prevalence, study population characteristics, and laboratory 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J."},{"issue":"1","key":"pone.0249382.ref009","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1186\/s12864-017-4260-y","article-title":"Development of amplicon deep sequencing markers and data analysis pipeline for genotyping multi-clonal malaria infections","volume":"18","author":"A Lerch","year":"2017","journal-title":"BMC Genomics"},{"issue":"6","key":"pone.0249382.ref010","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/infdis\/jiv142","article-title":"Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse","volume":"212","author":"JT Lin","year":"2015","journal-title":"J Infect Dis"},{"issue":"5","key":"pone.0249382.ref011","doi-asserted-by":"crossref","first-page":"e0008295","DOI":"10.1371\/journal.pntd.0008295","article-title":"Molecular surveillance over 14 years confirms reduction of Plasmodium vivax and falciparum transmission after implementation of Artemisinin-based combination therapy in Papua, 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intensity","volume":"19","author":"MA Pacheco","year":"2020","journal-title":"Malar J."},{"issue":"1","key":"pone.0249382.ref015","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1186\/s13071-020-04302-z","article-title":"Determinants of Plasmodium falciparum multiplicity of infection and genetic diversity in Burkina Faso","volume":"13","author":"P Sondo","year":"2020","journal-title":"Parasit Vectors"},{"issue":"3","key":"pone.0249382.ref016","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4269\/ajtmh.16-0716","article-title":"Higher Complexity of Infection and Genetic Diversity of Plasmodium vivax Than Plasmodium falciparum Across All Malaria Transmission Zones of Papua New Guinea","volume":"96","author":"AA Fola","year":"2017","journal-title":"Am J Trop Med Hyg"},{"issue":"11","key":"pone.0249382.ref017","doi-asserted-by":"crossref","first-page":"ofy240","DOI":"10.1093\/ofid\/ofy240","article-title":"Multiplicity of Infection Is a Poor Predictor of Village-Level 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recommendations for accurate reporting","volume":"13","author":"Q Cheng","year":"2014","journal-title":"Malar J."},{"key":"pone.0249382.ref021","first-page":"8","article-title":"Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions","author":"OJ Watson","year":"2019","journal-title":"Elife"},{"issue":"1","key":"pone.0249382.ref022","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/bioinformatics\/btx530","article-title":"Deconvolution of multiple infections in Plasmodium falciparum from high throughput sequencing data","volume":"34","author":"SJ Zhu","year":"2018","journal-title":"Bioinformatics"},{"issue":"5","key":"pone.0249382.ref023","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/infdis\/jiz510","article-title":"Multiplicity of Asymptomatic Plasmodium falciparum Infections and Risk of Clinical Malaria: A Systematic Review and Pooled Analysis of Individual Participant Data","volume":"221","author":"M Eldh","year":"2019","journal-title":"J Infect Dis"},{"issue":"6","key":"pone.0249382.ref024","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.4269\/ajtmh.17-0364","article-title":"Passively versus Actively Detected Malaria: Similar Genetic Diversity but Different Complexity of Infection","volume":"97","author":"Z Pava","year":"2017","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"pone.0249382.ref025","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1186\/s12936-019-3039-9","article-title":"Genetic diversity of Plasmodium falciparum isolates from patients with uncomplicated and severe malaria based on msp-1 and msp-2 genes in Gublak, North West Ethiopia","volume":"18","author":"H Mohammed","year":"2019","journal-title":"Malar J"},{"issue":"8\u20139","key":"pone.0249382.ref026","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.ijpara.2007.02.010","article-title":"Contrasting genetic structure in Plasmodium vivax populations from Asia and South America","volume":"37","author":"M Imwong","year":"2007","journal-title":"Int J Parasitol"},{"issue":"7","key":"pone.0249382.ref027","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1086\/597303","article-title":"Evaluation of Plasmodium vivax genotyping markers for molecular monitoring in clinical trials","volume":"199","author":"C Koepfli","year":"2009","journal-title":"J Infect Dis"},{"key":"pone.0249382.ref028","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/ncomms2241","article-title":"Factors determining the occurrence of submicroscopic malaria infections and their relevance for control.","volume":"3","author":"LC Okell","year":"2012","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0249382.ref029","doi-asserted-by":"crossref","first-page":"e3413","DOI":"10.1371\/journal.pntd.0003413","article-title":"Systematic review of sub-microscopic P. vivax infections: prevalence and determining 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Probability of molecular detection of human Plasmodia in the field","volume":"6","author":"C Koepfli","year":"2011","journal-title":"PLoS One"},{"issue":"6","key":"pone.0249382.ref031","doi-asserted-by":"crossref","first-page":"944","DOI":"10.4269\/ajtmh.2006.74.944","article-title":"Comparison of PCR-RFLP and Genescan-based genotyping for analyzing infection dynamics of Plasmodium falciparum","volume":"74","author":"N Falk","year":"2006","journal-title":"Am J Trop Med Hyg"},{"key":"pone.0249382.ref032","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1475-2875-9-19","article-title":"Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda","volume":"9","author":"V Gupta","year":"2010","journal-title":"Malar J"},{"issue":"1","key":"pone.0249382.ref033","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0035-9203(99)90322-X","article-title":"Age dependence of the multiplicity of Plasmodium falciparum infections and of other malariological indices in an area of high endemicity","volume":"93","author":"T Smith","year":"1999","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"1","key":"pone.0249382.ref034","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1038\/s41598-019-39656-7","article-title":"Longitudinal tracking and quantification of individual Plasmodium falciparum clones in complex infections","volume":"9","author":"A Lerch","year":"2019","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0249382.ref035","doi-asserted-by":"crossref","first-page":"667","DOI":"10.4269\/ajtmh.17-0621","article-title":"Genetic Diversity of the Plasmodium falciparum Glutamate-Rich Protein R2 Region Before and Twelve Years after Introduction of Artemisinin Combination Therapies among Febrile Children in Nigeria","volume":"98","author":"CN Nguetse","year":"2018","journal-title":"American Journal of Tropical Medicine and Hygiene"},{"issue":"25","key":"pone.0249382.ref036","doi-asserted-by":"crossref","first-page":"10030","DOI":"10.1073\/pnas.1200841109","article-title":"Force of infection is key to understanding the epidemiology of Plasmodium falciparum malaria in Papua New Guinean children","volume":"109","author":"I Mueller","year":"2012","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249382","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T13:39:43Z","timestamp":1725197983000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249382"}},"subtitle":[],"editor":[{"given":"Luzia Helena","family":"Carvalho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0249382","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.18.436023","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,11]]}}}