دورية أكاديمية
A randomized, open-label study of the tolerability and efficacy of one or three daily doses of ivermectin plus diethylcarbamazine and albendazole (IDA) versus one dose of ivermectin plus albendazole (IA) for treatment of onchocerciasis.
| العنوان: | A randomized, open-label study of the tolerability and efficacy of one or three daily doses of ivermectin plus diethylcarbamazine and albendazole (IDA) versus one dose of ivermectin plus albendazole (IA) for treatment of onchocerciasis. |
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| المؤلفون: | Opoku NO; Fred Newton Binka School of Public Health, University of Health and Allied Sciences, Ho, Ghana., Doe F; Hohoe Municipal Hospital, Hohoe, Ghana., Dubben B; Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany., Fetcho N; Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America., Fischer K; Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America., Fischer PU; Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America., Gordor S; Fred Newton Binka School of Public Health, University of Health and Allied Sciences, Ho, Ghana., Goss CW; Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri., Gyasi ME; St. Thomas Eye Hospital, Accra, Ghana., Hoerauf A; Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany., Hong AR; Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Kanza E; Fred Newton Binka School of Public Health, University of Health and Allied Sciences, Ho, Ghana.; Centre de Recherche Clinique de Butembo, Université Catholique du Graben, Site Horizon, Butembo, Democratic Republic of the Congo (DRC)., King CL; Center for Global Health and Diseases, Case-Western Reserve University, Cleveland, Ohio, United States of America., Laryea R; Fred Newton Binka School of Public Health, University of Health and Allied Sciences, Ho, Ghana., Lew D; Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri., Seidu MA; Department of Medical Laboratory Science, School of Biomedical and Allied Sciences, University of Ghana, Accra, Ghana., Weil GJ; Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America. |
| المصدر: | PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 May 19; Vol. 17 (5), pp. e0011365. Date of Electronic Publication: 2023 May 19 (Print Publication: 2023). |
| نوع المنشور: | Randomized Controlled Trial; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
| مواضيع طبية MeSH: | Onchocerciasis*/drug therapy , Elephantiasis, Filarial*/drug therapy , Filaricides*/adverse effects, Humans ; Female ; Ivermectin/therapeutic use ; Diethylcarbamazine/adverse effects ; Albendazole ; Pilot Projects ; Drug Therapy, Combination |
| مستخلص: | Background: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. Methods and Findings: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 μg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 μg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. Conclusions: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. Trial Registration: The study is registered at Cinicaltrials.gov under the number NCT04188301. Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Opoku et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT04188301 |
| المشرفين على المادة: | 70288-86-7 (Ivermectin) V867Q8X3ZD (Diethylcarbamazine) F4216019LN (Albendazole) 0 (Filaricides) |
| تواريخ الأحداث: | Date Created: 20230519 Date Completed: 20230605 Latest Revision: 20230613 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC10234528 |
| DOI: | 10.1371/journal.pntd.0011365 |
| PMID: | 37205721 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1935-2735 |
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| DOI: | 10.1371/journal.pntd.0011365 |