A Randomized Clinical Trial Comparing Single- And Multi-Dose Combination Therapy With Diethylcarbamazine and Albendazole for Treatment of Bancroftian Filariasis

Abstract

The Global Program for Elimination of Lymphatic Filariasis calls for mass drug administration for endemic populations outside of sub-Saharan Africa with a single dose of diethylcarbamazine (DEC) and albendazole (Alb) annually for 4-6 years. Single-dose DEC/Alb dramatically reduces blood microfilaria (MF) counts, but most treated subjects fail to completely clear MF after a single dose. A more effective regimen might reduce the number of years required for elimination programs. We performed a randomized clinical trial in Egyptian adults with asymptomatic microfilaremia to compare treatment with seven daily doses of oral DEC (6 mg/kg) and Alb (400 mg) with a single dose of the same combination. We also studied the effect of re-treatment with single-dose DEC/Alb 12 months after the first treatment course. Multi-dose DEC/Alb was significantly more effective than single-dose therapy for reducing and clearing microfilaremia (mean reduction in MF/ml relative to pretreatment counts at 12 months, 99.6% versus 85.7%, with complete clearance in 75% versus 23.1%). The two regimens had similar activity against adult filarial worms, as indicated by serial ultrasound assessments. Neither regimen resulted in complete clearance of filarial antigenemia. There was no difference in adverse events, which were mild to moderate. Blood microfilaria and parasite antigen clearance rates increased following re-treatment. Multi-dose DEC/Alb may be a useful option for filariasis elimination programs, especially in the first year (when enthusiasm for mass drug administration and coverage rates are high), to quickly reduce community MF loads and transmission rates.

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

“…Finally, these results originated from subjects of both sexes. Because it is known that the detection rate of adult filariae in lymphatic vessels in women is lower than in men, 20,27 the data from this study are not directly comparable to those from the other trials.…”

“…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.…”

The Effect of Compliance on the Impact of Mass Drug Administration for Elimination of Lymphatic Filariasis in Egypt

“…22,29 Additional rounds of MDA should improve cumulative compliance rates (the percentage of people who have taken one or more doses of MDA) and improve mf clearance rates in infected people. 30 Although five rounds is a reasonable guideline for planning MDA programs, GPELF guidelines call for repeating MDA until targets are reached.…”

“…Subjects with positive filariasis antigen test results were tested for mf by membrane filtration of 1 mL of venous blood collected between 9:00 PM and 1:00 AM as previously described. 22 The mf prevalence rate was defined as the number of people with mf divided by the number of people tested for filarial antigenemia. This rate slightly underestimates the true mf prevalence rate because the sensitivity of the antigen card test in mf carriers (as detected by membrane filter) is approximately 95%.…”

Coverage and compliance of mass drug administration against lymphatic filariasis in Kalaburgi district

“…7 World Health Organization has recommended single-dose DEC and albendazole as a preferred combination for repeated, annual MDA in filariasis endemic areas, which reduces blood microfilaria (MF) counts. 8,9 The World health Assembly targeted lymphatic filariasis for elimination mainly through a strategy of mass drug administration (MDA). The effectiveness of the lymphatic filariasis elimination depends on upon the consumption of the recommended drug by the affected population.…”