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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,7,26]]},"abstract":"<jats:p>\n                    Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite\u2019s optimal life history strategy. Here, we explore whether declining infection rates can alter\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    \u2019s investment in sexual versus asexual growth. Using a multiscale mathematical model, we demonstrate how the proportion of polyclonal infections, which decreases as parasite prevalence declines, affects the optimal sexual development strategy: Within-host competition in multiclone infections favors a greater investment in asexual growth whereas single-clone infections benefit from higher conversion to sexual forms. At the same time, drug treatment also imposes selection pressure on sexual development by shortening infection length and reducing within-host competition. We assess these models using 148\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    parasite genomes sampled in French Guiana over an 18-y period of intensive intervention (1998 to 2015). During this time frame, multiple public health measures, including the introduction of new drugs and expanded rapid diagnostic testing, were implemented, reducing\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    malaria cases by an order of magnitude. Consistent with this prevalence decline, we see an increase in the relatedness among parasites, but no single clonal background grew to dominate the population. Analyzing individual allele frequency trajectories, we identify genes that likely experienced selective sweeps. Supporting our model predictions, genes showing the strongest signatures of selection include transcription factors involved in the development of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    \u2019s sexual gametocyte form. These results highlight how public health interventions impose wide-ranging selection pressures that affect basic parasite life history traits.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2122165119","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T14:08:49Z","timestamp":1658498929000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Declines in prevalence alter the optimal level of sexual investment for the malaria parasite\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3169-2324","authenticated-orcid":false,"given":"Angela M.","family":"Early","sequence":"first","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA 02142"},{"name":"Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9762-851X","authenticated-orcid":false,"given":"Flavia","family":"Camponovo","sequence":"additional","affiliation":[{"name":"Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7070-2177","authenticated-orcid":false,"given":"St\u00e9phane","family":"Pelleau","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, 97300 Cayenne, French Guiana"},{"name":"Infectious Diseases Epidemiology and Analytics Unit, Department of Global Health, Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo C.","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassamine","family":"Lazrek","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, 97300 Cayenne, French Guiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Volney","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, 97300 Cayenne, French Guiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-4376","authenticated-orcid":false,"given":"Manuela","family":"Carrasquilla","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-5112","authenticated-orcid":false,"given":"Beno\u00eet","family":"de Thoisy","sequence":"additional","affiliation":[{"name":"Laboratoire des Interactions Virus H\u00f4tes, Institut Pasteur de la Guyane, 97306 Cayenne, French Guiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8386-5899","authenticated-orcid":false,"given":"Caroline O.","family":"Buckee","sequence":"additional","affiliation":[{"name":"Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-3895","authenticated-orcid":false,"given":"Lauren M.","family":"Childs","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Virginia Tech, Blacksburg, VA 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-4110","authenticated-orcid":false,"given":"Lise","family":"Musset","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, World Health Organization Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur de la Guyane, 97300 Cayenne, French Guiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1665-9323","authenticated-orcid":false,"given":"Daniel E.","family":"Neafsey","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA 02142"},{"name":"Department of Immunology and Infectious Diseases, Harvard T. 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Chan School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu106"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520426112"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41559-017-0419-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.16168.1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752-4571.2008.00060.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001140050763"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004718"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(01)90016-1"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49058"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19988-z"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/evo.13840"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2004.08.021"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2007.1545"},{"key":"e_1_3_4_14_2","first-page":"151","volume-title":"Advances in Parasitology","author":"Tusting L. S.","year":"2014","unstructured":"L. S. Tusting, T. Bousema, D. L. Smith, C. Drakeley, \u201cMeasuring changes in Plasmodium falciparum transmission. Precision, accuracy and costs of metrics\u201d in Advances in Parasitology (Academic Press, 2014), vol. 84, pp. 151\u2013208."},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1959.11685899"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2002.66.467"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1590\/0074-0276140031"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009287"},{"key":"e_1_3_4_19_2","unstructured":"WHO World Malaria Report 2008 (World Health Organization Geneva Switzerland 2008)."},{"key":"e_1_3_4_20_2","unstructured":"WHO World Malaria Report 2016 (World Health Organization Geneva Switzerland 2016)."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507142112"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30068-9"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009050"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00197-15"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.12.003"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04295-5"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw6957"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608828113"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090817-062712"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24280"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.14645.3"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-6322-9"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12920"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep41303"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14676"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab683"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.631444"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217712110"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2014.1379"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-021-03813-z"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025452"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1084-0"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22573-7"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60058"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00898-20"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2021.111375"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007371"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/evo.12969"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/emph\/eot011"},{"key":"e_1_3_4_50_2","first-page":"3721","article-title":"Density-dependent impact of the human malaria parasite Plasmodium falciparum gametocyte sex ratio on mosquito infection rates","volume":"276","author":"Mitri C.","year":"2009","unstructured":"C. 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