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The World Health Organization (WHO) endorsed the use of triple-drug mass drug administration (MDA) regimen with ivermectin, diethylcarbamazine (DEC) and albendazole (commonly abbreviated as IDA) to accelerate the elimination of lymphatic filariasis (LF) as a public health problem in settings where onchocerciasis is not co-endemic. The National Programme for Elimination of LF (NPELF) in Kenya was among the first adopters of the IDA-MDA and two annual rounds were provided in 2018 and 2019 to the residents of Lamu County and Jomvu sub-County in the coast region. This study documented the feasibility of successfully delivering the two rounds of IDA-MDA. An operational research study was undertaken to determine efficient sampling strategies, indicators, and the appropriate population groups that could be used for the monitoring and evaluation of LF programs using IDA-MDA for the elimination of the disease as a public health problem. Two cross-sectional surveys were conducted at baseline in 2018 before IDA-MDA and an impact assessment 17 months after the second round of IDA-MDA. The reported epidemiological treatment coverage was at least 80% in all implementation units during each round of IDA-MDA. Blood samples were tested for filarial antigenemia using commercial Filariasis Test Strips (FTS) and any individual found to be positive was tested again at night for the presence of microfilariae in finger prick blood smears using microscopy. The overall prevalence of circulating filarial antigen (CFA) was relatively low at the baseline survey with Jomvu having 1.39% (95% CI: 0.91, 2.11) and Lamu having 0.48% (95% CI: 0.21, 1.13). Significant reduction in CFA prevalence was observed during the impact assessment after two annual rounds of treatment. The overall relative reduction (%) in CFA prevalence following the two rounds of MDA with IDA was significant in both Jomvu (52.45%, Z = -2.46, P < 0.02) and Lamu (52.71%, Z = -1.97, P < 0.05). Heterogeneity, however, was observed in the CFA prevalence reduction between random and purposive clusters, as well as between adult and child populations. The results of the impact assessment survey offered strong evidence that it was safe to stop the IDA-MDA in the two EUs because transmission appears to have been interrupted. It is also important to implement a post-treatment surveillance system which would enable efficient detection of any recrudescence of LF transmission at a sub-evaluation unit level. Our findings show that IDA-MDA may be considered for acceleration of LF elimination in other settings where onchocerciasis is not co-endemic. Author summary: Preventive chemotherapy with antifilarial drugs is currently the mainstay public health intervention recommended for the elimination of lymphatic filariasis (commonly known as elephantiasis) in endemic countries. Two-drug regimen mass drug administration of albendazole plus either diethylcarbamazine or ivermectin has been used widely in most countries since the launch of the Global Programme to Eliminate Lymphatic Filariasis by the World Health Organization in 2000. Safety and efficacy clinical studies conducted in Papua New Guinea have shown that co-administration of three antifilarial drugs namely, ivermectin, diethylcarbamazine and albendazole is superior to the two-drug regimen diethylcarbamazine and albendazole in clearance of microfilariae from the bloodstream. Consequently, the triple-drug regimen was endorsed for accelerating efforts to eliminate lymphatic filariasis as a public health problem in areas where onchocerciasis is not co-endemic. The aim of this study was to assess the feasibility of delivering mass treatment with the triple-drug regimen under programmatic conditions. An operational research study was conducted to determine the optimal sampling strategies, indicator (or set of indicators), and study populations for monitoring and evaluation of lymphatic filariasis elimination programs using the triple-drug regimen mass treatment. Two rounds of mass treatment with the triple-drug regimen were given to the residents of Lamu County (comprising of Lamu East and Lamu West sub-counties) and Jomvu sub-County (in Mombasa) in November 2018 and November 2019. The programme epidemiological treatment coverage was at least 80% in each implementation unit during the two treatment rounds. The preventive treatment resulted in significant reductions in the prevalence of the disease with the number of positive cases being fewer than the threshold recommended for areas where transmission is likely to be no longer sustainable. [ABSTRACT FROM AUTHOR]