Modelling the impact of curtailing antibiotic usage in food animals on antibiotic resistance in humans

Effect of curtailing antibiotic consumption in human

How to make predictions about future infectious disease risks

Formal, quantitative approaches are now widely used to make predictions about the likelihood of an infectious disease outbreak, how the disease will spread, and how to control it. Several well-established methodologies are available, including risk factor analysis, risk modelling and dynamic modelling. Even so, predictive modelling is very much the ‘art of the possible’, which tends to drive research effort towards some areas and away from others which may be at least as important. Building on the undoubted success of quantitative modelling of the epidemiology and control of human and animal diseases such as AIDS, influenza, foot-and-mouth disease and BSE, attention needs to be paid to developing a more holistic framework that captures the role of the underlying drivers of disease risks, from demography and behaviour to land use and climate change. At the same time, there is still considerable room for improvement in how quantitative analyses and their outputs are communicated to policy makers and other stakeholders. A starting point would be generally accepted guidelines for ‘good practice’ for the development and the use of predictive models

Failure of vaccination to prevent outbreaks of foot-and-mouth disease

Outbreaks of foot-and-mouth disease persist in dairy cattle herds in Saudi Arabia despite revaccination at intervals of 4-6 months. Vaccine trials provide data on antibody responses following vaccination. Using this information we developed a mathematical model of the decay of protective antibodies with which we estimated the fraction of susceptible animals at a given time after vaccination. The model describes the data well, suggesting over 95% take with an antibody half-life of 43 days. Farm records provided data on the time course of five outbreaks. We applied a 'SLIR' epidemiological model to these data, fitting a single parameter representing disease transmission rate. The analysis provides estimates of the basic reproduction number R(0), which may exceed 70 in some cases. We conclude that the critical intervaccination interval which would provide herd immunity against FMDV is unrealistically short, especially for heterologous challenge. We suggest that it may not be possible to prevent foot-and-mouth disease outbreaks on these farms using currently available vaccines

Explaining Observed Infection and Antibody Age-Profiles in Populations with Urogenital Schistosomiasis

Urogenital schistosomiasis is a tropical disease infecting more than 100 million people in sub-Saharan Africa. Individuals in endemic areas endure repeated infections with long-lived schistosome worms, and also encounter larval and egg stages of the life cycle. Protective immunity against infection develops slowly with age. Distinctive age-related patterns of infection and specific antibody responses are seen in endemic areas, including an infection ‘peak shift’ and a switch in the antibody types produced. Deterministic models describing changing levels of infection and antibody with age in homogeneously exposed populations were developed to identify the key mechanisms underlying the antibody switch, and to test two theories for the slow development of protective immunity: that (i) exposure to dying (long-lived) worms, or (ii) experience of a threshold level of antigen, is necessary to stimulate protective antibody. Different model structures were explored, including alternative stages of the life cycle as the main antigenic source and the principal target of protective antibody, different worm survival distributions, antigen thresholds and immune cross-regulation. Models were identified which could reproduce patterns of infection and antibody consistent with field data. Models with dying worms as the main source of protective antigen could reproduce all of these patterns, but so could some models with other continually-encountered life stages acting as the principal antigen source. An antigen threshold enhanced the ability of the model to replicate these patterns, but was not essential for it to do so. Models including either non-exponential worm survival or cross-regulation were more likely to be able to reproduce field patterns, but neither of these was absolutely required. The combination of life cycle stage stimulating, and targeted by, antibody was found to be critical in determining whether models could successfully reproduce patterns in the data, and a number of combinations were excluded as being inconsistent with field data

Evaluation of risks of foot-and-mouth disease in Scotland to assist with decision making during the 2007 outbreak in the UK

An outbreak of foot-and-mouth disease (FMD) occurred in Surrey on August 3, 2007. A Great Britain-wide ban on livestock movements was implemented immediately. This coincided with the start of seasonal sheep movements off the hills in Scotland; the majority of these animals are sold via markets. The ban therefore posed severe economic and animal-welfare hardships if it was to last through September and beyond. The Scottish Government commissioned an analysis to assess the risk of re-opening markets given the uncertainty about whether FMD had entered Scotland. Tracing of livestock moved from within the risk zone in England between July 16 and August 3 identified contact chains to 12 Scottish premises; veterinary field inspections found a further three unrecorded movements. No signs of infection were found on these holdings. Under the conservative assumption that a single unknown Scottish holding was infected with FMD, an estimate of the time-dependent probability of Scotland being FMD free given no detection was made. Analyses indicated that if FMD was not detected by early to mid-September then it was highly probable that Scotland was FMD free. Risk maps were produced to visualise the potential spread of FMD across Scotland if it was to spread either locally or via market sales

Escherichia coli O157 infection on Scottish cattle farms: dynamics and control

In this study, we parametrize a stochastic individual-based model of the transmission dynamics of Escherichia coli O157 infection among Scottish cattle farms and use the model to predict the impacts of both targeted and non-targeted interventions. We first generate distributions of model parameter estimates using Markov chain Monte Carlo methods. Despite considerable uncertainty in parameter values, each set of parameter values within the 95th percentile range implies a fairly similar impact of interventions. Interventions that reduce the transmission coefficient and/or increase the recovery rate of infected farms (e.g. via vaccination and biosecurity) are much more effective in reducing the level of infection than reducing cattle movement rates, which improves effectiveness only when the overall control effort is small. Targeted interventions based on farm-level risk factors are more efficient than non-targeted interventions. Herd size is a major determinant of risk of infection, and our simulations confirmed that targeting interventions at farms with the largest herds is almost as effective as targeting based on overall risk. However, because of the striking characteristic that the infection force depends weakly on the number of infected farms, no interventions that are less than 100 per cent effective can eradicate E. coli O157 infection from Scottish cattle farms, implying that eliminating the disease is impractical

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations