An open label, randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia

Abstract

Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DEC plus albendazole (DA, 27 subjects). Participants were actively monitored for adverse events (AE) for two days after treatment by nurses and physicians who were masked regarding treatment assignments. Passive monitoring was performed by clinical teams that visited participant’s home villages for an additional five days. Microfilaremia was assessed by membrane filtration of 1 ml night blood at baseline, at 24h and one year after treatment. IDA was more effective than DA for completely clearing Mf at 24 hours (25/28, 89% vs. 11/27, 41%, P < 0.001). By 12 months after treatment, only one of 28 IDA recipients had Mf in their blood (4%) vs. 10 of 27 (37%) in persons treated with DA (P = 0.002). Approximately 90% of participants had antibodies to recombinant filarial antigen BmR1 at baseline. Antibody prevalence decreased to approximately 30% in both treatment groups at 12 months. About 45% of persons in both treatment groups experienced AE such as fever, muscle aches, lower back, joint and abdominal pain. These were mostly mild and most common during the first two days after treatment. No participant experienced a severe or serious AE. This study showed that IDA was well-tolerated and significantly more effective for clearing B. timori Mf from the blood than DA. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis. Trial Registration: NCT02899936.

Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial

“…In conclusion, community MDA with IDA was safe, well tolerated and significantly more effective than the reference MDA regimen (DA) for clearing Mf. These results are consistent with observations of superior Mf clearance with IDA in similar studies in Haiti, India and Indonesia [ 28 , 30 , 31 ], noting that IDA was observed to have comparable efficacy to DA in a similar study in Fiji [ 32 ]. The new regimen has the potential to fast-track LF elimination in PNG and in many other endemic areas.…”

“…This is likely due to the more rapid clearance of Mf after drug treatment with IDA because of the additional microfilaricidal activity of ivermectin giving rise to increased filarial DNA and circulating filarial antigens activating inflammatory responses and elevated cytokine levels [19]. The higher rate of AEs in adults is likely due to their higher infection prevalence relative to children and was similarly observed in the other trial sites of India, Indonesia, Haiti and Fiji [28][29][30][31].…”

“…The new regimen has the potential to fast-track LF elimination in PNG and in many other endemic areas. Evidence from this trial, from clinical trials conducted in PNG [ 15 , 16 ], Côte d’Ivoire [ 17 , 18 ], and from community studies performed in Haiti [ 28 ], India [ 30 ], Indonesia [ 31 ] and Fiji [ 22 , 29 ] was reviewed by a WHO LF Guidelines Review Committee in 2017. WHO formally endorsed the use of IDA for LF elimination programs in specific settings in late 2017 [ 24 ]. Since that time, 11 countries including PNG have started to use IDA MDA to accelerate their LF elimination programs.…”

Current Use of Ivermectin in Dermatology, Tropical Medicine, and COVID-19

“…An overview of the various uses and dosimetry is listed in Table 1 . [ 1 41 42 43 51 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 ]…”

“…A recent trial showed that triple-drug treatment with an oral dose of IVM (200 μg/kg body weight), DEC (6 mg/kg), and albendazole (a fixed dose of 400 mg) was better than DEC and albendazole and this would seem to be a better option for brugian filariasis. [ 60 61 ]…”