The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drug administration (MDA). Preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti (W. bancrofti) infection was highly endemic in the Sikasso district. W. bancrofti prevalence and transmission in this region were confirmed in baseline human and entomologic studies in 6 villages in 2001 (prior to the start of yearly MDA with albendazole and ivermectin) and monitored yearly from 2002 to 2007 during MDA. Microfilaremia was determined by calibrated thick smear of night blood in adult volunteers and circulating filarial antigen was measured using the ICT test in children <5 years old. Mosquitoes were collected by human landing catch from July to December. None of the 686 subjects tested were microfilaremic 12 months after the 6th MDA round. More importantly, circulating antigen was not detected in any of the 120 children tested, as compared to 53% (103/194) prior to the institution of MDA. The number of infective bites/man/year decreased from 4.8 in 2002 to 0.04 in 2007. Although these data were consistent with ongoing transmission at a very low level, they met criteria for transmission interruption based on current WHO transmission assessment survey (TAS). To assess the utility of TAS approach, we used standard TAS methodology (ICT positive prevalence in 6-7 year olds) and compared it to xenomonitoring, night blood microfilariae counts and IgG4 antibody to Wb123 (for the last 3 years) over a five year period (2009-2014) following the cessation of MDA in 6 villages in the region of Sikasso in southern Mali. In 2009 (at the start of the surveillance period) all 289 children aged 6-7 years were negative for circulating filarial antigen (CFA) by ICT, by calibrated thick smears of blood collected at night, and by IgG4 antibody to Wb123. Despite this, 2/4391 (0.11%) dissected mosquitoes were positive for larvae of Wuchereria bancrofti (Wb). In 2011, there was a CFA prevalence by ICT of 2.6% (8/301) in the 6-7 year olds, a prevalence of 1.09% (1/92) for antibody responses to Wb123, but negative xenomonitoring. In the subsequent 2 years (2012 and 2013), there were consistent and significant increases in the prevalence of CFA (Trend Chi2= 11.49, p=0.0007) to 3.9% (11/285) in 2012, and 4.1% (13/316) and in the prevalence of anti-Wb123 IgG4 to 3.2% (10/316) in 2013. Despite this increase in both ICT and Wb123 IgG4 antibody prevalence, no infected anopheles mosquito was found in 2011, 2012 and 2013. These data suggest that despite having met the criteria for cessation of MDA at the beginning of the surveillance, that there appears to be low level emergence of Wb transmission and that antibody monitoring may provide a better early warning tool than more standard TAS tools. To begin to identify potential causes for re-emergence of infection after apparently successful transmission interruption as assessed by TAS, a questionnaire was administered to randomly selected adult residents of the six villages to assess the prevalence of and reasons for systematic non-compliance with MDA. Coverage rates in the villages ranged from 67% to 89.6% over the 7 years of MDA and all stopping criteria were met at the beginning of the surveillance period. A total of 486 subjects (170 men and 316 women) were questioned, of whom 16.1% (79/486) reported never swallowing MDA drugs. The most common reasons given were being unaware of MDA (24/486; 4.9%), being pregnant or breast-feeding (8/486; 1.6%) and not willing to take the drugs (6/486; 1.2%). Although systematic non-compliers were more likely to be younger OR = 1.7 (1.006-2.921) for individuals 15-30 vs. >30 years of age, compliant and systematically non-compliant subjects were similar with respect to participants instruction level OR = 1.2 (0.59-2.51) and the presence of lymphoedema / hydrocele OR = 0.5 (0.11-2.63). These data suggest that significant rates of systematic non-compliance can be present despite adequate overall coverage rates. Whether persistent infection in systematic non-compliers provided the reservoir for re-emergence of transmission in the 6 study villages requires further study.