Individual efficacy and community impact of ivermectin, diethylcarbamazine and albendazole mass drug administration for lymphatic filariasis control in Fiji: a cluster randomised trial

Bancroftian filariasis remains endemic in Fiji despite over 10 years of mass drug administration (MDA) using diethylcarbamazine and albendazole (DA). The addition of ivermectin to this combination (IDA) has improved efficacy of microfilarial clearance at 12 months in individually randomised trials in nocturnal transmission settings, but impact in a setting of diurnally subperiodic filarial transmission has not been evaluated. This cluster randomised study compared the individual efficacy and community impact of IDA versus DA as MDA for lymphatic filariasis in 35 villages on two islands of Fiji. Participants were tested at enrolment for circulating filarial antigen and, if positive, for microfilariae (Mf). Weight-dosed treatment was offered according to village randomisation. Communities were visited at 12 months and retested for lymphatic filariasis. Infected individuals from Rotuma retested at 24 months. 3816 participants were enrolled and 3616 treated. At 12 months, Mf clearance was achieved in 72 of 111 participants detected with infection at baseline, with no difference in efficacy between treatment groups: DA 69.2%, 95% CI 57.2-79.1% versus IDA 62.5%, 43.6-78.2%, risk difference 11.3 %, 95% CI -10-32.7%, P = 0.30. There was no difference between treatment groups in community prevalence of Mf at 12 months or individual clearance at 24 months. We found no difference between IDA and DA in individual clearance or community prevalence of lymphatic filariasis at 12 months, and no improved efficacy following a second annual round of IDA. Possible explanations for the apparent lack of benefit of IDA compared to DA include drug and parasite factors affecting clearance, and higher than expected re-infection rates.