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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 i...

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Autores principales: Levecke, Bruno, Speybroeck, Niko, Dobson, Robert J., Vercruysse, Jozef, Charlier, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236725/
https://www.ncbi.nlm.nih.gov/pubmed/22180801
http://dx.doi.org/10.1371/journal.pntd.0001427
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author Levecke, Bruno
Speybroeck, Niko
Dobson, Robert J.
Vercruysse, Jozef
Charlier, Johannes
author_facet Levecke, Bruno
Speybroeck, Niko
Dobson, Robert J.
Vercruysse, Jozef
Charlier, Johannes
author_sort Levecke, Bruno
collection PubMed
description 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.
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spelling pubmed-32367252011-12-16 Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs Levecke, Bruno Speybroeck, Niko Dobson, Robert J. Vercruysse, Jozef Charlier, Johannes PLoS Negl Trop Dis Research Article 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. Public Library of Science 2011-12-13 /pmc/articles/PMC3236725/ /pubmed/22180801 http://dx.doi.org/10.1371/journal.pntd.0001427 Text en Levecke et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Levecke, Bruno
Speybroeck, Niko
Dobson, Robert J.
Vercruysse, Jozef
Charlier, Johannes
Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
title Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
title_full Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
title_fullStr Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
title_full_unstemmed Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
title_short Novel Insights in the Fecal Egg Count Reduction Test for Monitoring Drug Efficacy against Soil-Transmitted Helminths in Large-Scale Treatment Programs
title_sort novel insights in the fecal egg count reduction test for monitoring drug efficacy against soil-transmitted helminths in large-scale treatment programs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236725/
https://www.ncbi.nlm.nih.gov/pubmed/22180801
http://dx.doi.org/10.1371/journal.pntd.0001427
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