Abstract
BackgroundThe 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 FindingsA 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/SignificanceThis 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.
Highlights
Infections with the soil-transmitted helminths (STHs), namely Ascaris lumbricoides, Trichuris trichiura and hookworm (Necator americanus and Ancylostoma duodenale) are among the most common infectious diseases in children of tropical countries causing malnutrition, growth stunting, intellectual retardation, and cognitive deficits [1]
Guidelines on how to conduct a fecal egg count reduction test (FECRT) in public health were published by the World Health Organization (WHO) in the late 1990s [10], providing recommendations on sample size (,200 infected subjects), stool sampling, the detection limit of the method to quantify the number of eggs (Kato-Katz thick smear with a detection limit of 24 eggs per gram of stool (EPG)) and thresholds defining reduced efficacy
We 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
Summary
Infections with the soil-transmitted helminths (STHs), namely Ascaris lumbricoides, Trichuris trichiura and hookworm (Necator americanus and Ancylostoma duodenale) are among the most common infectious diseases in children of tropical countries causing malnutrition, growth stunting, intellectual retardation, and cognitive deficits [1]. The large-scale administration of benzimidazole drugs (i.e., albendazole and mebendazole) is the most widely used method to control morbidity due to STH infections, and a scale-up of these large-scale treatment programs is underway in Africa, Asia, and Latin America (donation of 400 million tablets of albendazole by GlaxoSmithKline and 200 million tablets of mebendazole by Johnson & Johnson). The fecal egg count reduction test (FECRT) is recommended to monitor anthelmintic efficacy against STH in animal [8] and public health [9]. The fecal egg count reduction test (FECRT) is recommended to monitor drug efficacy against soil-transmitted helminths (STHs) in public health. 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
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