Summary of Methodology Used in Enterotoxigenic Escherichia coli (ETEC) Challenge Experiments in Weanling Pigs and Quantitative Assessment of Observed Variability

Payton L. Dahmer, Joel M. DeRouchey, Jordan T. Gebhardt, Chad B. Paulk, Cassandra K. Jones
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Abstract

Post-weaning diarrhea in pigs can be caused by the F4 or F18 strains of enterotoxigenic Escherichia coli (ETEC). To evaluate interventions for ETEC, experimental infection via a challenge model is critical. To our knowledge, there is a lack of explanation for the variability in responses observed across ETEC challenge studies. Our objective was to quantitatively summarize the responses and variability among recent ETEC challenge studies and develop a tool for sample size calculation. The most widely evaluated response criteria across ETEC challenge studies are growth performance, fecal consistency and bacterial shedding, intestinal morphology, and immune responses. Factors that contribute to the variability seen across studies include the type of ETEC studied, dose and timing of inoculation, and the number of replications. Generally, a reduction in average daily gain (ADG) and average daily feed intake (ADFI) are seen following an ETEC challenge, as well as a rapid increase in diarrhea. Fecal bacterial shedding is a common indicator of ETEC infection, but the responses seen across the literature are not consistent due to differences in bacterial enumeration procedures. Emphasis should also be placed on the piglet’s immune response to ETEC, which is commonly assessed by quantifying levels of immunoglobulins and pro-inflammatory cytokines. Again, there is variability in these responses across published work. Small intestinal morphology is drastically altered following infection with ETEC and appears to be a less variable response criterion to evaluate. While there is a large degree of variability across ETEC challenge experiments, we have provided a quantitative summary of these studies, and a Microsoft Excel-based tool was created to help calculate sample sizes for future studies.
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断奶仔猪产肠毒素大肠杆菌(ETEC)攻毒试验方法学综述及观察变异的定量评估
猪断奶后腹泻可由产肠毒素大肠杆菌(ETEC) F4或F18菌株引起。为了评估ETEC的干预措施,通过挑战模型进行实验感染至关重要。据我们所知,缺乏对ETEC挑战研究中观察到的反应变异性的解释。我们的目标是定量总结最近ETEC挑战研究的反应和变异性,并开发一种计算样本量的工具。在ETEC挑战研究中,最广泛评估的反应标准是生长性能、粪便一致性和细菌脱落、肠道形态和免疫反应。导致研究间差异的因素包括所研究的ETEC类型、接种剂量和时间以及重复次数。一般来说,在ETEC挑战后,平均日增重(ADG)和平均日采食量(ADFI)会下降,腹泻会迅速增加。粪便细菌脱落是ETEC感染的常见指标,但由于细菌计数程序的差异,在文献中看到的反应并不一致。重点还应放在仔猪对ETEC的免疫反应上,通常通过定量免疫球蛋白和促炎细胞因子的水平来评估。同样,在不同发表的作品中,这些反应也存在差异。小肠形态在感染ETEC后急剧改变,似乎是一个较少变化的反应标准来评估。虽然在ETEC挑战实验中存在很大程度的可变性,但我们已经提供了这些研究的定量总结,并创建了一个基于Microsoft excel的工具来帮助计算未来研究的样本量。
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