{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:44:32Z","timestamp":1780991072834,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011135","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000}}],"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1098475"],"award-info":[{"award-number":["OPP1098475"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1017584"],"award-info":[{"award-number":["OPP1017584"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Onchocerciasis (river blindness) caused by the filarial worm <jats:italic>Onchocerca volvulus<\/jats:italic> is a neglected tropical disease that affects the skin and eyes of humans. Mass drug administration with ivermectin (IVM) to control the disease often suffers from severe adverse events in individuals co-injected with high loads of <jats:italic>Loa loa<\/jats:italic> microfilariae (mf). Thus loiasis animal models for counter-screening of compounds effective against onchocerciasis are needed, as are the corresponding onchocerciasis screening models. The repertoire of such models is highly limiting. Therefore, this study was aimed at developing and validating mf immunocompetent small animal models to increase tools for onchocerciasis drug discovery.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal findings<\/jats:title>\n<jats:p><jats:italic>O<\/jats:italic>. <jats:italic>ochengi<\/jats:italic> mf from cattle skin and <jats:italic>L<\/jats:italic>. <jats:italic>loa<\/jats:italic> mf from human blood were used to infect BALB\/c mice and Mongolian gerbils, and IVM was used for model validation. <jats:italic>O<\/jats:italic>. <jats:italic>ochengi<\/jats:italic> mf were given subcutaneously to both rodents while <jats:italic>L<\/jats:italic>. <jats:italic>loa<\/jats:italic> mf were administered intravenously to mice and intraperitoneally to gerbils. IVM was given orally. In an 8-day model of <jats:italic>O<\/jats:italic>. <jats:italic>ochengi<\/jats:italic> mf in BALB\/c mice, treatment with IVM depleted all mf in the mice, unlike the controls. Also, in a 2.5-day model of <jats:italic>L<\/jats:italic>. <jats:italic>loa<\/jats:italic> mf in BALB\/c, IVM significantly reduced mf in treated mice compared to the untreated. Furthermore, the gerbils were very susceptible to <jats:italic>O<\/jats:italic>. <jats:italic>ochengi<\/jats:italic> mf and IVM eradicated all mf in the treated animals. In the peritoneal <jats:italic>L<\/jats:italic>. <jats:italic>loa<\/jats:italic> mf gerbil model, IVM reduced mf motility in treated animals compared to the controls. In a 30-day gerbil co-injection model, IVM treatment cleared all <jats:italic>O<\/jats:italic>. <jats:italic>ochengi<\/jats:italic> mf and reduced motility of <jats:italic>L<\/jats:italic>. <jats:italic>loa<\/jats:italic> mf. Both mf survived for up to 50 days in a gerbil co-injection model.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/Significance<\/jats:title>\n<jats:p>We have developed two immunocompetent small animal models for onchocerciasis and loiasis that can be used for microfilaricide discovery and to counter-screen onchocerciasis macrofilarides<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011135","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T19:06:13Z","timestamp":1677265573000},"page":"e0011135","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development and validation of small animal models for onchocerciasis and loiasis microfilaricide discovery"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-1666","authenticated-orcid":true,"given":"Rene Bilingwe","family":"Ayiseh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glory Enjong","family":"Mbah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvis","family":"Monya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel Menang","family":"Ndi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Sakanari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-8771","authenticated-orcid":true,"given":"Fidelis","family":"Cho-Ngwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"pntd.0011135.ref001","author":"WHO","year":"2017","journal-title":"Onchocerciasis"},{"issue":"9070","key":"pntd.0011135.ref002","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0140-6736(96)11094-1","article-title":"Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.","volume":"350","author":"J Gardon","journal-title":"Lancet1997"},{"issue":"1","key":"pntd.0011135.ref003","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1371\/journal.pntd.0000076","article-title":"Ivermectin resistance in Onchocerca volvulus: toward a genetic basis","volume":"1","author":"S Lustigman","year":"2007","journal-title":"PLoS neglected tropical diseases"},{"issue":"3","key":"pntd.0011135.ref004","doi-asserted-by":"crossref","first-page":"e998","DOI":"10.1371\/journal.pntd.0000998","article-title":"Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus.","volume":"5","author":"MY Osei-Atweneboana","year":"2011","journal-title":"PLoS neglected tropical diseases"},{"issue":"4","key":"pntd.0011135.ref005","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1473-3099(13)70263-9","article-title":"Loa loa\u2014does it deserve to be neglected","volume":"14","author":"WG Metzger","journal-title":"The Lancet Infectious Diseases2013"},{"issue":"6","key":"pntd.0011135.ref006","doi-asserted-by":"crossref","first-page":"e1210","DOI":"10.1371\/journal.pntd.0001210","article-title":"The geographic distribution of Loa loa in Africa: results of large-scale implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA).","volume":"5","author":"HG Zoure","year":"2011","journal-title":"PLoS neglected tropical diseases"},{"issue":"3","key":"pntd.0011135.ref007","doi-asserted-by":"crossref","first-page":"331","DOI":"10.4269\/ajtmh.1989.41.331","article-title":"Clinical and biological study of Loa loa filariasis","volume":"41","author":"B Carme","journal-title":"Congolese. 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