{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:53:36Z","timestamp":1753890816808,"version":"3.41.2"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI146849"],"award-info":[{"award-number":["R01AI146849"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Epidemiol."],"abstract":"<jats:p>A primary use of malaria parasite genomics is identifying highly related infections to quantify epidemiological, spatial, or temporal factors associated with patterns of transmission. For example, spatial clustering of highly related parasites can indicate foci of transmission and temporal differences in relatedness can serve as evidence for changes in transmission over time. However, for infections in settings of moderate to high endemicity, understanding patterns of relatedness is compromised by complex infections, overall high forces of infection, and a highly diverse parasite population. It is not clear how much these factors limit the utility of using genomic data to better understand transmission in these settings. In particular, further investigation is required to determine which patterns of relatedness we expect to see with high quality, densely sampled genomic data in a high transmission setting and how these observations change under different study designs, missingness, and biases in sample collection. Here we investigate two identity-by-state measures of relatedness and apply them to amplicon deep sequencing data collected as part of a longitudinal cohort in Western Kenya that has previously been analysed to identify individual-factors associated with sharing parasites with infected mosquitoes. With these data we use permutation tests, to evaluate several hypotheses about spatiotemporal patterns of relatedness compared to a null distribution. We observe evidence of temporal structure, but not of fine-scale spatial structure in the cohort data. To explore factors associated with the lack of spatial structure in these data, we construct a series of simplified simulation scenarios using an agent based model calibrated to entomological, epidemiological and genomic data from this cohort study to investigate whether the lack of spatial structure observed in the cohort could be due to inherent power limitations of this analytical method. We further investigate how our hypothesis testing behaves under different sampling schemes, levels of completely random and systematic missingness, and different transmission intensities.<\/jats:p>","DOI":"10.3389\/fepid.2023.1058871","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T05:36:01Z","timestamp":1676612161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring how space, time, and sampling impact our ability to measure genetic structure across Plasmodium falciparum populations"],"prefix":"10.3389","volume":"3","author":[{"given":"Rohan","family":"Arambepola","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"B\u00e9rub\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betsy","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve M.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Prudhomme O\u2019Meara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"Obala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Wesolowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7067","DOI":"10.1073\/pnas.1505691112","article-title":"Modeling malaria genomics reveals transmission decline and rebound in Senegal","volume":"112","author":"Daniels","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.4269\/ajtmh.2012.12-0308","article-title":"Alterations in plasmodium falciparum genetic structure two years after increased malaria control efforts in western Kenya","volume":"88","author":"Vardo-Zalik","year":"2013","journal-title":"Am J Trop Med Hyg"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0000285","DOI":"10.1371\/journal.pgph.0000285","article-title":"Indoor residual spraying with a non-pyrethroid insecticide reduces the reservoir of plasmodium falciparum in a high-transmission area in northern Ghana","volume":"2","author":"Tiedje","year":"2022","journal-title":"PLOS Glob Public Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3974","DOI":"10.1111\/mec.16029","article-title":"The impact of indoor residual spraying on plasmodium falciparum microsatellite variation in an area of high seasonal malaria transmission in Ghana, West Africa","volume":"30","author":"Argyropoulos","year":"2021","journal-title":"Mol Ecol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"311","DOI":"10.4269\/ajtmh.12-0695","article-title":"Molecular surveillance as monitoring tool for drug-resistant plasmodium falciparum in Suriname","volume":"89","author":"Adhin","year":"2013","journal-title":"Am J Trop Med Hyg"},{"key":"B6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s13059-017-1204-4","article-title":"Longitudinal genomic surveillance of plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance","volume":"18","author":"Cerqueira","year":"2017","journal-title":"Genome Biol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1056\/NEJMoa2101746","article-title":"Evidence of artemisinin-resistant malaria in Africa","volume":"385","author":"Balikagala","year":"2021","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e72083","DOI":"10.7554\/eLife.72083","article-title":"High-throughput plasmodium falciparum hrp2 and hrp3 gene deletion typing by digital PCR to monitor malaria rapid diagnostic test efficacy","volume":"11","author":"Vera-Arias","year":"2022","journal-title":"Elife"},{"key":"B9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s12936-021-03629-x","article-title":"Detection of high prevalence of plasmodium falciparum histidine-rich protein 2\/3 gene deletions in assosa zone, Ethiopia: implication for malaria diagnosis","volume":"20","author":"Alemayehu","year":"2021","journal-title":"Malar J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/s12936-019-3023-4","article-title":"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","volume":"18","author":"Pringle","year":"2019","journal-title":"Malar J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s12936-019-2880-1","article-title":"Applying next-generation sequencing to track falciparum malaria in sub-Saharan Africa","volume":"18","author":"Tessema","year":"2019","journal-title":"Malar J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e43510","DOI":"10.7554\/eLife.43510","article-title":"Using parasite genetic and human mobility data to infer local and cross-border malaria connectivity in Southern Africa","volume":"8","author":"Tessema","year":"2019","journal-title":"Elife"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1007065","DOI":"10.1371\/journal.pgen.1007065","article-title":"Quantifying connectivity between local Plasmodium falciparum malaria parasite populations using identity by descent","volume":"13","author":"Taylor","year":"2017","journal-title":"PLoS Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1159\/000345607","article-title":"Malaria diagnostics and surveillance in the post-genomic era","volume":"16","author":"Lucchi","year":"2013","journal-title":"Public Health Genomics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"a025544","DOI":"10.1101\/cshperspect.a025544","article-title":"Malaria genomics in the era of eradication","volume":"7","author":"Neafsey","year":"2017","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrg3821","article-title":"Relatedness in the post-genomic era: is it still useful?","volume":"16","author":"Speed","year":"2015","journal-title":"Nat Rev Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nrg1960","article-title":"Genetic relatedness analysis: modern data and new challenges","volume":"7","author":"Weir","year":"2006","journal-title":"Nat Rev Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1534\/genetics.112.148825","article-title":"Identity by descent: variation in meiosis, across genomes, and in populations","volume":"194","author":"Thompson","year":"2013","journal-title":"Genetics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1002287","DOI":"10.1371\/journal.pgen.1002287","article-title":"Inference of relationships in population data using identity-by-descent and identity-by-state","volume":"7","author":"Stevens","year":"2011","journal-title":"PLoS Genet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1534\/genetics.111.137570","article-title":"Inferring coancestry in population samples in the presence of linkage disequilibrium","volume":"190","author":"Brown","year":"2012","journal-title":"Genetics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s12936-018-2349-7","article-title":"hmmIBD: software to infer pairwise identity by descent between haploid genotypes","volume":"17","author":"Schaffner","year":"2018","journal-title":"Malar J"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1007279","DOI":"10.1371\/journal.pgen.1007279","article-title":"Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens","volume":"14","author":"Henden","year":"2018","journal-title":"PLoS Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1086\/378207","article-title":"Estimation of the inbreeding coefficient through use of genomic data","volume":"73","author":"Leutenegger","year":"2003","journal-title":"Am J Hum Genet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1534\/genetics.119.302120","article-title":"Estimating relatedness between malaria parasites","volume":"212","author":"Taylor","year":"2019","journal-title":"Genetics"},{"year":"","key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg1802s62"},{"key":"B26","doi-asserted-by":"publisher","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":"Zhu","year":"2018","journal-title":"Bioinformatics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/B978-0-12-800099-1.00003-X","article-title":"Measuring changes in plasmodium falciparum transmission: precision, accuracy and costs of metrics","volume":"84","author":"Tusting","year":"2014","journal-title":"Adv Parasitol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1017\/S0031182001008162","article-title":"Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season","volume":"123","author":"Ofosu-Okyere","year":"2001","journal-title":"Parasitology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/1475-2875-9-353","article-title":"Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in Western Kenya","volume":"9","author":"Gatei","year":"2010","journal-title":"Malar J"},{"key":"B30","doi-asserted-by":"publisher","first-page":"79","DOI":"10.4269\/ajtmh.15-0005","article-title":"Malaria molecular epidemiology: lessons from the international centers of excellence for malaria research network","volume":"93","author":"Escalante","year":"2015","journal-title":"Am J Trop Med Hyg"},{"key":"B31","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1186\/1475-2875-11-410","article-title":"Reduction of multiplicity of infections but no change in msp2 genetic diversity in Plasmodium falciparum isolates from Congolese children after introduction of artemisinin-combination therapy","volume":"11","author":"Ibara-Okabande","year":"2012","journal-title":"Malar J"},{"key":"B32","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/1475-2875-9-244","article-title":"Multiplicity of Plasmodium falciparum infection following intermittent preventive treatment in infants","volume":"9","author":"Buchholz","year":"2010","journal-title":"Malar J"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1093\/infdis\/jiy640","article-title":"Genetic\u00a0evidence of focal plasmodium falciparum transmission in a pre-elimination setting in southern province, Zambia","volume":"219","author":"Pringle","year":"2019","journal-title":"J Infect Dis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1534\/genetics.115.180992","article-title":"Estimating the number of subpopulations (K) in structured populations","volume":"203","author":"Verity","year":"2016","journal-title":"Genetics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1093\/genetics\/155.2.945","article-title":"Inference of population structure using\u00a0multilocus genotype data","volume":"155","author":"Pritchard","year":"2000","journal-title":"Genetics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1093\/infdis\/jiz561","article-title":"Mosquito exposure and malaria morbidity: a microlevel analysis of household mosquito populations and malaria in a population-based longitudinal cohort in Western Kenya","volume":"221","author":"O\u2019Meara","year":"2020","journal-title":"J Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e0202031","DOI":"10.1371\/journal.pone.0202031","article-title":"THe current malaria morbidity and mortality in different transmission settings in Western Kenya","volume":"13","author":"Kapesa","year":"2018","journal-title":"PLOS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e20318","DOI":"10.1371\/journal.pone.0020318","article-title":"Changing patterns of malaria epidemiology between 2002 and 2010 in Western Kenya: the fall and rise of malaria","volume":"6","author":"Zhou","year":"2011","journal-title":"PLOS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/s41467-021-21269-2","article-title":"Genotyping cognate plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections","volume":"12","author":"Sumner","year":"2021","journal-title":"Nat Commun"},{"volume-title":"The genetic structure of populations","year":"1970","author":"Jacquard","key":"B40"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1101\/2022.12.23.521802","article-title":"Superinfection plays an important role in the acquisition of complex Plasmodium falciparum infections among female Anopheles mosquitoes","author":"B\u00e9rub\u00e9","year":""},{"key":"B42","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/1756-3305-6-340","article-title":"Biting patterns and seasonality of anopheles gambiae sensu lato and anopheles funestus mosquitoes in kamuli district, Uganda","volume":"6","author":"Kabbale","year":"2013","journal-title":"Parasit Vectors"},{"key":"B43","first-page":"225","article-title":"Bloodfeeding behavior of anopheles gambiae s.l. And anopheles funestus in kilifi district, Kenya","volume":"9","author":"Mbogo","year":"1993","journal-title":"J Am Mosq Control Assoc"},{"key":"B44","doi-asserted-by":"publisher","first-page":"7783","DOI":"10.1128\/IAI.69.12.7783-7792.2001","article-title":"Plasmodium falciparum genotypes, low complexity of infection, and resistance to subsequent malaria in participants in the asembo bay cohort project","volume":"69","author":"Branch","year":"2001","journal-title":"Infect Immun"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0249382","DOI":"10.1371\/journal.pone.0249382","article-title":"Systematic review of plasmodium falciparum and plasmodium vivax polyclonal infections: impact of prevalence, study population characteristics, and laboratory procedures","volume":"16","author":"Lopez","year":"2021","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1093\/cid\/cix1123","article-title":"The relative contribution of symptomatic and asymptomatic plasmodium vivax and plasmodium falciparum infections to the infectious reservoir in a low-endemic setting in Ethiopia","volume":"66","author":"Tadesse","year":"2018","journal-title":"Clin Infect Dis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1016\/S1473-3099(21)00072-4","article-title":"Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study","volume":"21","author":"Andolina","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"B48","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/nrmicro3364","article-title":"Asymptomatic malaria infections: detectability, transmissibility and public health relevance","volume":"12","author":"Bousema","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1586\/eri.13.45","article-title":"The silent threat: asymptomatic parasitemia and malaria transmission","volume":"11","author":"Lindblade","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"key":"B50","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12936-021-03603-7","article-title":"Within-household clustering of genetically related plasmodium falciparum infections in a moderate transmission area of Uganda","volume":"20","author":"Briggs","year":"2021","journal-title":"Malar J"},{"key":"B51","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S1473-3099(15)00423-5","article-title":"Potential for reduction of burden and local elimination of malaria by reducing plasmodium falciparum malaria transmission: a mathematical modelling study","volume":"16","author":"Griffin","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1093\/cid\/ciab357","article-title":"Exposure to diverse plasmodium falciparum genotypes shapes the risk of symptomatic malaria in incident and persistent infections: a longitudinal molecular epidemiologic study in Kenya","volume":"73","author":"Sumner","year":"2021","journal-title":"Clin Infect Dis"}],"container-title":["Frontiers in Epidemiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fepid.2023.1058871\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T12:58:54Z","timestamp":1709816334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fepid.2023.1058871\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":52,"alternative-id":["10.3389\/fepid.2023.1058871"],"URL":"https:\/\/doi.org\/10.3389\/fepid.2023.1058871","relation":{},"ISSN":["2674-1199"],"issn-type":[{"type":"electronic","value":"2674-1199"}],"subject":[],"published":{"date-parts":[[2023,2,17]]},"article-number":"1058871"}}