{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:25:46Z","timestamp":1789644346444,"version":"4.0.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T00:00:00Z","timestamp":1357516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"AntiMal Consortium","award":["018834"],"award-info":[{"award-number":["018834"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Medical Primatology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Drug resistance against first\u2010line antimalarials warrants search for new lead compounds and repurposing of drugs such as methotrexate. Animal models are required for preclinical drug development before clinical testing. This study aimed to develop a preclinical drug development system in baboons infected with <jats:italic>Plasmodium knowlesi<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Protocols for drug administration, pharmacokinetics, clinical chemistry and haematology were developed in the baboon model. Baboons were infected with <jats:italic>P.\u00a0knowlesi<\/jats:italic> and methotrexate administered orally for 5\u00a0days. Clinical signs, parasitaemia, gross and histopathology examinations were conducted to determine effect of methotrexate in baboons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No major clinical chemistry, haematology and pathological changes attributable to methotrexate were observed. Parasitaemia suppression of 77.67% was achieved at a methotrexate dose of 3.0\u00a0mg\/kg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A protocol for preclinical drug development in the baboon was optimized. Methotrexate suppressed <jats:italic>P.\u00a0knowlesi<\/jats:italic> malaria in baboons. These findings warrant further characterization of methotrexate for use in combination therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jmp.12034","type":"journal-article","created":{"date-parts":[[2013,1,8]],"date-time":"2013-01-08T23:23:05Z","timestamp":1357687385000},"page":"62-70","source":"Crossref","is-referenced-by-count":2,"title":["Preclinical drug evaluation system in the <i>Plasmodium knowlesi<\/i> baboon model of malaria: the methotrexate study"],"prefix":"10.1111","volume":"42","author":[{"given":"M.","family":"Ichagichu","sequence":"first","affiliation":[{"name":"Department of Tropical and Infectious Diseases Institute of Primate Research Karen, Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ngotho","sequence":"additional","affiliation":[{"name":"Department of Tropical and Infectious Diseases Institute of Primate Research Karen, Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.M.","family":"Karanja","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine and Infectious Diseases Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Kokwaro","sequence":"additional","affiliation":[{"name":"Consortium for National Health Research Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kariuki","sequence":"additional","affiliation":[{"name":"Department of Tropical and Infectious Diseases Institute of Primate Research Karen, Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Nzila","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI) \u2010 Wellcome Trust Research Program Kilifi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ozwara","sequence":"additional","affiliation":[{"name":"Department of Tropical and Infectious Diseases Institute of Primate Research Karen, Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(00)00184-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000406"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2012.013"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.4049\/jimmunol.128.1.224","article-title":"Altered expression of Plasmodium knowlesi variant antigen on the erythrocyte membrane in splenectomized rhesus monkeys","volume":"128","author":"Barnwell JW","year":"1982","journal-title":"J Immunol"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-63"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.149.3686.865"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3461"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002401"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.3"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.7883\/yoken.JJID.2008.210"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1416"},{"key":"e_1_2_7_13_1","first-page":"101","article-title":"Adverse effects of low dose methotrexate in rheumatoid arthritis patients","volume":"22","author":"Gilani STA","year":"2012","journal-title":"J Coll Physicians Surg Pak"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(00)00184-3"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/978396"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2009.06.007"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00308-09"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-23"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002015"},{"key":"e_1_2_7_20_1","first-page":"54","article-title":"Characterisation of placental malaria in olive baboons (Papio anubis) infected with Plasmodium knowlesi H strain","volume":"9","author":"Mustafa B","year":"2010","journal-title":"Int J Integr Biol"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70064-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-008-0897-4"},{"key":"e_1_2_7_23_1","first-page":"1202","article-title":"Multiple sclerosis","volume":"2012","author":"Nicholas R","year":"2012","journal-title":"Clin Evid (Online)"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2144"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9390-1"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2003.69.188"},{"key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1177\/026119299502300306","article-title":"The development of the three Rs concept","volume":"23","author":"Russell WMS","year":"1995","journal-title":"Altern Lab Anim"},{"key":"e_1_2_7_28_1","first-page":"5","article-title":"Plasmodium knowlesi: from Malaysia, a novel health care threat","volume":"20","author":"Sabbatani S","year":"2012","journal-title":"Infez Med"},{"key":"e_1_2_7_29_1","first-page":"299","article-title":"The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern?","volume":"14","author":"Sabbatani S","year":"2010","journal-title":"Braz J Infect Dis"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2006.02.022"},{"key":"e_1_2_7_31_1","first-page":"473","article-title":"Methotrexate in rheumatoid arthritis","volume":"58","author":"Swierkot J","year":"2006","journal-title":"Pharmacol Rep"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(01)00317-5"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000402"},{"key":"e_1_2_7_34_1","first-page":"168","article-title":"Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis","volume":"65","author":"Tian H","year":"2007","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/524889"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939552"}],"container-title":["Journal of Medical Primatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjmp.12034","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjmp.12034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jmp.12034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T04:58:49Z","timestamp":1698641929000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jmp.12034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,7]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1111\/jmp.12034"],"URL":"https:\/\/doi.org\/10.1111\/jmp.12034","archive":["Portico"],"relation":{},"ISSN":["0047-2565","1600-0684"],"issn-type":[{"value":"0047-2565","type":"print"},{"value":"1600-0684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,7]]}}}