{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:47:40Z","timestamp":1791910060918,"version":"4.3.4"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"24","funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PTDC\/SAU-MET\/118199\/2010"],"award-info":[{"award-number":["PTDC\/SAU-MET\/118199\/2010"]}]},{"name":"European Research Council","award":["ERC-2015-PoC- DL3\u2013713691-REUSE4MALARIA"],"award-info":[{"award-number":["ERC-2015-PoC- DL3\u2013713691-REUSE4MALARIA"]}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"crossref","award":["FP7\/2007- 2013,grant agreement N. 242095 (EVIMalaR)"],"award-info":[{"award-number":["FP7\/2007- 2013,grant agreement N. 242095 (EVIMalaR)"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,19]]},"abstract":"<jats:p>\n                    Despite an unprecedented 2 decades of success, the combat against malaria \u2014 the mosquito-transmitted disease caused by\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasites \u2014 is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise in antiparasite drug resistance. Alternative approaches are urgently needed. Repurposing of available, approved drugs with distinct modes of action are being considered as viable and immediate adjuncts to standard antimicrobial treatment. Such strategies may be well suited to the obligatory and clinically silent first phase of\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    infection, where massive parasite replication occurs within hepatocytes in the liver. Here, we report that the widely used antidiabetic drug, metformin, impairs parasite liver stage development of both rodent-infecting\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    <jats:italic>berghei<\/jats:italic>\n                    and human-infecting\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    parasites. Prophylactic treatment with metformin curtails parasite intracellular growth in vitro. An additional effect was observed in mice with a decrease in the numbers of infected hepatocytes. Moreover, metformin provided in combination with conventional liver- or blood-acting antimalarial drugs further reduced the total burden of\n                    <jats:italic>P. berghei<\/jats:italic>\n                    infection and substantially lessened disease severity in mice. Together, our findings indicate that repurposing of metformin in a prophylactic regimen could be considered for malaria chemoprevention.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127441","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T11:01:07Z","timestamp":1576666867000},"source":"Crossref","is-referenced-by-count":41,"title":["Targeting liver stage malaria with metformin"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3373-9683","authenticated-orcid":true,"given":"Iset Medina","family":"Vera","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida T.","family":"Grilo Ruivo","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo F.","family":"Lemos Rocha","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Marques","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-2097","authenticated-orcid":true,"given":"Sangeeta N.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA."},{"name":"Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, USA."},{"name":"Howard Hughes Medical Institute, Cambridge, Masschusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Mota","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-018X","authenticated-orcid":true,"given":"Liliana","family":"Mancio-Silva","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal."},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA."},{"name":"Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"B1","unstructured":"World Health Organization. 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