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Population genomic studies have been instrumental in mapping malaria genes associated with drug resistance. However, to understand the impact of regional malaria control strategies on the malaria genome, it is necessary to examine parasite subpopulations at the country level. Here, we use selective whole-genome amplification (SWGA) to analyze 120 samples from patients with severe malaria in Mozambique, a country with high malaria burden and risk of emerging drug resistance. We demonstrate that SWGA allows for the generation of near-complete whole-genome sequences from clinical\n            <jats:italic>P. falciparum<\/jats:italic>\n            isolates. Our analysis shows that Mozambique parasite genomes show strong diversification of vaccine targets including the circumsporozoite protein (\n            <jats:italic>csp<\/jats:italic>\n            ), the target of the RTS,S vaccine. Parasites in this population appear fully sensitive to chloroquine, bearing no likely resistance conferring mutations in the chloroquine resistance transporter,\n            <jats:italic>pfcrt<\/jats:italic>\n            (PF3D7_0709000) and highly resistant to sulfadoxine-pyrimethamine, exhibiting resistant haplotypes at near fixation. Despite a long history of artemisinin use in Mozambique, we find no evidence of selection near\n            <jats:italic>pfkelch13<\/jats:italic>\n            (PF3D7_1343700) nor evidence of artemisinin resistance conferring mutations in\n            <jats:italic>pfkelch13<\/jats:italic>\n            . Using identity by descent analysis, we show positive selection at genomic regions on chromosomes 6, 8, 12, 13, and 14. Gene candidates within these regions include the amino acid transporter 1 (\n            <jats:italic>pfaat1<\/jats:italic>\n            , PF3D7_0629500) on chromosome 6 which bears an S258L substitution in &gt;80% of parasites, and a region on chromosome 14 previously amplified under artemisinin pressure.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Malaria is a devastating disease caused by\n              <jats:italic>Plasmodium<\/jats:italic>\n              parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden. We present an analysis of the parasite genome in Mozambique, a country with one of the highest malaria burdens globally and limited available genomic data, revealing current selection pressure. We contribute additional evidence to limited prior studies supporting the effectiveness of SWGA in producing reliable genomic data from complex clinical samples. Our results provide the identity of genomic loci that may be associated with current antimalarial drug use, including artemisinin and lumefantrine, and reveal selection pressure predicted to compromise the efficacy of current vaccine candidates.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01768-23","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T13:05:42Z","timestamp":1695733542000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Whole-genome surveillance identifies markers of\n            <i>Plasmodium falciparum<\/i>\n            drug resistance and novel genomic regions under selection in Mozambique"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6619-7761","authenticated-orcid":false,"given":"Erin","family":"Coonahan","sequence":"first","affiliation":[{"name":"School of Medicine, University of California San Diego , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Gage","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego (UCSD) , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia Virginia","family":"Noormahomed","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego , La Jolla, California, USA"},{"name":"Department of Microbiology, Parasitology Laboratory, Faculty of Medicine, Eduardo Mondlane University , Maputo, Mozambique"},{"name":"Mozambique Institute of Health Education and Research (MIHER) , Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titos Paulo","family":"Buene","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Parasitology Laboratory, Faculty of Medicine, Eduardo Mondlane University , Maputo, Mozambique"},{"name":"Mozambique Institute of Health Education and Research (MIHER) , Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Mendes de Sousa","sequence":"additional","affiliation":[{"name":"Mozambique Institute of Health Education and Research (MIHER) , Maputo, Mozambique"},{"name":"Biological Sciences Department, Faculty of Sciences, Eduardo Mondlane University , Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevan","family":"Akrami","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego , La Jolla, California, USA"},{"name":"Faculdade de Medicina da Bahia, Universidade Federal da Bahia , Salvador, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Chambal","sequence":"additional","affiliation":[{"name":"Mozambique Institute of Health Education and Research (MIHER) , Maputo, Mozambique"},{"name":"Department of Internal Medicine, Faculty of Medicine, Eduardo Mondlane University , Maputo, Mozambique"},{"name":"Maputo Central Hospital , Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Schooley","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Winzeler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego (UCSD) , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie N.","family":"Cowell","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California San Diego , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_3_2","unstructured":"Evaluation IfHMa . 2021. 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