title: The feasibility of testing whether Fasciola hepatica is associated with increased risk of verocytotoxin producing Escherichia coli O157 from an existing study protocol.
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.
authors.affiliation: Department of Epidemiology and Population Health, Institute of Infection and Global Heath, University of Liverpool, The Farr Institute@HeRC, Waterhouse Building, 1-5 Brownlow Street, Liverpool L69 3GL, UK. Electronic address: graeme.hickey@liverpool.ac.uk.
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Hickey
authors.affiliation: Department of Epidemiology and Population Health, Institute of Infection and Global Heath, University of Liverpool, The Farr Institute@HeRC, Waterhouse Building, 1-5 Brownlow Street, Liverpool L69 3GL, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Diggle
authors.affiliation: Moredun Research Institute, Pentlands, Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK.
authors.forename: Tom N
authors.initials: TN
authors.lastname: McNeilly
authors.affiliation: SRUC (Scotland's Rural College), West Mains Road, Edinburgh, Scotland EH9 3JG, UK.
authors.forename: Sue C
authors.initials: SC
authors.lastname: Tongue
authors.affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Charlotte Auerbach Road, Edinburgh, EH9 3FL, UK.
authors.forename: Margo E
authors.initials: ME
authors.lastname: Chase-Topping
authors.affiliation: Department of Infection Biology, Institute of Infection and Global Heath, University of Liverpool, Liverpool L69 7ZJ, UK; School of Veterinary Science, University of Liverpool, Leahurst Campus, Chester High Road, Neston CH64 7TE, UK.
authors.forename: Diana J L
authors.initials: DJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D057138:Bacterial Shedding; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology; D060085:Coinfection / Q000453:epidemiology / Q000382:microbiology / Q000469:parasitology / Q000662:veterinary*; D004739:England / Q000453:epidemiology; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology / Q000662:veterinary*; D019453:Escherichia coli O157 / Q000502:physiology*; D005210:Fasciola hepatica / Q000302:isolation & purification*; D005211:Fascioliasis / Q000453:epidemiology / Q000469:parasitology / Q000662:veterinary*; D005240:Feasibility Studies; D005260:Female; D010865:Pilot Projects; D015995:Prevalence; D011446:Prospective Studies; D018570:Risk Assessment; D012606:Scotland / Q000453:epidemiology; D014852:Wales / Q000453:epidemiology
keywords: Co-infection; Fasciola hepatica; Mixed effects model; Power; Sample size; Verocytotoxigenic Escherichia coli O157