03751nas a2200589   4500000000100000008004100001260004600042653002400088653001500112653001600127653002700143653001700170653002900187653001800216653001400234653001800248100001600266700002200282700001300304700001200317700001300329700001200342700001700354700001600371700001600387700001200403700001400415700001300429700001400442700001200456700001800468700001200486700001200498700001600510700001300526700001300539700001600552700001300568700002100581700001400602700002100616700001400637700001400651700001400665700001700679245009100696856009900787300001100886490000700897520224300904022001403147       2026                            d  c08/2026bPublic Library of Science (PLoS)10aEfficacy assessment10aRifampicin10aAlbendazole10aOnchocerciasis-endemic10aDrug Therapy10aMass drug administration10aAdverse event10aHistology10aembryogenesis1 aAhiadorme M1 aKlarmann-Schulz U1 aDubben B1 aNadal J1 aKorir PJ1 aPfarr K1 aKuehlwein JM1 aLenz-Plet F1 aRicchiuto A1 aKutu ED1 aMensah DA1 aOpoku VS1 aBoateng J1 aOpoku J1 aOsei-Mensah J1 aGyasi C1 aObeng P1 aKuutiero EK1 aObeng MA1 aEmikpe B1 aRahamani AA1 aAtisu PD1 aAyisi-Boateng NK1 aKontoh DB1 aTwumasi-Ankrah S1 aHoerauf A1 aDebrah LB1 aDebrah AY1 aMakepeace BL00aAssessing the efficacy of high-dose rifampicin plus albendazole against onchocerciasis  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014594&type=printable  a1 - 250 v203 a<p><strong>Background</strong></p>

<p>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.</p>

<p><strong>Methods</strong></p>

<p>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.</p>

<p><strong>Results</strong></p>

<p>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 &lt; 0.05 ). However, no macrofilaricidal effect or sustained Wolbachia depletion in adult worms was observed in any group.</p>

<p><strong>Conclusion</strong></p>

<p>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.&nbsp;</p>
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