{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:45:30Z","timestamp":1788245130867,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["671055"],"award-info":[{"award-number":["671055"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: There is anecdotal evidence that ivermectin may decrease seizure frequency in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods: In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy experiencing \u22652 seizures\/month were randomly allocated to receive, over a one-year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs. Data was analyzed using multiple logistic regression. Results: We enrolled 197 participants. In an intent-to-treat analysis (data from group 1 and 2 combined), seizure freedom was more likely among OIPWE treated with ivermectin thrice (OR: 5.087, 95% CI: 1.378\u201319.749; p = 0.018) and twice (OR: 2.471, 95% CI: 0.944\u20136.769; p = 0.075) than in those treated once. Similarly, &gt;50% seizure reduction was more likely among those treated with ivermectin twice (OR: 4.469, 95% CI: 1.250\u201316.620) and thrice (OR: 2.693, 95% CI: 1.077\u20136.998). Absence of microfilariae during the last 4 months increased the odds of seizure freedom (p = 0.027). Conclusions: Increasing the number of ivermectin treatments was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures.<\/jats:p>","DOI":"10.3390\/pathogens9030205","type":"journal-article","created":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T11:59:36Z","timestamp":1583841576000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo"],"prefix":"10.3390","volume":"9","author":[{"given":"Michel","family":"Mandro","sequence":"first","affiliation":[{"name":"Provincial Health Division Ituri, Ministry of Health, P.O. Box 57 Ituri, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-1239","authenticated-orcid":false,"given":"Joseph Nelson","family":"Siewe Fodjo","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Dusabimana","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deby","family":"Mukendi","sequence":"additional","affiliation":[{"name":"Centre Neuro-Psycho Pathologique, University of Kinshasa, P.O. Box 127 Kinshasa, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-3686","authenticated-orcid":false,"given":"Steven","family":"Haesendonckx","sequence":"additional","affiliation":[{"name":"Interuniversity Institute for Biostatistics and statistical Bioinformatics, Hasselt University, 3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lokonda","sequence":"additional","affiliation":[{"name":"Centre Neuro-Psycho Pathologique, University of Kinshasa, P.O. Box 127 Kinshasa, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swabra","family":"Nakato","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Nyisi","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Maladies Tropicales de l\u2019Ituri, Rethy, P.O. Box 143 Bunia, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germain","family":"Abhafule","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Maladies Tropicales de l\u2019Ituri, Rethy, P.O. Box 143 Bunia, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Wonya\u2019rossi","sequence":"additional","affiliation":[{"name":"Programme National de Lutte contre l\u2019Onchocercose, P.O. Box 185 Bunia, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-4032","authenticated-orcid":false,"given":"An","family":"Hotterbeekx","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-9304","authenticated-orcid":false,"given":"Steven","family":"Abrams","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Interuniversity Institute for Biostatistics and statistical Bioinformatics, Hasselt University, 3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1919-1340","authenticated-orcid":false,"given":"Robert","family":"Colebunders","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"ref_1","first-page":"11","article-title":"El sindrome epileptico y sus reaciones con onchocercosis","volume":"1","author":"Casis","year":"1938","journal-title":"Bol. Salubr. Hig."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pion, S.D., Kaiser, C., Boutros-Toni, F., Cournil, A., Taylor, M.M., Meredith, S.E., Stufe, A., Bertocchi, I., Kipp, W., and Preux, P.M. (2009). Epilepsy in onchocerciasis endemic areas: Systematic review and meta-analysis of population-based surveys. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000461"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0035-9203(02)90433-5","article-title":"Relationship between onchocerciasis and epilepsy: A matched case-control study in the Mbam Valley, Republic of Cameroon","volume":"96","author":"Boussinesq","year":"2002","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s40249-018-0465-9","article-title":"Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis endemic regions in the Democratic Republic of Congo: A case control study","volume":"7","author":"Mandro","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijid.2018.10.021","article-title":"High prevalence of epilepsy in an onchocerciasis endemic health zone in the Democratic Republic of the Congo, despite 14 years of community-directed treatment with ivermectin: A mixed-method assessment","volume":"79","author":"Mukendi","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S1473-3099(18)30425-0","article-title":"The temporal relationship between onchocerciasis and epilepsy: A population-based cohort study","volume":"18","author":"Chesnais","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40249-018-0452-1","article-title":"High prevalence of epilepsy in onchocerciasis endemic health areas in Democratic Republic of the Congo","volume":"7","author":"Lenaerts","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Colebunders, R., Siewe Fodjo, J.N., Hopkins, A., Hotterbeekx, A., Lakwo, T.L., Kalinga, A., Logora, M.Y., and Basanez, M.G. (2019). From river blindness to river epilepsy: Implications for onchocerciasis elimination programmes. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007407"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mandro, M., Siewe Fodjo, J.N., Mukendi, D., Dusabimana, A., Menon, S., Haesendonckx, S., Lokonda, R., Nakato, S., Nyisi, F., and Abhafule, G. (2020). Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0007966"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Osei-Atweneboana, M.Y., Awadzi, K., Attah, S.K., Boakye, D.A., Gyapong, J.O., and Prichard, R.K. (2011). Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0000998"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/epi.12550","article-title":"ILAE official report: A practical clinical definition of epilepsy","volume":"55","author":"Fisher","year":"2014","journal-title":"Epilepsia"},{"key":"ref_12","unstructured":"Merck & Co., INC (2020, January 09). Stromectol FDA Approved Package Insert. Available online: https:\/\/www.merck.com\/product\/usa\/pi_circulars\/s\/stromectol\/stromectol_pi.pdf."},{"key":"ref_13","unstructured":"Harmonization, I.C.O. (2020, January 09). Available online: www.ich.org\/products\/guidelines.html."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.0006-341X.2001.00120.x","article-title":"Akaike\u2019s information criterion in generalized estimating equations","volume":"57","author":"Pan","year":"2001","journal-title":"Biometrics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1002\/sim.1047","article-title":"A solution to the problem of separation in logistic regression","volume":"21","author":"Heinze","year":"2002","journal-title":"Stat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Atif, M., Smith, J.J., Estrada-Mondragon, A., Xiao, X., Salim, A.A., Capon, R.J., Lynch, J.W., and Keramidas, A. (2019). GluClR-mediated inhibitory postsynaptic currents reveal targets for ivermectin and potential mechanisms of ivermectin resistance. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007570"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/jbt.2570060408","article-title":"Activation of gamma-aminobutyric acid insensitive chloride channels in mouse brain synaptic vesicles by avermectin B1a","volume":"6","author":"Payne","year":"1991","journal-title":"J. Biochem. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1292\/jvms.10-0424","article-title":"Central and peripheral neurotoxic effects of ivermectin in rats","volume":"73","author":"Trailovic","year":"2011","journal-title":"J. Vet. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s11259-007-0050-3","article-title":"The effect of ivermectin on convulsions in rats produced by lidocaine and strychnine","volume":"31","author":"Trailovic","year":"2007","journal-title":"Vet. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/0278-6915(89)90048-3","article-title":"Effects of ivermectin on reproduction and neonatal toxicity in rats","volume":"27","author":"Lankas","year":"1989","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"382","DOI":"10.4269\/ajtmh.17-0042","article-title":"Serious neurological adverse events after ivermectin-do they occur beyond the indication of onchocerciasis?","volume":"98","author":"Chandler","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Siewe Fodjo, J.N., Mandro, M., Mukendi, D., Tepage, F., Menon, S., Nakato, S., Nyisi, F., Abhafule, G., Wonya\u2019rossi, D., and Anyolito, A. (2019). Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density. PLoS Negl. Trop. Dis., 13.","DOI":"10.1101\/577247"},{"key":"ref_23","first-page":"303","article-title":"Ivermectin as an adjunct in the treatment of refractory epilepsy","volume":"65","author":"Costa","year":"2017","journal-title":"Rev. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.seizure.2018.11.004","article-title":"High prevalence of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan: A community-based survey","volume":"63","author":"Colebunders","year":"2018","journal-title":"Seizure"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1046\/j.1528-1157.2003.59302.x","article-title":"Demographic impact of epilepsy in Africa: Results of a 10-year cohort study in a rural area of Cameroon","volume":"44","author":"Kamgno","year":"2003","journal-title":"Epilepsia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40249-019-0523-y","article-title":"Comprehensive management of epilepsy in onchocerciasis-endemic areas: Lessons learnt from community-based surveys","volume":"8","author":"Dekker","year":"2019","journal-title":"Infect. Dis. Poverty"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Inada, A., Oyama, S., Niinomi, I., Wakabayashi, T., Iwanaga, K., and Hosohata, K. (2019). Association of Stevens-Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs in pediatric patients: Subgroup analysis based on a Japanese spontaneous database. J. Clin. Pharm. Ther.","DOI":"10.1111\/jcpt.13001"},{"key":"ref_28","first-page":"202","article-title":"Toxic epidermal necrolysis induced by phenobarbital in a Rwandan child: Report of a case","volume":"17","author":"Misson","year":"2014","journal-title":"Pan. Afr. Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/pai.12058","article-title":"Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children","volume":"24","author":"Manuyakorn","year":"2013","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/S1474-4422(18)30107-8","article-title":"Comparative risk of major congenital malformations with eight different antiepileptic drugs: A prospective cohort study of the EURAP registry","volume":"17","author":"Tomson","year":"2018","journal-title":"Lancet Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S1474-4422(18)30495-2","article-title":"Management of epilepsy in women","volume":"18","author":"Stephen","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.seizure.2019.08.016","article-title":"Women with epilepsy in sub-Saharan Africa: A review of the reproductive health challenges and perspectives for management","volume":"71","author":"Menon","year":"2019","journal-title":"Seizure"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/3\/205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:05:54Z","timestamp":1760173554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/3\/205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,10]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["pathogens9030205"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9030205","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202001.0259.v1","asserted-by":"object"}]},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,10]]}}}