Histopathological evaluation of Onchocerca volvulus nodules by microscopy and by digital image analysis for the study of macrofilaricidal drug efficacy

Fischer, Kerstin; Dubben, Bettina; Debrah, Linda Batsa; Kuehlwein, Janina M.; Ricchiuto, Arcangelo; Debrah, Alexander Yaw; Hoerauf, Achim; Weil, Gary J.; Fischer, Peter U.; Klarmann‐Schulz, Ute

doi:10.3389/fmed.2023.1099926

Cited by 1 publication

(2 citation statements)

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“…volvulus aspartic protease (APR, GenBank U81605) for assessment of worm viability [ 25 ]. Stained slides were scanned using an Olympus scanner (Olympus VS120 Brightfield Slide Scanning System, Tokyo, Japan) at 20X magnification [ 26 ]. The digital images were checked for quality and uploaded to a secure cloud server for assessment.…”

Section: Methodsmentioning

confidence: 99%

“…Two consecutive sections were stained with Meyer's hematoxylin & eosin (H&E, Merck, Darmstadt, Germany), and a polyclonal rabbit antibody directed against an O. volvulus aspartic protease (APR, GenBank U81605) for assessment of worm viability [25]. Stained slides were scanned using an Olympus scanner (Olympus VS120 Brightfield Slide Scanning System, Tokyo, Japan) at 20X magnification [26]. The digital images were checked for quality and uploaded to a secure cloud server for assessment.…”

Section: Histology Digitalization and Evaluation Of Nodulesmentioning

confidence: 99%

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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

Opoku,

Doe,

Dubben

et al. 2023

PLoS Negl Trop Dis

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Histology Digitalization and Evaluation Of Nodulesmentioning

confidence: 99%