{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:35:43Z","timestamp":1791894943153,"version":"4.3.4"},"reference-count":78,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"crossref","award":["grant 2020-67015-30881"],"award-info":[{"award-number":["grant 2020-67015-30881"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | National Institutes of Health","award":["grant R01 HD102487"],"award-info":[{"award-number":["grant R01 HD102487"]}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["grant No. 310030_214897"],"award-info":[{"award-number":["grant No. 310030_214897"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Drug development for congenital toxoplasmosis is challenging since first-line therapy has a high rate of adverse effects and exhibits suboptimal efficacy. Bumped kinase inhibitors (BKIs), targeting protein kinases with small gatekeeper residues, have been found to be effective against\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              . The efficacy of BKI-1748 administered later than 2 days post-infection (p.i.), a scenario that may better reflect its real-world use as a therapeutic candidate, has not been investigated in\n              <jats:italic>T. gondii<\/jats:italic>\n              -infected pregnant sheep. For this purpose, 19 pregnant sheep were assigned to three experimental groups. Group 1 (G1,\n              <jats:italic>n<\/jats:italic>\n              = 8) and group 2 (G2,\n              <jats:italic>n<\/jats:italic>\n              = 8) were dosed orally with 10 TgShSp1 sporulated oocysts at 90 days of gestation (dg). Animals from group 3 (G3,\n              <jats:italic>n<\/jats:italic>\n              = 3) were simultaneously mock dosed with phosphate-buffered solution (PBS). In G1, BKI-1748 was administered orally from day 7 p.i. (fever and increased serum IFN\u03b3 levels) onward, maintaining drug exposure for 20 days (10 doses at 15 mg\/kg every 2 days). Treated animals (G1) exhibited significantly lower rectal temperatures (on days 8 and 9 p.i.), serum IFN\u03b3 levels (on day 10 p.i.), and specific IgG levels when compared with non-treated animals (G2). At delivery, significantly higher percentages of healthy lambs were found in infected\/treated sheep in G1 (73.3%) and in uninfected sheep in G3 (80%) compared with infected\/untreated sheep in G2 (31.3%). Concerning congenital transmission, parasite DNA was neither detected in placenta nor target tissues (brain and lungs) from the fetuses\/lambs in G1(infected\/treated) and G3 (uninfected). By contrast, parasite DNA was detected in all placentas and lambs from G2 (infected\/untreated), except for one sheep that aborted on day 13 p.i.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01448-24","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:00:46Z","timestamp":1735650046000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Treatment with BKI-1748 after\n            <i>Toxoplasma gondii<\/i>\n            systemic dissemination in experimentally infected pregnant sheep improves fetal and lamb mortality and morbidity and prevents congenital infection"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5067-2636","authenticated-orcid":false,"given":"Roberto","family":"S\u00e1nchez-S\u00e1nchez","sequence":"first","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Huertas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]},{"name":"Animal Health Department, University of Murcia","place":["Murcia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Largo-de la Torre","sequence":"additional","affiliation":[{"name":"SALUVET-Innova S.L., Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Ferre","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo Maria","family":"Dini","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Re","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]},{"name":"Animal Medicine and Surgery Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Moreno-Gonzalo","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]},{"name":"Animal Medicine and Surgery Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington","place":["Seattle, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3413-4969","authenticated-orcid":true,"given":"Matthew A.","family":"Hulverson","sequence":"additional","affiliation":[{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington","place":["Seattle, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayode K.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington","place":["Seattle, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-2347","authenticated-orcid":true,"given":"Samuel L. M.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Washington","place":["Seattle, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hemphill","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne","place":["Berne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley C.","family":"Van Voorhis","sequence":"additional","affiliation":[{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington","place":["Seattle, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-6783","authenticated-orcid":true,"given":"Luis Miguel","family":"Ortega-Mora","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s\/n","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781003199373"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.12.111732"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-3860"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.894573"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11101187"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182021001013"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fawpar.2019.e00037"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vprsr.2021.100623"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.06.002"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221709"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit032"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.09.023"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fawpar.2019.e00036"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2005.04.011"},{"key":"e_1_3_4_16_2","volume-title":"Conn\u2019s current therapy","author":"Contini C","year":"2016","unstructured":"ContiniC. 2016. Edited by ET Bope and RD Kellerman. Conn\u2019s current therapy. Elsevier, Amsterdam, The Netherlands."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5758"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.08.001"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-017-0206-8"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-80569-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.138.18.434"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026618666181002113617"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2016.04.024"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00436"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.01.004"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00005-17"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.580425"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007000200"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02009-15"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S60973"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00057-17"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00115-19"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011045200"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09022"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/ml100096t"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1818"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.299"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182017001901"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2017.01.001"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2013.04.001"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2014.12.001"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106099"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2021.05.001"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy664"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.01.006"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23042381"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad470"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx134"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144203"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216393"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02527-18"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-021-04769-4"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2023.105052"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2020.109195"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03544.x"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2023.109889"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02324-16"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.08140718"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fawpar.2019.e00052"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.842595"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-021-00953-7"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1021556"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/ani12243453"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-019-0681-8"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.11.114"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114019"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12893"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114812"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-016-0327-z"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.3906\/vet-0910-170"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2012.09.037"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.applanim.2021.105281"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vprsr.2018.01.001"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.129.5.89"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.132.16.409"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9975(88)90021-7"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0259890"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1051\/vetres:2003009"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0304-4017(01)00526-x"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01448-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01448-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T15:05:56Z","timestamp":1739459156000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01448-24"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":78,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,13]]}},"alternative-id":["10.1128\/aac.01448-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01448-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]},"assertion":[{"value":"2024-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01448-24"}}