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Assessing the efficacy of high-dose rifampicin plus albendazole against onchocerciasis.

PLoS neglected tropical diseases

Authors: Monica Ahiadorme, Ute Klarmann-Schulz, Bettina Dubben, Jennifer Nadal, Patricia Jebett Korir, Kenneth Pfarr, Janina M Kuehlwein, Franziska Lenz-Plet, Arcangelo Ricchiuto, Emmanuel Donawobuge Kutu, Derrick Adu Mensah, Vera Serwaa Opoku, John Boateng, John Opoku, Jubin Osei-Mensah, Charles Gyasi, Prince Obeng, Eunice Kyaakyile Kuutiero, Michael Agyemang Obeng, Benjamin Emikpe, Abu Abudu Rahamani, Prince Dennis Atisu, Nana Kwame Ayisi-Boateng, Derrick Boateng Kontoh, Sampson Twumasi-Ankrah, Achim Hoerauf, Linda Batsa Debrah, Alexander Yaw Debrah

BACKGROUND: Onchocerciasis, also known as river blindness, remains a public health challenge in tropical regions. Despite significant gains through mass drug administration (MDA) with ivermectin, the infection remains persistent in many endemic foci. While the disease burden has reduced, elimination may require alternative strategies, including macrofilaricidal therapies. Rifampicin (RIF) has demonstrated strong anti-Wolbachia activity in vitro and in animal models, but its clinical efficacy in humans remains uncertain.

METHODS: We conducted a phase II randomized, controlled trial in Ghana to evaluate the safety and efficacy of high-dose RIF (35 mg/kg/day) combined with albendazole (ALB, 400 mg/day) as an alternative treatment for onchocerciasis. The study randomized 120 infected participants into one of four arms: RIF + ALB for 14 days (TA1), RIF + ALB for 7 days (TA2), ALB alone for 14 days (TA3), and a No Treatment control group (TA4). Treatment efficacy, including Wolbachia and microfilariae (MF) depletion, adult worm vitality and embryogenesis were assessed following treatment at 4-, 18-, and 20-months.

RESULTS: High-dose RIF + ALB was safe and well-tolerated, associated with only mild, transient adverse events. Treatment with RIF + ALB for 14 days reduced Wolbachia load in skin MF at 4 months (47.9%; p = 0.018). ALB monotherapy showed sustained reductions in skin microfilarial densities at the 18- and 20-month time points (p < 0.05). However, no macrofilaricidal effect or sustained Wolbachia depletion in adult worms was observed in any group.

CONCLUSION: High-dose RIF + ALB is safe with limited macrofilaricidal efficacy in clinical settings, contrasting with the superiority observed from preclinical trials. ALB alone shows promise as an alternative microfilaricidal treatment to ivermectin or as a complementary regimen. The lack of sustained efficacy of RIF as an anti-Wolbachia regimen may reflect suboptimal dosing, highlighting the need for further optimization of RIF-based regimens for onchocerciasis treatment.

TRIAL REGISTRATION: PACTR202009704006025 (https://pactr.samrc.ac.za/Search.aspx). Date of trial registration: September 9, 2020.

Copyright: © 2026 Ahiadorme 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.

PMID: 42585242

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