Transmission Assessment Surveys (TAS) to Define Endpoints for Lymphatic Filariasis Mass Drug Administration: A Multicenter Evaluation

Abstract

BackgroundLymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings.MethodologyThe TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6–7 year olds or 1st–2nd graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs.Principal Findings/ConclusionsIn 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation.

Modelling Lymphatic Filariasis Transmission and Control: Modelling Frameworks, Lessons Learned and Future Directions

“…Different attempts were made to determine the breakpoint prevalence for specific settings, but models have also highlighted the dependency of this breakpoint on setting characteristics and there is no final conclusion on the endpoint that should be used in practice or even which diagnostic tool to use. Modelling can help to evaluate the adequacy of current algorithms for determining whether interventions can be stopped (Chu et al, 2013). Secondly, models should be used to study more systematically how elimination can be accelerated most costeffectively, e.g.…”

“…Guidelines for determining whether mass treatment can be stopped were developed and tested for their assumptions, accuracy and practicality (Chu et al, 2013;WHO, 2011). However, the validation of the guidelines for longer-term post-MDA surveillance needs further empirical evidence, since uncertainty remains about the microfilarial (mf) or worm-antigen prevalence threshold levels, below which transmission cannot be sustained even in the absence of any further treatments.…”

The global distribution and transmission limits of lymphatic filariasis: past and present

“…Alternatively, the presence of W. bancrofti antigenaemia can be detected using the ICT card test [33][34][35] and presence of specific IgG4 antibodies to Brugia spp can be detected using the Brugia Rapid™ test [36][37][38]. Surveys for the mapping of LF have been based on a variety of sampling designs, including the rapid geographical assessment of Bancroftian filariasis (RAGFIL) method [29,63], lot quality assurance sampling [64,65], population-based household surveys [66] and sentinel site surveys [43,67,68], with the choice of survey methodology dependent on available resources and the stage of the control programme [69].…”

Presence ofWuchereria bancroftimicrofilaremia despite 7 years of annual ivermectin monotherapy mass drug administration for onchocerciasis control: a study in north-west Ethiopia

“…21,22 However, it is difficult to draw conclusions about the effectiveness of onchocerciasis MDA against LF from this study because no village achieved more than three consecutive 'effective' MDA rounds where coverage was ≥65% ( Table 2).…”