{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:48:04Z","timestamp":1790880484640,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["#54497"],"award-info":[{"award-number":["#54497"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","award":["MR\/P02520X\/1"],"award-info":[{"award-number":["MR\/P02520X\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI116811"],"award-info":[{"award-number":["R01AI116811"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["RSWF\\FT\\180003"],"award-info":[{"award-number":["RSWF\\FT\\180003"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Ecology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies of insecticide resistance provide insights into the capacity of populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs). Resistance in the major malaria vectors has increased in concert with the expansion of LLIN distributions. Identifying genetic mechanisms underlying high\u2010level resistance is crucial for the development and deployment of resistance\u2010breaking tools. Using the <jats:italic>Anopheles gambiae<\/jats:italic> 1000 genomes (Ag1000g) data we identified a very recent selective sweep in mosquitoes from Uganda which localized to a cluster of cytochrome P450 genes. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in <jats:italic>Cyp6p4<\/jats:italic> (I236M), an upstream insertion of a partial Zanzibar\u2010like transposable element (TE) and a duplication of the <jats:italic>Cyp6aa1<\/jats:italic> gene. The mutations appear to have originated recently in <jats:italic>An. gambiae<\/jats:italic> from the Kenya\u2010Uganda border, with stepwise replacement of the double\u2010mutant (Zanzibar\u2010like TE and <jats:italic>Cyp6p4\u2010236\u2009M<\/jats:italic>) with the triple\u2010mutant haplotype (including <jats:italic>Cyp6aa1<\/jats:italic> duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple\u2010mutant haplotype is strongly associated with increased expression of genes able to metabolize pyrethroids and is strongly predictive of resistance to pyrethroids most notably deltamethrin. Importantly, there was increased mortality in mosquitoes carrying the triple\u2010mutation when exposed to nets cotreated with the synergist piperonyl butoxide (PBO). Frequencies of the triple\u2010mutant haplotype remain spatially variable within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO\u2010pyrethroid cotreated LLINs across African countries.<\/jats:p>","DOI":"10.1111\/mec.16591","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T07:43:48Z","timestamp":1656661428000},"page":"4307-4318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Identification of a rapidly\u2010spreading triple mutant for high\u2010level metabolic insecticide resistance in <i>Anopheles gambiae<\/i> provides a real\u2010time molecular diagnostic for antimalarial intervention deployment"],"prefix":"10.1111","volume":"31","author":[{"given":"Harun","family":"Njoroge","sequence":"first","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"},{"name":"Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Coast KEMRI\u2010Wellcome Trust Research Programme  Kilifi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen","family":"van't Hof","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrose","family":"Oruni","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"},{"name":"College of Veterinary Medicine Animal Resources and Bio\u2010security Makerere University  Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Pipini","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-8523","authenticated-orcid":false,"given":"Sanjay\u00a0C.","family":"Nagi","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Lynd","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3892-1668","authenticated-orcid":false,"given":"Eric R.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavi","family":"Grau\u2010Bove","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis T.","family":"Wat'senga","sequence":"additional","affiliation":[{"name":"Institut National de Recherche Biom\u00e9dicale  Kinshasa Democratic Republic of Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile Z.","family":"Manzambi","sequence":"additional","affiliation":[{"name":"Institut National de Recherche Biom\u00e9dicale  Kinshasa Democratic Republic of Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiacre R.","family":"Agossa","sequence":"additional","affiliation":[{"name":"USAID President's Malaria Initiative, VectorLink Project, Abt Associates  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlette","family":"Mokuba","sequence":"additional","affiliation":[{"name":"USAID President's Malaria Initiative, VectorLink Project, Abt Associates  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Irish","sequence":"additional","affiliation":[{"name":"U.S. President's Malaria Initiative and Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilali","family":"Kabula","sequence":"additional","affiliation":[{"name":"Amani Research Centre National Institute for Medical Research  Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Mbogo","sequence":"additional","affiliation":[{"name":"Population Health Unit KEMRI\u2010Wellcome Trust Research Programme  Nairobi Kenya"},{"name":"KEMRI\u2010Centre for Geographic Medicine Research Coast  Kilifi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Bargul","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Jomo Kenyatta University of Agriculture and Technology  Juja Kenya"},{"name":"The Animal Health Department International Centre of Insect Physiology and Ecology  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J. I.","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Weetman","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-1497","authenticated-orcid":false,"given":"Martin J.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Vector Biology Liverpool School of Tropical Medicine  Liverpool UK"},{"name":"Parasites and Microbes Programme Wellcome Sanger Institute  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23707-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15535"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2004.02.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/mec.15845"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-8-70"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212890"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2015.12.001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004236"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msaa128"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000633"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9030140"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201475109"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30844-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30172-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.01.036"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv604"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty458"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.119.400445"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.245795.118"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-019-3353-7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msq002"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2561-5"},{"key":"e_1_2_8_25_1","article-title":"Cggh\/scikit\u2010allel","author":"Miles A.","year":"2019","journal-title":"Zenodo"},{"key":"e_1_2_8_26_1","volume-title":"Insecticide Resistance Management Plan, Kenya 2020\u20132024","author":"Ministry of Health, Republic of Kenya","year":"2019"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203452109"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092662"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12686-5"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000286"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1258522"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138878"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30427-6"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2015.11.010"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-019-2838-3"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqaa113"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000998"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30214-2"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24995"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.262790.120"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719663115"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-020-03240-6"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat7386"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/trstmh\/trv017"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21265-5"},{"key":"e_1_2_8_47_1","first-page":"56","volume-title":"Test procedures for insecticide resistance monitoring in malaria vector mosquitoes (Second edition)","author":"WHO","year":"2016"},{"key":"e_1_2_8_48_1","first-page":"232","volume-title":"World malaria report 2019","author":"WHO","year":"2019"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2011.03.004"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2019.06.007"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143387"}],"container-title":["Molecular Ecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mec.16591","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/mec.16591","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mec.16591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T22:06:25Z","timestamp":1692741985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mec.16591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":50,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1111\/mec.16591"],"URL":"https:\/\/doi.org\/10.1111\/mec.16591","archive":["Portico"],"relation":{},"ISSN":["0962-1083","1365-294X"],"issn-type":[{"value":"0962-1083","type":"print"},{"value":"1365-294X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,12]]},"assertion":[{"value":"2022-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}