Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs.

Background: The fecal egg count reduction test (FECRT) is recommended to monitor drug efficacy against soil-transmitted helminths (STHs) in public health. However, the impact of factors inherent to study design (sample size and detection limit of the fecal egg count (FEC) method) and host-parasite interactions (mean baseline FEC and aggregation of FEC across host population) on the reliability of FECRT is poorly understood. Methodology/Principal Findings: A simulation study was performed in which FECRT was assessed under varying conditions of the aforementioned factors. Classification trees were built to explore critical values for these factors required to obtain conclusive FECRT results. The outcome of this analysis was subsequently validated on five efficacy trials across Africa, Asia, and Latin America. Unsatisfactory (<85.0%) sensitivity and specificity results to detect reduced efficacy were found if sample sizes were small (<10) or if sample sizes were moderate (10–49) combined with highly aggregated FEC (k<0.25). FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The most discriminatory study design required 200 subjects independent of STH status (including subjects who are not excreting eggs). For this sample size, the detection limit of the FEC method and the level of aggregation of the FEC did not affect the interpretation of the FECRT. Only for a threshold of 90%, mean baseline FEC <150 eggs per gram of stool led to a reduced discriminatory power. Conclusions/Significance: This study confirms that the interpretation of FECRT is affected by a complex interplay of factors inherent to both study design and host-parasite interactions. The results also highlight that revision of the current World Health Organization guidelines to monitor drug efficacy is indicated. We, therefore, propose novel guidelines to support future monitoring programs. Author Summary: The reduction in number of eggs excreted in stools after drug administration is a primary parameter to monitor the efficacy of drugs against parasitic worms. Guidelines on how to perform such a fecal egg count reduction test (FECRT) are provided by the World Health Organization. However, it remains unclear to which extent these guidelines are cost-effective. We, therefore, performed a simulation study in which the FECRT was performed under varying conditions to determine the critical values for sample size, the detection limit of the fecal egg count (FEC) method, mean baseline FEC, and variation of FEC across host population that allow for conclusive FECRT results. The results revealed that a reliable monitoring system demands a sample size of 200 subjects and that in some cases FECRT results may be thwarted by low mean baseline FEC. For this sample size, the detection of the FEC method or the variation of FEC across the host population did not affect the FECRT results. Our findings underscore that the current guidelines are not cost-effective, demanding too much financial and technical resources. We, therefore, propose novel guidelines to support future monitoring programs. [ABSTRACT FROM AUTHOR]