Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
PLoS Negl Trop Dis. 2011 Dec;5(12):e1427. doi: 10.1371/journal.pntd.0001427. Epub 2011 Dec 13.
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.
粪卵计数减少试验（FECRT）被推荐用于监测公共卫生领域中针对土壤传播性蠕虫（STHs）的药物疗效。然而，研究设计中固有因素（粪便虫卵计数（FEC）方法的样本量和检测下限）和宿主-寄生虫相互作用（平均基线 FEC 和宿主群体中 FEC 的聚集）对 FECRT 可靠性的影响尚未得到充分理解。
方法/主要发现：进行了一项模拟研究，在不同的上述因素条件下评估了 FECRT。构建分类树以探索获得明确 FECRT 结果所需的这些因素的临界值。然后，在非洲、亚洲和拉丁美洲的五项疗效试验中验证了该分析的结果。如果样本量较小（<10）或样本量适中（10-49）且 FEC 高度聚集（k<0.25），则无法获得令人满意的（<85.0%）降低疗效的敏感性和特异性结果来检测。对于降低疗效阈值为 90%的 87.5%至 92.5%和降低疗效阈值为 95%的 92.5%至 97.5%的药物疗效，FECRT 在任何评估条件下均不确定。最具鉴别力的研究设计需要 200 名独立于 STH 状态的受试者（包括不排虫卵的受试者）。对于这个样本量，FEC 方法的检测下限和 FEC 的聚集程度不会影响 FECRT 的解释。只有在阈值为 90%的情况下，基线 FEC<150 个每克粪便虫卵才会降低鉴别能力。
结论/意义：本研究证实，FECRT 的解释受到研究设计和宿主-寄生虫相互作用固有因素复杂相互作用的影响。结果还强调了修订现行世界卫生组织监测药物疗效指南的必要性。因此，我们提出了新的指南来支持未来的监测计划。
