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This work provides guidance for in vitro endectocide and ectocide experiments and raises biological points for further evaluation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Three experiments with ivermectin were performed with <jats:italic>Anopheles dirus<\/jats:italic> and <jats:italic>Anopheles minimus<\/jats:italic>. The first experiment assessed the impact of a sugar diet (10% sucrose, \u201c<jats:italic>Sucrose<\/jats:italic>\u201d; multivitamin syrup, \u201c<jats:italic>Multivitamin<\/jats:italic>\u201d; or multivitamin syrup followed by 10% sucrose, \u201c<jats:italic>Mix<\/jats:italic>\u201d) on mosquito mortality following ingestion of a range of ivermectin-spiked blood meal concentrations. The lethal concentrations that kill 50% (LC<jats:sub>50<\/jats:sub>) and 90% (LC<jats:sub>90<\/jats:sub>) of mosquitoes were estimated using a normalized concentration\u2013response analysis (IC<jats:sub>50<\/jats:sub> and Hill slope). The second experiment assessed the impact on mosquito mortality after ingesting ivermectin spiked into a plasma meal or a blood meal that was either fresh or previously frozen. Log-rank survival curve analysis (Mantel\u2013Cox method) was used to compare mosquito survival between groups. The third experiment sought to quantify the concentration of ivermectin in a blood meal compared to the amount imbibed into the mosquito midgut as measured by liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The Multivitamin diet was found to substantially increase <jats:italic>An. dirus<\/jats:italic> LC<jats:sub>50<\/jats:sub> compared to Sucrose and Mix diets, while the Sucrose diet had reduced control survival post-blood meal for both <jats:italic>An. dirus<\/jats:italic> and <jats:italic>An. minimus<\/jats:italic>. Ivermectin mortality response was substantially increased when ingested in a blood meal compared to a plasma meal for <jats:italic>An. dirus<\/jats:italic>, while the inverse was observed for <jats:italic>An. minimus<\/jats:italic>. For both <jats:italic>An. dirus<\/jats:italic> and <jats:italic>An. minimus<\/jats:italic>, an approximately 20% loss in ivermectin concentration was observed in the midgut compared to the blood meal.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The Mix diet appears to be best for minimizing control mosquito mortality, without altering the mosquito survival response following ivermectin ingestion. An unexplained biological phenomenon occurred when ivermectin was ingested in either a blood meal or a plasma meal. The concentration of ivermectin imbibed by the mosquito was lower than that observed in the blood meal, suggesting that some of the ivermectin may be excreted by the mosquito during the blood meal.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s13071-025-07040-2","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:20:47Z","timestamp":1760707247000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimizing endectocide and ectocide compound evaluation in Anopheles malaria vectors"],"prefix":"10.1186","volume":"18","author":[{"given":"Kevin C.","family":"Kobylinski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thitipong","family":"Hongsuwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattarapon","family":"Khemrattrakool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natpapat","family":"Kaewkhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattawan","family":"Kullasakboonsri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theerawit","family":"Phanphoowong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patchara","family":"Sriwichai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borimas","family":"Hanboonkunupakarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Podjanee","family":"Jittamala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"7040_CR1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.actatropica.2011.10.007","volume":"121","author":"M Butters","year":"2012","unstructured":"Butters M, Kobylinski K, Deus K, da Silva I, Gray M, Sylla M, et al. 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The animal study protocol was approved by the Animal Care and Use Committee of the Faculty of Tropical Medicine, Mahidol University (007-2023). All experiments were performed in accordance with the relevant guidelines and regulations of the above-listed institutions. Each blood donor volunteer was provided with an explanation of the study and signed a written informed consent before study entry.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"417"}}