{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:58:03Z","timestamp":1790369883137,"version":"4.1.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"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>\n                      Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control\n                      <jats:italic>Aedes<\/jats:italic>\n                      and\n                      <jats:italic>Anopheles<\/jats:italic>\n                      species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Third-instar larvae of pyrethroid-resistant\n                      <jats:italic>Anopheles arabiensis<\/jats:italic>\n                      (both laboratory-reared and field-collected) were reared in different PPF concentrations, between 1\u00d710\n                      <jats:sup>\u22129<\/jats:sup>\n                      milligrams active ingredient per litre of water (mgAI\/L) and 1\u00d710\n                      <jats:sup>\u22124<\/jats:sup>\n                      mgAI\/L, or no PPF at all. Emergent adults escaping these sub-lethal exposures were tested using WHO-standard susceptibility assays on pyrethroids (0.75% permethrin and 0.05% deltamethrin), carbamates (0.1% bendiocarb) and organochlorides (4% DDT). Biochemical basis of pyrethroid resistance was investigated by pre-exposure to 4% PBO. Bio-efficacies of long-lasting insecticide-treated nets, Olyset\n                      <jats:sup>\u00ae<\/jats:sup>\n                      and PermaNet 2.0 were also examined against adult mosquitoes with or without previous aquatic exposure to PPF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Addition of sub-lethal doses of PPF to larval habitats of pyrethroid-resistant\n                      <jats:italic>An<\/jats:italic>\n                      .\n                      <jats:italic>arabiensis<\/jats:italic>\n                      , consistently resulted in significantly reduced mortalities of emergent adults when exposed to pyrethroids, but not to bendiocarb or DDT. Mortality rates after exposure to Olyset\n                      <jats:sup>\u00ae<\/jats:sup>\n                      nets, but not PermaNet 2.0 were also reduced following aquatic exposures to PPF. Pre-exposure to PBO followed by permethrin or deltamethrin resulted in significant increases in mortality, compared to either insecticide alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Partially-resistant mosquitoes exposed to sub-lethal aquatic concentrations of PPF may become more resistant to pyrethroids than they already are without such pre-exposures. Studies should be conducted to examine whether field applications of PPF, either by larviciding or other means actually exacerbates pyrethroid-resistance in areas where signs of such resistance already exist in wild the vector populations. The studies should also investigate mechanisms underlying such magnification of resistance, and how this may impact the potential of PPF-based interventions in areas with pyrethroid resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0248538","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T13:55:49Z","timestamp":1616075749000},"page":"e0248538","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0432-0418","authenticated-orcid":true,"given":"Mercy A.","family":"Opiyo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halfan S.","family":"Ngowo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salum A.","family":"Mapua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Mpingwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuru","family":"Nchimbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy S.","family":"Matowo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silas","family":"Majambere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredros O.","family":"Okumu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"pone.0248538.ref001","volume-title":"Global Technical Strategy for Malaria elimination","author":"WHO","year":"2015"},{"key":"pone.0248538.ref002","volume-title":"World malaria report 2017","author":"WHO","year":"2017"},{"key":"pone.0248538.ref003","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":"S Bhatt","year":"2015","journal-title":"Nature"},{"key":"pone.0248538.ref004","volume-title":"World Malaria Report 2018","author":"WHO","year":"2018"},{"key":"pone.0248538.ref005","volume-title":"World Malaria Report","author":"WHO","year":"2019"},{"key":"pone.0248538.ref006","volume-title":"List of WHO Prequalified Vector Control Products.","author":"WHO","year":"2019"},{"key":"pone.0248538.ref007","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1016\/S0140-6736(15)00417-1","article-title":"Averting a malaria disaster: will insecticide resistance derail malaria control?","volume":"387","author":"J Hemingway","year":"2016","journal-title":"The Lancet"},{"key":"pone.0248538.ref008","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/526198a","article-title":"Malaria: fifteen years of interventions","volume":"526","author":"J Hemingway","year":"2015","journal-title":"Nature"},{"key":"pone.0248538.ref009","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev-ento-010814-020828","article-title":"Insecticide resistance in mosquitoes: impact, mechanisms, and research directions","volume":"60","author":"N. Liu","year":"2015","journal-title":"Annu Rev Entomol"},{"key":"pone.0248538.ref010","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12936-020-03321-6","article-title":"The fabric of life: what if mosquito nets were durable and widely available but insecticide-free?","volume":"19","author":"F Okumu","year":"2020","journal-title":"Malar J"},{"key":"pone.0248538.ref011","article-title":"Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa (2018)","volume":"11","author":"K Gleave","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0248538.ref012","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/s13063-019-3382-8","article-title":"LLIN Evaluation in Uganda Project (LLINEUP)\u2014Impact of long-lasting insecticidal nets with, and without, piperonyl butoxide on malaria indicators in Uganda: study protocol for a cluster-randomised trial","volume":"20","author":"SG Staedke","year":"2019","journal-title":"Trials"},{"key":"pone.0248538.ref013","doi-asserted-by":"crossref","first-page":"0075134","DOI":"10.1371\/journal.pone.0075134","article-title":"Efficacy of Olyset\u00ae Plus, a New Long-Lasting Insecticidal Net Incorporating Permethrin and Piperonil-Butoxide against Multi-Resistant Malaria Vectors","volume":"8","author":"C Pennetier","year":"2013","journal-title":"PLoS One"},{"key":"pone.0248538.ref014","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.7554\/eLife.16090","article-title":"The impact of pyrethroid resistance on the efficacy and effectiveness of bednets for malaria control in Africa","author":"TS Churcher","year":"2016","journal-title":"ELife"},{"key":"pone.0248538.ref015","article-title":"Prequalification Vector Control: Prequalified lists of vector control products","author":"World Health 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Rev"},{"key":"pone.0248538.ref020","first-page":"CD008923","article-title":"Mosquito larval source management for controlling malaria","volume":"8","author":"LS Tusting","year":"2013","journal-title":"The Cochrane Database Syst Rev"},{"key":"pone.0248538.ref021","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev.ento.43.1.545","article-title":"New insecticides with ecdysteroidal and juvenile hormone activity","volume":"43","author":"TS Dhadialla","year":"1998","journal-title":"Annual review of entomology"},{"key":"pone.0248538.ref022","author":"WHO","year":"2006","journal-title":"WHO Specifications and Evaluations for Public Health Pesticides"},{"key":"pone.0248538.ref023","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1603\/ME12006","article-title":"Efficacy of pyriproxyfen-treated nets in sterilizing and shortening the longevity of Anopheles gambiaeDiptera: Culicidae).","volume":"49","author":"K Ohashi","year":"2012","journal-title":"J Med Entomol"},{"key":"pone.0248538.ref024","doi-asserted-by":"crossref","first-page":"0093603","DOI":"10.1371\/journal.pone.0093603","article-title":"Olyset Duo\u00ae (a Pyriproxyfen and Permethrin Mixture Net): An Experimental Hut Trial against Pyrethroid Resistant Anopheles gambiae and Culex quinquifasciatus in Southern Benin","volume":"9","author":"C Ngufor","year":"2014","journal-title":"PLoS One"},{"key":"pone.0248538.ref025","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/1756-3305-6-144","article-title":"Sterilising effects of pyriproxyfen on Anopheles arabiensis and its potential use in malaria control","volume":"6","author":"C Harris","year":"2013","journal-title":"Parasit Vectors"},{"key":"pone.0248538.ref026","doi-asserted-by":"crossref","first-page":"852","DOI":"10.4269\/ajtmh.13-0550","article-title":"Comprehensive Sterilization of Malaria Vectors Using Pyriproxyfen: A Step Closer to Malaria Elimination","volume":"90","author":"DW Lwetoijera","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"pone.0248538.ref027","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/1756-3305-7-280","article-title":"Pyriproxyfen for mosquito control: female sterilization or horizontal transfer to oviposition substrates by Anopheles gambiae sensu stricto and Culex quinquifasciatus","volume":"7","author":"O Mbare","year":"2014","journal-title":"Parasit Vectors"},{"key":"pone.0248538.ref028","first-page":"e0067045","article-title":"The Effect of Pyriproxyfen as a \u201cPopulation Growth Regulator\u201d against Aedes albopictus under Semi- Field Conditions","volume":"8","author":"S-y Ohba","year":"2013","journal-title":"PLoS One"},{"key":"pone.0248538.ref029","doi-asserted-by":"crossref","first-page":"e95640","DOI":"10.1371\/journal.pone.0095640","article-title":"Negative Cross Resistance Mediated by Co-Treated Bed Nets: A Potential Means of Restoring Pyrethroid-Susceptibility to Malaria Vectors","volume":"9","author":"MT White","year":"2014","journal-title":"PLoS One"},{"key":"pone.0248538.ref030","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1603\/0022-2585-41.5.930","article-title":"Investigation of negative cross-resistance as a resistance-management tool for insecticide-treated nets","volume":"41","author":"J Kolaczinski","year":"2004","journal-title":"Journal of medical entomology"},{"key":"pone.0248538.ref031","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1051\/parasite\/2015027","article-title":"Insecticidal and sterilizing effect of Olyset Duo (\u00ae), a permethrin and pyriproxyfen mixture net against pyrethroid-susceptible and -resistant strains of Anopheles gambiae s.s.: a release- recapture assay in experimental huts","volume":"22","author":"A Dj\u00e8nontin","year":"2015","journal-title":"Parasite"},{"key":"pone.0248538.ref032","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12936-017-1727-x","article-title":"WHO cone bio-assays of classical and new-generation long-lasting insecticidal nets call for innovative insecticides targeting the knock-down resistance mechanism","volume":"16","author":"M Allossogbe","year":"2017","journal-title":"Benin. Malar J"},{"key":"pone.0248538.ref033","first-page":"395","article-title":"Control of Vectors and Incidence of Malaria in an Irrigated Settlement Scheme in Sri Lanka When Using the Insect Growth Regulator Pyriproxyfen","volume":"20","author":"A Yapabandara","year":"2004","journal-title":"J Am Mosq Control Assoc"},{"key":"pone.0248538.ref034","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1371\/journal.pntd.0001793","article-title":"The \u201cAuto- Dissemination\u201d Approach: A Novel Concept to Fight Aedes albopictus in Urban Areas","volume":"6","author":"B Caputo","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"pone.0248538.ref035","doi-asserted-by":"crossref","first-page":"11530","DOI":"10.1073\/pnas.0901369106","article-title":"Using adult mosquitoes to transfer insecticides to Aedes aegypti larval habitats","volume":"106","author":"GJ Devine","year":"2009","journal-title":"Proc Natl Acad Sci"},{"key":"pone.0248538.ref036","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/1475-2875-9-142","article-title":"The potential of a new larviciding method for the control of malaria vectors","volume":"9","author":"GJ Devine","year":"2010","journal-title":"Malar J"},{"key":"pone.0248538.ref037","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1475-2875-13-161","article-title":"Effective autodissemination of pyriproxyfen to breeding sites by the exophilic malaria vector Anopheles arabiensis in semi-field settings in Tanzania","volume":"13","author":"D Lwetoijera","year":"2014","journal-title":"Malar J"},{"key":"pone.0248538.ref038","doi-asserted-by":"crossref","first-page":"e1002213","DOI":"10.1371\/journal.pmed.1002213","article-title":"Mosquito-Disseminated Insecticide for Citywide Vector Control and Its Potential to Block Arbovirus Epidemics: Entomological Observations and Modeling Results from Amazonian Brazil","volume":"14","author":"F Abad-Franch","year":"2017","journal-title":"PLoS Med"},{"key":"pone.0248538.ref039","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1093\/jme\/tjw133","article-title":"Attractive Toxic Sugar Bait (ATSB) Mixed With Pyriproxyfen for Control of Larval Aedes albopictus (Diptera: Culicidae) Through Fecal Deposits of Adult Mosquitoes","volume":"54","author":"JM Scott","year":"2017","journal-title":"J Med Entomol"},{"key":"pone.0248538.ref040","author":"WHO","year":"2013","journal-title":"Test procedures for insecticide resistance monitoring in malaria vector mosquitoes"},{"key":"pone.0248538.ref041","author":"WHO","year":"2013","journal-title":"Guidelines for laboratory and field-testing of long-lasting insecticidal nets"},{"key":"pone.0248538.ref042","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.actatropica.2013.10.020","article-title":"Synergist bioassays: A simple method for initial metabolic resistance investigation of field Anopheles gambiae s.l. populations","volume":"130","author":"M Choua\u00efbou","year":"2014","journal-title":"Acta Trop"},{"key":"pone.0248538.ref043","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/tox.20386","article-title":"Synergist efficacy of piperonyl butoxide with deltamethrin as pyrethroid insecticide on Culex tritaeniorhynchus (Diptera: Culicidae) and other mosquitoe species","volume":"24","author":"M Fakoorziba","year":"2009","journal-title":"Environ Toxicol"},{"key":"pone.0248538.ref044","article-title":"R: A Language and Environment for Statistical Computing","author":"R R Core Team","year":"2011"},{"key":"pone.0248538.ref045","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ibmb.2016.09.001","article-title":"Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An. gambiae","volume":"78","author":"C Yunta","year":"2016","journal-title":"Insect Biochem Mol Biol"},{"key":"pone.0248538.ref046","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.actatropica.2014.11.016","article-title":"Inheritance mode, cross-resistance and realized heritability of pyriproxyfen resistance in a field strain of Musca domestica L. (Diptera: Muscidae)","volume":"142","author":"RM Shah","year":"2015","journal-title":"Acta Trop"},{"key":"pone.0248538.ref047","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s00436-015-4872-6","article-title":"Toxicity and resistance of field collected Musca domestica (Diptera: Muscidae) against insect growth regulator insecticides","volume":"115","author":"HAA Khan","year":"2016","journal-title":"Parasitol Res"},{"key":"pone.0248538.ref048","doi-asserted-by":"crossref","first-page":"e31077","DOI":"10.1371\/journal.pone.0031077","article-title":"Over-Expression of a Cytochrome P450 Is Associated with Resistance to Pyriproxyfen in the Greenhouse Whitefly Trialeurodes vaporariorum","volume":"7","author":"N Karatolos","year":"2012","journal-title":"PLoS One"},{"key":"pone.0248538.ref049","doi-asserted-by":"crossref","first-page":"863","DOI":"10.7150\/ijbs.6744","article-title":"Permethrin Induction of Multiple Cytochrome P450 Genes in Insecticide Resistant Mosquitoes, Culex quinquefasciatus","volume":"9","author":"Y Gong","year":"2013","journal-title":"Int J Biol Sci"},{"key":"pone.0248538.ref050","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/1756-3305-5-159","article-title":"Bio-efficacy of selected long-lasting insecticidal nets against pyrethroid resistant Anopheles arabiensis from South-Western Ethiopia","volume":"5","author":"D Yewhalaw","year":"2012","journal-title":"Parasit Vectors"},{"key":"pone.0248538.ref051","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1756-3305-6-130","article-title":"Bioefficacy of long-lasting insecticidal nets against pyrethroid-resistant populations of Anopheles gambiae s.s. from different malaria transmission zones","volume":"6","author":"M Okia","year":"2013","journal-title":"Uganda. 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Ranson","journal-title":"Trends parasitol"},{"key":"pone.0248538.ref055","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/ps.1336","article-title":"Temporal synergism by microencapsulation of piperonyl butoxide and \u03b1\u2010cypermethrin overcomes insecticide resistance in crop pests","volume":"63","author":"G Bingham","year":"2007","journal-title":"Pest Manag Sci"},{"key":"pone.0248538.ref056","first-page":"159","article-title":"Efficacy of piperonyl butoxide (PBO) as a synergist with deltamethrin on five species of mosquitoes","volume":"39","author":"VA Vijayan","year":"2007","journal-title":"J Commun Dis"},{"key":"pone.0248538.ref057","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/ps.3446","article-title":"Efficacy of six neonicotinoid insecticides alone and in combination with deltamethrin and piperonyl butoxide against pyrethroid\u2010resistant Aedes aegypti and Anopheles gambiae (Diptera: Culicidae)","volume":"69","author":"F Darriet","year":"2013","journal-title":"Pest Manag Sci"},{"key":"pone.0248538.ref058","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/j.1365-3156.2010.02717.x","article-title":"Can piperonyl butoxide enhance the efficacy of pyrethroids against pyrethroid-resistant Aedes aegypti?","volume":"16","author":"G Bingham","year":"2011","journal-title":"Trop Med Int Hlth"},{"key":"pone.0248538.ref059","first-page":"1691","article-title":"Increased Pyrethroid Resistance in Malaria Vectors and Decreased Bed Net Effectiveness, Burkina Faso","volume":"20","author":"KH To\u00e9","year":"2014","journal-title":"Emerg Infect Dis"},{"key":"pone.0248538.ref060","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12936-015-0721-4","article-title":"When a discriminating dose assay is not enough: measuring the intensity of insecticide resistance in malaria vectors","volume":"14","author":"J Bagi","year":"2015","journal-title":"Malar J"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0248538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T13:56:30Z","timestamp":1616075790000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0248538"}},"subtitle":[],"editor":[{"given":"John","family":"Vontas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0248538","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.11.426299","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]}}}