Although the current two-drug regimen has been successful in many places, it is clear
that augmented treatment regimens, other alternative strategies, or both are needed to
accelerate global elimination. Fortunately, recent scientific studies, led by the DOLF
project at Washington University in St. Louis, found that a three-drug regimen, using all
three of the medicines typically delivered as a standard two-drug regimen to prevent LF
(ivermectin + albendazole or diethycarbamazine + albendazole), is dramatically more
effective for achieving sustained clearance of microfilariae from infected persons [2].
WHO conducted a rigorous and thorough review process of data from safety and efficacy
trials of the triple drug regimen. In November, 2017, WHO endorsed and provided updated
treatment guidelines that endorsed the use of IDA as a MDA regimen for LF elimination
programs [3]. Following WHO's formal approval and release of the alternative treatment
guidelines, in late November Merck & Co. committed to increase its Mectizan donation by
100 million treatments annually to eliminate LF [4], making the IDA regimen financially
feasible for countries to adopt.
According to the recently published guidelines, WHO recommends the use of annual IDA in
settings where onchocerciasis is not co-endemic with LF in districts have not yet started
MDA, in areas that have received fewer than 4 effective rounds of MDA, and in areas where
MDA results have been suboptimal. These guidelines call for the current epidemiological
criteria (<1% microfilaremia or <2% antigenemia) to be applied to sentinel and spot check
sites to determine whether the IU is eligible to proceed with the transmission assessment
survey (TAS) and for the TAS to be used to base MDA-stopping decisions [3]. While the TAS
has proven to be an effective tool for basing stopping decisions under the standard
two-drug regimens, it is unclear whether the target age group (6-7 year olds) and
epidemiologic target (<2% antigenemia in areas with W. bancrofti and <2% BmR1 antibodies
in areas with Brugia spp. infections) are appropriate when IDA is used. Because IDA will
result in an accelerated interruption of transmission and because the effects of this
regimen on adult worms are not yet fully understood, it is possible that new target
populations, infection indicators, sampling strategies, and/or thresholds will be
required to determine when it is safe to stop IDA.
The purpose of this protocol is to describe the operational research (OR) that is
necessary to develop a set of recommendations for WHO to consider regarding appropriate
monitoring and evaluation (M&E) strategies for countries implementing IDA. Generating the
information necessary to establish robust M&E guidelines requires a significant OR effort
to ensure that all relevant information is collected, innovative strategies are
considered, and that the ultimate recommendations are supported by evidence across
multiple countries. It is important to emphasize that the study design described in this
protocol is not what would be recommended of all countries implementing IDA. This
protocol is for OR purposes only, with the goal that study findings will lead to a
simplified M&E framework that is feasible for use by national LF elimination programs.