{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:50:30Z","timestamp":1783335030181,"version":"3.54.6"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"a Wellcome Trust Senior Research Fellowships in Biomedical Sciences","doi-asserted-by":"publisher","award":["217188\/Z\/19\/Z"],"award-info":[{"award-number":["217188\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"a Wellcome Trust Senior Research Fellowships in Biomedical Sciences","doi-asserted-by":"publisher","award":["INV-006003"],"award-info":[{"award-number":["INV-006003"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"a Bill and Melinda Gates Foundation","award":["217188\/Z\/19\/Z"],"award-info":[{"award-number":["217188\/Z\/19\/Z"]}]},{"name":"a Bill and Melinda Gates Foundation","award":["INV-006003"],"award-info":[{"award-number":["INV-006003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>(1) Background: Malaria remains a global public health problem. Unfortunately, the resistance of malaria vectors to commonly used insecticides threatens disease control and elimination efforts. Field mosquitoes have been shown to survive upon exposure to high insecticide concentrations. The molecular mechanisms driving this pronounced resistance remain poorly understood. Here, we elucidated the pattern of resistance escalation in the main malaria vector Anopheles gambiae in a pesticide-driven agricultural hotspot in Cameroon and its impact on vector control tools; (2) Methods: Larval stages and indoor blood-fed female mosquitoes (F0) were collected in Mangoum in May and November and forced to lay eggs; the emerged mosquitoes were used for WHO tube, synergist and cone tests. Molecular identification was performed using SINE PCR, whereas TaqMan-based PCR was used for genotyping of L1014F\/S and N1575Y kdr and the G119S-ACE1 resistance markers. The transcription profile of candidate resistance genes was performed using qRT-PCR methods. Characterization of the breeding water and soil from Mangoum was achieved using the HPLC technique; (3) Results: An. gambiae s.s. was the only species in Mangoum with 4.10% infection with Plasmodium. These mosquitoes were resistant to all the four classes of insecticides with mortality rates &lt;7% for pyrethroids and DDT and &lt;54% for carbamates and organophophates. This population also exhibited high resistance intensity to pyrethroids (permethrin, alpha-cypermethrin and deltamethrin) after exposure to 5\u00d7 and 10\u00d7 discriminating doses. Synergist assays with PBO revealed only a partial recovery of susceptibility to permethrin, alpha-cypermethrin and deltamethrin. Only PBO-based nets (Olyset plus and permaNet 3.0) and Royal Guard showed an optimal efficacy. A high amount of alpha-cypermethrin was detected in breeding sites (5.16-fold LOD) suggesting ongoing selection from agricultural pesticides. The 1014F-kdr allele was fixed (100%) whereas the 1575Y-kdr (37.5%) and the 119S Ace-1R (51.1%) were moderately present. Elevated expression of P450s, respectively, in permethrin and deltamethrin resistant mosquitoes [CYP6M2 (10 and 34-fold), CYP6Z1(17 and 29-fold), CYP6Z2 (13 and 65-fold), CYP9K1 (13 and 87-fold)] supports their role in the observed resistance besides other mechanisms including chemosensory genes as SAP1 (28 and 13-fold), SAP2 (5 and 5-fold), SAP3 (24 and 8-fold) and cuticular genes as CYP4G16 (6 and 8-fold) and CYP4G17 (5 and 27-fold). However, these candidate genes were not associated with resistance escalation as the expression levels did not differ significantly between 1\u00d7, 5\u00d7 and 10\u00d7 surviving mosquitoes; (4) Conclusions: Intensive and multiple resistance is being selected in malaria vectors from a pesticide-based agricultural hotspot of Cameroon leading to loss in the efficacy of pyrethroid-only nets. Further studies are needed to decipher the molecular basis underlying such resistance escalation to better assess its impact on control interventions.<\/jats:p>","DOI":"10.3390\/genes13071206","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Molecular Drivers of Multiple and Elevated Resistance to Insecticides in a Population of the Malaria Vector Anopheles gambiae in Agriculture Hotspot of West Cameroon"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-7681","authenticated-orcid":false,"given":"Arnaud","family":"Tepa","sequence":"first","affiliation":[{"name":"Medical Entomology Department, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9 P.O. Box 13591, Cameroon"},{"name":"Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaound\u00e9 P.O. Box 1364, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3516-8498","authenticated-orcid":false,"given":"Jonas A.","family":"Kengne-Ouafo","sequence":"additional","affiliation":[{"name":"Medical Entomology Department, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9 P.O. Box 13591, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-8632","authenticated-orcid":false,"given":"Valdi S.","family":"Djova","sequence":"additional","affiliation":[{"name":"Medical Entomology Department, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9 P.O. Box 13591, Cameroon"},{"name":"Department of Biochemistry, University of Bamenda, Bambili P.O. Box 39, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-8057","authenticated-orcid":false,"given":"Magellan","family":"Tchouakui","sequence":"additional","affiliation":[{"name":"Medical Entomology Department, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9 P.O. Box 13591, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon M. J.","family":"Mugenzi","sequence":"additional","affiliation":[{"name":"Medical Entomology Department, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9 P.O. Box 13591, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rousseau","family":"Djouaka","sequence":"additional","affiliation":[{"name":"International Institute of Tropical Agriculture, Cotonou P.O. Box 0932, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-6494","authenticated-orcid":false,"given":"Constant A.","family":"Pieme","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaound\u00e9 P.O. Box 1364, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-3673","authenticated-orcid":false,"given":"Charles S.","family":"Wondji","sequence":"additional","affiliation":[{"name":"Medical Entomology Department, Centre for Research in Infectious Diseases (CRID), Yaound\u00e9 P.O. Box 13591, Cameroon"},{"name":"International Institute of Tropical Agriculture, Yaound\u00e9 P.O. Box 2008, Cameroon"},{"name":"Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","unstructured":"World Health Organisation (2019). World Malaria Report 2019, World Health Organisation."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature15535","article-title":"The Effect of Malaria Control on Plasmodium Falciparum in Africa between 2000 and 2015","volume":"526","author":"Bhatt","year":"2015","journal-title":"Nature"},{"key":"ref_3","unstructured":"World Health Organisation (2013). 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