부산대학교 도서관

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. Author summary: Why was this study done?: Onchocerciasis is a neglected tropical disease caused by parasitic round worms. The infective worm larvae are transmitted by black flies that breed near rivers in sub-Saharan Africa. The parasites cause severe skin disease with itching and ocular disease; the common name for the infection is "river blindness". WHO has targeted onchocerciasis for elimination and mass drug administration is the key intervention strategy. There is an urgent need for improved treatments to kill or permanently sterilize the adult parasites. This study tested a combination drug treatment that is quite effective for treating other related worm infections. What did the researchers do and find?: We performed a randomized clinical trial that compared a triple drug combination with a standard of care two-drug treatment that is widely used in Africa. We found that the new treatment was as safe as the standard treatment. More importantly, analysis of adult female worms surgically removed from study participants suggested that the new treatment might be more effective than the standard treatment for killing or permanently sterilizing the parasites. However, this first study was too small to provide conclusive results. What do these findings mean?: An improved treatment could improve chances for eliminating onchocerciasis in Africa. Results from this study can be used to better plan follow-up studies to explore the value of this and other new combination treatments for onchocerciasis. [ABSTRACT FROM AUTHOR]