Climate, human behaviour or environment: individual-based modelling of Campylobacter seasonality and strategies to reduce disease burden.

BACKGROUND: With over 800 million cases globally, campylobacteriosis is a major cause of food borne disease. In temperate climates incidence is highly seasonal but the underlying mechanisms are poorly understood, making human disease control difficult. We hypothesised that observed disease patterns reflect complex interactions between weather, patterns of human risk behaviour, immune status and level of food contamination. Only by understanding these can we find effective interventions. METHODS: We analysed trends in human Campylobacter cases in NE England from 2004 to 2009, investigating the associations between different risk factors and disease using time-series models. We then developed an individual-based (IB) model of risk behaviour, human immunological responses to infection and environmental contamination driven by weather and land use. We parameterised the IB model for NE England and compared outputs to observed numbers of reported cases each month in the population in 2004-2009. Finally, we used it to investigate different community level disease reduction strategies. RESULTS: Risk behaviours like countryside visits (t = 3.665, P < 0.001 and t = - 2.187, P = 0.029 for temperature and rainfall respectively), and consumption of barbecued food were strongly associated with weather, (t = 3.219, P = 0.002 and t = 2.015, P = 0.045 for weekly average temperature and average maximum temperature respectively) and also rain (t = 2.254, P = 0.02527). This suggests that the effect of weather was indirect, acting through changes in risk behaviour. The seasonal pattern of cases predicted by the IB model was significantly related to observed patterns (r = 0.72, P < 0.001) indicating that simulating risk behaviour could produce the observed seasonal patterns of cases. A vaccination strategy providing short-term immunity was more effective than educational interventions to modify human risk behaviour. Extending immunity to 1 year from 20 days reduced disease burden by an order of magnitude (from 2412-2414 to 203-309 cases per 50,000 person-years). CONCLUSIONS: This is the first interdisciplinary study to integrate environment, risk behaviour, socio-demographics and immunology to model Campylobacter infection, including pathways to mitigation. We conclude that vaccination is likely to be the best route for intervening against campylobacteriosis despite the technical problems associated with understanding both the underlying human immunology and genetic variation in the pathogen, and the likely cost of vaccine development.

Spatio-temporal models to determine association between Campylobacter cases and environment.

Background: Campylobacteriosis is a major cause of gastroenteritis in the UK, and although 70% of cases are associated with food sources, the remainder are probably associated with wider environmental exposure. Methods: In order to investigate wider environmental transmission, we conducted a spatio-temporal analysis of the association of human cases of Campylobacter in the Tyne catchment with weather, climate, hydrology and land use. A hydrological model was used to predict surface-water flow in the Tyne catchment over 5 years. We analysed associations between population-adjusted Campylobacter case rate and environmental factors hypothesized to be important in disease using a two-stage modelling framework. First, we investigated associations between temporal variation in case rate in relation to surface-water flow, temperature, evapotranspiration and rainfall, using linear mixed-effects models. Second, we used the random effects for the first model to quantify how spatial variation in static landscape features of soil and land use impacted on the likely differences between subcatchment associations of case rate with the temporal variables. Results: Population-adjusted Campylobacter case rates were associated with periods of high predicted surface-water flow, and during above average temperatures. Subcatchments with cattle on stagnogley soils, and to a lesser extent sheep plus cattle grazing, had higher Campylobacter case rates. Conclusions: Areas of stagnogley soils with mixed livestock grazing may be more vulnerable to both Campylobacter spread and exposure during periods of high rainfall, with resultant increased risk of human cases of the disease.

Modelling responses to nutritional, endocrine and genetic strategies to increase fertility in the UK dairy herd.

The United Kingdom, as in most countries using intensive dairy management programmes, is facing serious challenges in terms of dairy cow fertility, as highlighted by a rapidly increasing calving interval (CI). A mechanistic, mathematical model is described that predicts the size of the future national dairy herd required to supply domestic requirements and its inherent sustainability in terms of production of replacement female numbers. The results from the model suggest that continuing use of current management strategies may result in the national dairy herd being unsustainable due to increasing CI and reduced fertility in as few as 10years. Adoption of nutritional, endocrine and genetic techniques that increase fertility can effectively and rapidly reverse this trend and reduce the required size of the national herd, thereby reducing methane emissions from dairy production.