{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:15:38Z","timestamp":1789708538524,"version":"4.0.1"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The widespread use of pyrethroid-only long-lasting insecticidal nets (LLINs) has contributed substantially to malaria control; however, increasing pyrethroid resistance in malaria vectors threatens their continued effectiveness. To address this challenge, LLINs incorporating additional active ingredients have been developed. MiraNet\u00ae Combi is a novel LLIN incorporating alpha-cypermethrin, the insect growth regulator pyriproxyfen (PPF), and the synergist piperonyl butoxide (PBO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the efficacy of MiraNet\u00ae Combi against pyrethroid-resistant\n                      <jats:italic>Anopheles funestus<\/jats:italic>\n                      in western Kenya using WHO cone bioassays, tunnel tests, experimental hut trials, and chemical analysis. Non-inferiority of MiraNet\u00ae Combi to Royal Guard\u00ae (alpha-cypermethrin\u2009+\u2009PPF) and superiority to Olyset\u00ae Plus (permethrin\u2009+\u2009PBO) and MiraNet\u00ae (alpha-cypermethrin-only) were assessed for mosquito mortality and blood-feeding inhibition following 20 standardized washes, in accordance with WHO guidelines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In laboratory assays, MiraNet\u00ae Combi achieved high efficacy, inducing 94.5% mortality (95% CI: 91.2\u201397.8%) and 93.8% blood-feeding inhibition (95% CI: 90.5\u201397.1%) across all wash points against susceptible and resistant mosquito strains. In experimental hut trials, MiraNet\u00ae Combi produced the highest mortality, with 23% (95% CI: 21\u201325%) in unwashed and 25% (95% CI: 23\u201327%) in washed nets, significantly exceeding unwashed Olyset\u00ae Plus (19.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002) and MiraNet\u00ae (21.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). Blood-feeding inhibition was comparable across all ITNs (90.2\u201398.4%). Unwashed MiraNet\u00ae Combi reduced ovary development by 37.5% (95% CI: 32.1\u201342.9%), decreasing to 14.3% (95% CI: 10.2\u201318.4%) after washing. MiraNet\u00ae Combi was non-inferior to Royal Guard\u00ae for mosquito mortality but not for blood-feeding inhibition, superior to Olyset\u00ae Plus and MiraNet\u00ae for mosquito mortality, superior to MiraNet\u00ae for blood-feeding inhibition, and inferior to Olyset\u00ae Plus for blood-feeding inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      MiraNet\u00ae Combi provides improved personal protection and enhanced efficacy against pyrethroid-resistant\n                      <jats:italic>An. funestus<\/jats:italic>\n                      compared with existing LLINs. The combination of a pyrethroid, PBO, and PPF represents a promising strategy for resistance management and malaria vector control in areas with high pyrethroid resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0331995","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:36:57Z","timestamp":1786556217000},"page":"e0331995","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of MiraNet Combi, a novel alpha-cypermethrin, pyriproxyfen, and piperonyl butoxide long-lasting insecticidal net against pyrethroid-resistant Anopheles funestus in western Kenya"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0685-0076","authenticated-orcid":true,"given":"Mathew","family":"Kipsum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silas","family":"Agumba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Moshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Muchoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seline","family":"Omondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celestine","family":"Wekesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8205-8887","authenticated-orcid":true,"given":"Collins","family":"Ouma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Abong\u2019o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-4970","authenticated-orcid":true,"given":"Eric","family":"Ochomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"11","key":"pone.0331995.ref001","article-title":"Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa","volume":"11","author":"K Gleave","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"issue":"10232","key":"pone.0331995.ref002","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/S0140-6736(20)30214-2","article-title":"Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign","volume":"395","author":"SG Staedke","year":"2020","journal-title":"Lancet"},{"issue":"10130","key":"pone.0331995.ref003","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(18)30427-6","article-title":"Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial","volume":"391","author":"N Protopopoff","year":"2018","journal-title":"Lancet"},{"key":"pone.0331995.ref004","unstructured":"Organization WH. WHO guidelines for malaria. 2023."},{"issue":"2","key":"pone.0331995.ref005","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3390\/genes11020143","article-title":"An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance","volume":"11","author":"BD Menze","year":"2020","journal-title":"Genes (Basel)"},{"issue":"4","key":"pone.0331995.ref006","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0215074","article-title":"Evaluation of standard pyrethroid based LNs (MiraNet and MagNet) in experimental huts against pyrethroid resistant Anopheles gambiae sl M\u2019b\u00e9, C\u00f4te d\u2019Ivoire: potential for impact on vectorial capacity","volume":"14","author":"WA Oumbouke","year":"2019","journal-title":"PLoS 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clinical malaria in an area with highly pyrethroid-resistant vectors in rural Burkina Faso: a cluster-randomised controlled trial","volume":"392","author":"AB Tiono","year":"2018","journal-title":"Lancet"},{"issue":"10331","key":"pone.0331995.ref010","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/S0140-6736(21)02499-5","article-title":"Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs in Tanzania: a four-arm, cluster-randomised trial","volume":"399","author":"JF Mosha","year":"2022","journal-title":"Lancet"},{"issue":"10375","key":"pone.0331995.ref011","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0140-6736(22)02319-4","article-title":"Efficacy of pyriproxyfen-pyrethroid long-lasting insecticidal nets (LLINs) and chlorfenapyr-pyrethroid LLINs compared with pyrethroid-only LLINs for malaria control in Benin: a cluster-randomised, superiority trial","volume":"401","author":"M Accrombessi","year":"2023","journal-title":"Lancet"},{"key":"pone.0331995.ref012","volume-title":"The evaluation process for vector control products","author":"WHO","year":"2017"},{"issue":"1","key":"pone.0331995.ref013","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1038\/s41467-022-30700-1","article-title":"Inferring the epidemiological benefit of indoor vector control interventions against malaria from mosquito data","volume":"13","author":"E Sherrard-Smith","year":"2022","journal-title":"Nat Commun"},{"key":"pone.0331995.ref014","volume-title":"Data requirements and protocol for determining non-inferiority of insecticide-treated net and indoor residual spraying products within an established WHO intervention class","author":"WHO","year":"2019"},{"issue":"1","key":"pone.0331995.ref015","doi-asserted-by":"crossref","first-page":"12227","DOI":"10.1038\/s41598-020-69109-5","article-title":"Efficacy of Royal Guard, a new 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efficacy and effectiveness of bednets for malaria control in Africa","volume":"5","author":"TS Churcher","year":"2016","journal-title":"Elife"},{"key":"pone.0331995.ref025","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/s12936-015-0890-1","article-title":"A new class of insecticide for malaria vector control: evaluation of mosquito nets treated singly with indoxacarb (oxadiazine) or with a pyrethroid mixture against Anopheles gambiae and Culex quinquefasciatus","volume":"14","author":"RM Oxborough","year":"2015","journal-title":"Malar J"},{"issue":"3","key":"pone.0331995.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001619","article-title":"The impact of pyrethroid resistance on the efficacy of insecticide-treated bed nets against African anopheline mosquitoes: systematic review and meta-analysis","volume":"11","author":"C Strode","year":"2014","journal-title":"PLoS 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that Needs Urgent Action to Maintain Malaria Control","volume":"32","author":"H Ranson","year":"2016","journal-title":"Trends Parasitol"},{"issue":"1","key":"pone.0331995.ref030","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12936-020-3138-7","article-title":"Physical integrity and survivorship of long-lasting insecticidal nets distributed to households of the same socio-cultural community in Benin, West Africa","volume":"19","author":"IB Ahogni","year":"2020","journal-title":"Malar J"},{"key":"pone.0331995.ref031","volume-title":"WHO guidelines for malaria, 14 March 2023","author":"Organization, W.H","year":"2023"},{"issue":"1","key":"pone.0331995.ref032","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s12936-021-03794-z","article-title":"Pyriproxyfen-treated bed nets reduce reproductive fitness and longevity of pyrethroid-resistant Anopheles gambiae under laboratory and field conditions","volume":"20","author":"N Grisales","year":"2021","journal-title":"Malar J"},{"key":"pone.0331995.ref033","doi-asserted-by":"crossref","first-page":"100115","DOI":"10.1016\/j.crpvbd.2023.100115","article-title":"Assessing the variability in experimental hut trials evaluating insecticide-treated nets against malaria vectors","volume":"3","author":"JD Challenger","year":"2023","journal-title":"Curr Res Parasitol Vector Borne Dis"}],"container-title":["PLOS 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