{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:59:36Z","timestamp":1782907176904,"version":"3.54.5"},"reference-count":45,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,5]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>The Oriental rat flea, <jats:italic>Xenopsylla cheopis<\/jats:italic>, is known worldwide as an efficient plague vector, including in Madagascar, where the disease remains a public health concern. Chemical control is the primary response method against <jats:italic>X. cheopis<\/jats:italic> in Madagascar. Previous bioassays focusing on different flea populations from Madagascar showed phenotypic resistance to various insecticides, including deltamethrin and fenitrothion, which, respectively, represent the previous and current chemicals for flea vector control. Despite apparent insecticide resistance, the associated mechanisms of this resistance remain poorly known. The aims of this study were to adjust diagnostic doses of deltamethrin and fenitrothion and to investigate the metabolism-based insecticide resistance of <jats:italic>X. cheopis<\/jats:italic> in Madagascar. Five available laboratory-reared flea strains of <jats:italic>X. cheopis<\/jats:italic> were selected, and their susceptibility statuses to deltamethrin and fenitrothion were determined using the WHO standard bioassay. Diagnostic doses of each insecticide were determined by the probit method, in accordance with concentration gradients. Biochemical microplate-based assays were performed to detect overproduction of cytochrome P450, alpha-\/beta-esterases, and glutathione S-transferase (GST), which are signatures of metabolic resistance. The five tested strains showed different susceptibility statuses against deltamethrin and fenitrothion. The diagnostic doses were estimated to be 0.07% for deltamethrin and 1.56% for fenitrothion. Increased activities of cytochrome P450, beta-esterase, and GST enzymes in the resistant strains were revealed in comparison with those of the susceptible strain. In conclusion, readjusted diagnostic doses will help to better understand the susceptibility status of <jats:italic>X. cheopis<\/jats:italic> to deltamethrin and fenitrothion. The overproduction of cytochrome P450, beta-esterase, and GST observed on deltamethrin<jats:bold>-<\/jats:bold>resistant flea strains suggests metabolic resistance.<\/jats:p>","DOI":"10.4269\/ajtmh.24-0258","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T20:35:06Z","timestamp":1733258106000},"page":"620-625","source":"Crossref","is-referenced-by-count":1,"title":["Insecticide Resistance of Xenopsylla cheopis in Madagascar: Revision of Diagnostic Doses for Bioassay and Exploration of Biochemical Mechanisms"],"prefix":"10.4269","volume":"112","author":[{"given":"Annick O.","family":"Raveloson","sequence":"first","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"},{"name":"Ecole Doctorale Sciences de la Vie et de l\u2019Environnement, Universit\u00e9 d\u2019Antananarivo, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiery","family":"Nepomichene","sequence":"additional","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tojo R.","family":"Ramihangihajason","sequence":"additional","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandimby","family":"Rajaonarimanana","sequence":"additional","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fara N.","family":"Raharimalala","sequence":"additional","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Harimalala","sequence":"additional","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"},{"name":"Ecole Doctorale Sciences de la Vie et de l\u2019Environnement, Universit\u00e9 d\u2019Antananarivo, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Girod","sequence":"additional","affiliation":[{"name":"Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Annu Rev Entomol","first-page":"61","article-title":"Transmission of flea-borne zoonotic agents","volume":"57","author":"Eisen","year":"2012"},{"key":"b2","series-title":"Wkly Epidemiol Rec","first-page":"289","article-title":"Plague around the world","volume":"94","author":"Bertherat","year":"2019"},{"key":"b3","series-title":"Emerg Infect Dis","first-page":"220","article-title":"Trends of human plague, Madagascar, 1998\u20132016","volume":"25","author":"Andrianaivoarimanana","year":"2019"},{"key":"b4","series-title":"Atlas de la Peste \u00e0 Madagascar","author":"Chanteau","year":"2006"},{"key":"b5","series-title":"Pasteur de Madagascar","first-page":"171","article-title":"Etude de X. cheopis et S. fonquerniei, puces pestig\u00e8nes malgaches\u2014Mise en \u00e9vidence de leur r\u00e9sistance aux DDT, Dieldrin et Malathion. 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