Safety, tolerability, efficacy and plasma concentrations of diethylcarbamazine and albendazole co-administration in a field study in an area endemic for lymphatic filariasis in India

Abstract

Filariasis control programmes are moving towards a strategy of repeated single-dose mass treatment of endemic populations. Using a combination, such as albendazole (ALB) to diethylcarbamazine (DEC) gives both macrofilaricidal and anti-helmintic activity. However, the safety of the combination versus DEC alone should be established in field studies in large populations prior to incorporation into national programmes. The present study compared the safety, tolerability, and efficacy of single doses of DEC 6 mg/kg + ALB placebo with DEC 6 mg/kg + ALB 400 mg in populations living in two filariasis endemic villages in the district of Wardha in western India. The study was double blind, parallel group, and randomized. Safety and tolerability study were studied in males and females older than 5 years. Safety was assessed by monitoring if adverse events (AEs) over 5 days affected daily acivities. Subjects in the 2 treatment groups experienced insignificantly different effects on daily activities and the combination was shown to be safe. Efficacy was evaluated by microfilaraemia (Mf), immunochromatographic test (ICT) and ultrasonography (USG) at 0, 3, 6, and 12 months of follow up. The efficacy study enrolled 103 male patients (aged 18-50 years) in microfilariae positive, clinical disease and asymptomatic, amicrofilaremic groups. There was no significant difference in efficacy between groups at 12 months. Within the Mf positive group, significant differences were seen in microfilaraemia (P < 0.001) with both treatments, and in USG (P < 0.001 and P < 0.004 respectively), at 12 months. The present field study has shown the combination of DEC + ALB to be as safe as the single drug DEC and thus the combination can be put in use in the national filariasis control programmes. Both drugs were adequately absorbed. The study at present does not provide evidence for the greater efficacy of the combination at 12 months follow up. While the safety of the combination has been ascertained, the incorporation or otherwise of ALB into national programmes for greater efficacy must await results of studies with longer follow up.

Filarial hydrocele: a neglected condition of a neglected tropical disease

“…In addition to ivermectin, DEC has a potent microfilaricidal effect as well as 50% macrofilaricidal activity [2,[52][53][54]. The combination of DEC and albendazole has macrofilaricidal effects of between 56% and 87% [54].…”

“…The combination of DEC and albendazole has macrofilaricidal effects of between 56% and 87% [54]. However, in Africa, DEC cannot be used due to co-endemicity of lymphatic filariasis and onchocerciasis; the rapid killing of O. volvulus worms results in the development of severe adverse events.…”

Macrofilaricidal Activity and Amelioration of Lymphatic Pathology in Bancroftian Filariasis after 3 Weeks of Doxycycline Followed by Single-Dose Diethylcarbamazine

“…The combination of DEC 6 mg/kg plus albendazole 400 mg resulted in the loss of 67% of FDS. 21 In contrast to these results, a more recent study showed 77.8% macrofilaricidal activity after DEC 6 mg/ kg alone compared with 43.7% after DEC plus albendazole, arguing against an additive effect of the combination of DEC + albendazole. 2 Contrary to the above-described studies with DEC alone, we saw only a trend to macrofilaricidal effects in our placebo group (33% worm nest reduction, not significant).…”

“…Although average Mf levels dropped 99.6% versus 85.7% within a year, complete clearance was only seen in 75% and 23% of the individuals, respectively. Kshirsagar and others 21 showed in India that 67% of the DEC-treated patients were Mf negative 12 months after a single dose. Compared with these results, the 21-day doxycycline course (followed by single-dose DEC) in this study is superior, with none of the individuals staying microfilaremic.…”

“…It is difficult to draw a comparison regarding antigenemia with trials not using doxycycline but DEC alone or in combination with ivermectin and/or albendazole, because in a number of clinical trials, the qualitative immuno-chromatography test (ICT) was used to determine antigen positivity. 20,21,28,29 In general, the TropBio is more sensitive; therefore, it is able to detect lower antigenemia levels, causing patients to appear positive for a longer time. 30 Amelioration of dilated scrotal lymphatic vessels.…”