BackgroundLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2020, with the main strategy being treatment of entire endemic communities. Since the inception of the Global Programme for the Elimination of LF in 2000, tremendous progress has been made in many endemic countries. However, current observations point to the need for improved treatment regimen, frequency of treatment or drug delivery strategies in order to achieve the elimination goals in certain endemic areas. In this randomised trial, we evaluate the use of twice-yearly treatment with ivermectin and albendazole in 18 LF-endemic communities in Ghana, where despite 15 years of yearly treatment the disease is still above the elimination thresholds.MethodsFollowing demographic data collection, Wuchereria bancrofti antigen, microfilaria and antibody prevalence were assessed in study participants using the Alere FTS kit, nucleopore filtration and Wb123 ELISA, respectively. The study assessed the perspectives of the communities’on persistent transmission of LF in view of implementing effective treatment uptake strategies.ResultsThe baseline assessments revealed antigen prevalence of 8.2% (95% CI=6.8–9.8), with overall microfilaria prevalence of 1.2%. Infections were higher in males and in individuals who spend significant amount of time outdoors for commercial activities. Barriers related to medication, personal, health system, disease and social structure were observed to affect mass drug administration compliance. Community members perceived that they were not susceptible to infection and this together with drug adverse effects strongly affect the ingestion of the drugs.ConclusionWhile this trial is still in an early phase, the baseline assessments reveal programmatic challenges to the implementation of a twice-yearly treatment strategy for the control of LF which must be addressed to enhance implementation success.