Abstract

BackgroundControl of soil-transmitted helminthiasis and schistosomiasis relies heavily on regular preventive chemotherapy. Monitoring drug efficacy is crucial to provide early warning of treatment failures. The World Health Organization (WHO) recommends a survey design in which only egg-positive individuals are retested after treatment. Although this practice makes more efficient use of resources, it may lead to biased drug efficacy estimates.MethodsWe performed a simulation study to assess the potential for bias when evaluating drug efficacy using the World Health Organization–recommended survey design, and to identify alternative designs for evaluating drug efficacy that are less affected by bias. These designs were also based on selection of egg-positive individuals, but involve retesting them a second time at baseline and up to 2 times at follow-up. The utility of the different designs was compared fairly by constraining them to the same budget.ResultsThe standard procedure of selecting egg-positive individuals can introduce a substantial positive bias in drug efficacy due to regression toward the mean, particularly when infection levels or drug efficacy are low. This bias was completely eliminated by using a second baseline sample, conditionally on the first sample being excluded from analysis. Precision of estimates can be improved by increasing the number of thick smears and/or samples per person at follow-up, despite fewer individuals being tested within the same budget.ConclusionsWe present optimized survey designs to monitor drug efficacy in field settings, which are highly relevant for sustained control of soil-transmitted helminths and schistosomiasis, as well as onchocerciasis and lymphatic filariasis.

Highlights

  • Control of soil-transmitted helminthiasis and schistosomiasis relies heavily on regular preventive chemotherapy

  • Given that drug resistance due to historical overuse or misuse of deworming drugs is widespread in veterinary helminth infections [2, 3], it is feared that drug resistance will develop eventually in soil-transmitted helminths (STH) and SCH [4]

  • We applied each survey design in the following steps: (1) draw observed baseline egg counts for each individual from a count distribution; (2) determine the number of individuals included in the survey, given the budget and survey design; (3) simulate the decrease in true egg density as a result of drug administration; (4) simulate observed post–drug administration egg counts from a count distribution; and (5) calculate the estimated egg reduction rate (ERR) for the simulated survey based on the relative difference in sample mean egg count before and after drug administration

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Summary

Objectives

The overall goal of the study was to optimize resource use by minimizing bias and maximizing precision of drug efficacy estimates, given a finite set of available resources

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