{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:24:30Z","timestamp":1793852670515,"version":"4.6.1"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,11,22]]},"abstract":"<jats:p>\n                    Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose- and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to\n                    <jats:italic>Anopheles<\/jats:italic>\n                    mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1112037108","type":"journal-article","created":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:21:08Z","timestamp":1320106868000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":316,"title":["Quantitative assessment of\n                    <i>Plasmodium falciparum<\/i>\n                    sexual development reveals potent transmission-blocking activity by methylene blue"],"prefix":"10.1073","volume":"108","author":[{"given":"Sophie H.","family":"Adjalley","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey L.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032;"},{"name":"School of International and Public Affairs, Columbia University, New York, NY 10027;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Sanaria, Inc., Rockville, MD 20850; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T.","family":"Eastman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Ekland","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham G.","family":"Eappen","sequence":"additional","affiliation":[{"name":"Sanaria, Inc., Rockville, MD 20850; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Richman","sequence":"additional","affiliation":[{"name":"Sanaria, Inc., Rockville, MD 20850; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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