The feasibility of testing whether Fasciola hepatica is associated with increased risk of verocytotoxin producing Escherichia coli O157 from an existing study protocol

Graeme L Hickey,Peter J Diggle,Tom N Mcneilly,Sue C Tongue,Margo E Chase-Topping,Diana J.L Williams

doi:10.1016/j.prevetmed.2015.02.022

Abstract

The parasite Fasciola hepatica is a major cause of economic loss to the agricultural community worldwide as a result of morbidity and mortality in livestock, including cattle. Cattle are the principle reservoir of verocytotoxigenic Escherichia coli O157 (VTEC O157), an important cause of disease in humans. To date there has been little empirical research on the interaction between F. hepatica and VTEC O157. It is hypothesised that F. hepatica, which is known to suppress type 1 immune responses and induce an anti-inflammatory or regulatory immune environment in the host, may promote colonisation of the bovine intestine with VTEC O157. Here we assess whether it is statistically feasible to augment a prospective study to quantify the prevalence of VTEC O157 in cattle in Great Britain with a pilot study to test this hypothesis. We simulate data under the framework of a mixed-effects logistic regression model in order to calculate the power to detect an association effect size (odds ratio) of 2. In order to reduce the resources required for such a study, we exploit the fact that the test results for VTEC O157 will be known in advance of testing for F. hepatica by restricting analysis to farms with a VTEC O157 sample prevalence of >0% and <100%.From a total of 270 farms (mean 27 cows per farm) that will be tested for VTEC O157, power of 87% can be achieved, whereby testing of F. hepatica would only be necessary for an expected 50 farms, thus considerably reducing costs. Pre-study sample size calculations are an important part of any study design. The framework developed here is applicable to the study of other co-infections.

Highlights

Fasciolosis caused by Fasciola hepatica, more commonly referred to as liver fluke, is a major cause of economic loss to the agricultural community worldwide as a result of morbidity and mortality in livestock (Claridge et al, 2012)
Recent evidence suggests a role for type 1 immune responses in control of Verocytotoxigenic Escherichia coli (VTEC) O157 in cattle, with clearance of the bacteria from the bovine intestine associated with an up-regulation of T-helper type 1 associated transcripts within the rectal mucosa, the principle site of colonisation by this bacteria (Corbishley et al, 2014; Naylor et al, 2003)
It is of interest to determine if infection with F. hepatica increases the risk that a cow will shed VTEC O157, as this will inform future control and risk management strategies aimed at reducing incidence of disease in humans

Summary

Introduction

Fasciolosis caused by Fasciola hepatica, more commonly referred to as liver fluke, is a major cause of economic loss to the agricultural community worldwide as a result of morbidity and mortality in livestock (Claridge et al, 2012). Verocytotoxigenic Escherichia coli (VTEC) O157 is a zoonotic bacteria of worldwide importance which, whilst largely asymptomatic in cattle, causes haemorrhagic colitis and potentially fatal haemolytic uraemic syndrome in humans as a result of systemic verocytotoxin activity (Chase-Topping et al, 2008). For both of these pathogens, cattle are a primary reservoir (Armstrong et al, 1996; McCann et al, 2010a,b). It is of interest to determine if infection with F. hepatica increases the risk that a cow will shed VTEC O157, as this will inform future control and risk management strategies aimed at reducing incidence of disease in humans

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