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

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.zoonoses | cross-species transmission | 80-20 rule | one health

Strain-Dependent Cellular Immune Responses in Cattle following Escherichia coli O157:H7 Colonization

“…In the United Kingdom, PT21/28 strains are associated with higher levels of shedding in cattle than PT32 strains (66) and represent the predominant isolates from human HUS cases (67). In addition, PT21/28 strains are more likely to possess both Stx2a and Stx2c genes, whereas bovine PT32 strains are more likely to possess the Stx2c genes only (68). While cattle do not suffer from the same severe endothelial sequelae of Stx exposure as humans, there is a significant body of evidence that Stx can affect bovine leukocyte function (40,(69)(70)(71)(72)(73)(74).…”

Shiga toxins and stx phages: highly diverse entities

“…Furthermore, particular stx subtypes could affect the level of STEC shedding by cattle and consequently the risk of transmission to humans (Matthews et al, 2013). Although most stx subtypes have been detected in STEC strains isolated from cattle and beef products, some predominate amongst bovine STEC strains whereas others are rarely detected in such strains (Bertin et al, 2001;Brett et al, 2003a;Gobius et al, 2003;Beutin et al, 2007;Krüger et al, 2011).…”

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

“…119 Vaccination has been promoted as one of the most efficient means to decrease the incidence and prevalence of STEC outbreaks. 119,[122][123][124][125][126] Two main intervention strategies have been proposed: i) vaccination of the infant population; and ii) vaccination of cattle, the main animal reservoir and the primary means of human contamination, due to the consumption of poorlycooked meat. 127 It should be noted that cattle colonized by STEC are generally asymptomatic, thus subsidies for farmers may be necessary to promote animal vaccination.…”

“…Hurd and Malladi 122 predicted a 60% decrease in human cases associated with O157:H7 assuming a bovine vaccination effectiveness of 80% and an adoption rate of 100%. The study by Matthews et al, 123 utilizing a different mathematical model, predicted an 85% decrease in the incidence of human cases associated with O157: H7 in Scotland, assuming a decrease of 50% in the bovine/ human transmission risk. However, the impossibility of experimentation in humans, due to the risk of developing HUS, and the lack of an animal model that reproduces the entire clinical profile caused by infection in humans have been important barriers for the development of an effective vaccine.…”