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Such blood-feeding insects include anopheline mosquitoes, which transmit malaria-causing\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasites. A US Food and Drug Administration\u2013approved HPPD enzyme inhibitor called nitisinone is a drug used to treat rare human-inherited disorders of the tyrosine pathway. Here, we demonstrate that feeding human blood containing nitisinone to insectary-reared female\n                    <jats:italic>Anopheles gambiae<\/jats:italic>\n                    mosquitoes was mosquitocidal to both young and old mosquitoes as well as insecticide-resistant\n                    <jats:italic>Anopheles<\/jats:italic>\n                    strains. Pharmacokinetic-pharmacodynamic (PK\/PD) modeling of nitisinone\u2019s dose-response relationship (when administered at the highest recommended doses for adults and children) demonstrated improved efficacy against mosquitoes compared with the gold standard endectocidal drug, ivermectin. Furthermore, blood samples from individuals with alkaptonuria (a rare genetic metabolic disorder in the tyrosine degradation pathway), who were taking a daily low dose of 2 milligrams of nitisinone, were shown to be lethal to mosquitoes. Thus, inhibiting the\n                    <jats:italic>Anopheles<\/jats:italic>\n                    HPPD enzyme with nitisinone warrants further investigation as a complementary intervention for vector control and the prevention of malaria transmission.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adr4827","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T14:15:38Z","timestamp":1742998538000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["<i>Anopheles<\/i>\n                    mosquito survival and pharmacokinetic modeling show the mosquitocidal activity of nitisinone"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-6479","authenticated-orcid":true,"given":"Lee R.","family":"Haines","sequence":"first","affiliation":[{"name":"Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, 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UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-3519","authenticated-orcid":true,"given":"Michael P.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK."},{"name":"Glasgow Polyomics, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-3204","authenticated-orcid":true,"given":"Didier","family":"Leroy","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-6068","authenticated-orcid":true,"given":"Jeremy N.","family":"Burrows","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland."},{"name":"Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-6595","authenticated-orcid":true,"given":"Giancarlo","family":"Biagini","sequence":"additional","affiliation":[{"name":"Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshminarayan R.","family":"Ranganath","sequence":"additional","affiliation":[{"name":"National Alkaptonuria Centre, Department of Clinical Biochemistry and Metabolism, Royal Liverpool University Hospital, Liverpool, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaith","family":"Aljayyoussi","sequence":"additional","affiliation":[{"name":"Department of Tropical 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