Predicting the public health benefit of vaccinating cattle against Escherichia coli O157

Louise Matthews,Mary F Hanson,Daniel T Haydon,David L Gally,Sean P Mcateer,Richard Reeve,Lesley J Allison,George J Gunn,J Chris Low,Margo E Chase-Topping,Mark E J Woolhouse,Stuart W J Reid,Mary E Locking

doi:10.1073/pnas.1304978110

Abstract

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle-human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human-animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases.

Highlights

Identifying the major sources of risk in disease transmission is key to designing effective controls
E. coli O157 strains from primary human cases and a large-scale cattle survey were used to ask whether supershedding strains were disproportionately frequent among human clinical isolates and determine the relationship between shedding density in the cattle reservoir and human risk
Strains were grouped by phage type (PT), a classification associated with shedding density

Summary

Introduction

Identifying the major sources of risk in disease transmission is key to designing effective controls. Understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Several preslaughter interventions have been tried, including altered diets, adding probiotics to feed, spraying cattle with bacteriophage, and vaccination [3] Of these interventions, vaccines have proven to be the most effective; in vaccine trials, both experimentally and naturally infected cattle show significant reductions in the frequency, duration, and intensity of E. coli O157 excretion in their feces [4,5,6,7,8]. Whether vaccination would ever be widely used in the United Kingdom, North America, or the wider world will depend on the number of illnesses and deaths prevented; the cost of vaccination; and whether costs could be shared between the public, government, and food industry to help make vaccination a viable option for the farming community

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Results

Conclusion